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pmc-6289586-1
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A 27-year-old, 43-kg British woman presented to the emergency department with a four-day history of yellow-colored diarrhea followed by vomiting and periumbilical cramping abdominal pain. Eight years prior, the patient had been investigated by gastroscopy only for iron deficiency anemia, but no other investigations were done. Initial investigations showed no signs of sepsis, yet a plain abdominal X-ray showed small bowel obstruction in a surgically virgin abdomen in Figure .
As the patient had mild symptoms and was very reluctant for operative intervention, a period of non-operative management was commenced, involving observation overnight, and had a contrast-enhanced abdominal computed tomography (CT) scan the next morning. The formal reporting of the next-day CT scan stated that the patient had a 9 cm cecum “representing either a volvulus or congenital malrotation pulled to the right upper abdomen...in keeping with enteritis or inflammatory bowel disease” in Figure .
The patient underwent an emergent diagnostic laparoscopy with plans for a right hemicolectomy, which was quickly converted to a midline laparotomy incision due to poor intraperitoneal vision from a markedly distended cecum. A necrotic distended cecal bascule with a sealed subhepatic perforation was found, thus a stapled cecectomy across the twist was done to prevent the intravascular release of toxic metabolites and to allow uncrowded access into the abdominal cavity. Other findings were an inflamed mid-ascending colocolic intussusception and two unexplained areas of ischaemic ulceration on the lateral walls of the descending colon. An initial abbreviated laparotomy was done to excise these pathological areas of the colon. The intussusceptum's lead-point is seen in Figure . At 48 hours, the patient underwent a relook laparotomy for subtotal colectomy with a diverting loop ileostomy and was eventually was discharged from hospital on Day 20. A formal referral was organized to the geneticist to determine the possibility of a predisposing polyposis syndrome in this young, adult female patient. This is the first reported case to describe this highly rare "pathological couplet." Investigations for possible prothrombotic states returned as negative and were thus unhelpful in explaining the cause of the ischaemic ulceration in the lateral aspect of the descending colon. Figure shows the gross anatomical specimens described by the pathologists.
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pmc-6289938-1
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8 years old Saudi girl known case of bronchial asthma, complaining of left nasal obstruction with mild eye proptosis for 9 months noticed by her parents. Her past medical and surgical histories were unremarkable. Drug history, family history and psychological history were insignificant. Examination showed left eye proptosis, enlarged medial canthus and polyps filling the left nasal cavity. CT sinuses showed a heterogeneous opacity of the left maxillary and frontoethmoidal sinuses with bone expansion and obliteration of the left nasal cavity (A) consistent with AFRS.
The patient and her family were fully counseled about the nature of the disease, the surgical management, treatment plans and recurrence. The patient underwent endoscopic sinus surgery and cleaning of the left sinuses from polyps, mud and mucin, performed by A.A. (rhinologist). Culture was positive for asperigillus. Initially the patient was doing well for one year follow up. However, one year later she started to complain of right nasal discharge and obstruction. Examination showed clear left nasal cavity with no recurrence of disease but there were right nasal polyps with mucin. CT sinuses showed recurrence of the disease in the right side with clear left nasal cavity (B).
The patient underwent endoscopic sinus surgery for right sinuses cleaning and polyp’s removal. Culture was positive for asperigillus. The patient had no recurrence after 3 years follow up.
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pmc-6289947-1
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This case report is of a 64 - year old female who presented to our institution with complaints of an enlarged swelling in the occipital region. The patient denied any symptoms of night sweats, fever, weight loss or any other swellings to other regions of her body. On examination she was noted to have a 1.5 × 2 cm node in the occipital region which was non-tender, non-erythematous and mobile. The patient had a full ENT examination done which also consisted of a flexible laryngoscopy, all of which proved normal. She was booked for excision of the node. The histology at this time revealed a lymph node with mild reactive features. She was discharged from our clinic at that time but returned with bilateral cervical lymphadenopathy which was again biopsied and showed reactive features.
Our patient was seen on several occasions and investigated extensively, but all tests were inconclusive. During one of these visits she was noted to have a lesion present on the left postero-lateral part of the anterior tongue, which was palpable below the mucosa but barely visible with the naked eye (a, b).
A biopsy was arranged of the left postero-lateral tongue and a left cervical lymph node biopsy. Immunohistochemistry was performed which showed a high-grade T Cell Lymphoma (). The patient was then referred to Haematology for further management of her condition.
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pmc-6289947-2
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This second case is of an 85 year old man who presented with a one-year complaint of dysphagia to solids which had been progressively getting worse. He had a sensation of a “lump in his throat”, but no complaints of weight loss, night sweats or fever. The patient was a heavy smoker with a 65 - pack year history. The patient had an examination of his ENT system which revealed a large mass in the base of his tongue which appeared quite vascular (). The oropharynx could not be visualised through the mouth.
A flexible laryngoscopy was then attempted which showed the mass extending from the level of the oropharynx down to the base of the tongue, with poor visualisation of the vocal cords. Arrangements were subsequently made for an urgent CT scan of his Head, Neck and Chest, which showed a large, irregular, solid lesion to the left side of the base of the tongue. It measured 7.4 cm (CC) × 6.9 cm (TS) × 4.6 cm (AP) and demonstrated no calcifications or internal cystic component (a, b).
A tracheostomy was then performed under local anaesthesia and biopsies taken from the mass after the patient was placed under general anaesthesia. Immunohistochemistry was done on the specimen which showed normal tonsillar lymphoid architecture effaced by a diffuse population of atypical lymphoid cells with a centroblastic appearance. The cells had a diffuse strong expression of both CD 10 and Bcl-2 and expressed the B-cell marker CD 20 but were negative for CD 3. A diagnosis of diffuse large B-Cell Lymphoma (DLBCL) was thus made. The patient was then referred to Haematology where he underwent treatment of his condition.
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pmc-6290220-1
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A 32 years old male patient presented to the emergency room with complete loss of consciousness since three hours after two weeks of night fever, sweating and considerable loss of weight with self-treatment by antipyretic drugs (Paracetamol and Ibuprofen). In the last two days, the patient develops confusion and altered behavior. Clinical examination of the patient revealed high-grade fever and coma. CXR revealed mild cardiomegaly with enlargement of the left atrium. Random blood sugar (RBS), Renal function tests (RFT) and Liver function tests (LFT) were unremarkable. Brain CT was unremarkable, no hemorrhagic stroke. Abdominal ultrasonography was normal. The patient admitted to the intensive care unit (ICU) and treatment started by intravenous fluids, antipyretics, and antibiotics.
, Echocardiography revealed mild Mitral regurgitation (MR), thickening of the pericardial membrane with mild pericardial effusion that suggested infective pericarditis – . ESR was elevated significantly (57 mm/hour). The same treatment continued.
of treatment without improvement, Tuberculosis suggested and laboratory investigations implemented. Brain MRI T1 weighted images with Gadolinium revealed basal meningeal enhancement with multiple small cerebral granulomas- .
FLAIR-weighted images revealed multiple tiny high signal intensity (SI) foci in bilateral temporal lobes and the basal ganglia strongly suggesting vasculitis and ischemic lesions- .
CSF sample and culture did, and treatment started with anti-tuberculous drugs, IV fluids, corticosteroids, and other supportive drugs. The results of CSF culture confirmed the diagnosis of tuberculous meningitis.
of coma with continuous anti-tuberculous treatment, the patient seemed to regain consciousness. The final diagnosis was Tuberculous meningitis, vasculitis, and pericarditis. The patient continued Rifampicin tab 700 mg, Isoniazid tab 350 mg, Ethambutol tab 400 mg, Pyridoxine tab 80 mg, Aspirin tab 100 mg and other supportive drugs for six months. The patient regained full health without any mental or motor disabilities. He didn’t remember anything about the period of coma.
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pmc-6290221-1
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A 20 years old man with no known co-morbid conditions presented with low grade fever and unilateral limb weakness for three weeks which increased gradually, associated with altered level of consciousness for the last five days. Rest of the history was unremarkable, except that he had positive contact history of pets.
On inspection ill looking young thin lean man was irritable and confused on verbal response. General physical examination revealed blood pressure of 125/80, pulse was 95 per minutes, respiratory rate was 22 breaths per minute and temperature was 39°C. Neurological exam showed Glasgow coma scale of 13/15 (E4, M5, V4). Neck stiffness was positive. Increased tone was noted in right lower limb, while bulk was normal and equal bilaterally. Power was decreased in right upper and lower limbs, measuring 1/5, while it was 5/5 in left upper and lower limbs. Planters were up going bilaterally and pupils were reactive to light in either eye.
Initial laboratory investigations included complete blood count, urea, creatinine and electrolytes, liver function tests, calcium, magnesium and albumin, all were within normal limits. Lumber puncture showed protein of 46mg/dl (20-40mg/dl), glucose of 72mg/dl (60% of plasma glucose), 6 RBCs (0-4/cumm) and 5 white blood cells (Nil). Blood culture, CSF culture and PCR were negative. MRI brain showed multiple ring enhancing lesions in white and grey matter involving corpus callosum, subcortical areas and periventricular region in frontal, parietal and temporal lobes. The lesions were surrounded by vasogenic edema appreciated on coronal FLAIR image. AFB smear and MTB DNA were negative. C3 (146.5) (normal range 90-180) and C4 (26.1) (normal range10-40) levels, done to rule out hypocomplementemia and were within normal limits. The ratio of CD4:CD8 was within normal range (0.98) (reference value 0.68-2.73). Toxoplasmosis IgM levels 36IU/mL (normal value<18 IU/mL) and IgG levels were raised 57.7IU/mL (normal range ≤ 8 IU/mL). Anti-HIV antibody test by CMIA method and HIV core protein p24 were negative. (Reference ranges>1.0).
He was treated with combination therapy of trimethoprim / Sulfamethoxazole and folic acid. Due to unavailability of 1st line treatment i.e. pyrimethamine and sulphadiazine in the country above mentioned drugs were used. IV steroid were used to subside the inflammatory reaction. Subsequent MRI after two weeks showed reduction with size of the lesions with decrease in surrounding edema.
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pmc-6290305-1
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A 54-year-old man with a past medical history significant only for hypertension presented to our clinic with a large soft tissue growth on hislower back which had been present for the past 20 years. Over the past three years it had been rapidly enlarging, nearly doubling in size over that time frame. He had recently re-established medical care after having not seen a physician since childhood. At the time of presentation, he denied any pain or tenderness over the mass and denied any systemic symptoms such as fever, night sweats, and weight loss. The patient had an unremarkable physical exam except for the large soft tissue mass over the lower back, with the maxiumum dimension measured to be 38cm () .
After evaluation by the surgical oncology and radiation oncology services, an abdominal CT scan was obtained and thisdemonstrated a large (35 cm, x 38 cm x 17 cm), heterogeneous soft tissue mass. A differential diagnosis consisting of teratoma versus liposarcoma was established based on the radiologic imaging. Subsequently, several core biopsies of the mass were performed, all of which revealed fat necrosis with calcifications.Surprisingly, given the size and rapid growth of the mass, a diagnosis of benign giant lipoma was made.
Four weeks after presentation, several surrgical teams performed a six hour operation to remove the 14 kilogram mass. After the patient was widely prepped and draped, the skin overlying the central portion of the tumor was shaved and harvested as multiple split thickess skin grafts (). Subsequently, an incision was made in the skin overlying the tumor in an area outside the skin graft donor sites, preserving significant flaps in all dimensions to permit primary closure (). Numerous, large variceal vessels feeding the tumor were ligated as the tumor was dissected off of the paraspinous muscles, which constituted the deep margin.
The specimen was sent for frozen section analysis,which was consistent with a lipoma, and was confirmed on final the pathology. The defect was able to be closed primarily with the preserved skin flaps, which measured greater than 200 cm × 40 cm (). The skin flaps were de-epithelialized and imbricated to achieve a multi-layered closure of the entire back wound, obliterating as much of the deadspace as possible. Two subcutaneous closed-suction drains were placed prior to the final closure. Postoperatively, the patient did well without complication (). After a brief and uneventful hospital stay postoperatively, he was discharged home in good condition. On follow-up, his drains were sequentially removed and the incision line has healed without problems. He has not had any evidence of recurrence or infection at six months postoperatively.
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pmc-6290306-1
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A 50-year old homeless gentleman, with a background of known epilepsy and chronic obstructive pulmonary disease, presented to the Emergency Department following a fall following a 7-minute witnessed tonic-clonic seizure. He complained of a rapidly worsening, excruciating pain generally all over his dominant right hand since the fall. Immediate referral to our plastic surgery team was performed. On examination, there was obvious bruising and swelling extending to the mid-forearm, with significantly reduced range of motion at the wrist and all finger joints as well as reduced sensation generally in the affected hand, particularly in the median nerve distribution ().
The radial and ulnar pulses were not palpable. Following an unremarkable hand radiograph, a diagnosis of acute hand compartment syndrome secondary to a crush injury was established, and immediate surgical exploration was performed 8 hours after the injury to decompress all dorsal and volar compartments, thenar and hypothenar compartments and mid palmar space (-). Although significant oedema was noted above and below the deep fascia, muscle was viable throughout. All incisions were left open and the hand dressed and immobilised in a volar splint. Strict post-operative elevation in a Bradford sling followed on the ward and the patient later went home.
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pmc-6290313-1
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A 81-year old woman was referred to our department to evaluate a wound dehiscence on her left knee with hardware exposure. The patient did not have any relevant comorbidities and her general status was good. The patient underwent a total left hip arthroplasty at the age of seventy four due to severe osteoarthritis pain that hindered baseline activities. Eight years later, the patient presented to the orthopedics department with a progressive pain in the affected hip, particularly when walking, causing difficulties in deambulation.
An X ray examination revealed an extensive femoral bone loss with displacement of the femoral component, and an MRI showed a femoral pseudo-tumor (bone proliferation). With this finding, a revision total hip arthroplasty was performed with the insertion of a reconstruction ring with cemented dual mobility cups. Three weeks after this last surgery, the patient started with early symptoms of infection (high fever, suppuration, no wound healing and laboratory abnormalities); an attempt at conservative management with intravenous antibiotic, irrigation and suction drainages was unsuccessful and a replacement of the endoprosthesis femur in two stages was planned.
In the first stage, the previous prosthesis was removed with enlarged osteotomy of the anterior tuberosity and a cement spacer with antibiotic was placed. Two months later, the spacer was removed and a new coated silver total femoral prosthesis was placed. The patient was referred to our unit four weeks after the last surgery for the assessment of wound dehiscence to the lateral knee with hardware exposure. The patient was taken to the operating room for retention debridement and wound coverage with a flap. Our first decision was to cover the defect with a lateral gastrocnemius flap, however, the surrounding area was highly scarred, and the gastrocnemius muscle was found to be very atrophic and no suitable to fit the large defect. shows no other local flaps to be large enough to cover the whole defect, so we opted for a free flap.
A lack of receptor vessels was evidenced, descending genicular artery was dissected, but small caliber and calcified plaques in the lumen discarded this option. With the need of a suitable and large vessel close to the defect, we opted for an AV loop that was constructed with ipsilateral greater saphenous vein. The femoral artery was found to be very atherosclerotic, but a healthy segment free of calcific plaque on the middle third of the vessel was used to perform the anastomosis of the vein graft in end-to-side fashion ().
A latissimus dorsi musculocutaneous flap with a large skin paddle was transferred to the lateral knee defect, and the thoracodorsal artery and vein were anastomosed in an end to end fashion to the limbs of the loop. The flap was properly inset to provide adequate bulk and to avoid dead spaces (). Donor site was closed primarily. Intraoperatively, no incidences occurred and the flap appeared well perfused. The patient was extubated and transferred to the recovery room in stable condition with standard clinical monitoring. Tissue oximetry system (INVOS CO.) was used 72 hours after the surgery. Three drainages were left, two of them in lower limb placed in lateral knee and lateral hip and one in donor area of the flap. Drainages were retained until output was less than 30 ml per day.
Wound healing properly evolved as well as the patient started rehabilitation during admission. The patient received Daptomycin (700 mg/d iv) and fosfomycin (2 g/6h iv) during 6 weeks, according to the infectious medicine protocol. The patient started walking uneventfully with a walking frame one month after surgery. The patient was enrolled in an outpatient rehabilitation program with close monitoring. At present time, the patient is able to ambulance without the need of assistant devices and there are no signsor symptoms of infection recurrence.
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pmc-6290314-1
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A 31 year-old female patient referred to our clinic due to a palatal perforation secondary to septorhinoplasty performed 2 years before, with minimal regurgitation and hypernasal speech. The patient had history of 2 failed fistula closure operations. On examination, a small perforation in the hard palate was observed (). There was not any undiagnosed underlying submucousal cleft palate or high palatine vault (). She was subjected to surgery under general anesthesia. Palatal perforation was repaired with mucosal hinge flap as nasal lining and a mucoperiosteal rotational flap for oral coverage. In the subsequent follow-up, no recurrence of fistula was observed and the problems of regurgitation and hypernasal speech were solved.
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pmc-6290385-1
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A 54-year-old woman was referred to our hospital because of abdominal pain. She had a history of adult Still’s disease at age 49 and underwent treatment with oral prednisolone, 90 mg/day and cyclosporine, 175 mg/day. A physical examination revealed deep tenderness in the abdomen. Laboratory data showed slight leukocytosis (white blood cell count 9100/μL) with a moderately elevated C-reactive protein level (9.3 mg/dL), while other data, including blood coagulation factor, were within normal ranges. Computed tomography (CT) revealed a small amount of extra-intestinal free air around the rectum and massive retroperitoneal emphysema between the rectum and the left kidney (Fig. a and b). Arterial aneurysm was not confirmed. Based on a preoperative diagnosis of rectal perforation, emergency laparotomy was performed, which confirmed peritoneal fluid collection (Fig. ) and rectum perforation on the retroperitoneal side. After aspiration of the pus and irrigation of the area with saline, Hartmann’s operation was performed (Fig. a). Although she was undergoing immunosuppressive treatment, pathological study disclosed no association between diverticulum perforation and cytomegalovirus enteritis (Fig. b). On postoperative Day 4, she suffered a sudden intolerable left flank pain; her hemoglobin level was 7.5 g/dL, and slight prolongation of prothrombin time was recognized. CT revealed a left retroperitoneal hematoma and extravasation from the left first lumbar arteries (Fig. a). Emergency transarterial angiography and lumbar artery embolization was performed (Fig. b). On Day 20 after the first operation the patient felt a sudden right flank pain, and CT confirmed intra-abdominal free air (Fig. a). A second emergency laparotomy was performed, which revealed cecal perforation with no obvious masses (Fig. b). Perforation resulting from diverticulum was suspected, and an ileostomy without intraperitoneal anastomosis was performed because of concern about anastomotic leakage. Postoperatively the patient developed an intra-abdominal abscess, surgical site infection (Clavien-Dindo IIIa) and pneumonia (Clavien-Dindo II), which were treated conservatively. Although it took time to rehabilitate the patient and control the adult Still’s disease, she was discharged on Day 212 after the first operation. The patient is now doing well with comfortable activity of daily life.
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pmc-6290498-1
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A 26-year-old primigravid woman, at 35 weeks gestation attended our obstetric department complaining of abdominal pain along with nausea and vomiting for 3 h. The woman’s antenatal care was uneventful. She had no significant medical, surgical or family history and no history suggestive of thromboembolism. She had never used oral contraceptives or any other hormonal therapy.
Upon arrival, she had a temperature of 36.8 °C, pulse rate of 80 beats per minute, respiratory rate of 20 breaths per minute and blood pressure of 119/71 mmHg. A physical examination on admission showed a gravid uterus just below the xiphoid process. No abdominal tenderness or rebound tenderness were appreciated. The bowel sounds were normal and there were no signs suggestive of peritonitis. A hematologic examination revealed a leukocyte count of 13.1 × 109/L (normal range 4.0 × 109/L - 10.0 × 109/L) with neutrophils accounting for 73.9% (normal range 50–70%), hemoglobin level of 98.6 g/L (normal range 100 g/L - 150 g/L), hematocrit of 0.317 (normal range 0.37–0.43), and platelet count of 187 × 109/L (normal range 100 × 109/L - 300 × 109/L). Coagulation profile and biological tests were within normal limits. Obstetric ultrasound revealed a normal fetus compatible with expected gestational age. The fetal monitor showed that fetal heart rate fluctuated between 150 and 160 beats per min and the uterus contracted occasionally. Threatened preterm labor was initially suspected and magnesium sulfate was given to inhibit uterine contractions. Acute gastritis was also considered.
The second day after admission, the patient complained of more intense abdominal pain that was centered in the right lower quadrant, and she experienced increased vomiting and abdominal distention. Physical examination demonstrated right lower quadrant tenderness without rebound tenderness and a distended abdomen and weak bowel sounds. Hematologic testing revealed leukocytosis with a left shift (leucocyte count of 26.9 × 109/L and neutrophils accounting for 91%) and hemoconcentration (hematocrit of 0.439). Serum amylase was normal. An abdominal ultrasound scan revealed dilation and effusion of the right intestinal canals, thickening of the intestinal wall and a small amount of ascites. Abdominal plain radiography was performed and showed no dilated bowel loops and no features of obstruction or pneumoperitoneum. Obstetric ultrasound revealed demise of the fetus.
Acute appendicitis with perforation was suspected and an emergency exploratory laparotomy was performed immediately. On exploration, approximately 1500 mL of serosanguineous peritoneal fluid was found in the abdomen. The entire ileum, part of the jejunum and part of the ascending colon were gangrenous, and thromboembolism in the corresponding mesenteric veins was noted. The necrotic intestine, measuring approximately 180 cm, was resected and an end-to-end jejunum-colon anastomosis was performed. Since there was no evidence of pending spontaneous labor and delivery and to avoid the release of fetally-derived necrotic materials that could complicate the clinical scenario via pro-coagulant and pro-inflammatory effects, a cesarean section was performed and the fetus and placenta were removed. The patient’s hematological values during the operation showed a white cell count of 14.58 × 109/L, neutrophils accounting for 91%, hemoglobin of 73 g/L, a hematocrit of 0.236 and a platelet count of 135 × 109/L. The pathologic examination revealed extensive mucosal denudation, edema, hemorrhage and neutrophil infiltration in the submucosa and muscularis propria of the bowel (Fig. a), and widespread thrombosis in mesenteric venous lumens (Fig. b).
The patient was transferred to the intensive care unit after surgery. Total parenteral nutrition, intravenous antibiotics and full anticoagulation with low molecular weight heparin were initiated postoperatively and continued until discharge. Thrombolytic therapy was withheld due to bleeding risk. The patient had a reasonably uneventful recovery and was discharged on postoperative day 36. Four years later, the patient was again pregnant and underwent thrombophilia testing (antithrombin, protein C, protein S, and coagulation parameters) at 30 weeks of gestation. At that time, antithrombin III activity was 64% (normal range 80–120%). Her antithrombin III activity returned to normal (96%) 4 weeks later. She delivered a healthy baby through a cesarean section at 38 weeks of gestation without thromboembolic event and without thromboprophylaxis. She has been recurrence-free for 10 years without anticoagulant therapy.
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pmc-6290501-1
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A healthy looking, 50-year-old Nepali man came to our clinic with a complaint of multiple growths on his scrotum for 15 years. The growths started as a single lesion on the right side of his scrotum, with the gradual appearance of similar lesions on other parts. Several of these lesions coalesced at various places to form large-sized nodules. The condition was mostly asymptomatic with an occasional complaint of itching. There was no history of pain, burning sensation, trauma, ulceration, or discharge. The lesions did not interfere with urination or sexual activities. He was worried because of the increasing size of the growth and hence came to us for advice. He did not give a history of any systemic illness including metabolic, autoimmune, or malignant disorders. There was also no history of a similar complaint in his family.
On physical examination, multiple pink to brown nodules ranging in size from 0.5 × 0.5 × 0.5 cm to 3 × 3 × 1 cm involving almost half of his scrotum were noticed (Fig. ). The skin over the nodules was shiny with several yellowish points indicative of underlying calcium deposition. The skin surrounding the nodules, testis, and penis was normal on palpation. The nodules were painless and firm in consistency. On laboratory examinations the following were found to be within normal limits: serum calcium, phosphorus, parathyroid hormone, and vitamin D hormone levels; uric acid; alkaline phosphatase; and lipid profile. Based on clinical features and laboratory reports, a diagnosis of ICCS was made.
He was advised a scrotectomy under spinal anesthesia, which he refused. The nodules were excised under local anesthesia in several sittings. The skin was sutured using chromic catgut (4–0). His postoperative period was unremarkable with good cosmetic result and no evidence of recurrence in a 1-year follow-up period. The cut section of nodules showed solid white to yellow homogenous areas. Histopathological examination revealed skin tissue lined by keratinized stratified squamous epithelium. The underlying dermis had areas of fibrosis and calcification (Fig. ). Numerous multinucleated giant cells were also seen (Fig. a and b). An obvious cystic structure was absent.
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pmc-6290520-1
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A 19-year-old Japanese woman underwent root canal treatment on tooth #47 by a general practitioner in 2005, but dull pain persisted after. Tooth #48, which was horizontally embedded, was extracted in August 2010, but the pain continued. In August 2015, she presented at the Department of Oral Surgery of another hospital with a purulent discharge from the pocket of tooth #47. Intraoral radiography showed insufficient root canal filling in the distal root and a foreign body, suspected to be extruded gutta-percha, outside the apex of the mesial root of tooth #47, accompanied by bone absorption around both roots (Fig. ). Two months later, she underwent extraction of tooth #47, removal of the foreign body, and curettage of the periapical lesion, resulting in the disappearance of the pain. However, she noted expansion of the right posterior mandibular bone in March 2016 and was thus referred in May 2016 to the Department of Oral and Maxillofacial Surgery, Tokyo Medical and Dental University, Japan. Her health and nutritional status were good in spite of a low body mass index (17.0). Both a blood test and a chest X-ray showed normal findings. She had neither lymphadenopathy nor paralysis of the mental/lingual nerve. The right inferior border of the mandibular bone slightly bulged. The socket of tooth #47 was epithelialized, and tooth #46 was vital, with a pocket depth of 3 mm. There was no sinus tract. Panoramic radiography revealed new bone formation at the equivalent sites of teeth #48 and #47 and a radiolucent region around the distal root of tooth #46 (Fig. ). Computed tomography showed continuous absorption from the alveolar bone of the distal root of tooth #46 to the lingual cortical bone at the equivalent of tooth #47 and six granulated hard tissues (Fig. , ). On magnetic resonance imaging, the right lower molar region was of low intensity on an enhanced T1-weighted image and high intensity on an enhanced T2-weighted image (Fig. ). This same region was enhanced heterogeneously by gadolinium, as was the soft tissue located between interior to the mandibular angle and anterior to the submandibular gland (Fig. ). She was diagnosed clinically as having osteomyelitis of the right mandible.
Surgical debridement under general anesthesia was performed. Via the submandibular region, an incision was made in the thickened periosteum at the inferior border of the mandible, after which the lingual periosteum was separated from the mandible (Fig. ). Tooth #46 was then extracted to achieve complete primary closure, and the gingiva incised (Fig. ) to enucleate the soft tissue including some of the hard tissues accompanying the periapical lesion of tooth #46 (Fig. ). There was no sequestrum and the intraoral wound was closed primarily. Our patient’s postoperative course was uneventful, with no exacerbation of the inflammation for more than 20 months.
On histopathologic examination, a large epithelioid cell granuloma with central caseating necrosis was observed in the dense fibrous tissue (Fig. ). The granuloma contained Langhans multinucleated giant cells. Acid-fast bacilli were not detected by either Ziehl–Neelsen staining or immunohistochemical staining using anti-BCG and anti-TB1 antibodies. Grocott staining revealed a slight presence of fungi. The pathological diagnosis was epithelioid cell granuloma including caseating necrosis.
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pmc-6290981-1
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The patient was a healthy 38-year-old male who was involved in a minor automobile accident and was complaining of intermittent back pain that he described as sore and stiff. His pain was 3/10 on visual analog scale. His pain was exacerbated by prolonged sitting and standing, and forward bending. He reported that there were no relieving factors. He was treated with therapy and had the MRI scan six weeks after the accident. It was originally read as a herniated L3-4 disc to the left side. The radiology report specifically stated L2 was normal. He started complaining of left leg pain, primarily in posterior thigh and calf, as well as tingling in the left leg. Because of failure to get symptomatic relief and complaints of tingling in the left leg, he was referred to a neurosurgeon. Neurologic examinations including sphincter function, reflexes, sensory and motor were normal. However, on review of the original MRI scan by the neurosurgeon, a possible intradural lesion was seen at L2 and a stat MRI with gadolinium contrast was ordered revealing a smooth, strongly homogeneously enhancing mass of 14 x 21 x 13 mm in the central and right intradural space behind the L2 vertebral body (Figure ). It was felt the symptoms were from the disc herniation and the intradural tumor was incidental. He subsequently had transforaminal microdiscectomy at L3-4 for the herniated L3-4 disc with complete resolution of his back and left leg pain and leg tingling. He was explained that the tumor was a separate lesion that would grow over time and was given the option of open laminotomy and tumor resection verse stereotactic radiosurgery. He elected for continued observation of the tumor with follow-up MRI scans and was programmed for stereotactic radiosurgery.
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pmc-6290981-2
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The patient was a healthy 47-year-old male who was involved in a minor automobile accident approximately five weeks prior to presentation. He was the restrained driver of a motor vehicle when it was struck on the driver’s side. He was complaining of constant low back pain that he described as sore, stiff and aching that radiated from the low back into the left hip. His pain was rated a 6-7/10 on a visual analog scale. Sitting and lying down exacerbated his symptoms. His symptoms improved with physical therapy, non-steroidal anti-inflammatory medication and rest. An MRI without gadolinium, of his lumbar spine was performed six weeks after his accident. It was read by the radiologist as a L4-5 posterior central and left paracentral disc herniation, L5-S1 broad-based disc bulge and an expansile mass in the conus medullaris and superior cauda equina. The radiologist recommended that the MRI be repeated with gadolinium contrast. The contrast MRI was compared to the previous MRI which also showed the intradural lesion and he was referred to a neurosurgeon. Neurologic examinations including sphincter function, sensory and motor were normal. His deep tendon reflex was normal except a decreased knee jerk on the right which was 1+/4. On review of the MRI with gadolinium contrast an intradural mass was seen in the conus at L1 measuring 2.4 cm x 1.5 cm with a non-enhancing irregular center and an enhancing periphery (Figure ). Electromyographic testing and bladder cystometrics both were normal. The patient elected for continued follow-up with serial MRI scans with contrast. He was recommended to have at minimum biopsy and radiosurgery and decided on radiosurgery.
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pmc-6290982-1
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A 43-year-old man was brought to the emergency room with deep machete lacerations to the right forearm, a superficial laceration to the left forearm, and a deep laceration and partial amputation of the right lower leg (Figure ).
Radiographs showed complete comminuted and displaced fractures of the right midshaft of the radius and ulna, as well as a comminuted fracture of the left proximal fibula (Figures ).
A chest radiograph was unremarkable. His past medical history included asthma and a hospital admission for an abscess of the right thumb in 2009.
Immediate care included antibiotic coverage with cloxacillin 500 mg IV every six hours and gentamicin 80 mg IV every eight hours. Intraoperative reconstruction and external fixation of the forearm was performed, as well as reconstruction of the fibula with common peroneal nerve and gastrocnemius muscle repair. Postoperatively, cloxacillin and gentamicin were continued for a total of seven and five days, respectively.
Five days after admission, the patient developed signs of infection in the right lower limb and debridement was performed twice in the operating theatre. Ceftazidime 1 g IV every eight hours and crystapen benzylpenicillin two megaunits IV every six hours were added to the antibiotic regime. Wound swabs were obtained, and Gram stains showed numerous Gram-negative bacilli and some Gram-positive cocci, as well as yeast cells. However, wound cultures grew only P. aeruginosa and P. luteola. The P. aeruginosa was sensitive to amikacin, ceftazidime, ciprofloxacin, gentamicin and tobramycin, but was resistant to carbenicillin. P. luteola displayed sensitivity to amikacin, ceftazidime, ciprofloxacin, gentamicin and tobramycin with resistance to ampicillin, augmentin, bactrim and imipenem, and intermediate sensitivity to cefotaxime and ceftriaxone.
On hospital day seven, the patient spiked a temperature of 38.1°C and the lower limb showed signs of gangrene (Figure ); the foot was cold and swollen with loss of sensation, peripheral pulses were absent, and palpable crepitations were present. A diagnosis of gas gangrene was made.
The patient and his family were informed of the available treatment options and together with the medical team, a decision was made to perform an above-knee amputation of the right leg. Post amputation, the patient’s health improved, and the rest of his hospital stay was uneventful. Three months after the trauma incident, the right stump was clean and healing well. The fractures of the right forearm were also healing, and good callus formation was seen.
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pmc-6291379-1
|
Physical examination showed the phenotype of a 3-year-old boy with a normal size penis. The testis was palpable in the left groin and a nonpalpable undescended testis was found on the right side.
On MRI, the left testis was located in the left hemiscrotum, was 1.3 × 0.6 cm in size, and associated with mild hydrocele. Another testis measuring 1.2 × 0.6 cm was noted on the ipsilateral side within the left inguinal canal (
).
Exploration of the left groin revealed the presence of both testes within the same side one above the other. They had separate vasa deferentia and testicular vessels for each testis and a common cremasteric muscle and tunical covering. After herniotomy, the ectopic testis was fixed transseptally to the right hemiscrotum (
).
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pmc-6291379-2
|
Physical examination showed a 1-year-old male with a normal size penis. The testis was felt in the left groin and a nonpalpable undescended testis was found on the right side. In comparison to the right side, the left scrotum was well developed.
On MRI, the left testis was located in the left hemiscrotum, was 1.2 × 0.6 cm in size, and associated with mild hydrocele. Another testis measuring 1.3 × 0.6 cm was noted at the same side just above the first one near the neck of the scrotum (
and
). At this point, the diagnosis of left side TTE was obvious. There was no evidence of inguinal hernia or Mullerian duct structures. Left groin exploration showed a testis over the other near the scrotal neck. Both cords were released followed by bilateral orchidopexy in a subdartos pouch after passing one of them through the median raphe onto the right hemiscrotum.
The suspected diagnosis of a right undescended testis was changed to a left-sided TTE.
Left groin exploration showed a testis over the other near the scrotal neck. Both having common coverings. Both cords were released followed by bilateral orchiopexy using a subdartos pouch after passing one of them through the median raphe onto the right hemiscrotum (
).
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pmc-6291507-1
|
Patient CS, a single 60-year-old male presenting with a history of generalized anxiety with panic, major depressive disorder, and excessive guilt, was referred from a county hospital to a tertiary psychiatric facility for clarification of diagnosis and a more comprehensive assessment. His sister, and the family physician that had been following the patient for the past 4 years, helped provide collateral history. His family noted that he was born with a large head. He had a history of meningitis at the age of 9 or 10 after which it is thought that he developed a non-communicating hydrocephalus. His past psychiatric diagnoses included major depressive disorder, generalized anxiety disorder with panic, personality disorder, and “borderline intelligence.” He had several admissions to a psychiatric ward over the past 3 years for low mood and had been trialed on numerous psychotropic medications (citalopram, lithium carbonate, risperidone, olanzapine, quetiapine, paliperidone, clomipramine, clonazepam, lorazepam) with little effect or benefit. At the time of admission, he did not smoke, drink alcohol, or take illicit drugs. His past medical history was significant for hypothyroidism corrected with the use of thyroxine, bowel resections secondary to possible malignant changes, fatty liver with lobar resection secondary to liver cancer and nephrolithiasis.
He was born and raised in Europe until the age of 5, when he immigrated to Canada, and is bilingual. His family reported that he had always had a large head, micropenis, central obesity and short stature. He had a history of being bullied for “looking like a girl” and being different. At school his peers were physically aggressive, hitting him on his head. Born the youngest of seven siblings, he was raised by his parents and lived under their care into adulthood, until both parents passed away—his father had Diabetes Miletus and his mother had a brain tumor. Thereafter, he was taken care of by his sister. He had an older brother who also passed away secondary to a brain malignancy. One brother has dyslipidemia, and two sisters and one brother are healthy. He had no employment history and as a child had always struggled in school, completing a vocational stream of education until grade 10. Socially, he was active in a band for a few years (plays guitar well) and sang in a church choir. However, he never lived independently, and had no romantic relationships.
Initial assessment revealed that he was a poor historian unable to give an accurate timeline of events. He often expressed fears that he was going to die. He suffered from delusions of guilt that he had caused the deaths of family members. His conversation was repetitive, he repeatedly asked the same questions and restated his fear of dying despite several reassurances. He had no history of self-harm or suicide attempts. On physical examination, he had a wide stance waddling gait, slow movements, limited arm swing and masked facies. He was noted to have enlarged head circumference (62.5 cm) and limited insight into his illness and the need for treatment. His clinical presentation prompted examination with magnetic resonance imagining (MRI) of the brain and formal neuropsychological testing.
A sagittal T1, axial T2, axial T2 FLAIR and diffusion-weighted images were acquired throughout the brain. Findings indicated a long-standing overt ventriculomegaly, likely due to aqueductal stenosis, with bilateral gross dilation of the lateral and third ventricles, with a small aqueduct and fourth ventricle, with significant thinning of the corpus callosum and overlying cerebral cortex. Vascular flow-voids at the base of the brain were normal and there were no mass lesions, significant sulcal effacement, downward tonsillar herniation or restricted diffusion observed.
Manual segmentation of gray and white matter and cerebrospinal fluid (CSF; Figure ) of high-resolution T1 weighted MRI images was completed with Freeviewer in FSL (Jenkinson et al., ). Automatic segmentation of a comparison group of sex and age matched healthy controls (HCs; one aged 60, three aged 55 years, Table ) was completed with the FreeSurfer () recon tool. The participant’s volumes were converted to Z scores for comparison. Compared to similarly aged control participants, the patient had extremely large ventricular volume (821,452 mm3, Z = 161), reduced white (333,606 mm3, Z = −2.655) and gray (432,184 mm3, Z = −3.07) matter volume, and within normal range total intracranial volume (1,587,242 mm3, Z = 0.57) see Table and Figure .
The patient’s neurological exam was unremarkable.
The Wechsler Adult Intelligence Scale (WAIS-III; Wechsler, ) revealed a borderline IQ of 79, with a verbal IQ of 88, non-verbal performance IQ of 74, poor working memory IQ of 71, verbal comprehension IQ of 93, and visual-spatial IQ of 80. The patient had difficulty completing tasks requiring working memory, which was in the 3rd percentile, and processing speed was extremely slow (in the 1st percentile). Hopkins Auditory Verbal Learning Test (Brandt, ) indicated severe memory impairment, with initial memory for only a few items, no significant recall between administrations, and inability to recall any information after a brief delay. Rey-Osterrieth Complex Figure Task (Osterrieth, ; Rey et al., ) performance indicated impaired visual spatial and working memory abilities with more attention to small details, missing elements and less attention to the overall image. The Stroop test (Stroop, ) indicated impaired executive function, scoring below the 1st percentile, with a severe inability to suppress automatic responses.
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pmc-6291814-1
|
A 3-year-old boy of Roma origin, clinically diagnosed with CDLS, was referred to the audiology clinic of our center for hearing impairment. His main clinical characteristics were low birth weight, delayed growth, bushy eyebrows with synophrys and excessive body hair. He did not have cleft palate, midfacial developmental anomalies, upper limb malformations or motor delays. Due to the poor compliance of his parents, he had never undergone any hearing assessment prior to our examination. Informed consent was obtained from the parents to allow their child to participate in the study.
The child presented with a total absence of speech and was only articulating some sounds; his non-verbal communication was based mainly on eye contact. Otoscopy and tympanometry were normal. The audiological examination, including auditory brainstem responses and otoacoustic emissions, revealed a bilateral profound sensorineural hearing loss. In visual reinforcement audiometry, performed with warble stimulus in free field, no response was obtained at frequencies of 250–8,000 Hz. The child also underwent a routine evaluation by our cochlear implant team child psychiatrist using psychometric tests (including Denver developmental screening test), and was considered to have border mental retardation. A computed tomography (CT) scan of the temporal bone showed normal patency of the basal turn on both sides ().
Three months after his assessment, the child successfully underwent cochlear implantation of the right ear with Med-el Sonata implant. After typical mastoidectomy and posterior tympanotomy, a Med-el standard electrode was totally inserted via cochleostomy. The postoperative period was uneventful. An X-ray confirmed the intracochlear position of the electrode array (). No complications were noted, and the boy was discharged from the hospital on the seventh postoperative day. One month later the child developed bilateral secretory otitis media which was conservatively treated.
In order to measure the child’s auditory-speech perception and speech intelligibility, we used internationally reliable instruments: i) Listening Progress Profile (LiP) to assess his auditory-speech perception; ii) Capacity of Auditory Performance (CAP), which comprised a nonlinear hierarchical scale of auditory receptive abilities, ranging from 0 to 7; and iii) Speech Intelligibility Rating (SIR), a 5-point rating scale that quantifies the speech production abilities of the child (). Preoperatively, the child's LiP score was very limited at 2%. He could respond to environmental sounds (CAP 1) and his speech was intelligible only when expressed as pre-recognizable words (SIR 1) ().
Two weeks postoperatively, the LiP score of the child had progressed slightly to 12% and his CAP score had increased from 1 to 2 (he could also respond to speech sounds); however, his SIR score remained at 1. At his latest follow up, 3 years postoperatively (at 6 years of age, ), the child demonstrated a moderate benefit in terms of auditory perception (mean LiP score: 36%), and he managed to identify environmental sounds (CAP 3), although he could not discriminate speech sounds without lipreading (CAP 4). His SIR score was improved from 1 to 2, as his speech was now intelligible when expressed in single words via context and lipreading cues, but it was still unintelligible to a listener who concentrated and lipread (SIR 3). Free-field audiometry using warbled pure tones revealed a satisfactory hearing threshold from 250 to 6,000 Hz in a range from 30 to 45 dB HL. Although the family is bilingual, it was advised to communicate with him only in the language of the home country, in order to match the language of the speech therapy.
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pmc-6291815-1
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A 14-year-old boy visited the ear, nose, and throat (ENT) outpatient department of our center, with a history of left-sided nasal obstruction gradually progressive over a period of 1 year, with recurrent history of associated rhinorrhea. There was no history of epistaxis or any other ENT complaints, and the patient’s past medical history and family history were insignificant.
On anterior rhinoscopy, a single polypoidal mass was seen filling the left nasal cavity extending up to the vestibule. The mass was firm in consistency, insensitive to touch and pain, and did not bleed upon touch. General and systemic examinations and an examination of the rest of the ENT were all within normal limits. A contrast-enhanced computed tomography (CT) scan showed a homogenous soft tissue lesion measuring 44×68×12 mm in the left nasal cavity, extending posteriorly into the nasopharynx ().
The mass extended superiorly into the left ethmoid air cells up to the cribriform plate with its thinning and breach. The rest of the sinuses was clear. On contrast study, there was heterogeneous enhancement. Based on the CT findings of the anterior skull base breach, gadolinium-enhanced magnetic resonance imaging (MRI) was performed to rule out intracranial extension, and revealed small sub-centimeter focus posteriorly without any significant intracranial extension ().
Rigid endoscopy was carried out and the mass was seen attached to the anterior part of the nasal septum. A punch biopsy was taken, which presented as an inflammatory polyp.
The patient was referred for standard endoscopic sinus surgery under general anesthetic after providing informed consent. The mass was removed endoscopically, and was seen to be extending intracranially but extradurally. Complete resection of the tumor was achieved and while managing the tumor in the region of the cribriform plate, there was an obvious CSF leak. The site of leakage was identified and closed using an underlay technique with septal cartilage, fascia lata, and tissue glue. The intra-operative blood loss was minimal.The post-operative recovery period was uneventful. Histopathology of the excised specimen showed the tumor mass lined by pseudostratified columnar epithelium with squamous metaplasia. The subepithelial tissue was composed of loose myxoid areas with mature adipose tissues and foci of cartilage. Foci of neuroepithelial cells occupying more than four low-power fields were seen. Grade 3 immature teratoma was given as final diagnosis (-).
Adjuvant chemotherapy was started based on the histological grading, with four cycles of bleomycin, etoposide, and cisplatin. A regular follow-up for a period of 2 years showed no signs of recurrence.
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pmc-6291816-1
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A 5-year old female presented with a wooden FB (pencil) penetrating the left orbit after falling while the pencil was in her hand at home. On examination, part of the pencil appeared at the entry wound inferior and lateral to the medial canthus, with mild right upper lid edema (). On ophthalmological examination, visual acuity and ocular mobility was not affected and both globes were intact. Both pupils were reactive.
A computed tomography (CT) scan showed that the pencil penetrated the left orbit through the lacrimal bone to the left nasal cavity then perforated the nasal septum, crossing the right nasal cavity. From there, it penetrated the lamina paperatea to the right orbit until its tip stopped very close to the right optic nerve ().
Ethical standards
The author obtained written informed consent from the parents of the reported case and the study was approved by the Institutional Review Board.
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pmc-6291818-1
|
A 68-year-old woman presented with headache, hearing loss, facial asymmetry and dysphagia for few months. On examination, the patient had right facial palsy (grade IV based on the House-Brackmann scale). Otoscopic and nasal endoscopic examinations were found to be normal. Examination of the oropharynx and larynx revealed right-sided 9th, 10th and 12th cranial nerve palsies with loss of the gag reflex, paralysis of the soft palate, paralysis of the right hypoglossal palsy with deviation of tongue to the right side and right-sided vocal cord palsy. Neck examination showed drooping of the right shoulder and there were no palpable neck nodes. Pure-tone audiogram demonstrated right-sided mixed hearing loss.
A computed tomography (CT) scan and contrast enhanced magnetic resonance imaging (MRI) showed soft tissue lesion in the mastoid with sclerosis in the basiocciput extending to the clivus and sphenoid; features suggestive of extensive mastoiditis with cholesteatoma (–). The bony changes in the occipital bone could possibly be due to fibrous dysplasia or metastases. The patient underwent biopsy and debulking of the tumor, and histopathological examination confirmed it to be a metastatic adenocarcinoma.
Positron Emission Tomography CT using 18-fluorodeoxyglucose (18F-FDG PET-CT) tracer demonstrated multiple bony involvement, with the skull base including the right petrous bone with intracranial extension and multilevel axial skeleton involvement including the upper cervical spine (C1 to C4), dorsal vertebral (D11) () and lumbar spines (L1,L3). There was also an intra-abdominal involvement with a large ‘doughnut-like’ lesion in the liver with subdiaphragmatic metastases (). Unfortunately, the patient refused further investigation and defaulted treatment.
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pmc-6291873-1
|
A 63-year-old female with chronic bilateral pleural effusions and small pericardial
effusion was transferred to the Mazankowski Alberta Heart Institute in October 2017
with respiratory failure secondary to flash pulmonary edema. She was intubated
shortly after arrival and responded to diuresis with the resolution of her pulmonary
edema. She was extubated after 2 days and had unchanged small pleural effusions. Her
electrocardiogram on presentation () showed sinus rhythm with a left bundle branch block that was
unchanged from her old electrocardiograms. Her transthoracic echocardiogram showed a
normal ejection fraction and severe concentric left ventricular hypertrophy with
diastolic dysfunction. Diastolic function was assessed using the American Society of
Echocardiography guidelines.
Her past medical history was significant for multiple hospital admissions with flash
pulmonary edema and chronic pleural effusions since December 2016. Her previous
investigations included a pleural biopsy that did not show any pathology, and
following an episode of acute kidney injury, she underwent a renal biopsy, which was
inconclusive. She also had a whole-body positron emission tomography scan that did
not show any evidence of malignancy. She was known to have hypertension, chronic
kidney disease, mild chronic obstructive pulmonary disease, schizoaffective
disorder, and mild cognitive impairment. Her social history was significant for
active smoking but no alcohol or illicit drug use. She was worked up for a possible
inflammatory condition to explain her chronic pleural effusions. Her serum ANA
(antinuclear antibody), anti-dsDNA, rheumatoid factor, erythrocyte sedimentation
rate, and C-reactive protein were all negative. She had a positive pANCA and was
referred to the rheumatology consult team. Her positive pANCA was felt to be
nonspecific for any rheumatologic condition. She was also seen by the neurology team
for a possible neurodegenerative disorder causing recurrent aspirations given her
recurrent hospitalizations with respiratory failure. However, her swallowing
assessment was completely normal, and she only had mild cognitive impairment on
formal cognitive testing.
During her hospital stay, she was noted to have elevated systolic blood pressure
above 190 mm Hg with diastolic blood pressure in 100 to 110 mm Hg range despite
being on maximum doses of 5 antihypertensive medications (hydrochlorothiazide,
bisoprolol, amlodipine, spironolactone, and terazosin). She developed anuric acute
kidney injury shortly after starting the ACE inhibitor, ramipril. This was
reversible with stopping the new medication, and her kidney function returned to
baseline (creatinine level of 120 µmol/L) but her blood pressure was still elevated.
At that point, bilateral renal artery stenosis (RAS) was suspected. A computed
tomography angiogram of the renal arteries confirmed the diagnosis of
atherosclerotic bilateral RAS (). She then underwent a renal angiogram with right renal artery
angioplasty and stenting (). The left RAS was believed to be chronic as the left kidney was
already atrophied. Her invasive systolic blood pressure was confirmed to be markedly
elevated at 210 mm Hg. She tolerated the procedure well, and on the following day,
her systolic blood pressure decreased to 120 mm Hg, and she felt lightheaded. Her
antihypertensive medications were held and blood pressure was closely monitored. She
was then introduced to a small dose (12.5 mg) of spironolactone for the
mineralocorticoid blocking effect and 2.5 mg of bisoprolol to avoid β-blocker
withdrawal. She tolerated both medications very well, and her blood pressure was in
the normal range. She was also started on enteric-coated aspirin 81 mg daily and
atorvastatin 80 mg daily for treatment of peripheral atherosclerotic disease.
She was followed closely as an outpatient and had no recurrent pulmonary edema. Her
follow-up echocardiogram 8 months later showed normalization of the left ventricular
mass, and reduction in the left atrial size and right ventricular systolic pressure
(; , available in the online version of the article.).
In summary, a unifying diagnosis that explained her chronic pleural effusions and
recurrent hospitalizations with respiratory failure (likely due to flash pulmonary
edema) was heart failure with preserved ejection fraction (HFpEF) secondary to
resistant hypertension due to bilateral RAS. This case demonstrates how HFpEF due to
RAS (a potentially curable condition) can easily go unrecognized especially in
patients with multiple comorbidities if a high index of suspicion is not
maintained.
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pmc-6291954-1
|
A 6-year-old boy was referred to our hospital due to a 9-day history of fever. On day 3 of illness, a diffuse maculopapular rash appeared. He was orally treated with cefcapene pivoxil prescribed by his family pediatrician. On admission, his weight and height were 24 kg and 124 cm, respectively. He had a temperature of 38.9 °C and had a diffuse maculopapular rash. His lips, hands, and feet were erythematous. In addition, he also developed hepatosplenomegaly and had pitting edema in his feet. There was no history or findings of conjunctival injection and cervical lymphadenopathy.
His clinical course is shown in Fig. . Blood examination revealed the following: white blood cell count of 12,800/μL (neutrophils, lymphocytes, and monocytes were 88, 9, and 3%, respectively). C-reactive protein of 5.85 mg/dL; hemoglobin level of 11.7 g/dL; and platelet count of 26.6 × 104/μL. Other blood findings were as follows: serum albumin of 2.7 g/dL, total bilirubin of 0.7 mg/dL, sodium of 131 mEq/L, potassium of 3.1 mEq/L, aspartate aminotransferase of 100 IU/L, alanine aminotransferase of 87 IU/L, lactate dehydrogenase of 613 IU/L, and ferritin of 19,740 ng/mL. His urinalysis showed leukocyturia without any bacteria (10–14 white blood cells/high power field). His chest radiograph showed normal findings. Echocardiography revealed a normal ejection fraction, but perivascular echo brightness of the coronary arteries was found.
Given that his clinical symptoms did not fulfill the diagnostic criteria for classic KD, he was diagnosed with an incomplete KD according to the American Heart Association guideline []. Therefore, intravenous immunoglobulin (IVIG, 2 g/kg/dose), intravenous prednisolone (PSL, 2 mg/kg/day), and oral aspirin (30 mg/kg/day) were administered on the 10th day of illness. In addition to IVIG, PSL was used for his treatments to prevent coronary artery abnormalities based on the result of RAISE study []. His temperature returned to normal soon after the first IVIG therapy was completed. On the 12th day of illness, however, he showed symptoms of arthritis in both knee joints, which led to a gait disturbance. sJIA was suspected based on the appearance of arthritis and an extremely high level of serum ferritin. To distinguish KD from sJIA, serum IL-6 and IL-18 levels were examined during that time. The serum levels of IL-6 and IL-18 were extremely low and high, respectively (Fig. and Table ). Given the markedly elevated serum ferritin and IL-18 levels, we suspected sJIA rather than incomplete KD. However, his rheumatoid factor and anti-nuclear antibody were negative. On the 17th day of illness, the elevated serum IL-18 level persisted (44,000 pg/mL) and his arthritis worsened. On the 18th day of illness, because skin desquamation of the fingertips occurred, he was diagnosed with incomplete KD. After the PSL treatment of 2 mg/kg/day for 11 days, PSL was tapered to 1 mg/kg/day for 5 days and then 0.5 mg/kg/day for 5 days. On the 32nd day of illness, the PSL treatment was discontinued, as his joint symptoms were markedly improved. After the aspirin treatment of 30 mg/kg/day for 5 days, aspirin of 5 mg/kg/day was discontinued after 2 months of the disease onset. On the 116th day of illness, serum IL-18 level returned to normal. At 16 months after the disease onset, he had never shown any signs of joint or skin involvement and cardiac abnormalities including coronary arteries.
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pmc-6291956-1
|
A 94-year-old male with a past ocular history of age-related macular degeneration (AMD) in both eyes presented to the ophthalmology clinic for a routine dilated fundus exam (DFE). On exam his Snellen visual acuity was 20/100 OD and count fingers (CF) OS. Exam findings were significant for end-stage AMD in the left eye and subretinal hemorrhage in the right eye. He was referred for ocular ultrasound and found to have subretinal hemorrhage secondary to progression of his exudative macular degeneration. Anti-VEGF treatment was initiated and continued for several months. The patient was then found to have a choroidal lesion that measured 14.5 × 14.6 mm in basal dimension with a thickness of 6.4 mm. There was low to medium reflectivity, moderate irregularity and trace spontaneous vascularity. These findings were consistent with a clinical diagnosis of choroidal melanoma.
The patient was referred for a liver ultrasound, which showed questionable focal lesions within the liver, and further evaluation with CT abdomen and pelvis was recommended. Given the liver ultrasound findings the patient was re-evaluated with ocular ultrasound, which did not show evidence of extrascleral extension (Fig. ). The patient underwent staging CT chest, abdomen and pelvis that were negative for metastatic disease. An MRI of the orbits with contrast showed a subcentimeter region of abnormal contrast enhancement extending into the immediately adjacent retro-bulbar fat, suspicious for scleral invasion and small extrascleral lesional extension (Fig. ).
The patient presented to the ophthalmology walk-in clinic several days after the MRI with complaints of right eye pain that he described as “monotonous friction” like pain. Exam findings were significant for visual acuity no light perception (NLP) OD, an intraocular pressure of 28 OD, diffuse hemorrhage in the anterior chamber and no view into the posterior pole secondary to vitreous hemorrhage. B-scan ocular ultrasound performed during that visit was consistent with hemorrhagic choroidal detachments with diffuse vitreous hemorrhage. Given the presence of a choroidal melanoma, questionable extrascleral extension and a painful eye, patient and providers decided to pursue enucleation. The patient underwent enucleation OD and the specimen was sent for analysis. Final pathology revealed malignant melanoma of the choroid (spindle B-type) with intact sclera and no obvious extrascleral extension posteriorly (Fig. ).
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pmc-6291978-1
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A 26-year-old woman presented with progressive shortness of breath. Her past medical history was notable for asthma diagnosed at age 3, hearing loss at age 23 (that was not fully worked up) and hypertension at age 24. Ten months prior to admission, her blood pressure was 143/91 mmHg, and urine dipstick detected large protein and blood, but she was lost to follow up. The family history was significant for asthma and hypertension in her mother, type II diabetes mellitus in her father and asthma in her brother; her sister was healthy.
On admission, she was afebrile, blood pressure was 191/125 mmHg and the physical examination was otherwise unremarkable; fundoscopy was not performed. Urine analysis detected 25–50 non-dysmorphic RBCs/HPF, 5–10 WBCs/HPF,100 mg/dl protein, positive leukocyte esterase, and numerous “muddy brown casts”. Relevant laboratory results were white blood cell count 7.2× 109/L, hemoglobin of 8.9 g/dL, platelet count 73,000/μL, BUN 71 mg/dL, and serum creatinine 10.11 mg/dL. Other studies include AST 34 u/L, ALT 36 u/L, haptoglobin 10 mg/dl (low), and LDH 2331 u/L (very high). Occasional schistocytes were seen on peripheral smear and ADAMTS13 was normal. Serological studies were normal including C3 (138), C4 (37.2), ANA (neg), anti-MPO (< 0.2), anti-PR3 (< 0.2), anti-GBM antibodies (< 0.1), hepatitis B, hepatitis C, HIV, and serum and urine immunoelectrophoresis. Chest x-ray showed pulmonary congestion and kidneys were echogenic on ultrasound. The patient was started on hemodialysis and a kidney biopsy was performed.
The light microscopy sample had only 2 glomeruli and they had circumferential cellular crescents (Fig. a) and compressed capillary loops. Prominent tubular atrophy and interstitial fibrosis was seen with sparse interstitial inflammation and a few interstitial foam cells. The interlobular arteries and arterioles were mostly well preserved, but one arteriole had endothelial swelling, karryorrhexis and fibrin thrombus (Fig. b). No vasculitis was identified. Immunofluorescence revealed one glomerulus (also with crescent) and segmental granular C3 (1+; scale 0–4). No staining was seen with IgG, IgA, IgM, C1q, κ and λ. Three glomeruli, again with crescents, were available for ultrastructural examination. In addition to the extravasated fibrin and basement membrane rupture, focal endothelial cell damage was apparent with expansion of the subendothelial space by electron lucent material. Several capillary loops had basement membrane irregularities and multi-lamination of lamina densa (Fig. c). No electron dense deposits were identified and podocytes overlying these compressed capillary loops displayed prominent foot process effacement.
The biopsy findings were most compatible with crescentic glomerulonephritis without extrarenal manifestations. Occasional arterioles had histological features of TMA. The glomerular basement membrane changes raised concern for Alport syndrome (AS), but due to the paucity of tissue sample, type IV collagen staining could not be performed. Given the suboptimal sample and concern for systemic TMA and AS, a second biopsy was performed 3 weeks after admission.
Eighteen glomeruli were sampled for light microscopy and three were globally sclerosed. Cellular/fibrocellular crescents were seen in 8 glomeruli with one fibrous crescent. Fibrin thrombi were identified in two glomeruli (Fig. d). Several other glomeruli had ischemic changes and the tubular atrophy and interstitial fibrosis involved over 80% of the cortex. Clusters of interstitial foam cells were seen throughout the cortex. Several cross sections of interlobular arteries and arterioles had intimal edema, fibrinoid necrosis, and concentric thickening of the wall; no vasculitis was identified (Fig. e). Immunofluorescence was negative. On ultrastructural examination of 3 ischemic glomeruli, extensive endothelial cell injury was seen with subendothelial electron lucent material; prominent mesangiolysis was also present (Fig. f). Lamina densa lamellation was again seen. Additional immunofluorescence was performed for type IV collagen α2, α3 and α5 chains (Fig. g-i). Alpha2 staining was normal, indicative of good antigen preservation. However, α3 was completely absent in both glomeruli and tubules, and α5 lacked staining along the glomerular basement membranes but had intact staining along Bowman’s capsules and distal tubular basement membranes.
Both kidney biopsies were stained for C4d (rabbit polyclonal, cat. no. 04-B1-RC4D, Biomedica, Austria, 1/20 dilution) and C5b-9 (mouse monoclonal, cat.no. M0777, DAKO, Denmark, 1/10 dilution). Intimal and medial staining was seen with both C4d and C5b-9 in arterioles affected by thrombotic microangiopathy. Glomerular staining was seen in crescents and sclerosed segments, albeit more strongly with C5b-9 (Fig. ). In addition, C5b-9 staining was seen in patchy peritubular capillaries and interstitium.
Both kidney biopsies demonstrate crescentic glomerulonephritis, with increased chronicity on the second biopsy. In addition, there was acute and subacute TMA, better visualized on second biopsy. A sequencing of 12 aHUS-related genes was performed using a database of over 400 aHUS-associated mutations, disease-associated polymorphisms, benign polymorphisms and other known variants of undetermined significance (Machoan Diagnostics, Oakland, CA). Our patient was negative for the large CFHR1-CFHR3 homozygous deletion associated with CFH auto-antibodies. However, she had a heterozygous missense variant (c.1246 A > C, p.lle416Leu) in exon 11 of CFI, reported in aHUS [, ]. A heterozygous missense variant (c.136C > T, p. Pro46Ser) in exon 2 of CFHR5, reported in dense deposit disease was also noted []. A heterozygous polymorphism (IVS9–78 G > A) within an intron in MCP/CD46 was present and there were also 5 SNPs near and within MCP/CD46 that comprised a haplotype, also associated with increased risk for aHUS [].
The clinical, laboratory and genetic findings indicate a diagnosis of aHUS coexistent with glomerular crescents seen on biopsy. The interstitial foam cells on light microscopy (in the absence of chronic nephrotic proteinuria), basement membrane abnormalities on electron microscopy and abnormal immunofluorescence for α3 and α5 chains of type IV collagen support a diagnosis of AS, that likely contributed to the underlying chronic kidney disease. The immunofluorescence pattern of α3 and α5 staining suggests a α3 gene mutation with autosomal recessive inheritance. A genetic analysis for AS was suggested.
The patient was treated on admission with pulse methylprednisolone followed by oral prednisone. Daily plasmapheresis was initiated, but was discontinued after a few days once the ADAMTS13 levels were found to be normal. Cytoxan was administrated after the first biopsy results. Eculizumab therapy was initiated after the second biopsy and she continued to receive it every 2 weeks at her 8-month follow up. Her kidney function remains poor requiring maintenance hemodialysis.
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pmc-6291996-1
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A 65-year-old man who never smoked and had consulted a local hospital 3 years earlier presented to our hospital, where he was diagnosed with PCS and treated with right pneumonectomy, followed by six cycles of adjuvant chemotherapy with cisplatin plus irinotecan, because the pTNM stage was pT3N1M0 stage IIIA according to the 7 th lung cancer TNM classification. One year later, he experienced the rapid onset of left lower extremity paralysis, and brain gadolinium contrast-enhanced magnetic resonance imaging (MRI) performed in our hospital revealed a new brain mass with active bleeding in the right parietal lobe (Fig. ). The patient was treated with surgical resection, followed by stereotactic radiosurgery to the resection cavity. Immunohistochemical analysis of resected tissue samples revealed sarcomatous tumors composed of spindle cells and cartilage and epithelial tumors expressing cytokeratin AE1/AE3 (Fig. a, b). These histological findings were quite similar to those observed with tissue from pneumonectomy specimens (Fig. c, d). Therefore, we made a definitive histological diagnosis of metastatic PCS on the brain tumor specimens. A year and a half after this operation, brain gadolinium contrast-enhanced MRI revealed meningeal dissemination (Fig. a), and chest radiography identified two nodules in the left lower lung field (Fig. b) which were diagnosed with lung recurrence although the lesions were not verified histologically for fear of fatal iatrogenic pneumothorax because of right pneumonectomy. The patient began treatment for PCS with pazopanib (Votrient®, GlaxoSmithKline, Uxbridge, Middlesex, UK) 800 mg orally once a day on the basis of the histological diagnosis because pazopanib has been approved for the treatment of soft tissue sarcoma in Japan. Two weeks after treatment initiation, the patient was withdrawn from the drug because his platelet count was reduced to 60,000/μL. Since the platelet count recovered to above the lower limit of normal 2 weeks later, he was permitted to resume pazopanib at 400 mg orally once a day. Although a brain MRI scan showed no change in the meningeal dissemination, a chest and abdominal computed tomography scan demonstrated a reduction in size of 60% in the lung metastatic lesions of PCS according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 after 2 months of treatment (Fig. a-d). His quality of life during the pazopanib treatment had kept adequate because there was little adverse event by pazopanib except thrombocytopenia. 6 months later, the patient showed consciousness disorder due to the progression of the meningeal dissemination and stopped taking pazopanib despite the lung metastatic lesions kept shrinking.
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pmc-6292035-1
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A 45-year-old male with known risk factors of endothelial dysfunction (including smoking and hyperlipidemia) had typical episodes of angina for 3 days. Characteristic dynamic changes of electrocardiogram (ECG) and cardiac marker of myocardial necrosis troponinT (cTnT) suggested posterior STEMI. Emergency coronary angiography (CAG) revealed complete proximal occlusion of the circumflex artery (Fig. a). A drug eluting stent was deployed to the proximal left circumflex artery (p-LCX). Final angiogram revealed that the PPCI was successful (Fig. b). Three hours later, the patient developed dyspnea and persistent pleural chest pain, and the ECG showed widespread concave ST segment elevations and PR segment depression (Fig. a). A follow-up CAG was performed 33 h after PPCI, and no stent thrombosis or any significant evidence of iatrogenic trauma due to the intervention procedures was found. But a significant slower TIMI flow (grade ≤ 2 grade) (Fig. c) and abnormal TIMI myocardial perfusion frame count (TMPFC = 140 frames, at a filming rate of 30 frames/sec.) in the culprit arteries were seen through CAG. Consistent ST segment elevation on ECG with an increase in cTnT, but no recurrent CK-MB peak, seemed to suggest that the persistent focal myocardial injury might possibly involve coronary microvascular dysfunction (CMD). In recent years, assessing coronary flow reserve (CFR) by intracoronary Doppler guide wire and positron emission tomography (PET) is considered the gold standard for quantitative assessment of coronary microcirculation disorder. But this method is technically complex and very expensive, and therefore not applicable to the present case based on the patient’s condition and intention. Chest CT scan showed mild pleural effusion and interstitial infiltration in both lungs (Fig. b, c), and UCG revealed mild pericardial effusion with posterior wall motion disappearance (Fig. d, e). Blood test showed that the serum concentration of HsCRP was persistently increasing; neutrophil count and the level of cTnT were elevated in parallel with HsCRP increase in the early and later stage of PCIS, respectively (Fig. ). The erythrocyte sedimentation rate (ESR) (83 m/s) was also significantly elevated as another inflammatory marker, while the concentration of Anti-Streptolysin O (ASO) and Antinuclear Antibody (ANA) associated with rheumatic and tuberculosis disease and B-type natriuretic peptide (BNP 107 pg/ml) was still in the normal range. So we concluded that the patient had developed PCIS. After receiving full anti-ischemic drug treatment and aspirin at an anti-inflammatory dose, the patient was symptom-free during hospitalization. The pericardial effusion was gradually resolved along with the recovery of serum concentration of HsCRP and cTnT to the normal levels at 3 weeks after PPCI.
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pmc-6292041-1
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A 34-year-old woman with platin-resistant metastatic ovarian cancer experimented fever and chills during intravenous infusion of the anti-PD-1 antibody, nivolumab. The patient’s temperature was 39.5 °C, pulse rate was 120/min, and blood pressure was 95/60. Physical examination showed nausea and a known pelvic mass. The cardiopulmonary auscultation was normal. There were neither cutaneous nor mucous abnormalities. Allergic reaction was suspected. Infusion was stopped, antihistamine and corticosteroids (1 mg/kg of methylprednisolone) were administered. The patient remained febrile. Gram stain of a positive blood culture revealed bacillus Gram-positive bacteria. Combination therapy with amoxicillin and gentamicin was started. Finally, three blood cultures, one drawn from the port-a-cath and two from a peripheral vein returned positive for rapidly growing mycobacteria. The port-a-cath was removed and the antibiotics were switched to gentamicin, clarithromycin, and ethambutol. Transthoracic echocardiography revealed no sign of endocarditis. The isolate was sent to a local referral laboratory for identification and susceptibility testing. Identification to the species level was performed by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF mass spectrometry) (Vitek MS, BioMerieux®, Marcy l’Etoile, France), leading to Mycobacterium mucogenicum identification. In the absence of clinical information, M. mucogenicum was considered as a contaminant, and susceptibility testing was not performed. Nevertheless, diagnosis of M. mucogenicum port-a-cath related bloodstream infection was retained. Two weeks after starting antibiotic treatment, renal impairment urged its change. Usual susceptibility of M. mucogenicum motivated switch to clarithromycin and moxifloxacin. Our isolate was sent to the National Consultant Laboratory for Mycobacteria for sensitivity testing. Identification was confirmed through sequencing analysis of hsp65 gene. Susceptibility testing was performed by standard broth microdilution method using Sensititre® RAPMYCO panel. The isolate was susceptible to clarithromycin and moxifloxacin (Table ). The occurrence of this infection prevented the poursuit of experimental infusion of nivolumab. After 2 months of combination antibiotherapy, cyclophosphamide was started because of worsening of peritoneal carcinomatosis. Antibiotics were pursued 6 months. No relapse of infection was observed after its discontinuation despite concomitant chemotherapy.
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pmc-6292057-1
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A 28-year-old female patient presented to our department due to blurry visual acuity for 10 years especially in the right eye with deterioration for 5 months. The best corrected visual acuity (BCVA) in the right and left eyes was 5.0 and 5.1 (logmar visual acuity chart), respectively. The intraocular pressure (IOP) in the right and left eyes was 17 mmHg and 18 mmHg, respectively. No abnormalities were observed in the anterior segment of both eyes. Fundus examination showed that the optic disc was normal, while the remarkable diffuse pinpoint or drusen-like speckle yellow white lesions affected the posterior fundus, with varying degrees of retina/retinal pigment epithelium (RPE)/choroid atrophy around the disc. The fovea light reflex was not clear (Figs. and ). Optical coherence tomography (OCT) scan showed extensive hyperreflective thickening beneath the retinal pigment epithelium (RPE, Fig. ). Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) assumed that RPE/choroidal disorder was featured by “honeycomb” appearance (Fig. ). Visual field showed defect in the temporal sides (Fig. ). Electrophysiological examination findings (e.g. ERG, EOG, and VEP) were normal.
Her 22-year-old brother showed BCVA of 5.0 (logmar visual acuity chart) in both eyes. Fundus examination showed diffuse pinpoint yellow white deposits throughout the macular and peripapillar area with honeycomb-like pigmentary changes around the disc (Fig. a and b). OCT scan showed a hyperreflective thickening beneath the pigmentary epithelium accompanied by wavy uplift (Fig. a and b).
Her 54-year-old mother complained of poor visual acuity for at least 20 years, especially at nighttime. The BCVA of the right eye was FC/10 cm, and the left eye was 4.0 (logmar visual acuity chart). She had corneal opacity in both eyes (Fig. a and b), and the fundus could not be observed clearly. Corneal scan of OCT showed granular cloudiness, and corneal endothelium detachment in the peripheral part (Fig. c and d). Color Doppler ultrasonography of eyeball showed thickening in the posterior wall of both eyeballs.
Her father showed no history of ocular diseases. He would not come to our hospital for the ocular examinations due to personal reasons.
After signing the informed consents, venous blood was collected from the female patient, her mother and her brother, respectively. Gene sequencing was performed by MyGenostics (Peking, China). Gene sequencing revealed heterozygous mutations in EFEMP1 gene, which was consistent with the DHRD/ML. The study protocols were approved by the Ethical Committee of Hainan General Hospital. For the gene sequencing, single heterozygous mutation (c.1033C > T) was observed in each of the three blood samples. This missense mutation triggered p.R345W (Fig. ).
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pmc-6292060-1
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A 62-year-old woman presented at our institution, having experienced pain in the lower left abdomen for two years. She was admitted to the urology unit at the hospital, and underwent a routine ophthalmic examination. She had a history of hypertension (10 years). The patient had no ophthalmological symptoms. Visual acuity (decimal) in the right and left eye was determined to be 0.6 and 0.8, respectively. The manifest refraction was + 1.50DS/− 0.75 DC× 100° in the right eye and + 1.00DS in the left eye.
The anterior segment examination results were normal. Ophthalmoscopy revealed RAH located at the inferior macular fovea in the right fundus (Fig. a) and at the subtemporal rim of the optic disc in the left fundus (Fig. b). Spectral domain optical coherence tomography (SD-OCT) revealed a retinal tumour in the inner layer of the retina in the right fundus (Fig. a). OCT demonstrated a pre-retinal membrane and retinal tumour located in the inner layer of the retina in the left fundus (Fig. b). Adenoma sebaceum was seen in the ala nasi, with no ash-leaf spots. Computed tomography (CT) revealed bilateral renal angiomyolipoma, multiple hepatic angiomyolipoma and multiple pulmonary nodules. Brain CT showed extensive bilateral calcification near the cella lateralis. The values obtained for the patient’s serum albumin and haemoglobin were 36.7 g/L and 99 g/L, respectively. The decreased serum albumin and haemoglobin levels may have been due to renal dysfunction affected by bilateral renal angiomyolipoma. The laboratory tests (erythrocyte sedimentation rate, C-reactive protein, tuberculin, syphilis, human immunodeficiency virus and hepatitis) were normal. The patient did not consent to an aspiration biopsy of renal angiomyolipoma. A clinical diagnosis of TSC was made. Everolimus was prescribed to the patient to improve abnormalities of the kidney.
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pmc-6292061-1
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We report a case of an 80-year old hypertensive and diabetic Saudi male referred to our center after developing sudden bilateral painless visual loss five days earlier. There was a history of a bilateral temporal headache that had started a year earlier. The headache was more prominent on the left side, mild to moderate in severity, and stabbing in nature. It used to occur on average once a week and would spontaneously resolve over several seconds. However, the frequency had increased in the months preceding visual loss, occurring almost daily. There was no report of any previous episodes of diplopia, transient visual loss, jaw claudication, myalgia, constitutional symptoms, motor or sensory symptoms.
Examination showed normal blood pressure, heart rate, and temperature. He was unable to perceive light in both eyes, and the pupils were bilaterally dilated, seven millimeters each, with no reaction to light. Fundoscopy showed normal appearing discs and retina. Ocular movements were full. The motor, sensory and coordination examination was normal. The C-reactive protein (CRP) upon admission was 132 mg/L and the erythrocyte sedimentation rate (ESR) was 40 mm/hr. A magnetic resonance imaging (MRI) of the brain was done (Fig. ) and it showed a lesion in right optic nerve suggesting acute ischemia. The ophthalmic arteries were not visualized bilaterally by contrast magnetic resonance angiography (MRA) (Fig. ). The clinical impression was of a bilateral Posterior Ischemic Optic Neuropathy (PION) due to giant cell arteritis (GCA).
The patient was started on intravenous Methylprednisolone 1000 mg for five days then shifted to daily prednisolone 60 mg orally. The vision did not improve but the headache improved significantly after a few days. A 2 cm segment of the left temporal artery was biopsied and the pathological findings confirmed giant cell arteritis (Fig. ).
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pmc-6292062-1
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A 64-year-old woman known to have cirrhosis secondary to Hepatitis C was transplanted in our center to treat drug-induced fulminant hepatitis failure. The patient received a standard post-op immunosuppressive protocol (including corticosteroids, tacrolimus, and mycophenolate mofetil).
She also received caspofungin (70 mg at day 1 then 50 mg/day) according to ESCMID recommendations as targeted prophylaxis against IA during 15 days []. The early post-operative period was associated with hemorrhagic episodes and peri-hepatic hematoma requiring several re-interventions whilst maintaining the antifungal prophylactic treatment. From post-operative day (POD) 31, the patient developed several septic shocks caused by Enterococcus faecium, Escherichia coli, and Candida glabrata, and all were treated by broad spectrum antibiotics and caspofungin was reintroduced.
On POD 63, the patient got fever resistant to antibiotics. Her chest CT-scan showed right-sided pleural effusion with passive atelectasis and alveolar opacity. Broncho-alveolar lavage (BAL) was performed and its direct examination displayed Aspergillus-like branched hyphae. At the same time, galactomannan (GM) antigen index (Platelia Aspergillus, BioRad) and (1–3)-β-D-glucan (BDG) (Cape Code) in serum, which were previously negative, became positive (GM antigen index > 6 (threshold index: 0.5), BDG = 234 pg/mL (threshold value: 80 pg/mL)). Aspergillus real-time PCR (qPCR), based on a target of 67-bp DNA fragment specific to the multicopy gene encoding the 28S rRNA of A. fumigatus, was positive in serum (Cq value = 35) []. Eventually, based upon data from the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) [], the patient was classified as having a probable IFI. Caspofungin was then switched to voriconazole (200 mg twice/day). On Sabouraud media, at 37 °C, the culture of BAL showed growth of several greenish to brownish colonies of filamentous fungi with a powdery aspect. Macroscopic examination revealed brown colonies on Malt media and surrounded by a white mycelium. The reversed side of the colonies was yellow. On Czapek Yeast Autolysated Agar (CYA) media, the detected colonies were much greener in color with velvety texture. Microscopic examination of the colonies showed Aspergillus biseriate conidial heads with curved conidiophores (Fig. ). On the basis of these macroscopic and microscopic examinations, the species can be suggested but must be confirmed by molecular identification. The follow-up GM antigen index, even with voriconazole, remained positive (index> 6 at POD 65 and 70). Antifungal drug susceptibilities were determined by Etest on RPMI medium supplemented with 2% glucose. MICs were read at 48 h of incubation at 35 °C. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, micafungin, and caspofungin were 0.75 μg/mL, 12 μg/mL, 4 μg/mL, 6 μg/mL, 0.016 μg/mL, and 0.5 μg/mL, respectively. Since the antifungal susceptibility revealed elevated MICs to azoles, voriconazole was then switched to liposomal amphotericin B. Additionally the results of EUCAST method confirmed the high MICs to azoles. On POD 81, the patient died from multiple organs failure and refractory septic shock secondary to pneumonia. Autopsy was not performed.
A molecular identification of this Aspergillus was performed. Complete genomic DNA was extracted from a mature subculture on Sabouraud agar using QIAamp DNA Blood Mini Kit (Qiagen Sciences Ing.) after a step of bead beading in MagNA Lyser Instrument (Roche). The rDNA of partial β-tubulin and calmodulin genes were amplified as described by Samson et al. []. Sequencing reactions were carried out for both strands. When compared with the partial calmodulin gene sequences available in the NCBI database, the highest identity was obtained with A. pseudodeflectus NRRL 278 strain (Genbank accession number EF652368.1) and NRRL 6135 strain (Genbank accession number EF652419.1) [] with nucleotide identity rates of 100 and 99%, respectively over a sequence length of 573 bp. For the partial β-tubulin sequences, identity rates of 99% were obtained with both strains, NRRL 278 (Genbank accession number EF652280.1) and CBS 596.65 (Genbank accession number EF591732.1). Phylogenetic trees of these two sequences, alone and combined, were built with the MEGA 6.05.1 software []. The neighbor-joining method, using the Kimura two-parameter model with 1000 bootstraps replications, was applied to each data set. The sequence relatedness of our strain with the species strains type of section Usti is shown in Fig. .
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pmc-6292076-1
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A 63-year-old Sinhalese man with diabetes mellitus of 8 years’ duration presented with fever, loose stools, and loss of appetite of 1 week’s duration. He was on diet control for diabetes with poor glycemic control and was not on a proper follow up. On admission he was ill and febrile. An abdominal examination revealed hepatomegaly, 2 cm from right costal margin, which was non-tender. Other systemic examination was unremarkable. An ophthalmoscope examination revealed non-proliferative diabetic retinopathy. A full blood count revealed white cell count of 18 × 109/L with neutrophil predominance. His hemoglobin was 12.2 g/dL and platelet count was 256 × 109/L initially and dropped up to 9.8 g/dl and 63 × 109/L, respectively. Blood film showed severe bacterial infection with sepsis and features suggestive of disseminated intravascular coagulation (DIC). A coagulation profile showed international normalized ratio of 1.7 and activated partial thromboplastin time of 37 seconds. Erythrocyte sedimentation rate was 75 mm/first hour. His C-reactive protein level was 197 mg/dL and his procalcitonin level was 59.9 ng/L. Consecutive blood cultures were positive for Klebsiella pneumoniae after 9 and 13 hours. The strain was sensitive to imipenem, meropenem, ceftriaxone, amikacin, and ciprofloxacin. A chest radiograph was normal. Retroviral screening was negative. His fasting blood sugar level was 212 mg/dl. A urine full report showed proteinuria (++) with 3–5 pus cells per high power field and the urine culture was negative. Stool examination was negative for amoebae, ova, or cysts. His initial serum creatinine level was 134 microgram/L and increased up to 647 microgram/L reflecting acute kidney injury. His urine output was satisfactory throughout the course. Serum potassium went up to 6.1 mmol/L and was managed medically. An ultrasound scan of his abdomen revealed a large ill-defined hypoechoic lesion suggestive of a liver abscess in the right lobe of his liver, at segments VII and VIII, measuring 8 × 6 × 5.5 cm in size (Fig. ). Lower gastrointestinal endoscopy was normal. The abscess was aspirated once by the interventional radiology team under ultrasound guidance yielding 100 ml of thick pus. He was treated with intravenously administered ceftriaxone for 2 weeks and a marked clinical and biochemical improvement was seen. His serum creatinine returned to upper normal limit following resolution of sepsis. A repeat ultrasonography performed at completion of intravenous antibiotic therapy revealed resolving abscess in segment VIII of his liver measuring 5 × 4 × 3.2 cm. As there was considerable clinical and biochemical improvement, he was discharged with a further course of orally administered cefixime and did not require further aspirations.
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pmc-6292083-1
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A 75-year-old female former smoker with a 30 pack-year history initially presented with fatigue, cough, and weight loss. She underwent a chest CT that demonstrated an 8.6 cm right upper lobe lesion with mediastinal invasion, extensive cervical and mediastinal adenopathy, and a malignant pericardial effusion (Fig. a). Upon biopsy this was proven to be squamous cell carcinoma that was TTF-1/NAPSIN negative and was staged as stage IV cT3N3M1b. Subsequently she developed hypercalcemia as a paraneoplastic complication. She was then initiated on palliative PT-DC with carboplatin and gemcitabine and then maintenance gemcitabine with a transient partial response. Thereafter she underwent palliative radiotherapy to her right lung, and subsequent salvage chemotherapy with docetaxel without response. She was then started on combination immunotherapy with PD-L1 and CTLA-4 antibody therapy. Histopathology did not reveal any PD-L1 expression on tumor cells prior to immune therapy initiation. After initial partial response, she developed oligo-progressive disease in a celiac lymph node that was resected with continuation of immunotherapy. Treatment holiday was initiated one year after starting combination immunotherapy, at which point no active disease was appreciated on imaging. Approximately nine months thereafter she was noted to have recurrence of disease and resumed the same combination immunotherapy for an additional one year. There was initially complete response during this course; however, the final staging study demonstrated focal progression of disease with multiple new cervical lymph nodes and a new aortocaval lymph node (Fig. ).
Tissues from the cervical lymph node and aortocaval lymph node biopsy confirmed poorly-differentiated squamous cell carcinoma consistent with her known lung cancer (Fig. b). The cervical lymph nodes were surgically excised. Given the sensitive location of the abdominal lymph node, image guided locoregional therapy was planned. The cryoablation was then performed on the aortocaval lymph node with complete response on follow-up imaging (Fig. b). Subsequent serial imaging showed durable complete control at the local aortocaval lymph node site for at least nine months with no additional oncologic therapy (Fig. c-e).
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pmc-6292103-1
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The tumor was diagnosed in a 64 year old, male Caucasian patient during a routine check-up.
Medical history: Besides atrial fibrillation, arterial hypertension and a hypothyroidism there is no relevant medical history especially no history of cancer.
During a routine check-up the patients physician performed a sonography when he detected an unclassified tumor of the pancreatic tail (see also Additional file ). The lab showed no pathologies. Tumor markers were negative for CA 19–9, CA 72–4 and CEA. Alpha-fetoprotein and NSE were both elevated (AFP 97kU/l, (< 5,8kU/l) and NSE 30.0 μg/l (16.4 μg/l)). A CT scan showed no metastases (Fig. a). A core needle biopsy was performed to define the tumor entity. The histology of the core needle biopsy extracted from the pancreatic tail area showed fibrotic fat with atypical adipocytes. The fluorescence-in-situ-hybridization (FISH) revealed MDM2-cluster amplification. Thus the diagnosis of a de-differentiated liposarcoma (DDL) was made.
With this histological diagnosis the solid tumor at the pancreatic tail was considered to be a dedifferentiated part of the liposarcoma. A primary surgical resection was recommended by the interdisciplinary tumor board.
A systematic left sided retroperitoneal compartment resection including en-bloc-left sided pancreatectomy, splenectomy, nephrectomy, hemicolectomy, adrenalectomy, partial gastrectomy and partial resection of the diaphragm were performed (Fig. b).
Having recovered from surgery and an anastomosis leak of the colon, the patient is now well. So far there were no signs of tumor recurrence.
The resected multivisceral specimen measured 35 × 19 × 12 cm and weighed 2520 g. The macroscopic examination showed a firm, inhomogeneous, yellowish gray, 7.6 cm diameter tumor between the pancreatic tail and spleen. The further investigation of the bordering retroperitoneal fat tissue revealed a 5.6 cm large area slightly solidified, marginally lobulated, yellow, lipomatous tumor without discrete margins.
Microscopic examination (Figs. a-d) of the tumor mass in the pancreatic tail showed an epithelial tumor with glandular structure, associated with a desmoplastic stroma reaction, continuously infiltrating the fat tissue and lymph nodes. The tumor cells with increased mitotic activity, nuclear pleomorphism and prominent cell nucleoli showed a cribriform and haphazard growth pattern. Furthermore there were necrotic areas and perineural as well as lymphatic vessel invasion definable (Fig. b). A tumor infiltration in spleen, kidney or colon was not detectable. In the directly adjacent retroperitoneum atypical lipomatous mesenchymal cells and multinucleated as well as vacuolated lipoblasts were found (Fig. c). These cells had been known from the punch biopsy and were also MDM2-cluster amplified, representing a liposarcoma of the retroperitoneum (Fig. d). Parts of this tumor approximated < 0.1 cm to the surgical margins. Taken together there was a completely resected pancreatic ductal adenocarcinoma and a well-differentiated liposarcoma with extended growth to the peritoneal margins. Additional molecular pathological investigation revealed a pathogenic category 5 mutation of pathogenic BRCA 2 of the adenocarcinoma. The pancreatic adenocarcinoma was classified as pT3, pN2 (11/33 ece+) L1 V0 Pn0, R0; G2 [UICC Stage III] with a drugable BRCA mutation and the liposarcoma as pT2, pN0 (0/33) L0 V0 Pn0, G1 [UICC Stage Ib]. Further treatment: The interdisciplinary tumor board recommended an adjuvant chemotherapy with the standard of treatment, being Gemcitabine and Capecitabine. The patient recovered well after surgery and is currently cancer free under frequent follow up for the last year. The latest follow-up examination revealed no evidence of tumor recurrence.
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pmc-6292130-1
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A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of her brachydactyly and right fibular fracture. She was born after a full-term pregnancy and normal delivery with an Apgar score of 10 as the only child in a non-consanguineous Chinese family. No prenatal investigation was performed, and the motor development was normal. Upon birth, her fingers and toes were significantly stubby with obvious shortening of the fourth metatarsal, although neither hyperdactylia nor syndactylism was observed. No intellectual impairment or multiple exostoses were noticed. Pubertal development was normal. She experienced a minor fall 1 month before being admitted to our department, and she was diagnosed with a fracture of the upper fibula in the right lower limb, which was treated by fibula internal fixation and fibula bone grafting in the Department of Pediatric Orthopedics. To investigate the reason for the brachydactyly, the patient was referred to the Department of Endocrinology and Diabetes.
Upon admission, a routine clinical examination revealed that the patient’s standing height was 144 cm, with her upper portion measuring 72 cm and her lower portion measuring 72 cm, and her arm span was 131.3 cm (Fig. a). Clinical examination also revealed sparse scalp hair, a high-bossed forehead, thick eyebrows with lateral rarefaction, a characteristic bulbous pear-shaped nose, a long philtrum and a thin upper lip, pointed chin, and large, protruding ears (Fig. b). Examination of the extremities showed brachydactyly with significant shortening of the fourth metatarsal, flat feet, thin nails and koilonychias (Fig. c, d). Radiography of both hands (Fig. a) showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Similarly, cone-shaped epiphyses were also spotted in the proximal phalanx of the toes of both feet (Fig. b).
Radiography was performed, and an osteolytic lesion was observed in the proximal right fibula before surgery. Radiography was performed 1 and 10 months following the surgery to monitor the recovery of the osteolytic lesion (Fig. c-g). Prior to the surgery, a large lesion protruding into the medullary cavity was found in the proximal right fibula with a pathologic fracture. A whole-body bone scan showed increased focal uptake only at the osteolytic lesion of the proximal right fibula (Fig. a).
A pathological cytological examination of the osteolytic lesion revealed that it was composed of benign spindle-shaped cells (fibroblasts) and histiocytes, with a scattering of xanthoma cells (Fig. b). Laboratory tests showed that the serum levels of calcium, inorganic phosphate, alkaline phosphatase, free T4, TSH, PTH, GH and IGF-1 were all normal.
The proband’s father presented with short stature (160 cm) (Fig. a), diffuse alopecia with fine hair, absence of lateral eyebrows, a large beaked nose and a long philtrum with a thin upper lip (Fig. b, c). He also presented with short metacarpals with brachydactyly, axial deviation of the middle finger and racket nails (Fig. d). No radiological examination was performed. The father declined radiological examination of his extremities.
Genetic analysis was performed using blood samples collected from the girl and her parents. A heterozygous variant, p.Ala932Thr, was identified in exon 6 of the TRPS1 gene in the girl (Fig. ). Subsequent targeted mutation analysis of exon 6 of her father confirmed the segregation of the variant in the girl. The healthy mother did not carry the sequence variant. Timeline depicting key milestones of diagnosis process and follow-up information was provided in the Additional file .
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pmc-6292170-1
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The current study patient was a 23-year-old woman with normal psychomotor development and healthy nonconsanguineous parents. She had frequent episodes of nausea, vomiting, stomachache and temporary elevated transaminase from about 4 years of age. Ammonia and plasma amino acid levels were measured when she was 5 years old. Her serum ammonia was 220 μg/dl (normal range 12 ~ 60 μg/dl) and she showed high levels of glutamine (1212 nmol/ml; normal value, 420–700), lower normal limits of citrulline (18.4 nmol/ml; normal value, 17–43), and lower plasma levels of arginine (32.2 nmol/ml; normal value, 54–130). A urine metabolic screen indicated a gross elevation in orotate (orotate/creatinine ratio 234.3 μmol/g creatinine; normal value, 4.7 ~ 15.9 μmol/g creatinine). These findings were consistent with OTC deficiency. She was therefore biochemically diagnosed with OTCD and her blood ammonia level has been well controlled since by a protein-restricted diet and by oral sodium phenylbutyrate and arginine. Recently, we performed genetic analysis to identify the genetic alterations of the OTC gene in this patient. However, Sanger sequencing revealed no pathogenic mutation.
Sanger sequencing was performed to screen for genetic variations at the nucleotide level throughout all coding exons of the OTC gene (Additional file ). We used UCSC genome browser () as human genome assembly. To screen for exonic deletions or duplications, multiplex ligation-dependent probe amplification (MLPA) was performed using the SALSA P079-A3 OTC MLPA kit (MRC Holland, Amsterdam, The Netherlands), in accordance with the manufacturer’s recommendations. MLPA products were separated by capillary electrophoresis on an ABI3730 genetic analyzer and then processed using GeneMapper software. The peak heights of the samples were compared with control probes and the ratios of these peaks were calculated for all exons. If the dosage quotient was 1.0, the results were considered normal. Thresholds for deletions and duplications were set at 0.5 and 1.5, respectively.
To demarcate the duplicated region, quantitative real-time PCR was conducted on blood DNA from the patient and a male control subject using the Applied Biosystems 7300 real time PCR system (Thermo Fisher Scientific). Several primer pairs were designed for OTC (upstream of exon 1 and intron 6) and RPP30 that was used as an autosomal single copy gene reference to generate amplicons suitable for real-time PCR (Fig. , Additional file ). The PCR reaction was performed in a 15 μL reaction system, containing 2 μL of template DNA (5 ng/μL), 0.6 μL of each primer set (10 μmol/L), 0.3 μL ROX Reference Dye, 4 μL distilled water, and 7.5 μL of 2xTB Green Premix Ex TaqII (Tli RNaseH Plus, TaKaRa). Two parallel PCR reactions were prepared for each sample. The amplification cycling conditions were as follows: 95 °C for 30 s, followed by 40 cycles at 95 °C 5 s and 60 °C for 1 min. Data evaluation was carried out using the 7300 system SDS software and Microsoft Excel. The threshold cycle number (Ct) was determined for all PCR reactions and the same threshold and baseline were set for all samples. The starting copy number of the samples was determined using theΔΔCt-Method. ΔΔCt method was a modification of the method described in Livak et al. for quantifying mRNA []. ΔCt represents the mean Ct value of each sample and was calculated for OTC and RPP30. The starting copy number of the unknown samples was determined relative to the known copy number of the control sample using the following formula:
ΔΔCt = [ΔCt OTC(patient)-ΔCt RPP30(patient)] - [ΔCt OTC(female)-ΔCt RPP30(female)]. The relative gene copy number was calculated by the expression2-Δ(ΔCt). The starting copy number of male control was also determined as a reference value.
Inverse PCR were performed using restriction enzyme TaqI (TaKaRa, Shiga, Japan) to isolate the unknown sequences adjacent to the duplicated region of the OTC gene in the study patient. ApE – A plasmid Editor software was used to identify the recognition sites for the restriction enzyme. The restriction enzyme was chosen based on the following criteria: (1) no cutting of the expected breakpoint area; and (2) endonuclease activity would be unaffected by CpG methylation of the target sequence. A 100 ng aliquot of genomic DNA from both our patient and a control female was digested with the selected restriction enzyme in a total volume of 30 μl at 65 °C for 90 min. The reaction was inactivated using the QiaQuick PCR Purification Kit. A 20 μL sample of digested DNA was then mixed with 23 μL of DW, 5 μL of 10 × T4 ligase buffer (TaKaRa, Shiga, Japan) and 2 μL of T4 DNA ligase to make a final volume of 50 μL. Ligation reactions were incubated at 16 °C for 16 h. For subsequent PCR, 1 μL of digested and re-ligated DNA template was used in a total reaction volume of 25 μL with Tks Gflex DNA Polymerase (TaKaRa, Shiga, Japan). Primers were designed to avoid repetitive sequences (Additional file ). The PCR conditions were as follows: 30 cycles of 10 s at 98 °C, 15 s at 60 °C, and 1 min at 68 °C. Amplified products were analyzed by gel electrophoresis and were purified following nested PCR (Additional file ). The purified PCR products were sequenced via the standard Sanger method.
PCR was performed using Tks Gflex (TaKaRa, Shiga, Japan) to confirm the other side of the breakpoint sequence. Primer R which was previously designed for real-time PCR analysis of OTC upstream of exon 1 (i.e. OTC intron 1) was used as primer F in this reaction (Additional file ). The PCR conditions and Sanger methodology were similar to those described above.
MLPA revealed the duplication of exons 1–6 of the OTC gene in our current study patient (Fig. ). We determined the range of the duplication using quantitative real-time PCR (Fig. b). We designed four qPCR experiments (U1-U4) between the promoter and enhancer regions to identify the upstream breakpoint. Likewise, we designed four qPCR assays (D1-D4) within intron 6 to identify the downstream breakpoint. In contrast to the male or female controls that showed ΔΔCt ratios of 0.5 or 1.0, respectively, the patient’s samples showed aΔΔCt ratio > 1.5 in some of these qPCR assays, suggesting that these regions were duplicated in this patient (Fig. ). The results indicated that the putative upstream breakpoints were located between PCR U3 and U4, and that the downstream breakpoints were between PCR D2 and D3.
We next performed inverse PCR to analyze the genomic structure of the duplicated region. TaqI-digested DNA was used as a template to produce a 3.5 kb PCR product when amplified with inversely oriented intron 6 primers (Fig. , ). However, an additional small PCR product was detected by agarose gel electrophoresis in the patient sample (Fig. ). The amplified products were sequenced after nested PCR (Fig. a). As expected, the breakpoint was located within intron 6 (Fig. , ). Unexpectedly however, this breakpoint was found to be connected with intron 1 of the OTC gene in the reverse orientation. The breakpoint junction contained 2 nucleotides of microhomology at the fusion junction (Fig. ).
The other side breakpoint was analyzed using standard PCR with primers for the upstream breakpoint region and the breakpoint region in intron 1. The primer pair amplified only products from the patient’s DNA (Fig. ). By Sanger sequencing, the upstream region of the OTC gene was found to make an inverted connection with 1 (Fig. , ). This breakpoint junction contained an additional 4 nucleotides (ACTA) of unknown origin (Fig. ). The positions of the two breakpoints in intron 1 were found to be chrX: 38365292 and chrX: 38366694, which were 1402 bp apart (Fig. c). We performed the same PCR amplification of both junctions in the patient’s parents but detected no products, suggesting that this complex rearrangement arose de novo. The patient’s duplicated region included a common single nucleotide variant (rs752750694, NM_000531.5:c.-844C > T). The patient’s father carries an A whereas the mother carries a G/G at this site (Fig. ). The patient was found to be an A/G heterozygote, but the peak of the A nucleotide was two-fold greater than the G-peak, suggesting that the patient carries two copies of A. These data suggest that the de novo duplication was of paternal origin.
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pmc-6292620-1
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Patient A (RP2): In this 16-years-old young woman (#80, ), unilateral reduced vision was first recognized at the age of four years, but no further examinations had been initiated at that time. When examined at the age of 12 years, she reported impaired central vision, but no nyctalopia. Visual acuity in the right and left eye was 20/63 and 20/20, respectively. The right eye was emmetropic and the left eye was myopic (spherical equivalent -3,5 dpt). The visual fields were severely constricted in the right eye, and there was a nasal superior visual field loss in the left eye. The ERG showed extinct rod responses in her right eye, while responses in her left eye were severely reduced. When she was examined at the age of 16, visual acuity had deteriorated only in the right eye (now 20/100). Fundus examination revealed narrowed vessels, outer retinal atrophy and bone spicule pigmentations, all much more pronounced in the right eye. In addition, the left eye showed a tapetal-like reflex (). Fundus AF confirmed the asymmetry and revealed a pattern of radial lines extending into the fundus periphery in the left eye, which is a characteristic finding in carriers of X-linked RP. NGS analysis identified a one base-pair duplication (c.829dupG, p.Ala277Glyfs*11) in exon 3 in the RP2 gene. No retinal disease was known in other family members, assessment of the parental retinal phenotype was not possible, and samples for segregation analysis were not available.
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pmc-6292620-2
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Patient B (RPGR): This 39-years-old myopic (spherical equivalent -5 dpt in the right eye and -6,75 dpt in the left eye) woman (#69, ) with nyctalopia since childhood reported decreasing visual acuity and visual fields since her twenties. Visual acuity was 20/400 in the right eye and 20/63 in the left eye. ERG examination was not tolerated by the patient. Funduscopy revealed changes characteristic for RP including bone spicule pigmentation and attenuated retinal vessels. Fundus AF showed areas of increased and decreased AF in the right eye and a fine pattern of radial lines radiating peripherally from the fovea in the left eye. On OCT imaging, there was widespread thinning of the photoreceptor layer in both eyes with foveal sparing in the left eye. Furthermore, OCT imaging revealed thickening of the inner retina mainly around the optic disc, which was more obvious in the right than in the left eye (). We identified a heterozygous four-base-pair deletion (c.2442_2445del, p.Gly817Lysfs*2) in ORF15 of RPGR. None of the patient’s parents had a history suggestive for retinal disease, and examination of the mother including AF-recordings showed no characteristics for a carrier state of X-linked RP. Genetic analysis of the mother revealed wild-type RPGR alleles, indicating a de novo RPGR mutation in the index patient.
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pmc-6292620-3
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Patient C (RPGR): This 52-years-old myopic (spherical equivalent approximately -4 dpt in both eyes) woman (#76, ) with difficulty in seeing in the dark since childhood reported a progressive reduction of visual acuity over the past 10–20 years. Visual acuity was above 20/50 in adolescence, 20/400-20/200 around the age of 40 years and now 20/800. ERG examination showed no detectable responses. Funduscopy revealed changes characteristic for RP in both eyes. There was symmetric and widespread thinning of the photoreceptor layer on OCT imaging (). Although fundus AF imaging showed no sign for an X-linked carrier state, we identified a heterozygous two-base-pair deletion (c.2405_2406delAG, p.Glu802Glyfs*32) in ORF15 of RPGR. The patient’s maternal great-uncle was visually impaired, and her maternal great-grandfather was blind, compatible with autosomal dominant inheritance with reduced penetrance. The mother of the patient died at the age of 50 years and had no visual problems.
Female carriers of X-linked RP consistently have peripheral retinal pigment epithelial atrophy.[] Most carriers may experience mild or moderate reduction of visual function, with a minority becoming legally blind.[] Although rare, severe RP may occur in female carriers of X-linked RP and simulate autosomal dominant inheritance[, , , –], as in Patient C. Comprehensive genetic testing has been shown to detect mutations in RPGR or RP2 in cohorts assumed to have autosomal dominant RP, leading to a genetic re-classification of those families.[, ] However, to the best of our knowledge, a sporadic female RP patient diagnosed with X-linked RP has only been reported once.[] Of note, parental testing for the RPGR mutation of patient B indicated that it occurred de novo.
Herein, severe manifestations of X-linked RP were found in two sporadic female carriers and in one patient with a family history suggesting autosomal dominant inheritance with variable expressivity. Two of these three patients revealed very subtle signs for X-linked RP which may easily be missed by standard clinical examinations. This includes asymmetry between eyes which has been reported as a typical sign in X-linked RP-carriers,[] although marked asymmetry was specifically mentioned in only one out of 61 carriers.[] Another peculiar finding on fundus AF imaging in female carriers of X-linked RP is a radial pattern extending peripherally from the fovea,[–] as observed in a more or less subtle form in the less affected eye of Patients A and B. Moreover, peripapillary thickening of inner retinal layers as observed in patient 2 has been reported in males with X-linked RP.[, ] Thus, a subtle X-linked RP carrier phenotype was present in the less severely affected eye in two patients, but not in the third patient who presented with a progressed bilateral disease stage. Unbiased molecular genetic testing eventually revealed the correct diagnosis in these female patients with sporadic RP or with a family history suggestive for autosomal dominant inheritance with variable expressivity.
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pmc-6292826-1
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A 74-year-old woman visited our station with squamous cell carcinoma (SCC) on the right buccal mucosa. Her past medical history included chronic obstructive airways disease, hypertension, and diabetes mellitus. The patient is a current smoker, with a history of 20 pack-years. Preoperative chest radiography, electrocardiogram, full blood count, and serum biochemistry were within the normal range. After being diagnosed with SCC as a result of incisional biopsy, the patient underwent the resection of SCC on the right buccal mucosa of the mandible, modified radical neck dissection, and primary reconstruction with a fibula-free flap. Tourniquet pressure was 300 mm/Hg, and its application time was 60 min. Total on-table time was approximately 7 h. Upon admission to the SICU after the 7-h operation, hypothermia and hypotension were noted. On the first postoperative day, the patient exhibited oliguria and proteinuria and elevation of CK, AST, ALT, and LDH. Together with the nephrology and neurology staff, we tried to figure out our patient’s symptoms and clinical findings. We thought that her clinical picture was based on an impression in which acute renal failure was diagnosed as secondary to rhabdomyolysis. Thus, she was managed with high-dose loop diuretic therapy. Additionally, we gave her hepatotonic to recover her liver function. The patient was supplemented with 150 to 250 mL/h of lactated Ringer’s solution and 0.9% NaCl. When the volume was full, urine output of above 100 mL/h was maintained by 20 mg intravenous injection with furosemide.
Her urine output for the first hour is at 20 mL/hour, but after the medication, her urine output began to improve on day 4 with a corresponding reversal in the serum creatinine. After postoperative day 4, the muscular enzyme showed a downward trend. We treated the patient with medication and hydration, and then the result became favorable. In the end, she was able to recover fully from the symptoms. Figures and show the change in serum enzyme levels during hospitalization (Figs. and ).
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pmc-6292835-1
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An 81-year-old woman was admitted with chest discomfort. She had a history of appendectomy, hypertension, colon polyps, and osteoporosis. Physical examination revealed no tenderness and no palpable mass in the abdomen. Laboratory investigation yielded unremarkable results, and the values for hemoglobin and tumor markers (including carcinoembryonic antigen and CA19-9) were normal. Barium esophagography, ordered because of the clinical findings, revealed a sliding esophageal hiatal hernia associated with a defect of the lower esophagus and the gastric wall that was caused by a huge tumor (Fig. ).
Esophagogastroscopy revealed a severe hiatal hernia and a huge, hard, elastic submucosal tumor, extending from the lower esophagus to the gastric fundus (Fig. ). Chest and abdominal computed tomography (CT) showed a 12.7-cm mass in the mediastinum; the mass was solid with some low-density areas (Fig. a, b). In addition, CT revealed that the mass was continuous with the gastric wall, and its border with the esophagus was clear. Therefore, we determined that the mass was a tumor that had arisen from the stomach. The diagnosis was of a submucosal tumor of the stomach, complicated by an esophageal hiatal hernia. On the basis of these findings, we opted for surgical resection.
In laparotomy, we first approached the tumor by dissection of the diaphragm (Fig. ). This revealed a huge tumor that arose from the stomach wall and adhered to the lower lobe of the left lung, the mediastinal pleura, the diaphragm, and the esophagus. Because further tumor dissection was difficult, we instead performed an additional thoracotomy through the left sixth intercostal space. Next, taking care to avoid damaging the outer membrane, we performed a total gastrectomy, a lower esophagectomy, and a Roux-en-Y jejunal reconstruction. The surgical time was 357 min, and the total blood loss was 292 mL.
The resected specimen was of a tumor measuring 14.0 × 13.5 cm in maximal diameter and arising from the greater curvature of the gastric fundus (Fig. a). The cut surface was yellowish-white and had some hemorrhagic areas, but no necrotic areas were discovered (Fig. b). The histopathological examination revealed that the inside of the tumor comprised spindle cells with high nuclear-cytoplasm ratios and hyperchromasia (Fig. a). The mitotic index was 2 per 50 high-power fields. Through immunostaining, the tumor cells were found to be positive for CD34 and c-kit (Fig. b, c), but negative for S100 and SMA. Therefore, the final diagnosis was of a GIST.
The patient recovered uneventfully and was discharged from the hospital 13 days after surgery having experienced no complications. We did not provide adjuvant chemotherapy with imatinib, at the patient’s request, who cited her advanced age as the main reason for refusal. However, we continued to offer follow-up, and 24 months after surgery, she was still alive and had remained disease-free.
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pmc-6292845-1
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A 47-year-old female was referred to the emergency department by her general practitioner after noticing a lump in her right groin. She mentioned that 2 days prior to presentation that a lump appeared suddenly and was initially uncomfortable but then developed increasing pain and erythema. The patient denied nausea, vomiting, fever, or change in bowel habit. The patient did not have any past significant medical history apart from being a smoker and had a BMI of 25.6. On arrival to the ED, the patient was resuscitated, and on examination, a 3 × 3 cm erythematous, irreducible lump with minor local tenderness was identified in the right groin below the inguinal ligament. The patient had a leucocytosis of 12.1 with normal serum biochemistry. A CT scan demonstrated a blind-ended structure with surrounding fat stranding inside the femoral canal (Fig. ). The patient was diagnosed with a de Garengeot hernia and was taken to the operating theatre.
The patient underwent laparoscopy where the appendix was found to have migrated through the femoral canal (Fig. ), and attempts at reduction into the peritoneal cavity proved to be unsuccessful. The mesoappendix was divided, and the base of the appendix was divided between endoloops. A standard low approach incision was made over the right groin swelling, and a strangulated right femoral hernia containing an inflamed appendix with strangulated extraperitoneal necrotic fat was identified. The hernia sac was opened, and the appendix delivered and removed (Fig. ), and after appropriate dissection, the necrotic tissue was excised and hernia sac suture ligated. Because of the presumed bacterial translocation, the femoral hernia defect was closed using interrupted non-absorbable sutures. The patient was able to be discharged the following day and underwent an uneventful recovery. The histopathology confirmed acute appendicitis.
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pmc-6292867-1
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A routine urine test of a 19-month-old male infant showed urine protein ++ and occult blood. Twenty-four-hour protein excretion was 1340 mg/24 h. Serum albumin was 39.3 g/l. Twenty days later, he was sent to our hospital for diagnosis and his urine protein and occult blood were tested in our ward; results were still positive. No other symptoms and abnormal laboratory examination results were found. Pregnancy and birth were normal and term. No known family member had shown similar symptoms, including his mother. The urine protein tested by electrophoresis analysis also showed LMW proteins (Table ), mainly RBP, α1-microglobulin, and β2-microglobulin. However, the urine calcium to creatinine ratio was in the normal range (0.236). Renal biopsy was not performed. Instead, NGS was directly used for screening for Dent disease. A hemizygotic mutation (c. A815G, p.Y272C) was found in the exon of the CLCN5 gene(ChrX:49850995), which has also been reported in another two Dent 1 case (, ). The same mutation was detected in his mother. Two months later, calcium to creatinine ratio was tested in the child showing 0.608 in a spot sample, which also reached the standard of hypercalciuria.
Table outlines the clinical characteristics of the two boys with Dent disease 1. Serum creatinine was measured using an enzymatic method and renal function was calculated using the modified Schwartz formula.
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pmc-6293128-1
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A 14-year-old girl, who in June 2010 had a primary molar (tooth 75) extracted on orthodontic indications, developed DSO. After a prolonged healing period involving pain and swelling, the patient was referred to a specialist in oral and maxillofacial surgery at Växjö County Hospital. The patient was diagnosed with acute osteomyelitis in November 2010 with swelling, pain, radiographic symptoms, and a biopsy that showed osteomyelitis with periosteal activity.
The acute osteomyelitis was treated with clindamycin and six months later the clinical and radiographic signs showed diffuse sclerosing osteomyelitis, without other signs of odontogenic infection, temporomandibular disorder, or impacted wisdom teeth in need of extraction that could explain her symptoms. The patient was then referred to the Department of Oral and Maxillofacial Surgery, Skåne University Hospital, Lund, for further diagnosis and treatment.
She was then treated for five years with corticosteroid and NSAID but with unsatisfactory results without pain relief. Therefore, other treatment options were discussed and due to the shorter half-life of denosumab compared with bisphosphonate, denosumab was considered. Before treatment with denosumab (Figure A,B), she was informed of the risk of medication-related osteonecrosis of the jaw (MRONJ) that could be initiated by denosumab.,
Subcutaneously, 120 mg denosumab (February 2014) was administered. Three days after the injection, she was in completely pain-free and in need of no other pain relief medication. During the first three months, she was given 120 mg every month. After completion of the initial treatment with denosumab, the pain then started again six months later but with less intensity and 120 mg denosumab (May 2015) was given. Three or four days after the injection, she was pain-free and this lasted another five months (October 2015), when the latest injection of denosumab was given with the same successful results as before (Figure C).
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pmc-6293128-2
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A 71-year-old woman diagnosed with DSO had been treated with analgesics (Diclofenac 50 mg x 3), Corticosteroids and antibiotics (Clindamycin 300 mg x 3), in periods between August 2014 and August 2016 but with poor pain relief. Cone-beam computer scan revealed radiopaque areas at the left corpus and anterior part of the mandible as well as periosteal bone formation. The diagnosis DSO was confirmed with bone biopsy and histological analysis. Clinical and radiological examination ruled out any odontogenic infection and temporomandibular disorder.
She classified her symptoms as “pain cannot be worse” and, since no other treatment had been successful and she was unwilling to undergo surgical resection of the jaw, she was offered treatment with denosumab. Before treatment, she was informed of the risk of developing MRONJ (Figure A).
In August 2016, the patient was given 60 mg denosumab subcutaneously and five days later she was completely pain-free and needed no analgesics. During the first three months, she required some analgesics (paracetamol, 1000 mg) at night. After four months (December 2016), the pain started again and a second treatment with 60 mg denosumab was given. Three days after the injection, she was pain-free and this period without any need of analgesics other than two times (paracetamol, 1000 mg) during a period of four months. After this, the pain started again and a third treatment with 60 mg denosumab (April 2017) was given. Again, three days after the injection, she was completely pain-free and this period without any need of analgesics, a period of 4 months, lasted until August 2017 when the last follow-up was recorded (Figure B).
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pmc-6293130-1
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A 44-year-old white woman with a 5-month history of distal joint pain was started on HCQ 200 mg daily. Five days after initiation of HCQ, the patient developed pruritic erythematous patches with pustules on upper chest and upper limbs.
Despite topical steroids, the lesions persisted and deteriorated. She visited her primary rheumatologist after 10 days, and she presented to rheumatology clinic. HCQ was immediately withdrawn after 10 days. She was started on 30 mg prednisolone daily and was visited by the dermatologist. Skin biopsy, stopping of HCQ, and supportive treatment including antihistamines, topical steroids, and intravenous hydration were planned for her.
Skin biopsy demonstrated nonfollicular Superficial pustules in the epidermis filled with neutrophils, a mixed eosinophilic and neutrophilic perivascular infiltration and absence of psoriasis-like changes that consisted with AGEP (Figure ).
After moderately controlled the lesions, the patient was discharged and 30 mg prednisolone was planned to taper gradually by 5-10 mg weekly, 2 weeks later when the patient was treated on 20 mg prednisolone, once daily she attended the dermatology clinic.
She developed a wide pustular exanthema on her trunk and limbs that gradually spread on the face and scalp. Some annular erythematous lesions and erythematous patches with targetoid appearance with scale and studded nonfollicular pinpoint pustules were also seen on her legs (Figure ).
Mucosal membrane, nail, and palmoplantar surface were spared.
She described the chills, lethargy, painful stinging, and pruritus sensation as the lesions spread. The patient had no personal/familial history of psoriasis.
She has a history of fever with a temperature of 38.7°C, but on admission, the vital signs were stable.
She had a high white blood cells count with a left shift (WBC 14 700, normal range, 4-10 × 109/L neutrophil count 10 900 equivalent to 86.1%).
Her septic workup including a CXR, blood culture, urine culture, and other routine laboratory including renal and liver function tests were unremarkable. Punch biopsy and swabs of the pustules were taken.
Bacterial and fungal cultures of the pustules were negative. The results of serologic screening for EBV, CMV, HBV, and mycoplasma were also negative. Later, we were informed that the initiation of hydroxychloroquine was due to a misdiagnosis and arthritis was ruled out by both laboratory and radiological investigations and her comfort was more related to arthralgia.
She was started topical steroids three times daily, antihistamine and oral prednisolone at a dosage of 35 mg daily. On second day, the eruption continued to persist and she reported development of new pustules and worsening of pain and pruritus. Antihistamine dosage was elevated and because of pathological demonstration of AGEP and rule out of psoriasis, prednisolone dosage was switched to 50 mg daily on fourth day.
After 15 days in hospital, the pustules and erythema were moderately improved and she had wide spread desquamations. She was discharged on tapering doses of oral prednisolone 50 mg/daily, antihistamine, and topical steroids twice daily. The patient visited 37 days after discharge with mild pruritic eruption and desquamation on upper limbs and trunk and distal lower extremities. She was instructed to taper prednisolone 5 mg weekly.
At a follow-up 3 months later, the eruption was completely resolved with no recurrence and the systemic corticosteroid was tapered totally. She was also referred to a psychologist because of intermittent complaint about joint pain.
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pmc-6293133-1
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The patient is a 70-year-old male, height 178 cm, weight 80 kg, who was admitted after a fall of unknown cause, complicated by traumatic brain injury (TBI) with bilateral fronto-basal contusional bleedings with perifocal edema and blood deposits along the falx and the right tentorium, and a subdural hematoma with subarachnoidal fractions extending along the right fronto-parieto-temporal convexity. His previous history was noteworthy for mild paraparesis of the lower limbs since birth being attributed to birth trauma, poliomyelitis, or cerebral palsy, bilateral hip dysplasia since birth, chronic alcoholism, arterial hypertension, inguinal hernia, reflux esophagitis, bougienage of the esophagus at age 66 years because of a cardia stenosis, right-sided hip total endoprosthesis, and deep venous thrombosis of the right lower limb, complicated by bilateral pulmonary embolism at age 66 years.
Shortly after TBI, the patient developed a series of generalized tonic clonic seizures, complicated by respiratory insufficiency requiring intubation and artificial ventilation (hospital day (hd) 1). As an antiepileptic treatment, levetiracetam (2000 mg/d) and midazolam (7 mg/h) were given. Additionally, he received norepinephrine, clonidine, ketamine, propofol, and sufentanil. Because of suspected increased intracranial pressure (ICP), an ICP probe was implanted from the left frontal side. There was lactic acidosis of 14 mmol/L, which regressed within 24 hours to normal values. Since the serum alcohol level was elevated to 1.92 g/L on admission, intravenous vitamin-B1 (300 mg/d) and oxazepam were given. On hd3, the patient was transferred to another intensive care unit. Despite rapid reduction of the sedating medication, the patient did not awake. There was megaloblastic anemia, when vitamin-B12 and folic acid were added. Hypothyroidism with a TSH level of 6.6U/mL (n, 0.2-3.7U/mL) was appropriately substituted. There was a mild, transient elevation of transaminases and the gamma-glutamyl-transpeptidase during hospitalization.
Because of suspected recurrence of seizures on hd5, PHT (1000 mg/d) was administered intravenously. Shortly after starting PHT, spontaneous, overshooting movements of the head, upper limbs, and lower limbs became apparent. Initially, these hyperkinesias were misinterpreted as exacerbation of seizures due to ineffectivity of LEV and PHT, why valproic acid (VPA) was added. Repeated EEG recordings, however, did not show epileptiform discharges. Hyperkinesias occurred daily, either induced by care treatments or spontaneously. They were described as choreoathetotic and occurred in waves every 30-60 minutes and lasted for about 1 minute. Treatment with tiapride or quetiapine was ineffective. On hd6, the ICP probe was removed since ICP values were recurrently within normal limits. Clinical neurologic exam on hd13 revealed spoor. Strong pain stimuli induced stereotypic flexion contractions of the lower arms and athetoid rolling motions of the head. There was skewed deviation of the bulbs and the Babinski sign was positive bilaterally. VPA was withdrawn without effect on the hyperkinesias.
On neurologic exam at hd15 under remifentanil, clonidine, tiapride, and artificial ventilation, the patient was awake, but did not follow any instructions. There was right-sided ptosis. Upon passive mobilization, he reacted with repeated stereotypic, choreatic head movements to the right and athetoid flexions of the upper limbs. These hyperkinesias also occurred spontaneously. There was mild rigor bilaterally. Patella tendon reflexes were exaggerated. Since PHT was suspected to be responsible for choreoathetosis, it was immediately discontinued. On hd16, the PHT serum level was still elevated to 118 µmol/L (n, 39.8-79.2 µmol/L). However, within 48 h after discontinuation of PHT, choreoathetosis completely resolved. Clinical neurologic exam on hd17 confirmed complete resolution of hyperkinesias. On hd19, the patient was tracheostomized. During the further course, the patient awaked and followed simple instructions. Hyperkinesias did not recur. One week after discontinuation of PHT, the serum level of PHT was zero.
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pmc-6293143-1
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We report on a 63-year-old female patient who presented in January 2016 with the following symptoms: complaint of cold sensation affecting the upper arms on both sides (left > right), weakness and arm claudication, with an increasing inability to perform work on the computer, and symptoms of a fatigue syndrome. The patient was unable to perform her employment as a hospital secretary. Clinically, pulselessness of the brachial and radial artery on both sides was noted. Bruits were discovered in the left and right subclavian artery. A blood test revealed increased levels of the inflammatory markers C-reactive protein (CRP 47.9 mg/dL) and an increased Erythrocyte Sedimentation Rate (ESR 74 mm/h). The patient had a history of hypertension, hyperlipoproteinemia, and osteoporosis; she was a former smoker and reported moderate daily alcohol consumption.
A neurological examination, an MRI of the cervical spine, and myocardial scintigraphy were without pathological findings. Duplex ultrasound of the carotid artery and upper extremities revealed noticeable intima-media thickening. For suspected large-vessel vasculitis, a diagnostic angiography was carried out, which revealed bilateral stenosis of the axillary artery at the transition to the brachial artery and, on the left side only, an additional stenosis in the proximal segment of the brachial artery. TA was diagnosed based on the American College of Rheumatology criteria, with four out of six criteria met.
The patient was admitted to a rheumatological specialist clinic in March 2016. Treatment with prednisolone 20 mg daily was started, but there was no improvement of the arm claudication. Therefore, the patient received cyclophosphamide 15 mg/kg body weight × 0.75 (=600 mg) plus prednisolone (75 mg/d initially, reduced in stages to 30 mg/d at the time of hospital discharge). Six cycles of cyclophosphamide at 3-week interval were planned, at the end of which treatment with methotrexate 15 mg subcutaneously once a week accompanied by a prednisolone maintenance dose of 10 mg/d was planned. Most of her symptoms regressed after initiation of the immunosuppressive therapy, but the arm claudication and weakness in the arms remained.
Therefore, in April 2016, she presented at our hospital for endovascular treatment. The first procedure was performed on the distal stenosis on the left side. PTA of the left proximal segment of the brachial artery was performed using a 4 × 60 mm drug-coated Chocolate balloon (mild oversizing). The patient received a loading dose of clopidogrel 300 mg followed by a postinterventional dose of 75 mg/d orally for two months. Figure shows the brachial artery with subtotal occlusion at two anatomical locations, and the artery after PTA dilatation of the distal, higher grade, stenosis. postinterventional, the patient was free of symptom on the left side. Being discharged from hospital, the patient developed mild symptoms on the left side again, although they were significantly milder than before the intervention. Moreover, the patient received a cumulative cyclophosphamide dose of 3.6 g (4 of 6 cycles).
In June 2016, a repetitive C-DEB PTA of the proximal stenosis on the left side was performed. This arterial segment had not been treated in the first intervention. However, due to the excellent distal result, C-DEB PTA was performed with a 4 × 60 mm drug-eluting Chocolate balloon on the remaining stenosis of the left axillary artery at the transition to the brachial artery, which had previously been moderate but was now presenting as higher grade (Figure ). Treatment with clopidogrel 75 mg/d was continued. The procedure resulted in complete disappearance of arm claudication on the left side; the patient reported that she was able to use her left arm without restriction or complaints.
Consequently, it was decided to also perform the endovascular intervention on the right-sided stenosis. By August 2016, the patient had completed all cyclophosphamide cycles (cumulative total dose of 5.6 g), and the medication plan consisted of methotrexate 15 mg subcutaneously once a week plus prednisolone 10 mg/d and acetylsalicylic acid 100 mg/d orally. PTA with a 5 × 200 mm drug-eluting balloon was performed on the stenosis of the right axillary artery at the transition to the brachial artery, which had previously been moderate but now presented as higher grade (Figure ). The successful effect of the previous two interventions on the left side was also confirmed at this time (Figure ). Medical treatment with clopidogrel 75 mg/d was continued. After this intervention, the patient was free of claudication symptoms and was able to perform her daily work. The treatment with methotrexate, prednisolone, and acetylsalicylic acid was continued.
The patient remained in remission until the last follow-up visit, in October 2017. A color-coded duplex sonographic flow profile was normal, with no evidence of pathology. As a result of the intervention, the patient felt very comfortable with the clinical result of her treatment. As a cobenefit, she could escape early retirement.
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pmc-6293148-1
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A 66-year-old woman was admitted to our hospital due to dizziness, hearing loss, facial hypoesthesia, and muco-cutaneous bleeding. A physical examination revealed bruises, hematomas, and petecchiae all over the body and in the mouth. A complete neurological examination highlighted left periocular and perioral hypoesthesia, postural instability and left hearing loss. A brain computed tomography (CT) scan was performed, showing a left cerebral subdural bleeding without mass effect. A pathological meningeal contrast enhancement in the left fronto-temporal hemisphere was demonstrated by magnetic resonance imaging (MRI), together with an infiltrative mass of cochlea, semicircular canals, and vestibulocochlear nerve, compatible with disease localization. Positron emission tomography and a CT scan of neck/chest/abdomen were negative except for homogeneous splenomegaly (15 cm longitudinal diameter). Informed consent about authorization for instrumental examinations and genetic analysis on biological sample, processing of personal data, and sample storage was obtained. All clinical findings together with BM morphologic, immunophenotypical, cytogenetic, and FISH evaluation led to a diagnosis of DHL with central nervous system and BM involvement, clinical stage IV.
The patient received a first cycle of R-HyperCVAD B (high doses of Methotrexate and Cytarabine). The chemotherapy was well tolerated with resolution of all the symptoms. However, during hospitalization a clinical relapse arose, characterized by headache, confusion, disorientation and recurrence of dizziness, ipoesthesia, and hearing loss was also observed. A brain MRI confirmed the progression of the disease. After the sixth cycle of R-ICE (Rituximab – Ifosfamide – Carboplatin AUC 5- Etoposide) complete remission (CR) was recorded by brain MRI and BM morphologic, immunophenotypical, cytogenetic, and FISH evaluation. An autologous PB stem cell transplantation was subsequently and successfully performed. The patient is now alive and in CR
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pmc-6293150-1
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A 47-year-old woman, gravida 2, para 2, non-obese, and with no chronic diseases underwent TLmRH as curative treatment for clinical stage IA endometrial cancer. She had sexual intercourse 6 months after surgery. She noticed organ prolapse during defecation the next day, recognizing something dropped in her vagina (Figure ).
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pmc-6293150-2
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A 33-year-old woman, gravida 3, para 3, non-obese and with no chronic diseases, underwent TLmRH as curative treatment for clinical stage IA1 cervical cancer. Two months later, she presented to our department with abdominal pain and genital bleeding after her first sexual intercourse after surgery from the previous day.
We sutured the vaginal cuff with absorbable sutures during initial surgery. We performed colpotomy with ultrasonic device and monopolar device in both cases.
Both patients were immediately diagnosed with VCD (Figure ). The prolapsed organ was found to be the intestine and it remained within the vagina without evisceration out of the vagina. The color of the intestine was normal, indicating that there was no ischemia present. After washing of the prolapsed intestine, we pushed back the prolapsed intestine, with sterilized gauze to prevent herniation outside of the vagina until operation. Vaginal approach repair (repair from the vaginal cavity), open approach repair, or laparoscopic approach repair were treatment choices. Suturing from the vagina could shorten vaginal length. To prevent recurrence, we thought it would be better to suture the peritoneum. We already resected the vagina about 2 cm in the initial surgery in both cases; thus, we would like to avoid further shortening. We thought that the open approach should be avoided considering its invasiveness if we could safely avoid this complication laparoscopically. Thus, we initially employed total laparoscopic repair.
The ureter was separated from the paravaginal tissue during initial cancer surgery, losing its normal anatomical position. This may cause ureteral damage during repair (Figure ). Thus, in order to avoid ureteral injury and to create a tight suture, the vaginal wall was separated by 1.0 cm, to the extent that concrete vaginal cuff suture could be made (Figure ), and suturing was complete (Figure ). The peritoneum was sutured to prevent recurrence, hematoma, and infection. The postoperative course was good. The cuff remained intact at 1-, 2-, 3- and 6-month examination. We suggested that sexual intercourse is safe 6 months after surgery.
Interviews conducted on these cases after the 6-month examination revealed that normal sexual intercourse was performed without troubles in both cases.
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pmc-6293152-1
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A 33-year-old African-American woman presented to her primary care physician for evaluation of a palpable right breast mass in the upper outer quadrant that she had identified several days prior to presentation. Bilateral mammography demonstrated a spiculated mass with pleomorphic calcifications in the axillary tail of the right breast at the 10:00 position, which corresponded with a palpable 4 cm mass on physical examination (Figure ). A second, less distinct mass in the upper inner left breast was also visualized. An ultrasound of the right breast demonstrated an irregular hypoechoic and vascular mass measuring 3.3 × 2.1 × 1.9 cm in diameter that abutted the underlying pectoralis major muscle at the 10:00 position in zone 3, 13 cm from the nipple. No abnormalities were identified in the upper inner left breast on subsequent imaging. Taken together, these findings were assigned a BI-RADS 5 classification. The patient was referred to the breast surgery team at the Stefanie Spielman Comprehensive Breast Center at The Ohio State University Wexner Medical Center for further management.
On establishment of care, the patient revealed a family history of breast cancer involving her maternal cousin, who was diagnosed with left breast cancer at age 27 and right breast cancer at 33 years of age. Of note, her cousin was positive for the T37K variant of uncertain significance in BRCA1, an allele suspicious for deleterious effects. The family history was also significant for a maternal aunt diagnosed with ovarian cancer at 58 years, and a maternal grandmother who developed breast and ovarian cancer during the 7th and 8th decades of life, respectively. On physical examination, the patient had a palpable, firm 3-4 cm mass within the upper outer quadrant of the right breast. No other masses or nodules were identified in the left or right breast. The nipples appeared normal bilaterally. There was no evidence of cervical, supraclavicular, or axillary lymphadenopathy. These findings were consistent with clinical stage IIA disease. An ultrasound-guided right core needle biopsy of the dominant breast mass demonstrated a grade 3 invasive ductal carcinoma that was ER-positive (85%) and PR-positive (70%). Tumor cells were negative for HER2/neu expression.
After consultation with the breast cancer surgery, medical oncology, and plastic surgery teams, the patient underwent total right breast mastectomy for invasive ductal carcinoma with sentinel lymph node biopsy and prophylactic total left breast mastectomy followed by immediate reconstruction. Given the patient's choice of procedure, it was felt that a referral to medical genetics could be made postoperatively. Two right axillary sentinel lymph nodes were identified via nuclear scintigraphy, but these were negative for carcinoma on intraoperative consultation with pathology. Following resection, the patient underwent immediate bilateral breast reconstruction with muscle-sparing free transverse rectus abdominis myocutaneous (MS-TRAM) flaps and implantation of prosthetic mesh in the abdomen without complication. An attempt was made to perform a reconstruction based on a superficial inferior epigastric artery flap (SIEA), but no usable segment of the SIEV was identified. The patient tolerated the procedure well, and the remaining hospital course was unremarkable. Pathologic evaluation of the right breast revealed a grade 3 invasive ductal carcinoma measuring 2.7 cm in diameter along with high nuclear grade ductal cell carcinoma in situ. Margins were clear on final pathology with a 1.1 cm margin. Evaluation of the left breast demonstrated benign parenchyma with usual type ductal hyperplasia, apocrine metaplasia, and cyst formation without evidence of carcinoma.
Due to her African-American ancestry, early age of presentation and strong family history of breast and ovarian malignancy the patient were referred to clinical cancer genetics for counseling. Testing revealed that the patient was indeed positive for the T37K variant in the BRCA1 gene. This was considered a deleterious mutation in the setting of known malignancy and strong family history of breast and ovarian cancer. The patient was definitively diagnosed with hereditary breast and ovarian cancer syndrome, and it was recommended she begin ovarian suppression and endocrine therapy. At this time, the patient's Oncotype Dx score was 18, indicative of a 12% likelihood of breast cancer recurrence within 10 years of initial diagnosis. Two months after mastectomy, the patient underwent placement of a PR ParaGard Copper IUD for ovarian suppression and started tamoxifen 20 mg daily. Prophylactic bilateral oophorectomy was also offered, but the patient declined at this time. The patient cited an interest in deferring this surgery until after her childbearing years. She declined adjuvant systemic chemotherapy as well, having been offered a regimen containing doxorubicin and cyclophosphamide.
The patient underwent further breast reconstruction 3.5 months postmastectomy that included bilateral nipple reconstruction and fat grafting. The patient was found to have a contour irregularity in the superolateral aspects of the bilateral-free flaps (left greater than right) at the junction of the mastectomy skin and the edge of the flap. Using standard Coleman technique, 30 cc of lidocaine with epinephrine was injected into the lateral aspect of the abdominal donor site. After allowing sufficient time for vasoconstrictive effect, approximately 68 cc of processed fat was harvested and processed by rolling the harvested fat on a Telfa pad. This material was then injected into the superior pole concavity at multiple sites bilaterally. The abdominal donor site was revised without complications. The patient presented to plastic surgery clinic 6.5 months after mastectomy for evaluation of two palpable nodules in the upper outer quadrant of the right reconstructed breast at the 9 and 10:00 positions. The nodules were thought to be consistent with fat necrosis in the postsurgical setting, and no further workup was obtained.
Four months later (7.5 months postmastectomy), the patient underwent repeat fat grafting to correct bilateral breast contour irregularities. For this procedure, the hips were chosen as the fat graft donor site and the Coleman technique was again utilized. In total, 61 cc of fat was injected into contour deformities of the upper and lateral aspects of the reconstructed left breast, and 27 g of fat was injected into similar irregularities of the right breast without complication. The patient recovered well and was pleased with the cosmetic outcome. The patient presented for follow-up of 5 months following the second fat grafting procedure (12 months postmastectomy) with four nodules at the periphery of the right reconstructed breast that were located at evenly spaced intervals from the 9:00 to 12:00 axes. These areas were believed to be fat necrosis. Again, no further workup was obtained. Approximately fifteen months postmastectomy, the patient was evaluated for rising CA-125 levels by her OB-GYN physician due to concern for possible BRCA-associated ovarian cancer. The initial CA-125 level was 12 at 2.5 months postmastectomy and increased to 81 by 15 months postmastectomy. Workup for the progressive increase in CA-125 of unknown etiology included transvaginal ultrasound and CT scan of the abdomen and pelvis. These scans were negative for gynecological malignancy but demonstrated significant skin thickening of the right reconstructed breast with nodularity involving the lateral aspect of the underlying muscle. Follow-up mammogram (Figure ) and ultrasound (Figure ) of the reconstructed breast demonstrated several suspicious masses. These included a mixed echogenic mass measuring 2.8 × 2.0 × 2.6 cm at the 9:00 position, a mixed echogenic mass measuring 3.0 × 1.7 × 2.8 cm at the 9-10:00 position, a hypoechoic mass measuring 1.7 × 1.4 × 2 cm at the 10:00 position, and a fourth mass measuring 3.4 × 2.8 × 4 cm at the 12:00 position of the right reconstructed breast. The mammogram received a BI-RADS 4 classification. These masses were located at equal intervals in a symmetrical arc in the extreme upper outer quadrant of the right breast (see Figure ).
The patient underwent ultrasound-guided biopsy of the suspicious masses in the right breast at the 9:00, 9-10:00, and 12:00 positions of zone 3. In total, 3 of the 4 masses were biopsied. The pathologic diagnosis of each specimen was consistent with grade 3 invasive ductal carcinoma. Estrogen receptors and progesterone receptors were positive at 70% and 60%, respectively. HER2/neu expression was negative. Staging CT scans of the chest demonstrated a dominant centrally necrotic mass with peripheral rim enhancement in the superior aspect of the right reconstructed breast and multiple other right subcutaneous nodules. Multiple enlarged right axillary and subpectoral lymph nodes were also observed. A whole body bone scan was negative for distant metastatic bone disease, with the exception of increased uptake noted in the L4 vertebral body. MRI evaluation of the lumbar spine was negative for contrast-enhancing lesions. The locoregional recurrence was consistent with clinical stage IIIC disease (T4a, pN3b, M0).
The patient was referred to medical oncology, and given the extent of disease; it was felt that pre-operative chemotherapy would assist the surgeon in obtaining margins when the area of recurrence was resected. The patient's systemic chemotherapy regimen consisted of six cycles of adriamycin/cyclophosphamide and three cycles of dose-dense paclitaxel. This treatment was initiated 17.5 months postmastectomy. The patient tolerated chemotherapy well without significant side effects. Interval imaging after 2.5 months of treatment demonstrated a decrease in the size of the four lesions to 1.3 × 1.0 × 1.5 (from 2.8 × 2.0 × 2.6 cm) at the 9:00 position, 1.6 × 0.9 × 1.3 (from 3.0 × 1.7 × 2.8 cm) at the 9-10:00 position, 1.5 × 1.5 × 1.9 (from 1.7 × 1.4 × 2 cm) at the 10:00 position, and 1.5 × 1.6 × 2.1 (from 3.4 × 2.8 × 4 cm) at the 12:00 position of the right reconstructed breast. En bloc resection of the right chest wall recurrences and right axillary lymph node dissection were performed approximately 1 month after the completion of chemotherapy. The recurrent cancers were encompassed within a single oval-shaped portion of chest wall, and the axillary contents were resected in continuity with this tissue.
The final pathology on the resection specimen revealed the presence of residual invasive ductal carcinoma, indicating an incomplete response to chemotherapy. Invasive carcinoma was present as clusters of individual tumor cells spread over three areas with maximum dimensions of 2.5, 1.8, and 1.4 cm. It was felt as this time that two of the previously identified masses at the 10:00 axis had become confluent during the course of chemotherapy. Therapy-related changes and biopsy site changes were seen, and all margins were negative for carcinoma. The invasive carcinoma was 0.5 cm from the closest superior margin. Macrometastatic carcinoma was identified in four lymph nodes. The largest tumor deposit measured 0.5 cm in greatest dimension and exhibited extracapsular extension. Four additional lymph nodes with isolated tumor cells and thirteen lymph nodes negative for carcinoma were also present. The invasive tumor was HER2-negative (IHC score: 0) and estrogen receptor and progesterone receptor-positive. The patient then underwent 6 weeks of daily radiation therapy to the right chest wall without any complications. Following completion of radiotherapy, the patient resumed chemotherapy that consisted of exemestane and goserelin for aromatase inhibition and ovarian suppression, respectively. The patient continues to follow-up with the multidisciplinary breast cancer team.
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pmc-6293175-1
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A 77-year-old woman presented to our hospital with progressive cognitive decline. Laboratory tests were significant for corrected calcium of 12.3 mg/dL reference (range: 8.8-10.1 mg/dL), phosphate of 2.4 mg/dL (range: 2.7-4.6 mg/dL), and elevated intact parathyroid hormone of 549 pg/mL (range: 10-65 pg/mL). Renal function was normal; a thyroid ultrasound demonstrated no tumors. Noncontrast computed tomography (CT) revealed a mass measuring 2 cm in diameter in the posterior mediastinum (Figure A, arrow). Contrast enhanced CT demonstrated a well-defined enhancing mass (Figure A, yellow arrow). 131I-methoxyisobutyl isonitrile (MIBI) single-photon emission computed tomography SPECT) showed specific uptake in the mass (Figure B, arrowheads). Because her cognitive impairment was persistent despite the administration of calcitonin plus normal saline infusion, she underwent surgical resection of ectopic mediastinal parathyroid adenoma. Her symptoms improved postoperatively, and she reverted to eucalcemia.
Ectopic parathyroid adenoma causes approximately 6% of all hyperparathyroidism cases, which is not uncommon. However, the diagnosis of ectopic parathyroid is often missed because of vague symptoms such as cognitive dysfunction due to hypercalcemia. It frequently occurs in the thymus and mediastinum. Because the sensitivity and specificity of identifying parathyroid adenoma with a single modality were low regardless of the technique, it should be considered to include chest CT and 131I-MIBI SPECT examinations in patients with possible hyperparathyroidism and normal thyroid ultrasound.
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pmc-6293180-1
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A 15-year-old female patient was first seen in our service in 2012 for a second opinion regarding the treatment of her cardiac arrhythmias. Her medical history includes mental retardation, delay of psychomotor development, and a progressive dorso-lumbar scoliosis (Figure ) for which she underwent an orthopedic correction at the age of 15 years, 5 months before she was first seen in our service. Her family's medical history is unremarkable. She was being followed in another institution for a sinus bradycardia discovered during the neonatal period. Since the age of 14 years old, she also presented paroxysmal atrial fibrillation. To allow an intensification of her antiarrhythmic treatment, a pacemaker implantation was one of the options proposed in the other institution.
Despite her mental retardation, the patient could express that she had no heart related symptoms such as dyspnea, palpitations, or chest pain, and had no limitations in her activities of daily living, such as walking or doing some indoor cycling. There was no history of syncope. This was confirmed by her parents, who were most of the time with her.
Her 12-lead electrocardiogram showed a junctional rhythm, with narrow QRS complexes (Figure ). A 6-day holter monitor revealed sinus bradycardia, junctional rhythm, sinus pauses, short episodes of Wenckebach atrioventricular block, 20% of atrial fibrillation, atrial flutter, and premature ventricular contractions with episodes of bigeminy (Figure A-F). Her echocardiography did not detect any abnormality, without left atrial dilatation. The patient supported a load of 120 Watt at her exercise test that allowed reaching a heart rate of 132 beats per minute (65% of the maximum heart rate).
An electrophysiological study was conducted in our institution, showing atrioventricular conduction abnormalities with episodes of Wenckebach atrioventricular block. AH interval was measured at 76 ms and HV interval at 53 ms. There was a duality of the atrioventricular conduction without induction of atrioventricular nodal reentrant tachycardia, with or without isoprenaline. The QTc interval was prolonged at 540 ms after isoprenaline infusion. Atrial fibrillation started at the transseptal puncture. The cycle length was 196 ms in the left atrial appendage and in the right atrium, 150 ms in the right pulmonary veins, and 110 ms in the left pulmonary veins (Figure ). The left and right ipsilateral pulmonary veins were circumferentially ablated using a point-by-point technique (Figure ). Sinus rhythm was restored during the antrum isolation of the left pulmonary veins. At the positioning of the lasso in the right pulmonary veins, an atypical left atrial flutter started with restoring sinus rhythm during the isolation of these veins.
No mutations associated with sick sinus syndrome (LMNA, SCN5A, CACNA1D, GJA5, HCN4, MYH6, PRKAG2, SCN1B, TBX5, TRPM4, NKX2-5, TBX3, and WWTR1) or long QT syndrome (KCNQ1 and KCNH2) were found in the DNA tests performed in 2013.
The patient is followed once a year in our service. She was seen for the last time, for her sixth follow-up consultation in March 2018, five years after the isolation of the pulmonary veins. She takes no medication and is still asymptomatic of her sick sinus syndrome. The 6-day holter monitor showed sinus bradycardia, junctional rhythm, sinus pauses, and premature supraventricular contractions, but no atrial fibrillation, atrial flutter and almost no premature ventricular contractions.
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pmc-6293182-1
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A 30-year-old G1P0 woman at 35 weeks and 2 days of gestation presented to obstetric (OB) triage with uterine contractions. She had a history of atrial septal defect repair as a child but was otherwise healthy. Ten days prior to admission, the patient had a noted oral mucosal lesions concerning for HSV-1 infection but declined treatment with oral acyclovir. Five days prior to admission, she presented to urgent care with flu-like symptoms and a temperature of up to 38.9°C for 2 weeks. She was given a course of azithromycin for presumed community-acquired pneumonia.
On presentation to OB triage, vitals were notable for a temperature of 39.3°C and a heart rate of 105 beats per minute. Review of symptoms was positive for nausea and emesis. She was visibly jaundiced. Laboratories revealed alkaline phosphatase 591 U/L (normal 34-104 U/L), total bilirubin 5.1 mg/dL (0-1.4 mg/dL), aspartate aminotransferase (AST) 142 U/L (13-39 U/L), hemoglobin 8.8 g/dL (11.5-15 g/dL), platelets 67 000 (150-400 × 103/μL), and fibrinogen 547 mg/dL (215-438 mg/dL). Haptoglobin was normal, 149 mg/dL (44-215 mg/dL), suggesting that hemolysis was not actively occurring, so a presumptive diagnosis of AFLP was made. The patient underwent an emergent cesarian section (C-section). A healthy male infant was delivered; to our knowledge, he was without any evidence of liver disease, particularly neonatal hemochromatosis. There was evidence of hypertrophic decimal vasculopathy in the placenta, which is seen in gestational hypertension (classically HEELP and pre-eclampsia). This pathology helped retrospectively change the diagnosis of her the acute hepatic failure to HELLP as these vascular changes are not seen in AFLP.
After delivery, the patient continued to be febrile and was started on ampicillin, gentamicin, and clindamycin for a possible chorioamnionitis. CT angiogram was negative for PE, but showed a 20 cm liver with heterogeneous enhancement; no lymphadenopathy was seen. Sputum and bronchoscopy cultures were negative. On day 8, she remained febrile to >38.0°C, and the diagnosis of HLH was considered. Of note, there was no family history of HLH. Laboratories revealed a ferritin of 10 800 ng/mL (10-107 ng/mL), increased from 2929 ng/mL on day 3, lactate dehydrogenase (LDH) 733 U/L (140-271 U/L), increased from 409 on day 3, AST 736 U/L, triglycerides 707 mg/dL (<150 mg/dL). On day 9, bone marrow biopsy was without evidence of hemophagocytosis. Demonstration of hemophagocytes on bone marrow biopsy is helpful in making the diagnosis of HLH, but lack of hemophagocytes does not exclude the diagnosis. On day 11, biopsy of the liver did show evidence of hemophagocytosis (see Figure ). Soluble IL-2R (sIL-2R) came back at 10 580 pg/mL (<1033 pg/mL). sIL-2R levels of >2515 have a 100% sensitivity and 72.5% specificity for the diagnosis of HLH. She was started on dexamethasone with weekly etoposide per the HLH-94 protocol. EBV viral load by PCR was 246 000 copies/mL via PCR. CMV viral load by PCR was positive at 104 161 IU/mL(<1600 IU/mL). She was negative for HIV, parvovirus, and influenza. She was started on antiviral therapy with ganciclovir. She clinically improved and was discharged home on day 52 to continue to receive etoposide in outpatient infusion (week 6 of HLH-94).
Unfortunately, 3 days after discharge, she represented with fevers to 39.4°C. Of note, she had not been able to get the valganciclovir that had been prescribed at discharge. EBV viral titer had increased from undetectable on day 35 of her prior admission to 658 000 copies/mL by PCR upon readmission. On day 4 of readmission, laboratories were notable for LDH 1015 U/L and ferritin>15 000 ng/mL. Her fevers persisted. The HLH-94 protocol was restarted, going back to twice-weekly etoposide. She was given a dose of rituximab 375 mg/m2 on day 15 of readmission for the EBV viremia.
Her clinical status was tenuous, requiring intensive care unit admission for supraventricular tachycardia, gastrointestinal bleeding from corticosteroid-induced gastritis and thrombocytopenia, and hypoxic respiratory distress. She was severely neutropenic and was placed on both G-CSF and GM-CSF. On day 17, blood cultures from both PICC and peripheral sources grew multiple drug-resistant organisms; this was the first time her cultures had been positive for bacteremia to date. Despite intensive antibiotic treatment, blood cultures remained persistently positive, and sepsis progressed to septic shock requiring multiple vasopressors. Granulocyte transfusions were considered, but declined by family given minimal likelihood of efficacy. She required mechanical intubation on day 20 due to acute respiratory distress syndrome. She passed on day 24 of her second admission due to ventricular fibrillation arrest.
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pmc-6293183-1
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A 52-year-old illiterate woman from the Gurung community of Nepal presented to the Emergency Department (ED) of Tribhuvan University Teaching Hospital (TUTH) with a chief complaint of a sudden onset, progressively worsening shortness of breath, and burning sensation in the chest. The episode started one day prior to the ED visit, immediately preceded by the consumption of four tablespoons of wild red honey. This was associated with visual hallucinations, blurring of vision, lightheadedness, a clumsy broad-based gait, and numbness in the peripheries that lasted 3-4 hours post-honey ingestion. There was otherwise no fever and localizing signs of infection, no history of lower limb swelling, pleuritic chest pain, cough or sputum production, no gastrointestinal symptoms such as abdominal pain, water brash, nausea, vomiting, or loose stool, and the patient did not give any history of vertigo, confusion, or syncope.
The patient reported the visual hallucinations as a one-episode sighting of a female god and wild beast at her home which no one else claimed to see. It resolved after sleeping. There was no associated auditory, tactile or gustatory hallucinations, and no associated passivity experiences, delusions, thought insertion or withdrawal. During the episode, the family members who were at the scene said the patient was muttering incomprehensibly, perhaps under the influence of her hallucinations.
She has no past medical or psychiatric history of note and no history of similar episodes in the past. She is not on any long-term medications, and other than the honey, she did not take any new food, medication, traditional therapies, or supplements in the past month. She is a smoker of 25-pack years and does not consume alcohol. She reported that a similar episode happened to her daughter few weeks back. Her daughter was feeling weak, given red honey and milk, and subsequently developed a cough, shortness of breath, and numbness in the peripheries. The incident resolved spontaneously and was otherwise not associated with any psychiatric symptoms.
On examination, the patient was ill-looking but was oriented to time, person, and place. Her sphygmomanometric blood pressure read 60/40 mm Hg, her heart rate was 40 beats/min, her respiratory rate was 20 breaths/min, and her spO2 was 85% on room air. She was afebrile with a temperature of 98°F.
Neurological examination revealed 15/15 Glasgow Coma Scale, pupils that were equal and reactive to light, all cranial nerves intact with no focal neurological deficits of the limbs. Her gait was normal, and there was no nystagmus, dysmetria or dysdiadochokinesia. Cardiovascular and abdominal examination was unremarkable. There was however, decreased air entry in the bilateral lung bases and pitting edema on bilateral lower limbs, up to the level of the ankles.
Mental state examination revealed that the patient struck good rapport with no abnormal deviations in rate, rhythm, and quantity of speech. Although she was in acute discomfort, she largely had a positive affect and had no recent alteration in her mood. There were no obsessions, delusions, passivity experiences, illusions, or hallucinations identified other than the one episode she experienced just after ingestion of red honey. She demonstrated good insight into her illness and practiced good social judgment.
Baseline investigations were within normal limit. A 12-lead electrocardiogram revealed sinus bradycardia with a first-degree atrioventricular block. She was given supplemental oxygen (nasal prongs 4 L/min) and two doses of IV 0.6 mg atropine given 5 minutes apart. Her symptoms resolved rapidly over few hours and she subsequently had an uneventful discharge.
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pmc-6293185-1
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A 35-year-old, Mrs MM, a widowed HIV-positive patient on antiretroviral therapy (ART) for 6 years presented to a general surgical unit with abdominal pain and distension, vomiting, foul-smelling vaginal discharge, and fever for a week. She has one child and lost the second child who was aged 8 months from HIV-related pneumonia. On examination, she was ill-looking, pale, and pyrexial. Her temperature and pulse rate were 38°C and 125 beats/min, respectively. Her blood pressure was 112/68. Her abdomen was distended but there was no guarding and rebound tenderness. She had deep sited tenderness in the left and right lower quadrants and in the suprapubic region. There was hyper-resonant percussion note and with decreased bowel sounds. There was tenderness on digital rectal examination. On vaginal examination, there was cervical excitation tenderness with a thick white foul smelling discharge on glove. Other systems were normal. A clinical diagnosis of pelvic abscess was made, and a gynecological consultation was made. A joint laparotomy was planned.
Her preoperative investigations included a chest X-ray and erect and supine abdominal X-rays. The chest X-ray showed air under the right hemidiaphragm and abdominal X-rays showed distended loops of small bowel. Her full blood count (FBC) showed an elevated white cell count of 13.0 × 109, a low hemoglobin of 9.6 g/dL and a platelet count of 606 × 109 cells/L. Sodium and Potassium were normal and were 140 and 4.4 mmol/L, respectively. Urea was raised to 9.8 mmol/L. Creatinine was 46 mmol/L. She had a low albumen and total protein of 22 and 67 g/dL, respectively. Her CD4 cell count was 230 cells/L.
Fluid resuscitation was commenced. A transurethral catheter and nasogastric tube were inserted. The patient was commenced on Ceftriaxone 1 g daily and Metronidazole 500 mg 8 hourly intravenously. Following good resuscitation, she was taken to theater for a laparotomy. At laparotomy, loops of small bowel matted by adhesions were noted. Adhesionolysis was done to free loops of small bowel. Approximately 2500 mL of pus were drained from the pelvis. Peritoneal lavage was done using 10 L of warm normal saline. An inadvertent enterotomy was noted intraoperatively and repaired with 3/0 PDS. The abdominal incision was closed in two layers with 0/PDS for the sheath and 2/0 Nylon for the skin. Intraoperatively the patient went into septic shock and required inotropic support. She was put on Dopamine infusion 4 mL/h.
Postoperatively the patient was admitted in the intensive care unit (ICU) for high care. Antibiotics, analgesia, fluid management, and monitoring were continued in ICU. By Day 3, the patient had shown much improvement. She was extubated and discharged to high care unit (HCU). Whilst in HDU on day 4, the patient was noted to be leaking fluid from the suture line. Fecal matter was noted when two skin sutures were removed. A colostomy bag was applied and the initial drainage noted on day 5 was 900 mL. A diagnosis of a high output enterocutaneous (ECF) fistula was made. Her white cell count went up to 21 × 109/fl. Fluid management, correction of electrolyte abnormalities, nutritional support, antibiotic management, skin protection, and monitoring and charting fistula daily fistula output were prioritized. Electrolytes were measured every other day. The following table (Table ) shows summary of results and progress of the patient until discharge on day 31:
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pmc-6293185-2
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A 28-year-old HIV-positive Mr EM on ART for the past 2 years was admitted with a 2-day history of abdominal distension, vomiting, and a fever. Three days prior to admission, he was being treated for diarrhea with oral rehydration fluids and Cotrimoxazole at a local clinic. He was referred to hospital because his condition was not getting better.
On examination, he was ill-looking and in respiratory distress. He had tachycardia and tachypnea with a pulse rate and respiratory rate of 110 beats/min and 30 breaths/min, respectively. His arterial oxygen saturation on free air was 89%. He had a temperature of 38°C and a blood pressure of 100/70. The abdomen was distended and moving minimally with respiration. Guarding, tenderness, and rebound tenderness were elicited on palpation. Bowel sounds were diminished. Other systems were normal.
A diagnosis of secondary peritonitis secondary to a perforated duodenal ulcer was made. Fluid resuscitation was commenced. The patient was propped up in bed and put on oxygen per face mask. Saturation improved to 94%. Ceftriaxone 1 g/d and Metronidazole 500 mg intravenously three times a day were commenced. A nasogastric tube for free drainage was inserted and a transurethral catheter was inserted to monitor urine output. Pethidine 100 mg 6 hourly was given for analgesia. The following were his preoperative laboratory investigations: Full blood count: Hb = 10 g/dL, WCC = 25 000 µmol/L Platelets = 190 × 103. Urea and electrolytes were normal. His preoperative albumin was low, 18 g/dL. His CD4 cell count was 350 cells/L.
The patient was taken to theater for laparotomy the same day in the evening because of worsening respiratory distress. At laparotomy, it was noted that the patient had multiple adhesions. Two small bowel perforation, each approximately 1 cm in diameter 2 cm apart and 25 cm from the ileocecal valve were noted. There was ascites and fecal contamination of the peritoneal cavity. There was no perforated duodenal ulcer. Ascitic fluid was suctioned out, and segment of small bowel with two perforations was resected followed by end-to-end small bowel anastomosis. Peritoneal lavage was done using 4 L of warm saline and the abdomen was closed in layers.
The patient was admitted in high dependence unit (HDU). Fluid management, oxygen per face mask and antibiotics were continued in HDU. Clexane 40 mg subcutaneously daily and chest physiotherapy were commenced. On day three postoperation, the patient was discharged to a general surgical ward. On the sixth day, the patient’s abdomen began to distend and he developed a fever of 37.9°C. A discharge was noted from the suture line and on removal of two skin sutures fecal material was noted coming out. A colostomy bag was applied and over 24 hours a fistula output of 1500 mL was recorded. A diagnosis of high output enterocutaneous fistula was made. Antibiotics, intravenous iv fluid were continued and a high calorie high protein diet was commenced. The following are the serial results and progress of the patient shown in Table until discharge on day 46.
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pmc-6293186-1
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An 85-year-old Caucasian male was admitted after sudden onset of expressive aphasia and weakness in both legs lasting 20 seconds. He was athletic, self-reliant and had no cognitive impairment. During the last 28 years, he had experienced 8-10 heterogeneous episodes of acute neurological symptoms, such as central facial palsy, hemiparesis, and non-fluent aphasia, lasting from seconds to 3-4 hours. Precerebral duplex and electrocardiography (ECG) were performed several times with normal results, and EEG registration and 24-hour Holter monitoring had been normal. Previous MRI scans showed no abnormal restricted diffusion, as seen in acute cerebral infarcts, but infarct sequelae in the left temporal lobe and both thalami. Several years later, three additional infarct sequelae were detected in the cerebellum. The patient was treated with platelet inhibitors, and medications and dosages were adjusted after new episodes. There was no suspicion of lack of compliance. Except from age, migraine, and previous smoking, with cessation 35 years ago, he had no known risk factors for cerebrovascular disease. On the current admission, he presented with reduced motor speed in his left arm and leg. Electrocardiography and Holter monitoring showed no signs of atrial fibrillation. CT and MRI revealed multiple, cortical infarct sequelae in the anterior and posterior circulation territories of both hemispheres, and MRI also detected two acute embolic infarcts in the right occipital lobe and one in the left parietal lobe (Figure ). CT and MRI angiograms and duplex sonography did not show significant plaques or stenoses, and pre- and intracerebral flow were normal with asymmetrical vertebral arteries, which were considered a normal anatomical variant. Cortical infarcts in several vascular territories strongly suggest cardioembolic etiology, but transthoracic echocardiogram showed no cardiac sources of emboli, and there was no sign of left atrial enlargement, which may be seen in the presence of atrial fibrillation. The patient concurred to further diagnostic tests aiming to determine the cause of recurrent cerebral emboli, although he was informed that the results would not necessarily alter treatment recommendations. We performed a transcranial Doppler (TCD) bubble test with 10 mL air-mixed saline injected into the left cubital vein while the left middle cerebral artery was insonated with a 2-MHz probe. Injection at resting state produced no microembolic signals, while injection after Valsalva maneuver resulted in a shower of microembolic signals followed by single signals persisting for over 30 seconds. The result implied the presence of a latent right-to-left shunt, and transesophageal echocardiography verified a large patent foramen ovale (PFO; Figure ). In agreement with the patient, we decided on non-operative treatment. Due to previous failure of antiplatelet treatment, we changed to a direct oral anticoagulant (dabigatran 110 mg twice daily), intended as a lifelong treatment. He had no subjective complaints at discharge.
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pmc-6293260-1
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A 35-year-old Caucasian female patient presented to her local emergency department in November 2016 with a chief complaint of neck pain. The patient had a past medical history significant for Hodgkin lymphoma diagnosed in 1998 following excision of a neck mass at age 16. She underwent chemotherapy and mantle field radiation in 1998. The radiation targeted lymph nodes in the neck, axilla, and behind the sternum in order to encompass the nodal basin of her cancer and the common lymph node drainage areas. The patient denied any history of radiation to her face. She reported remission at the time of presentation for this complaint of neck pain and was not following with anyone for her history of HL. She had no notable past surgical history. Menarche was at age 13 and she gave birth to one child at age 18. The patient’s family history was unremarkable with the exception of ovarian cancer in her maternal great aunt. There was no family history of breast or thyroid cancer. The patient was a previous smoker, quitting after about 10 years of use. No drug or alcohol use was recorded.
In the emergency department, a neck CT revealed a subcutaneous mass over the mid-clavicle, a breast mass, and multiple nodules in the thyroid gland with the largest nodule measuring 1.5 × 1.6 × 2.0 cm. The breast mass had dimensions of 2.6 × 4.0 × 4.9 cm by ultrasound. The patient was instructed to follow-up in breast and thyroid clinics for these findings.
The patient followed the emergency department’s recommendations and was examined by a surgical oncologist. In the breast clinic, she stated that the large right upper-outer quadrant breast mass had been present for 1 year. She was unsure how long the mass overlying the clavicle had been present, as it had been asymptomatic. On physical examination, the patient appeared well developed and well nourished. Respiratory, abdominal, musculoskeletal, and cardiovascular systems were normal. An 8.0 cm mass was located in the upper-outer quadrant of the right breast centered at the 10:00 axis about two fingerbreadths on the nipple border. Nipples were normal bilaterally. There was no cervical, supraclavicular, or axillary lymphadenopathy. Directly overlying the clavicle about two fingerbreadths medial to the mid-clavicular line was a 0.6 cm mobile mass within the skin. It was not associated with any regional lymphadenopathy. Laboratory workup was negative and unremarkable.
The patient underwent a bilateral mammogram in December 2016, followed by ultrasound-guided core biopsy of the breast mass. Initial core biopsy performed at an outside institution of the right breast mass came back as fibrocystic change. The outside biopsy was not reviewed at our institution. Based on a high level of clinical suspicion, additional imaging and a repeat biopsy were performed at our institution in January 2017. The repeat biopsy of the right upper-outer quadrant breast mass showed a phyllodes tumor. Pathology results described a fibroepithelial lesion with hypercellular stroma, mild-moderate stromal cytologic atypia, increased stromal mitotic activity (4-5/10 HPF), and focal areas suggestive of phyllodes architecture. The nature of the margins (pushing or infiltrative) could not be determined from the biopsy material. MRI showed the phyllodes tumor in the right breast measuring 4.7 cm. An excisional biopsy of the clavicular mass was done in a separate operation. The biopsy result was a cutaneous adnexal adenocarcinoma with eccrine differentiation. Surgical excision was recommended for both the breast and clavicular masses (Figures and ).
The patient also followed up in thyroid clinic for the multinodular goiter seen on her CT scan of the neck in the emergency department. Review of systems in the thyroid clinic was negative for change in voice or positional dyspnea but was significant for difficulty swallowing that started roughly 3 months prior. The patient also had pain in the right lower neck. She described the pain as constant, with an intensity of 5/10, and alleviated by acetaminophen. Ultrasound revealed three complex nodules with the largest in the left lobe measuring 1.3 × 1.8 × 2.5 cm, and other smaller nodules. The patient was diagnosed with multinodular goiter at this time. Two nodules met criteria for FNA. Cytology for both nodules was benign. The patient elected to defer any intervention and did not continue to follow-up.
In early March 2017, the patient underwent wide local excision of the phyllodes tumor, wide local excision of the cutaneous adnexal adenocarcinoma and right axillary sentinel lymph node biopsy, and concurrent post-reduction bilateral oncoplastic reconstruction. Surgery entailed intra-dermal injections of Tc99m-filtered sulfur colloid 1-2 cm from the margins of the lesion located over the right clavicle. Lymphoscintigraphy revealed uptake in two right axillary nodes. Once in the operating room, a standard axillary incision was made and 2 “hot” and blue lymph nodes were identified and removed. The cutaneous adnexal adenocarcinoma was then resected with a 1.5 cm margin which created a 4 × 10 cm ellipse. A lumpectomy was performed through predesigned incisions to ensure a cosmetically favorable closure for the phyllodes tumor in the right upper-outer breast. After removal, the plastic surgery team completed a bilateral breast tissue rearrangement and left breast reduction for symmetry. All aspects of the operation went smoothly, and the patient recovered uneventfully.
Pathology confirmed a phyllodes tumor measuring 4.1 cm in greatest diameter and clear margins. The phyllodes tumor pathology showed a circumscribed border, mild to moderate stromal cellularity, mild stromal cytologic atypia, and a mitotic rate of 4-5/10 HPF. Necrosis and malignant heterologous elements or stromal overgrowth were not identified. Overall, features were consistent with a benign phyllodes tumor (Figure ).
The adnexal neoplasm in the right chest was resected with negative surgical margins, and 0 of 2 nodes were positive for metastatic disease. The pathology report noted the presence of mitotic figures and rare atypical mitotic figures, favoring the diagnosis of a malignant adnexal neoplasm. The report adds that since the breast is a modified sweat gland, it is impossible to distinguish a primary cutaneous adnexal neoplasm from a primary breast neoplasm based on histologic features and that no immunoperoxidase stains can distinguish these two entities.
On her first postoperative clinic visit, the patient was recovering well. Her incisions were clean, dry and intact without erythema, drainage, hematoma or seroma. The patient has since continued to follow-up and has not experienced any complication or recurrence. She is recommended to follow-up annually.
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pmc-6293261-1
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A 28-year-old woman presented with epigastric pain. She had eaten sushi 1 day prior and developed intermittent epigastric pain after approximately 15 minutes. She did not have nausea or diarrhea. She was in the early pregnancy condition, and there was no abnormality during pregnancy. She had mild epigastric tenderness and no rebound tenderness or guarding. Her laboratory, electrocardiogram, and abdominal ultrasonography results were normal. She did not undergo radiography and computed tomography because of pregnancy. We suspected anisakiasis initially; therefore, esophagogastroduodenoscopy was performed. Her gastric mucosa was nonatrophic, and there was a linear foreign material stuck in the lesser curvature of the antrum (Figure A). We grasped the end of the material, which was hard, with alligator forceps and took it out carefully. There were no bleeding and signs of perforation; then, we clipped the wound in order to be certain that bleeding and perforation will not occur. Subsequently, we removed the foreign body with a sharp tip pointing toward the caudal side, without using any device to protect the esophagus, and we determined that the material was a broken wooden toothpick, approximately 4 cm in length (Figure B). Although we recommended that the patient to be admitted to our hospital, she did not agree; therefore, we carefully conducted outpatient follow-up. We instructed her to fast for 1 day and eat fluid diet from the second day onwards. Three days later, she returned to our hospital with no symptoms, she was subsequently permitted to eat regular meals.
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pmc-6293262-1
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The patient was a 7-year-old Japanese boy born at 38 weeks of gestation after an uncomplicated pregnancy and delivery. His parents were nonconsanguineous and phenotypically normal. He had no family history of pituitary dysfunction. His birth length was 51.0 cm (1.0 SD), and weight was 3.4 kg (0.9 SD). At birth, several dysmorphic features including hypertelorism, synophrys, midface hypoplasia, right preauricular pits, prominent antihelix, short philtrum, and thin upper lip with downturned corners of the mouth were observed. Echography revealed an atrial septal defect and left renal hydronephrosis. An auditory brainstem response examination revealed mild hearing impairment in both ears. The testes were undescended. Neonatal screening levels of thyroid-stimulating hormone (TSH) and free T4 were normal. At the age of 1 years and 5 months, his height was 77.2 cm (−0.9 SD), weight was 8.35 kg (−1.8 SD), and head circumference was 44.6 cm (−1.3 SD), respectively.
He was referred to us at 4 years of age because of his short stature. His height and weight were 87.7 cm (−3.2 SD) and 10.2 kg (−2.7 SD), respectively. He showed micropenis, with a stretched penile length of 2.5 cm. Brain magnetic resonance imaging revealed an anterior pituitary hypoplasia with a visible but thin stalk, as well as an eutopic posterior pituitary gland (Figure ). No other abnormalities in the central nervous system were found. Hormonal data revealed growth hormone (GH) and TSH deficiencies (Table ). The cortisol peak response during the corticotropin-releasing hormone (CRH) test was normal (peak cortisol = 17.3 μg/dL, Ref > 20.0 μg/dL or increment of 10 μg/dL). A replacement therapy with l-thyroxine was started. Replacement therapy with GH was refused by the parents.
At the age of 6 years and 4 months, the patient exhibited hypoglycemia without an apparent cause. The blood glucose level was 35 mg/dL when he was admitted to our hospital. Hyperinsulinism was excluded based on the analysis of critical samples (serum insulin levels were below 0.60 μIU/mL). We reevaluated his pituitary function by provocation tests, and an impaired cortisol response was observed during the CRH test (peak cortisol 13.3 μg/dL). He was then diagnosed with central adrenal insufficiency due to adrenocorticotropic hormone (ACTH) deficiency (Table ), and a replacement therapy with hydrocortisone was started. After starting hydrocortisone therapy, hypoglycemia has not been recorded since. At his last examination at the age of 7 years and 6 months, his height and weight were 106.0 cm (−3.2 SD) and 16.4 kg (−1.8 SD), respectively. Owing to severe psychomotor retardation, he remains wheelchair-bound and nonverbal.
Genomic DNA from the patient was subjected to array comparative genomic hybridization with the Agilent 4 × 180 K SurePrint G3 Human CGH Microarray (catalog no. G4449A; Agilent Technologies). We identified a heterozygous 1.3-Mb subtelomeric deletion at 9q34.3 (Figure ). Multiplex ligation-dependent probe amplification (MLPA) analysis of the parents revealed that this deletion was de novo (data not shown). The list of the deleted genes is provided as Data .
The combination of two relatively rare conditions, 9qSTDS and hypopituitarism, led us to perform additional study: whole-exome sequence (WES) to obtain additional genetic information for the etiology of the hypopituitarism. Detailed are described in Data . We provide the list of variants of unknown significance (VUS) detected in WES as Data . The number of variants remaining after each filtering step is provided in Supplemental Table . No mutations were found in the currently known hypopituitarism-related genes (POU1F1, PROP1, HESX1, LHX4, OTX2, SOX2, SOX3, GLI2, PAX6, IGSF1, GPR161, FGF8, KAL1, PROK2R, and LHX3). As one allele was lost for the region of chromosome 9q34.3 in the patient, any mutations in this region in the remained allele could be functionally null. However, we were unable to identify any pathological sequence variations in the genes located in the deleted region. Trio de novo approach using the DNAs from parents was refused.
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pmc-6293263-1
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A 70-year-old man was addressed to the emergency department with a suspicion of prostatitis. His medical history included urethral stricture requiring self-urinary catheterization, and kidney failure. Anamnesis and clinical examination revealed an alteration of general state (asthenia, anorexia and status 2 of WHO performance) associated with fever at 39.6°C and sweats that had lasted for 2 weeks. Two different antibiotic treatments (Sulfamethoxazol-Trimethoprim first, then Amoxicillin) were given, without any improvement. The initial blood count showed a anaemia (haemoglobin at 12.1 g/dL), neutrophilia (neutrophils at 16.8 × 109/L), and lymphocytosis (lymphocytes at 10.9 × 109/L). Blood smear showed medium large lymphocytes with regular nucleus and nucleoli (Figure A,B), and rare atypical large lymphocytes (Figure C,D). Cytobacteriological examination of urine was negative. An abdominal computerized tomography (CT) scan revealed a hepato-splenomegaly associated with coeliac and mesenteric adenopathy. The patient was admitted to the hospital in order to explore a probable hematologic malignancy.
A biochemistry panel showed highly increased levels of blood ferritin levels at 51 681 pmol/L, associated with hypertriglyceridemia at 3 mmol/L and discrete cytolysis, leading to a strong suspicion of hemophagocytic syndrome, with a Fardet probability score of 88.2%. A marrow aspiration was carried out. There was a major infiltration of bone marrow with macrophages but no clear diagnosis of hemophagocytosis could be performed. Nearly, half of the lymphocytes observed had morphology compatible with a DLBCL including large lymphocytes, with a basophilic cytoplasm; a regular nucleus and a compacted chromatin including a nucleolus (Figure A). Cytological analysis revealed also the presence of large atypical cells with intense basophilic cytoplasm containing vacuoles, with irregular nuclei, and some binucleated cells with decondensed chromatin and multiple nucleoli (Figure B). These cells were thought to be Reed-Sternberg-like cells which may be observed in patients with DLBCL., , Immunophenotypic analysis performed on the bone marrow aspirate demonstrated the presence of a heterogeneous B population monotypic kappa (Figure A,B), with a strong expression of CD20 and expression CD10, and negative for CD5 and CD38 expression (Figure C,D). Cytology and immunophenotyping were in favor of a diffuse large B-cell lymphoma (DLBCL), but were insufficient to make a precise diagnostic. Moreover, virological tests were performed on a whole blood sample and revealed the presence of Epstein-Barr virus (EBV) DNA with a viral load of 4.24 log10 copies/mL.
A bone marrow biopsy was performed. It revealed typical Reed-Sternberg cells (Figure A) suggesting the diagnosis of Hodgkin lymphoma, associated with large numbers of macrophages typical of a hemophagocytic syndrome. An interstitial and intrasinusoidal infiltrate of small lymphocytes was also observed. Immunohistochemistry tests highlighted a population of CD30+ (Figure B), CD15+ (Figure C), LMP1−, CD20−, CD79a−, CD3−, CD5−, and ALK− cells. The use of anti-CD20 antibodies made possible to identify a contingent of CD5− and CD10− cells, compatible with a marginal zone lymphoma (Figure D). Surprisingly, the population of CD10+ lymphocytes detected with the bone marrow immunophenotyping could not be detected in the bone marrow biopsy.
The final diagnosis was a Richter syndrome transforming a marginal zone lymphoma into a DLBCL associated with a stage IV lymphocyte-depleted classic Hodgkin lymphoma revealed by a hemophagocytic syndrome.
Before the results of the biopsy, the patient received one cycle of COP chemotherapy (Cyclophosphamide, Vincristine and Prednisone) aiming to treat his DLBCL. When the diagnosis of HL was firmly established, he was treated by ABVD chemotherapy (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine) associated with VP16 (Etoposide) to treat the hemophagocytic syndrome. After two cycles of ABVD chemotherapy, a slight lymphocytosis remained. A second immunophenotyping revealed a persistent CD20+ CD10+ lymphocyte population. The patient was then treated by three cycles of R-CHOEP chemotherapy (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Etoposide, and Prednisone). The initial response to this therapy was satisfactory, with improvement of the hemophagocytic syndrome and decrease in the ferritin levels from 29 211 to 9437 pmol/L. After the third R-CHOEP cycle, the patient was admitted to the hospital because of a sepsis triggered by a urinary infection. His general state quickly worsened, and a second bone marrow aspirate revealed a relapse of the hemophagocytic syndrome (Figure C) and a persistence of the Hodgkin lymphoma (Figure D). Despite antibiotic treatment and chemotherapy with high doses of Etoposide, Rituximab, and Cisplatin, there was no amelioration and a multiple organ failure led to the patient’s decease.
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pmc-6293264-1
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A 65-year-old woman presented with a complaint of progressive hearing loss without dizziness or vertigo. Hearing loss was of mixed conductive and sensorineural (Figure A). Physical examination was normal, without nystagmus or eye deviation, with the exception of negative Rinne tuning fork (512 Hz) testing. Computed tomography scan (Figure ) depicted bilateral otosclrosis (Figure A,B) and right-sided superior semicircular canal dehiscence (Figure C). A successful left-sided stapedectomy was performed, confirming the diagnosis of otoscelrosis and closing the air-bone gap to less than 10 dB (Figure B). Six months after the procedure, the patient expressed her wish to have the same surgery on the right but was advised to use a hearing aid instead. Electro-physiological assessment (vestibular evoked myogenic potentials, video nystagmography, and video head impulse test) was not performed since the patient decided to avoid surgery on the right side. The total follow-up duration was 2 years.
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pmc-6293265-1
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A 15-year-old African American male presented with a history of persistent pneumonia, dyspnea, expectorating cough with thick yellow sputum, intermittent sharp left-sided chest pain and single episode of a small amount of hemoptysis. Seven months prior to presentation, he had developed cough and low-grade fever which was diagnosed as left lower lobe pneumonia and received a course of azithromycin. Two weeks later, he had a relapse of symptoms with worsening of productive cough,yellow-colored sputum, wheezing, and chest pain which has since continued on and off. There was no history of atopy and no findings to suggest hypersensitivity. No history of travel. Physical examination showed decreased breath sounds bilaterally at the bases with few wet crackles in the left lower chest. Chest X-ray(CXR) confirmed the presence of persistent left lower lobe nonhomogenous patchy infiltrates, segmental atelectasis, peri-bronchial inflammation, and concerns of bronchiectasis with adjacent compensatory hyperinflation of lingula and left upper lobe. Pulmonary function test was performed (Table ). Hematologic evaluation was within normal limits except eosinophilia—20% with absolute eosinophil count of 1.73 × 103/μL. Upon diagnostic fiber-optic bronchoscopy with bronchoalveolar lavage(BAL): left upper and lower lobe bronchi were obstructed by avascular yellow firm mass although, the lingular bronchus was patent (Figure ). BAL of left lower lobe showed marked eosinophilia (54%). CT Chest with contrast (Figure ) was consistent with complete occlusion of left main lower lobe bronchus extending to segmental and subsegmental bronchi with partial sparing of the superior segmental bronchus. Opacification of diffusely dilated left lower lobe bronchi was seen which represents mucoid impaction in the setting of bronchiectasis throughout the basal segments with sparing of superior segments. A similar process was seen involving left upper lobe apical bronchus without associated bronchiectasis. Presence of hilar mass of 2 × 2.6 cm, posterior to left main bronchus was noticed. Based on bronchoscopy results with supportive evidence from CT chest and clinical picture, a diagnosis of plastic/cast bronchitis with eosinophilic lung disease and bronchiectasis was made. Flexible fiber-optic bronchoscopy & endobronchial ultrasound bronchoscopy were then performed for cast removal with a therapeutic bronchoscope and application of secondary agents. Multiple fine needle aspiration biopsies of the suspicious mass were performed. BAL from right middle lobe showed the presence of eosinophils (26%), left upper lobe eosinophils (8%) & left lower lobe showed eosinophils (54%). Surgical pathology and cytology of the extracted tan friable foreign body of 2.5 × 2.5 × 1.0 cm showed mucoid material with an infiltration of acute inflammation largely of granular eosinophilic cytoplasm with an abundant background of eosinophils. Crystalloid structures compatible with the appearance of Charcot-Leydon crystals were noticed. The background mucoid material showed light reactivity to mucicarmine and PAS special stain. Consent for lung biopsy was declined by the mother. A summary of work-up which was concluded as negative (Table ). Meanwhile, the patient was started on airway clearance therapy with fluticasone, albuterol, mucomyst, 7% hypertonic saline and chest physiotherapy using high-frequency chest wall oscillation (HFCWO). One-month course of systemic steroids also failed to improve symptoms, CXR, or eosinophilia. Azithromycin as anti-inflammatory medication was continued. On follow-up, the patient reported continued cough with expectoration of thick yellow pellets remaining unchanged over time. Repeat CXR revealed new infiltrate in left upper lobe with worsening of left lower lobe infiltrates due to cast reformation. Flexible bronchoscopy with cryoprobe application was performed with the aim to remove recollected bronchial cast. The left upper and lower lobes with lingular bronchi were observed to be completely obstructed by yellowish thick casts. Persistence and reformation of the unilateral bronchial cast with no clear etiology, in the presence of eosinophilia and bronchiectasis despite comprehensive interventions, leave the case to be managed by periodic cast removal using therapeutic flexible bronchoscopy with suction, cryoprobe, and foreign body extraction basket along with continued airway clearance therapy.
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pmc-6293520-1
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A 28-year-old Japanese woman was referred to our hospital for the treatment of hyperglycemia and partial lipoatrophy. She had acute promyelocytic leukemia and had received allogeneic bone marrow transplantation from her older brother at 4 years of age. When she was 19 years of age, she developed diabetic ketoacidosis and started insulin injection therapy. Although she had been treated with daily doses of 40 units of insulin detemir, 30 units of insulin lispro, 50 mg of sitagliptin, 15 mg of pioglitazone, 750 mg of metformin, and 200 mg of bezafibrate, her hemoglobin A1c and serum triglyceride levels remained high, ranging between 8.5 and 9.0% and 900 and 1000 mg/dL, respectively. Under nutritional guidance, she had been on a 1600 kcal diet consisting of 60% carbohydrates, 20% protein, and 20% fat.
On admission, her height was 158 cm, body weight 42.6 kg, body mass index (BMI) 16.9 kg/m2, and systemic blood pressure 122/75 mmHg. She manifested almost complete loss of subdermal adipose tissues of the bilateral forearms and lower legs, but her upper arms, thighs, face, and trunk were spared from lipoatrophy (Fig. ). Her fasting glucose was 232 mg/dL and HbA1c 8.7%. Serum C-reactive protein (CRP) was 2.8 ng/mL, ΔCRP 2.7 ng/mL after the injection of glucagon, and daily urinary excretion 80.9 μg/day, while her serum leptin levels was 6.5 ng/mL (range for women, 2.5–21.8). She had no elevation of liver enzymes: aspartate transaminase (AST) 21 IU/L, alanine aminotransferase (ALT) 19 IU/L, and gamma-glutamyl transferase (GGT) 32 IU/L.
However, reduced subdermal adipose tissues (47.3 cm2) and the accumulation of visceral adipose tissues (99.3 cm2) along with notable fatty liver were found by computed tomography (Fig. a). She also had dyslipidemia with low high-density lipoprotein (HDL) cholesterol (40 mg/dL) and high triglyceride (968 mg/dL) levels. Acrylamide gel electrophoresis demonstrated the elevation of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (Fig. b). A euglycemic hyperinsulinemic clamp study targeting a plasma glucose concentration of 100 mg/dL with an insulin infusion rate of 1.25 mU/kg/min suggested a prominent insulin resistance, since a glucose infusion rate of 2.32 mg/kg/min (normal range 8.0–12.0 mg/kg/min) was required to maintain the target glucose levels. The presence of hyperglycemia, prominent insulin resistance, hypertriglyceridemia, fatty liver, and acquired partial lipoatrophy suggested she was suffering from lipodystrophic syndrome.
The daily administration of recombinant methionyl human leptin (metreleptin; 0.04 mg/kg/day) was started and increased to a maintenance dose (0.08 mg/kg/day). Subsequently, all metabolic profiles, including the HbA1c and triglyceride levels, returned to the normal range.
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pmc-6293520-2
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A 40-year-old Japanese woman underwent partial liver transplantation from her husband as a living donor for alcoholic liver disease after abstinence from alcohol for 2 years. After transplantation, she developed non-alcoholic steatohepatitis (NASH), and the insulin therapy was initiated because of new onset of diabetes. A total daily insulin dose of 44 units was required to achieve glycemic control, and she manifested prominent insulin resistance although she was lean. NASH progressed to liver failure, and a second liver transplantation from a brain-dead donor was performed at 42 years of age. She received standard and maintenance immunosuppression regimens, including prednisolone 5–10 mg/day and tacrolimus 1–3 mg/day with trough concentration of 5–10 ng/mL.
After her second liver transplantation, marked hypertriglyceridemia of 1000 to 1900 mg/dL developed even under combination therapy with 200 mg/day of bezafibrate and 10 mg/day of ezetimibe. She was admitted to our hospital for the treatment of NASH and hypertriglyceridemia. Under nutritional guidance, she had been on a 1600-kcal diet consisting of 60% carbohydrates, 20% protein, and 20% fat. On admission, her height was 149 cm, body weight 37.9 kg, BMI 17.1 kg/m2, and systemic blood pressure 143/83 mmHg. Similar to Case 1, she manifested almost complete loss of subdermal adipose tissues of the bilateral forearms and lower legs, but the upper arms, thighs, face, and trunk were spared from lipoatrophy (Fig. a). The almost complete loss of subdermal adipose tissues was confirmed by magnetic resonance imaging (MRI) (Fig. b and c). Her HbA1c was 5.3%, serum CRP 4.2 ng/ml, ΔCRP 1.9 ng/ml after the injection of glucagon, and daily urinary excretion 20.2 μg/day, while her serum leptin levels were 3.5 ng/mL (range for women, 2.5–21.8). She had elevation of liver enzymes: AST 38 IU/L, ALT 13 IU/L, and GGT 241 IU/L. She demonstrated prominent fatty liver by computed tomography and severe NASH by a liver biopsy (Fig. c and a). She also had dyslipidemia with low HDL-cholesterol (40 mg/dL) and high triglyceride (968 mg/dL), VLDL, and IDL levels (Fig. d). Loss of subdermal fat tissues in the extremities, NASH, and severe dyslipidemia suggested acquired partial lipoatrophy.
Metreleptin therapy (0.08 mg/kg/day) was started to prevent repeated liver failure. Her hypertriglyceridemia was ameliorated, and her fatty liver significantly improved, as demonstrated by a repeated liver biopsy (Fig. b).
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pmc-6293546-1
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The patient is a 78-year-old man referred to our department for splenomegaly seen on abdominal computed tomography (CT) scan. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma (WHO classification, AB type; Masaoka classification/TNM classification, stage II) with subsequent follow-up. Five years after resection, a low density, isolated nodule in the spleen was seen on CT scan. Although follow-up continued for three years thereafter, the lesion was noted to continually increase in size, and the patient was then referred for further examination and treatment.
The patient underwent appendectomy for acute appendicitis at the age of 23 years, treatment for hypertension since he was 61 years old, extended thymectomy at age 71 years, and laparoscopic left hemicolectomy for cancer of the descending colon (stage I) at age of 73 years of age. The remainder of the history and physical examination were unremarkable, except for healed surgical scars from the previous thymectomy and the laparoscopic left hemicolectomy. Laboratory studies showed no abnormalities. Serum tumor marker levels were within normal limits (CEA 1.9 ng/ml, CA19–9 12 U/ml, SCC 1.5 ng/ml, CYFRA 2.0 ng/ml, PSA 1.29 ng/ml).
CT scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous enhancing lesion in the spleen with no intraperitoneal lymphadenopathy (Fig. ). On Magnetic Resonance Imaging (MRI), T2-weighted images, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and had a low-signal spoke-wheel sign in the margin, enhanced gradually on the dynamic study (Fig. ). Follow-up CT scan showed the tumor gradually increased in size over three years. On positron emission tomography (PET)-CT, the tumor had relatively low accumulation (Fig. ).
Based on these diagnostic imaging studies, we considered metastatic thymoma, hemangioma or lymphangioma with bleeding and organization, and sclerosing angiomatoid nodular transformation in the differential diagnosis. Surgical resection was then recommended to the patient and undertaken. The lesion was visually confirmed intraoperatively. No extracapsular invasion was observed. A laparoscopic splenectomy without lymphadenectomy was performed.
Pathological examination showed that the spleen was 12 × 7 × 6 cm in size. A lobulated medullary tumor was seen, 6 × 5 × 4.5 cm in size, yellow-brown in color on cut surface (Fig. ). The capsular structure of the spleen was maintained. Histologically, spindle to slightly epithelioid-shaped cells homogeneous in size with abundant nuclear divisions were growing in a medullary manner with blood vessels. The lesion was morphologically similar to the previously resected thymoma (Fig. ). Pancytokeratin and p63 were positive, while CD5 and c-Kit were negative histochemically. Vascular endothelium markers (CD31/CD34/factor VIII) were negative. TdT-positive lymphocytes were not discovered on immunostaining. Based on its histological appearance, the splenic mass was unlikely to be a primary splenic tumor or related to a hematological disease. The lesion was not consistent with a metastasis from the previous colon cancer. The histological appearance of the tumor was similar to the previously resected thymoma, and the final pathological diagnosis was metastatic thymoma (Fig. ).
The patient is now three years status post resection of the spleen and is followed every three months. He is in good condition without recurrence or any other symptoms.
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pmc-6293549-1
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A 38-year-old Japanese woman, gravida 0, presented with abdominal distension and frequent urination, was found to have a pelvic mass on radiologic examinations. She had a history of laparoscopic uterine myomectomy about a year before the onset, where the bilateral ovaries were macroscopically normal (Fig. ). She had no menstrual irregularities or dysfunctional uterine bleeding. Serum estradiol (E2) level was elevated to 214.5 pg/ml (normal 70–160 pg/ml), while testosterone was within the normal range. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) were 2.0 mIU/ml (normal 1-14mIU/ml) and less than 0.1 mIU/ml (normal 1.5-8mIU/ml) respectively, indicating E2-mediated negative feedback. CA 125 level was slightly elevated to 39.2 U/ml (normal < 35.0 U/ml). CEA, CA 19–9 and SCC antigen were within the normal range.
The MR showed a large, multiloculated cystic mass with numerous septations in the pelvis measuring approximately 10 × 10 × 12 cm. On T2-weighted images, fluid-fluid levels were demonstrated in several cystic components (Fig. a). T1-weighted images demonstrated intracystic high signal intensities suggesting intracystic hemorrhage (Fig. b). Contrast-enhanced fat-suppressed T1-weighted images showed strong enhancement of the septations similar to uterine myometrium (Fig. c). The mass was suspected to originate from the right ovary because the right ovary was not identified. The left ovary was atrophic for her age (Fig. a). On diffusion-weighted imaging, the septations showed high signal intensity (Fig. d). The uterus was of normal size without endometrial thickening. There was a small amount of ascites which was limited to the pouch of Douglas and vesicouterine pouch (Fig. e). Any calcifications were not detected on CT images. GCT was suspected from these findings.
Abdominal right ovarian tumor resection was performed. During the operation, the frozen section of the right ovarian tumor showed that malignancy could not be excluded due to its nuclear atypia. The differential diagnoses of the tumor included yolk sac tumor, malignant mucinous tumor and AGCT despite of the lack of any typical findings such as coffee-bean nuclei and Call-Exner bodies. Based on this report, abdominal simple total hysterectomy, bilateral oophoro-salpingectomy, partial omentectomy and appendectomy were performed.
The gross appearance of the cut surface of the right ovarian tumor, measuring 13 cm in diameter, showed multiloculated cystic tumor accompanied by intracystic hemorrhagic foci. The left ovary had a maximum diameter of 1.7 cm, suggesting atrophy for her age (Fig. ). Microscopic examination of the right ovary showed round cells that surrounded the macrofolliculars with eosinophilic material and hemorrhage (Fig. a).The tumor cells had scant cytoplasm, round-to-oval vesicular nuclei with small eosinophilic nucleoli, and irregular nuclear contours. The typical findings for AGCT such as longitudinal nuclear grooves (coffee-bean nuclei) and Call-Exner bodies were not identified. The mitotic activity was focally brisk, with an average of 10 mitoses per 10 high-power fields in these areas (Fig. b). Immunohistochemically, tumor cells were positive for vimentin, calretinin, CD99, a-inhibin and MIB-1 labeling index was about 30%. The above findings supported the diagnosis of JGCT. Accordingly, the definitive diagnosis of JGCT, FIGO Stage IA led to no additional treatment.
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pmc-6293582-1
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A 56-year-old woman presented with 6 years of radicular symptoms of the right upper extremity. Over the previous year she experienced progressive neck pain with radiation into the right hand in a C6 and C7 distribution. Six years prior she had undergone a posterior cervical laminotomy and foraminotomy without complete resolution of her symptoms. On examination of the right upper extremity, she had normal strength of the deltoid and wrist extensors with reduced strength of the biceps, triceps, and wrist flexors. She also had a positive Spurling’s sign on the right and diminished sensation of the C6 and C7 dermatomes. Her left upper extremity had normal strength and sensation. A cervical computed tomography imaging (CT) showed broad-based bulging of the C5-C6 disc and uncal hypertrophy causing severe right-sided foraminal stenosis [Fig. ].
Upon consultation with neurosurgery, she elected to pursue the spine surgery. The morning prior to the surgery, her platelet count was 189, INR was 1.05, PTT was 28, bleeding time was within normal limits. A standard Smith-Robertson approach was used to access the anterior spine from the patient’s left side for an anterior cervical discectomy, removal of osteophytes at C5 and C6, prosthetic disc replacement, bilateral foraminotomies at C5 and C6, and an anterior C5 and C6 spinal fusion. Patient was induced with propofol and re-positioned at which point there was a blood-pressure elevation of 155/98 which corrected within five minutes to baseline. Upon awakening in the post-anesthesia care unit, she was found to have altered mental status and was minimally responsive to verbal and sternal stimuli. She could follow some commands with her right arm and leg but was unable to move her left upper or lower extremities. A computed tomography (CT) scan showed bilateral acute basal ganglia hemorrhages with intraventricular extension of the hemorrhage and a small amount of subarachnoid hemorrhage within both cerebral hemispheres [Fig. ]. It is worth mentioning that the patient had minimal medical problems prior to this surgery and notably was without hypertension, known amyloid angiopathy, or diabetes.
She was immediately transferred to the neurocritical care unit, where she subsequently underwent a diagnostic cervicocerebral angiogram that was normal. Platelet function assays assessed after the surgery were without abnormalities. Twenty-four hours later, the patient acutely declined after an episode of non-bloody emesis and several generalized tonic-clonic seizures. On physical examination, she had anisocoria – left pupil was 5 mm and right pupil was 4 mm – with extensor posturing of the right upper and lower extremities. A computed tomography (CT) brain scan showed an expanding intraparenchymal hematoma of the right basal ganglia [Fig. ]. She was emergently intubated and underwent emergent placement of an external ventricular drain (EVD). She was extubated one week later. Over the next several weeks she failed numerous EVD clamping trials due to intracranial pressures rising greater than 20 mmHg. She was scheduled for placement of a ventriculoperitoneal shunt; however, this was ultimately aborted after she developed ventriculitis due to colonization with Propionibacterium acnes. Throughout this course she gradually developed a left facial droop, mildly dysarthric speech, left visual neglect, and a right gaze preference.
After almost 4 weeks in the neuro-ICU, the patient eventually regained spontaneous movements of her right upper and lower extremities. However, she continued to have extensor posturing in the left upper extremity and triple flexion in the left lower extremity. Sensation was intact throughout all extremities. Serial CT brain scans showed a decrease in the size of the bilateral basal ganglia and intraventricular hemorrhages. She was discharged in this condition to an acute rehabilitation unit 30 days after her elective spinal surgery. During the course of her rehabilitation, her aphasia and right hemiparesis recovered substantially, however, she continued to have profound left hemiparesis three months post-operatively. She requires an AFO and wrist extension brace on her left side and primarily uses a wheel chair.
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pmc-6294159-1
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A 15-year-old girl attended the paediatric diabetes clinic of Tygerberg Hospital, Cape Town, South Africa for a routine check-up. On presentation she was found to have faecal loading and mild diabetic ketoacidosis (DKA). She was known to have type 2 diabetes mellitus (DM) since 2014, as well as non-alcoholic fatty liver disease, overweight and metabolic syndrome (DM, hypertension, and increased waist circumference, hypertriglyceridaemia and low high-density lipoprotein cholesterol). Management included lifestyle modification, metformin, insulin, bezafibrate and enalapril, yet her glycaemic control remained suboptimal. Poor adherence to therapy was confirmed by the patient. Right sided abdominal pain and constipation were her only presenting complaints. On physical examination she was not dehydrated or shocked. Acanthosis nigricans was noted. Lipohypertrophy, eruptive xanthomata or lipaemia retinalis were not detected. Her body mass index (BMI) was 26.0 kg/m2 (95th percentile on UK BMI chart). Abdominal examination revealed an enlarged liver (3 cm from the costal margin in midclavicular line) and palpable faeces. The rest of the examination was unremarkable. The capillary blood glucose concentration was 22.1 mmol/L (FreeStyle Optium Neo, Abbott, Doncaster, Australia), the β-hydroxybutyrate concentration was 3.7 mmol/L (FreeStyle Optium Neo, Abbott, Doncaster, Australia). Urinalysis showed 4+ glycosuria and 4+ ketonuria (RightSign, Biotest, China). Additionally, urea, creatinine and a venous blood gas were requested. A venous blood gas could not be performed due to severe lipaemia. The blood was collected in a capillary for blood gas analysis which on visual inspection appeared clogged with severely turbid content and was therefore thought not suitable for analysis. The point of care β-hydroxybutyrate determination may be affected by triglyceride concentrations greater than 21.2 mmol/L (). A mild DKA was diagnosed on the basis of hyperglycaemia > 11 mmol/L, β-hydroxybutyrate concentration > 3 mmol/L and ketonuria (). The patient was treated with hourly subcutaneous insulin and recovered speedily.
Biochemical analysis was performed on a Roche Cobas 6000 analyser (Roche Diagnostics, Mannheim, Germany). Sodium concentration was determined by indirect ISE potentiometry. The triglyceride concentration was determined by an enzymatic colorimetric method. Osmometry was performed on an Advanced® Micro-Osmometer Model 3320 (Advanced instruments, Inc., Massachusetts, USA) using freeze point depression. The blood gas analyser was an ABL80 FLEX (Radiometer Medical ApS, Denmark) using a direct ISE method for electrolyte determination. The Roche Cobas 6000 analyser detects lipaemia using spectrophotometry. The lipaemia index has a semi-quantitative measuring range of 10 to 2000. The method uses diluted samples (with 0.9% sodium chloride) to measure absorbances at two different wavelengths for each analyte. The primary wavelength for lipaemia is 660 nm and secondary wavelength 700 nm ().
Informed consent was obtained from the patient and her mother. The Health Research Ethics Committee of Stellenbosch University, Cape Town (South Africa) approved this case report (C18/05/011).
shows the patient’s biochemistry results on the first day of admission. Her sodium concentration on admission was 116 mmol/L (sodium corrected for a glucose of 22.1 mmol/L was 123 mmol/L) with a semi-quantitative lipaemic index of 1661 (). As the lipaemic index was below the instrument alert level of 2000, this result was not flagged by the laboratory information system (LIS). The treating paediatrician was contacted, because the sodium was critically low. The paediatrician was informed that pseudohyponatraemia was suspected in the light of the high lipaemic index, but the sample was insufficient for further investigations. The biochemistry tests were repeated on the same day, which again revealed a critically low sodium concentration of 118 mmol/L and semi-quantitative lipaemic index of 1320. The capillary blood glucose was 13.7 mmol/L and therefore, the corrected sodium was 122 mmol/L. After high-speed centrifugation, the sodium concentration of the infranatant was 128 mmol/L. The sodium concentration was also determined by direct ISE on a blood gas analyser, which was 134 mmol/L (sodium corrected for glucose of 13.7 mmol/L, was 138 mmol/L). The measured serum osmolality was 303 mmol/kg, with a calculated osmolarity of 269.9 mmol/L (calc osmo = 2 x Na+ + Urea + Glucose). This revealed an increased osmolal gap of 33.1 mmol/L (osmolal gap = measured osmolality – calculated osmolarity) (). The triglyceride concentration was extremely high, with a concentration of 100.1 mmol/L after a 1:50 dilution. Acute pancreatitis was excluded as the lipase level was only mildly elevated and the patient did not have symptoms suggestive of acute pancreatitis.
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pmc-6294276-1
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An 83-year-old male, living alone and independently, presented to St. Ann’s Hospital Wound Clinic on December 29, 2017. Less than a week prior, he stated to the family that "I fell into a bar stool at home." Upon further exploration, the family felt that he fell asleep in his power recliner resulting in his right leg being lodged in the hinge portion of the footrest. Initial presentation as related by the patient and family included a hematoma on the medial portion of the right calf, tingling in the right leg and foot, and some weakness of the involved extremity. Watchful waiting was employed by the patient and family. Over the next 24-48 hours, the patient and family reported that the hematoma increased in size and severity resulting in significant wound involvement and tissue necrosis (Figures -). This increase in the severity of symptoms prompted their visit to St. Ann’s Hospital Wound Clinic, Westerville, Ohio.
The initial exam demonstrated extensive soft tissue damage with muscle necrosis and old gelatinous hematoma involvement. The neurologic exam demonstrated intact deep tendon reflexes, no sensation loss, but some mild subjective parasthesias. Vascular and orthopedic exams showed no gross deformity, an adequate range of motion with some guarding, and intact peripheral pulses with spongy edema. The patient was promptly admitted for appropriate medical workup in preparation for surgical debridement. Imaging failed to reveal any fractures and the full-body exam was without remark. Surgery included evacuation of the residual hematoma, extensive surgical debridement of necrotic tissues including muscle, mechanical cleansing with pulsed lavage, and deep tissue cultures (Figures -).
Once the surgery was completed, NPWTi-d was initiated in the operating room. The primary foam dressing layer was a novel dressing consisting polyurethane reticulated open cell foam with through holes (V.A.C. VeraFlo Cleanse Choice™ Dressing, KCI, an Acelity company, San Antonio, TX, USA). The second layer of thin polyurethane foam was placed over the through hole layer. Standard negative pressure wound therapy draping and trackpad placement were carried out (Figures -).
NPWTi-d was initiated by instilling normal saline that dwelled in the wound bed for eight minutes, followed by three-and-a-half hours of continuous -125 mmHg negative pressure. The amount of solution instilled was 30 ml. The patient received this therapy during his hospital stay of six days. An interval dressing change was performed at 48 hours postoperative. After 48 hours of therapy, significant hypergranular tissue plug changes were seen in the wound bed (Figures -).
Surgical wound cultures were negative other than skin flora. Initial parenteral antibiotics were changed to oral antibiotics before hospital discharge. After six days of NPWTi-d, the patient was transferred to a skilled nursing facility and he continued to receive traditional NPWT without instillation (V.A.C. Freedom®, KCI, an Acelity company, San Antonio, TX, USA). The pressure was maintained at continuous -125 mmHg. Interval dressing changes were performed every 48-72 hours. Overall improvement in wound size and disposition was noted over the next month of care (Figure ). Leg parasthesias improved gradually and completely resolved within the first postoperative month. Limb pain resolved within this time period as well.
Approximately six weeks from surgery, the wound bed was noted to be entirely granular with no depth. NPWT was discontinued and the patient was offered a traditional split-thickness skin graft or automated suction blister epidermal harvesting and grafting using the Cellutome™ device. Risks and benefits of both techniques were discussed with the patient. He opted for the minimally invasive automated technique. The procedure was done in the clinic setting and no anesthesia was required. Because of the wound size, bilateral harvesters were utilized to procure the epidermis from both the right and left thighs (Figure ).
Postoperative care included simple bandage protection of the donor and recipient sites together with edema control in the form of disposable compression bandages (Figure ). Normal daily activities and physical therapy were continued. Automated epidermal suction blister harvesting and grafting was carried out in serial fashion in the light of the wound size and was performed a total of three times with procedures spaced six to eight weeks apart (Figure ).
Complete closure was achieved approximately six weeks after the third epidermal harvesting and grafting technique (Figures -). The patient recovered completely without any loss of sensation or function.
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pmc-6294278-1
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A 42-year-old Malay gentleman, with significant past medical history of diabetes mellitus and mechanical mitral valve replacement (MVR) (St. Jude Medical Masters 29 mm) due to Staphylococcal endocarditis in 2015, on lifelong anticoagulation with warfarin, was first admitted for a one-week history of fever. Two days before his admission, he had a molar tooth extraction, and was given amoxicillin postoperatively for dental prophylaxis. He was not given any antibiotic prophylaxis before his tooth extraction. Other than fever, chills and cough, he had no other infective symptoms.
He also had significant bleeding of the tooth extraction wound causing symptomatic anemia with giddiness and dyspnea.
Physical examination revealed pyrexia (temperature of 38.6℃) and stable haemodynamics. His heart sounds were crisp with a metallic first heart sound. There were no peripheral stigmata of IE.
Routine investigations showed slightly elevated inflammatory markers and severe anemia (Table ). The chest radiograph did not reveal any opacities suggestive of septic embolism (Table ). International normalized ratio (INR) was found to be 4.99 (latest INR before admission: 2.9). Two sets of blood culture showed no bacterial growth (Table ). Transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) were not done.
He was given 4 units of packed cell transfusions for his symptomatic anemia and oral vitamin K for warfarin reversal. Adrenaline gauze packing and tranexamic acid gargle were given for hemostasis of the tooth extraction wound. He was started on amoxicillin/clavulanic acid for dental prophylaxis. He remained afebrile in the ward and was discharged. INR before discharge was 2.32.
One week later, he was admitted for another episode of fever. This time, the first two sets of blood culture again did not reveal any bacterial growth. However, the third and fourth sets of blood culture were positive and grew Parvimonas micra (Table ). TTE showed a stable MVR with no vegetation and normal function of the MVR. However, TOE showed that the MVR had at least two vegetations, with a new severe mitral regurgitation (MR) (Figure ).
He was referred to the cardiologist and the infectious disease (ID) specialist. Initial antibiotic treatment was ceftriaxone and vancomycin. After two repeated sets of negative blood culture (Table ), antibiotic was switched to penicillin G with the intention to complete a six-week course.
However, one month later, he was readmitted for exertional dyspnea and orthopnea. He had no fever. Inflammatory markers were unremarkable (Table ). TTE showed a normal MVR again and was unable to quantify the severity of the MR, but unchanged mean mitral valve pressure gradient (MVPG). TOE further showed shrinkage of vegetations but severe MR, and also increased MVPG.
Penicillin G was continued. He was given diuretic for his heart failure. After consulting the cardiothoracic surgeon, the patient underwent a repair operation of the mitral paravalvular leak. Intraoperative tissue culture showed no bacterial growth. Postoperative blood culture was negative.
He remained stable after repair of his MVR.
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pmc-6294281-1
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A 23-year-old female presented to the ED with six episodes of left-sided headaches in two and a half weeks. She reported photophobia, nausea, and vomiting and had an improvement in her symptoms with the use of medications such as prochlorperazine, diphenhydramine, and ketorolac. Despite multiple evaluations in the ED, a negative head computed tomography (CT), negative brain magnetic resonance imaging (MRI), and prescriptions for medications that were helpful in the ED, the patient kept returning with a headache. The patient denied any previous history of migraines prior to her first presentation but was given the label of "migraines" and was treated repeatedly with "migraine cocktails."
On this visit, the patient was seen about two hours before shift change and was reported to be alert, oriented, and with a Glasglow Coma Scale (GCS) of 15. The patient had received prochlorperazine, diphenhydramine, and ketorolac and was then signed out as: “a migraine, medicated, discharge pending improvement.” The patient was examined without the pre-handoff provider after sign-out and was noted to be drowsy, presumably due to prochlorperazine and diphenhydramine. However, after several hours of observation (three hours after medication administration) in the ED, with frequent examinations (patient persistently drowsy, GCS 10) the patient never returned to her neurologic baseline per her family at the bedside. While she had no focal deficits at this time, concerns from the family were raised as she began answering questions regarding her history incorrectly (per her family) and was displaying a change from her "normal" effect.
The patient’s initial diagnosis was a migraine headache and treatment for a migraine had been provided appropriately. When the patient was found to have altered mental status, as opposed to being drowsy from medication administration, the differential diagnosis was expanded. The expanded differential included medication effects (less likely due to the duration of symptoms) and acute intracranial processes such as bleeding, masses, and infections.
Based on this new development, an emergent CT scan of the head was ordered, which revealed rapidly progressive sinusitis that eroded through the left orbital wall, causing an inflammation of the left orbital apex with radiographic evidence of meningitis concerning for a possible fungal infection (Figure ).
Once the diagnosis of rapidly progressive sinusitis with CNS involvement (radiographically evident meningitis with a later confirmed epidural abscess) was made, the patient was started on intravenous (IV) vancomycin, 25 mg/kg, rocephin, 2 g, and amphotericin B, 5 mg/kg, concurrently. After ED intervention, the patient was emergently transferred to a tertiary care facility for evaluation by otolaryngology/ear, nose, and throat (ENT), and neurosurgery.
On arrival to the neurosurgical intensive care unit (ICU) of the tertiary care facility, the patient was evaluated by ENT and taken immediately to the operating room for left total ethmoidectomy and bilateral sphenoidotomy with the removal of contents. Cultures were obtained at the time of surgery, which grew methicillin-resistant Staphylococcus aureus. The patient continued with IV antibiotics, physical therapy, and occupational therapy and was discharged to a rehabilitation facility.
A week after admission, the patient suffered a left basal ganglia stroke, which was thought to have been caused by infective arteritis. She initially struggled with expressive aphasia but rapidly improved after the initiation of steroids and aggressive rehabilitation. At the time of discharge from the rehabilitation facility, the patient had a near-complete resolution of her mucosal disease (sinusitis), a complete resolution of her epidural abscess, and significant improvement in her leptomeningeal inflammatory enhancement on MRI (Figure ). Additionally, the patient had a full return of speech and could perform all activities of daily living. However, walking still required supervision but difficulty was only noted with uneven surfaces.
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pmc-6294860-1
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A 21-year-old female patient was referred to a general training hospital, Tehran, Iran in 2013 due to cough and skin lesions initiating from lower abdomen spreading to medial part of right shin. The cough and rhinorrhea were begun since 20 d ago and two weeks later the erythematous plaque with hemorrhagic bulla was presented in lower abdomen (). Three days after admission, the skin lesions were extended and the abdominal pain was initiated.
The study was approve by Ethics Committee of Iran University of Medical Sciences, Tehran, Iran. The patient had known as Wegener’s granulomatosis since four years ago. She also had anemia, arthritis, and arthralgia. She has also admitted two years ago for hematuria and hemoptysis. Patient had negative history for smoking, addiction, diabetes mellitus, and allergy. Nevertheless, anemia was present in her with a suspicious bone marrow aspiration sample.
The patient was receiving mycophenolate mofetil (500 mg three times a daily, cotrimoxazole (two tablets at bedtime) and methylprednisolone (20 mg three times a day). The findings in laboratory tests were as below; hemoglobin 8 gr/dl, BUN 34, creatinin 2.1, positive CRP, ESR 90 mm/hour, positive Anti-PR3 and negative ANA, positive blood culture for Staphylococcus aureus, hematuria, proteinuria, and glycosuria.
During recent admission, the skin lesions and productive cough were developed. However, the vital signs were normal. There was a low-grade fever. A fine crackle was heard at upper chest considered because of Wegener’s granulomatosis-related cavity in lung initially seen in at first admission. The ulcerative skin lesions and accompanied ecchymosis were seen at lower abdomen and right shin. These were expanded after corticosteroid and cyclophosphamide therapy. Histological examination of deep incisional biopsies of skin lesion revealed infiltrating lymphocytes, neutrophils, multinucleated giant cells. Hematoxylineosin (H&E) and periodic acid Schiff (PAS) staining showed numerous broad, aseptate and irregularly branched fungal hyphae indicative of mucormycosis deposited within the hypoderm and vessel wall (). Ten days after admission acute respiratory distress was developed leading to admission in intensive care unit. After 24 h, the patient was expired due to cardiopulmonary arrest and 45 min cardiopulmonary resuscitation was ineffective. The final CT-scan revealed extensive alveolar hemorrhage.
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pmc-6295019-1
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A 29-year-old Chinese woman presented at 38 weeks’ gestation with GDM and was admitted to hospital awaiting delivery. Her blood test showed mild thrombocytopenia (PLT 73 × 109/L). Her fibrinogen level (0.667 g/L) was decreased, while her anti-thrombin III (ATIII; 108.2%) and D-dimer (6.68 mg/L; normal range, 0–0.55 mg/L) levels were elevated. An evaluation of our patient according to International Society on Thrombosis and Haemostasis (ISTH) criteria (Table ) [] suggested overt disseminated intravascular coagulation (DIC) with a score of 5. After an intravenous injection of fibrinogen, her fibrinogen level reached 1.9 g/L and she delivered a normal baby girl weighing 3000 g. The Apgar score was 10–10 at 21:46 on the same day. One hour after her delivery, her blood pressure (BP) reached 180/110 mmHg.
Her physical examination results were as follows: temperature 36.8 °C, pulse 92 beats/minute, respiration 20 breaths/minute, and BP 180/110 mmHg; she was mentally healthy and moderately nourished. Her thoracic respiration was regular, and her chest expansion was symmetrical. Vesicular breathing sounds were normal and no moist rales were heard. Her heart rate was approximately 92 beats/minute with regular rhythm. There was no capillary pulsation and water hammer pulse, and no edema on either lower limb. Pathological reflexes were negative.
The laboratory findings were as follows: lactic dehydrogenase (LDH) 654.0 u/L, PLT 71 × 109/L, fibrinogen 0.719 g/L, and urine protein (+). She was transfused with 400 mL of fresh frozen plasma, five units of blood coagulation factor, and 4 g of fibrinogen. She was then transferred to the maternity intensive care unit where magnesium sulfate seizure prophylaxis continued for 24 hours after the procedure. She was given the magnesium sulfate in small doses of 1–2 g to keep her magnesium level in the low therapeutic range. Her BP was steady and her coagulation function was improving but she needed continuous oxygen therapy to maintain oxygenation.
A chest X-ray showed evidence of lung edema. She had a history of a persistent cough and exertional asthma 4 weeks before she was admitted to hospital. She ignored these symptoms and consequently received no therapeutic intervention. There was no history of cardiovascular disease, family disease, or psychosocial disease.
Six days after hospitalization, her blood PLT count reached 96 × 109/L, her fibrinogen level was increased to 1.784 g/L, and D-dimer was also elevated (9.51 mg/L). Her prothrombin time (PT), activated partial thromboplastin time (APTT), and ATIII were all normal. However, she constantly needed oxygen inhalation at 33% oxygen concentration to maintain oxygenation and her hypoxemia was difficult to control. Laboratory investigations revealed elevated carcinoembryonic antigen (CEA), (24.4 ng/mL), carbohydrate antigen (CA) 19-9 (> 1000 U/mL), and CA72-4 > 300 U/ml. A transthoracic echocardiography (TTE) examination showed normal dimension of the atrium and ventricle, but decreased left ventricular function. The left ventricular ejection fraction was 55%. Moderate tricuspid regurgitation with a peak velocity of approximately 3.56 m/s was recorded. The estimated pressure of the pulmonary artery from the tricuspid regurgitation was approximately 56 mmHg. Arterial and venous Doppler ultrasonography was performed on both legs and the results were normal. PET-CT showed malignant carcinoma of the head of the pancreas with lymph node involvement, bone metastases, peritoneal metastasis, bilateral lung cancer lymphangitis, and left adrenal metastasis. She died 2 weeks after the diagnosis before the scheduled initiation of chemotherapy.
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pmc-6295021-1
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A 33-year-old female was diagnosed with SLE 3 years previously in another hospital. She visited our hospital in May 2018 due to pain in lower back and began to take methotrexate. Advice from her physician was methotrexate (10 mg) once a week, but she made the mistake of taking this dose every day. She developed severe bleeding from an ulcer in the oral mucosa, and was admitted to our hospital 1 month later. She was diagnosed with SLE and methotrexate poisoning.
Even though she had stopped using methotrexate, her white blood cell (WBC) count was 1.67 × 109/L, red blood cell (RBC) count was 3.02 × 109/L, hemoglobin level was 119 g/L, and platelet count was 66 × 109/L, which suggested bone suppression. On day-7 of hospital administration, the patient developed fever (38.3 °C) and infection was suspected. Laboratory analyses revealed a level of C-reactive protein (CRP) of 19.19 mg/L, lactate dehydrogenase (LDH) of 5 U/L, aspartate transaminase (AST) of 8 U/L, alanine transaminase (ALT) of 91 U/L, and erythrocyte sedimentation rate (ESR) of 23 mm/h. Blood samples were taken and empirical therapy with metronidazole and cefoperazone/tazobactam was started because of fever with oral mucositis. At day- 11 of hospital admission, spindle-shaped Gram-negative rods were isolated from one of four blood samples (Fig. ). After 24 h of incubation in an anaerobic environment with 5% CO2, growth on blood agar showed light yellow-pigmented colonies that were smooth, gray, catalase-positive and oxidase-negative (Fig. ). The organism was identified as Leptotrichia trevisanii by matrix-assisted laser desorption ionization- time of flight-mass spectrometry (MALDI-TOF-MS) undertaken on a Biotyper system (Bruker, Bremen, Germany) (Fig. ). In addition, the organism was confirmed as L. trevisanii using 16S ribosomal RNA (rRNA) gene sequencing as described previously [], which matched 98% with the L. trevisanii strain (NR 029805.1). Therefore, the patient was diagnosed with L. trevisanii bacteremia and received the therapy mentioned above continuously.
Next, we collected samples of the ulcer in the oral mucosa using a swab for anaerobic culture but L. trevisanii was not isolated, which might have been caused by exposure to an aerobic environment. After 10 days of treatment, the fever disappeared and the mucositis improved obviously. Routine blood analyses revealed the WBC count to be 11.19 × 109/L, RBC count to be 3.7 × 1012/L, hemoglobin level to be 110 g/L and platelet count to be 256 × 109/L, suggesting that bone-marrow suppression was also restored. Therefore, sepsis had resolved and there was no recurrence of bacteremia.
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pmc-6295047-1
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A 25-year-old male presented to our hospital with a one-month history of bloody stool. He denied any tobacco or alcohol use. His serum level of carcinoembryonic antigen (CEA) was 21.0 ng/mL (normal < 2.5).The colonoscopy examination revealed a circumferential rectal lesion at 7 cm from the anal verge (Fig. a). An endoscopic biopsy confirmed the diagnosis of poor differentiated adenocarcinoma (Fig. b). Immunohistochemical staining for mismatch repair proteins MSH6 (BD Transduction Laboratory; clone 44, 1:1000 dilution), MSH2 (Calbiochem, Oncogene Sciences; clone FE11, 1:100 dilution), MLH1 (BD Biosciences Pharmingen; clone G168–15, 1:100dilution) and PMS2 (BD Pharmingen; clone A16–4, 1:500 dilution) was performed as described previously []. And the results showed proficient mismatch repair (pMMR) for this patient (Fig. c-f). Magnetic resonance imaging (MRI) of the pelvis revealed heterogeneously enhancing irregular circumferential mural wall thickness involving the mesorectal fat measuring 5 cm in its length with enlarged perirectal lymph nodes (Fig. a). The computed tomography findings of the chest were negative. Based on the above findings, he was diagnosed with rectal cancer (cT3N2M0). The patient was originally planned to receive standard preoperative 5-FU-based CRT. However, he refused any radiotherapy concerning the increased risk of radiation-induced infertility and received 4 cycles of neoadjuvant chemotherapy with mFOLFOX6 regimen that consisted of oxaliplatin 85 mg/m2 intravenously, leucovorin 400 mg/m2 intravenously followed by fluorouracil 400 mg/m2 intravenously and fluorouracil 2.4 g/m2 by 48 h continuous intravenous infusion. The patient experienced only grade I gastrointestinal and hematological toxicities, after which he underwent re-staging with CT or MRI scans of the chest, abdomen, and pelvis. Re-examination of pelvic MRI 4 weeks after diagnosis revealed evidence of tumor regression (Fig. b). Consequently, the patient received laparoscopic TME for rectal cancer, and histological examination of the surgical specimen revealed chronic ulcerative lesions but no evidence of residual adenocarcinoma cells (Fig. ), consistent with the concept of a complete response according to the AJCC TRG system. All 13 lymph nodes resected were negative (ypN0). Another 8 cycles of mFOLFOX6 adjuvant therapy was given following surgery. His CT scans showed no evidence of recurrence3 and 6 months after operation, and CEA is normal. No evident recurrence has been found in the patient for 12 months.
Given the significant tumor response, we next performed next-generation sequencing (NGS) using DNA from the endoscopic specimen as described []. DNA sample was extracted from the endoscopic specimen and peripheral blood samples (DNeasy Blood and Tissue Kit, QIAGEN, Hilden, Germany). After quality control, DNA sequencing libraries were prepared according to the protocols recommended in the Illumina TruSeq DNA Library Preparation Kit (Illumina, San Diego, CA, USA). Libraries were hybridized to custom-designed biotinylated oligonucleotide probes (Roche NimbleGen, Madison, WI, USA) covering ~ 1.1 Mbp of sequence. DNA sequencing was carried out with the HiSeq CN500 Sequencing System (Illumina, San Diego, CA, USA). After removing the terminal adaptor sequences and low-quality data, the reads were mapped to the reference human genome. GATK (, The Genome Analysis Toolkit) and MuTect were used to call small insertions and deletions (indels) and single nucleotide variants in the somatic DNA by filtering peripheral blood sequencing data. Out of our expectation, a total of 159 somatic mutations were identified with TP53 p.R213* as the mutation with the highest allele frequency (53.3%). Moreover, KRAS p.G12D mutation was also detected at the allele frequency of 51.4%. Intriguingly, presence of BRCA2 somatic mutation (c.2231C > A p.S744*) was observed. The number of somatic mutations detected on NGS (interrogating 1.2 mb of the genome) is quantified and that value extrapolated to the whole exom. TMB was measured in mutations per megabase (Mb) and classified into high (20 mut/Mb), intermediate (6–19 mut/Mb) and low (< 6 mut/Mb). Consequently, the tumor mutation burden of our patient was described as high (22 mut/Mb).
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pmc-6295090-1
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A 2-month-old male child was admitted to the Academic Department of Pediatrics of the Bambino Gesù Children’s Hospital (BGCH) due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks’ gestation after a bicorial, biamniotic pregnancy with birth weight of 2.080 kg. He was the first of non-identical twins. The mother was a 30-year-old migrant woman from Nigeria, who arrived in Italy at 27 weeks gestation. At presentation, she tested seropositive for HIV and cytomegalovirus (CMV) and started antiretroviral therapy. Her absolute lymphocyte count was 1410/µl; CD4 count and the HIV viral load were not reported in the documentation received from the Hospital where the mother was admitted in emergency when she arrived in Italy.
The twins were tested for HIV at birth with PCR for HIV-RNA searching. The female twin was positive for HIV and CMV infection, while the male twin was HIV negative at birth and treated with zidovudin as post-exposure prophylaxis for 6 weeks. TORCH screening (toxoplasmosis, rubella, cytomegalovirus, herpes simplex), abdominal and cerebral ultrasounds were performed to exclude other congenital infections on both twins. A week before admission at our Department the male twin was admitted to another hospital due to anaemia (Hb 5.1 g/dl), hence receiving a blood transfusion. On initial evaluation at BGCH, he was in good general condition, weighed 3.910 kg, with temperature of 36.5 °C, heart rate of 135 beats per minute, respiratory rate of 35 for minute. His abdomen was soft, the liver was palpable 4 cm below the right costal margin. The findings of the rest of the examination were unremarkable.
Laboratory tests at the admission, after a week from the first blood transfusion, revealed a leukocyte count of 12.000/mm3; a haemoglobin (Hb) level of 9.1 g/dl; a platelet count of 198.000/mm3 and a reticulocyte count of 169.000/mm3. His bilirubin level was 1.31 g/dl with direct bilirubin of 0.64 mg/dl; lactate dehydrogenase level of 945 UI/L and normal renal and liver function values.
A myelosuppression effect due to the zidovudin was initially hypothesized, then the haemoglobin concentration was monitored and a supportive therapy with folic acid and iron per os was started.
During hospitalization, a progressive decrease of Hb levels to 6.8 g/dl was observed, therefore, requiring additional blood transfusions. Causes of haemolytic anaemia and blood loss were excluded, due to persistently high reticulocyte count; also, direct and indirect Coombs and faecal occult blood tests were performed, resulting all of which were negative. Haemoglobin electrophoresis was also performed, although in the presence of blood transfusions, to exclude hereditary haemoglobinopathies. A subsequent physical examination was then performed, revealing an increase of spleen enlargement, also confirmed by ultrasound examination. A diagnostic of malaria was then considered.
Because of the infants’ age and the origin of the mother who came from an endemic area for malaria, the malaria panel provided in BGCH was performed on twins and mother’s blood. The panel included the following routine algorithm: (i) Rapid diagnostic test (RDT); (ii) microscopy of Giemsa-stained thick and thin blood smears for Plasmodium spp. identification (ID) and parasitaemia index assigned by two independent microscopists; (iii) molecular screening and typing of Plasmodium spp. by an end-point multiplex qualitative polymerase chain reaction (PCR) assay.
The RDT, based on either Plasmodium spp. lactate dehydrogenase (pLDH) and P. falciparum histidine-rich protein 2 (HRP2) antigens, was performed by using SD Bioline Malaria Antigen P.f/Pan (Standard Diagnostic), whose performance is periodically monitored by the World Health Organization Malaria Control Programmes [].
Briefly, about PCR assay, DNA was extracted from 200 μl of EDTA blood with the QIAamp DNA Mini Kit (QIAGEN) and 5 μl of each DNA sample were probed with the 18S rRNA gene target of the multiplex PCR STAT-NAT Malaria Screening and Typing (Sentinel-Diagnostics). PCR products were visualized using 2.2% agarose (Lonza FlashGel®System) and a UV trans-illuminator BioRad.
The RDT for Plasmodium spp. was negative for mother and female infant specimens, while male infant resulted positive (Fig. ). PCR analysis confirmed a positive result for mother and male twin, revealing a P. falciparum infection, while samples from the other twin were consistently negative with both techniques (Figs. , ). Thick and thin blood films stained by Giemsa revealed trophozoite forms of P. falciparum with parasitaemia index of 1% for the male infant and < 1% for the mother. The RBCs of the mother infected with malarial parasites were of normal size and poly-parasitized by trophozoites (Fig. ).
Genotyping of Plasmodium spp. isolates was carried out to identify infectious clones in both mother and infant. The genotyping was performed by amplification of a neutral microsatellite marker (MS-TA109) [] and four highly polymorphic markers: P. falciparum merozoite surface protein 1 (Pfmsp1) and its allelic subfamilies (K1, RO33, MAD20) [], P. falciparum merozoite surface protein 2 (Pfmsp2) and its allelic subfamilies (3D7, FC27) [], P. falciparum histidine-rich protein 2 (Pfhrp2) and t P. falciparum histidine-rich protein 3 (Pfhrp3) []. For allele detections, PCR was done in a 25 μl PCR mixture containing 10 μl of extracted DNA, 1× of MgCl2 free buffer Fast Start Roche, 2 mM of MgCl2, 200 μM of dNTPs, 10 μM of each primer and 0.25 U of FastStart Taq polymerase Roche. The cycling conditions for Pfmsp1 were as follows: denaturation at 95 °C for 5 min, followed by 45 cycles at 94 °C for 30 min, annealing at 47 °C for 45 s and extension at 72 °C for 1.5 min and a final extension at 72 °C for 5 min. The cycling conditions for Pfmsp1/Pfmsp2 families were: 95 °C for 5 min followed by 45 cycles at 94 °C for 1 min, 55 °C for 45 s, 72 °C for 1.5 min, and a final extension at 72 °C for 5 min. The Pfhrp3 gene, FC27, K1 and TA109 microsatellites were amplified as described in Menegon et al. and Anderson et al. [, ]. The amplification products were analysed using a high-resolution capillary electrophoresis (QIAxcel Advanced system, Qiagen).
Genotypic characterization of P. falciparum isolates showed the presence of a single isolate in each of the analysed blood samples. All five P. falciparum polymorphic markers were genotyped for isolate present in the newborn’s infection, whereas only four markers (Ta109, Pfmsp1, Pfmsp2 and Pfhrp3) were successfully amplified for the maternal isolate. Both isolates belonged to the K1 and the FC27 allelic subfamilies. The comparison of allelic profiles, based on length polymorphism of analysed markers, showed dissimilar size alleles for two molecular markers, Pfmsp2 and Pfhrp3, indicating that two different parasite isolates were present in the mother and child at the time of blood collection, 2 month after delivery. Moreover, the amplification failure of Pfhrp2 gene in the maternal sample was presumable due to the hrp2—deletion in the isolate infecting the mother (Fig. ).
Because of the P. falciparum ID in the male infant, oral administration of atovaquone/proguanil (125 mg/50 mg daily for 3 days) was immediately started. The parasitaemia index on infant’s blood performed after treatment confirmed the clearance of the parasites; the following blood exams revealed a normalization of Hb level.
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pmc-6295096-1
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A 7 years old male mix breed Husky weighing 23 kg was presented to our Veterinary Teaching Hospital the owner reporting weight loss, inappetence and exercise intolerance and on presentation exhibited breathlessness and an enlarged abdomen. Physical examination revealed cyanotic mucosal membranes, severe subcutaneous edema in the head area, thorax and limbs and respiratory effort with a rate of 42 breaths per minute. Palpation of the abdomen revealed a positive ballottement reaction suggesting the presence of ascites. Cardiac sounds were muffled during auscultation and the femoral pulse was fast and weak. A 5 minutes six leads electrocardiogram (PolySpectrum ECG) and echocardiography (Esaote AU5), were performed using previously described methods [, ]. Complete blood count, serum liver enzyme activities and renal parameters were assessed.
Electrocardiography revealed a fast sinus rhythm of 140 bpm, absence of respiratory arrhythmia and low voltage QRS complexes (R wave in lead II = 0.09 mV), with a positive polarity in leads I, II, aVL, aVF and negative in leads III and aVR, with a left axis deviation.
A brief cardiac echocardiography revealed right atrial and ventricle enlargement with a hyperechoic heterogenous mobile mass of 4.26 × 2.64 cm inside the right ventricle extending into the right atrial cavity through the tricuspid annulus (Fig. ). A subjective assessment of the left ventricle revealed thickened left ventricular septum and free wall and reduced lumen size, suggesting concentric hypertrophy. The left atrial cavity appeared normal. Also, free pleural fluid was observed. A complete echocardiographic examination was not possible because of the dog’s clinical status. Red and white cell numbers were within the reference range and the haematocrit was mildly decreased Ht%: 38.4 (reference range 40–60%). Serum biochemistry revealed increased activity of serum alanin aminotransferase: 111 U/L (reference ranges 18–86 U/L), alkaline phosphatase: 203 U/L (reference range 12–121 U/L), normal total protein: 5.5 g/dL (reference range 5.4–7.5 g/dL) and increased BUN: 96 mg/dL (reference range 8–29 mg/dL).
Shortly after the cardiologic examination, the dog died and necropsy was performed. The necropsy revealed typical changes of right sided congestive heart failure. Severe cyanosis of oral mucosae, of the tongue and skin were observed. Also, generalized edema of the subcutaneous tissue, more evident in the head area, ventral part of the body and limbs was observed. In both peritoneal and pleural cavities, a large amount (2.5 respectively 0.5 l) of free serous fluid was present. The lung had a pale appearance and higher density than normal at palpation, while the floating thest was negative, likely as a result of compression by pleural fluid.
Inside the right heart (atrium and ventricle), an elongated and branched mass with a smooth surface was observed. It extended from the right ventricle, retrograde to the right atrium, and then into the cranial vena cava, continued into the right brachiocephalic vein and split into the subclavian and external jugular vein. The subclavian branch was short. From the jugular vein, the tumour extended to the linguofacial and maxillary veins (Fig. a). The caudal vena cava and left brachiocephalic veins were enlarged, but no mass was found inside the lumen.
The mass was attached dorsally to the endocardial insertion of the septal tricuspid valve leaflet, suggesting a diagnosis of a primary endocardial tumour. The consistency was firm to elastic, with a smooth surface and an overall whitish colour with small red areas evident dispersed throughout the mass. The sectioned surface of this mass was nonhomogeneous, slightly fatty, with red and yellow striae inside.
The gross examination of the left heart revealed an apparently hypertrophied left ventricle with a reduced ventricular lumen (Fig. b). The mitral and aortic valves were normal, as well as the left ventricle outflow tract.
The liver, spleen and pancreas were increased in volume based on gross pathology inspection and a very dark red colour, presumably as a consequence of chronic venous congestion.
During necropsy, multiple fragments were harvested from the intracardiac and intravascular locations of the mass as well as the connection of the mass and the endocardial insertion. Samples were also taken from liver, lung, pancreas, left and right kidney, spleen, brain, both of adrenal glands and myocardium.
Microscopic examination was performed on formalin-fixed and paraffin embedded tissues. The slides were routinely processed and stained with Masson’s trichrome and alcian blue. Selected sections of the tumour were immunostained using the labelled CD34 (QBEnd-10; Dako), vimentin (Novocastra – Liquid mouse monoclonal antibody), desmin (Novocastra – Liquid mouse monoclonal antibody), CD31 (Novocastra – Lyophilized mouse monoclonal antibody), alpha – smooth muscle actin (Novocastra - Lyophilized mouse monoclonal antibody), epithelial membrane antigen (Novocastra - Liquid mouse monoclonal antibody), S-100 protein (Novocastra – Liquid mouse polyclonal antibody) and MUC1 (Novocastra – Lyophilized mouse monoclonal antibody).
Histological examination of the mass revealed a mixed tumour with two microscopical aspects: fibrosarcoma and myxoma. The two different types of the tumor were intercalated, resulting into a tumoral tissue organized in two structures with different architectures (Fig. a).
One type was organized in compact structure with spindle shaped cells. These cells had big, irregular and vesicular nuclei (anisokaryosis) with chromatin of a dusty appearance and a marked nucleolus, morphology corresponding to fibrosarcoma tumour. This type showed 8–12 mitotic figures per 400× field consistent with high grade of malignancy (Fig. b). The other type had an organisation typical of a myxomatous tumour, formed by pleomorphic cells arranged in cords, trabeculae and small groups. The cells presented spindle, triangular and stellate shapes, anisokaryosis, low mitotic figures (1–3 per 400× field) and syncitia (Fig. c). Within the tumor, neoformation blood vessels and a very poor stroma were present. The myxoid matrix was strongly positive for alcian blue stain.
The examination of the contact area between the tumor and the atrial wall revealed tumoral cells among the myocardiocytes (Fig. a). Within the tumoral mass, extended areas of necrosis were observed, with the persistance of the tumoral arhitecture.
The microscopical lung metastasis had the same mixed structure as the primary tumor. A capsule-like structure represented by condensed lung tissue around the tumoral metastasis, lung atelectasis and compensatory emphysema near the metastasis were observed (Fig. b).
The fibrosarcomatous type of the cardiac tumor was positive for vimentin (Fig. a), S-100 protein and alpha-smooth muscle actin and negative for desmin, CD31, CD34, MUC1 and epitelial membrane antigen. The myxomatous type of the mass was positive for vimentin also (Fig. b), alpha-smooth muscle actin, weak positive for S-100 protein and negative for desmin, CD31, CD34, epitelial membrane antigen and MUC1. Desmin was positive only for myocardial tissue where the tumoral mass inserted.
No metastases were found in other organs except the lungs. However, lesions secondary to right sided congestion heart failure were observed in different organs. These lesions consisted of congestion and hypoxia-induced degeneration in the liver, spleen, pancreas and kidneys. Liver congestion was characterised by enlarged sinusoid capillaries, filled with agglutinated red blood cells and within the hepatic lobules, due to hypoxia, large groups of degenerated hepatocytes with pyknotic nuclei were observed. The kidney examination revealed distension of the interstitial capillaries, filled with red blood cells and proximal tubules epitelium degeneration secondary to hypoxia. Histopathological examination of the left ventricle wall revealed an increase in myocardiocytes size and a moderate congestion of the interstitial blood vessels.
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pmc-6295314-1
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A 60-year-old Japanese man visited our department for heart failure. He did not smoke tobacco; he had two histories of cardioembolic cerebral infarction at ages 47 and 59. Also, he had hypertrophic cardiomyopathy at age 58, but had no coronary risk factors including hypertension. His blood pressure was 107/72 mmHg with a heart rate of 60 beats per minute. He had a grade 2/6 systolic murmur and mild pretibial edema. Carpal tunnel syndrome, polyneuropathy, and autonomic dysfunction were unremarkable. An electrocardiogram showed normal sinus rhythm with QS waves in inferior leads, and with low QRS voltages in leads V1 to V4 (Fig. a). A chest X-ray showed cardiomegaly (Fig. b). An echocardiogram demonstrated severe asymmetric left ventricular hypertrophy (LVH; the interventricular septum and the posterior wall were 13 mm and 16 mm, respectively), biatrial dilatation, pericardial effusion, and preserved left ventricular ejection fraction of 50% (Fig. a). Increased right ventricular wall thickness was also seen. There was grade III diastolic dysfunction (Fig. b). The unexplained LVH led us to suspect cardiac amyloidosis. Technetium pyrophosphate (99mTc-PYP) scintigraphy indicated marked diffuse myocardial uptake of 99mTc-PYP (Fig. a), which strongly suggested TTR cardiac amyloidosis. In addition, cardiac magnetic resonance imaging revealed wide-spreading transmural late gadolinium enhancement at the ventricular and atrial walls, also supporting this notion (Fig. b). A left ventricular endomyocardial biopsy confirmed TTR-related amyloid deposits (Fig. ). DNA sequence analysis demonstrated a TTR C70T (Pro24Ser) heterozygous mutation (Fig. a). Therefore, we assume that the Pro24Ser mutation is responsible for cardiac amyloidosis. Further genotyping of TTR of the family members of our patient revealed that his third son has the identical mutation (Fig. b), while he showed no clinical signs. Our patient was ineligible for heart transplantation due to his age (over 60) and renal dysfunction; thus, a combined usage of diuretics and tafamidis, a TTR stabilizer, was administered. His cardiac symptoms remained unchanged for 12 months.
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pmc-6295679-1
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A 52-year-old man presented to the clinic with a right scrotal and inguinal tumour that had progressed over the past 2 years. The patient had no other medical conditions.
On physical exam, the patient had a 10 cm × 15 cm warty and friable scrotal mass. He had two fixed voluminous inguinal lymph nodes bilaterally.
An abdominal and pelvic computed tomographic (CT) scan, a pelvic magnetic resonance imaging (MRI) and a positron emission tomography (PET) scan were performed. The PET scan revealed increased uptake of the inguino-scrotal mass. Metastatic inguinal and pelvic lymph nodes were identified, the biggest measuring 7 cm on the left inguinal side. There were no other primary lesions noted. There was no distant metastasis.
Many biopsies were taken from the cutaneous inguinal mass and revealed a dense proliferation of atypical epithelial cells in the dermis extending and ulcerating the epidermis. Numerous mitotic figures and apoptotic cells were observed as well as focal squamous and glandular differentiation. Immunohistochemistry was performed and the tumour was diffusely positive for CK5/6 and CK AE1/AE3. It was also positive for p63 except in the cells bordering the lumen of the glands. GATA3 was positive in a proportion of the tumour cells.
Initially, our differential diagnosis included a malignant adnexal carcinoma and an adenosquamous carcinoma. Moreover, because of GATA3 positivity, a urothelial origin could not be excluded. Although an adnexal malignant carcinoma cannot be entirely excluded since the whole tumour was not examined pathologically for a residual benign component, the clinical history is negative for transformation of a long-standing tumour. Finally, a urothelial origin was less probable in the light of a negative radiology workup.
The patient was not immunosuppressed and was seronegative for HIV. The patient’s diagnosis was a primary cutaneous adenosquamous cell carcinoma with regional lymph node metastasis.
The initial treatment plan consisted of neoadjuvant chemotherapy with 15 cycles of cisplatin 5-FU followed by surgical excision. The tumour regressed after three cycles of chemotherapy but subsequently started progressing again. Given this evolution, the patient was referred for palliative radiotherapy.
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pmc-6295774-1
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A 7-month-old, 14.8 kg, intact male Border collie was presented at the Onderstepoort Veterinary Academic Hospital with a history of chronic lameness. The owner reported that a traumatic event may have been associated with the onset of this lameness. On clinical examination, a predominantly non-weight-bearing lameness of the right hindlimb was confirmed. Additionally, moderate muscle atrophy of predominantly the quadriceps muscle group was evident on the right (mid-femoral circumference of 30.5 centimetres (cm) vs. 33.5 cm on the left). Subjectively, when the dog was placed in dorsal recumbency with hip and stifle joints flexed to 90 degrees (°) bilaterally, the right femur was markedly shorter than the left femur. Full extension of the right stifle joint was not possible with the range of motion being limited to 54° in flexion and 115° in extension (normal range of motion of the stifle joint in Labrador retrievers is 41° in flexion and 162° in extension (Jaegger, Marcellin-Little & Levine ). Crepitus was palpable over the patella on manipulation of the right stifle. The patella could not be luxated and no instability was evident on palpation of the stifle joint.
Radiography of the affected and contralateral femur was performed. A true craniocaudal radiograph of the affected right femur could not be obtained because of an inability to fully extend the stifle joint. This resulted in a foreshortened radiograph of the right femur. A true craniocaudal radiograph of the femur is where the patella is situated in the centre of the distal femur, the lateral and medial fabella are bisected by their respective femoral cortices and there is slight protrusion of the lesser trochanter (Dismukes et al. ). Mediolateral radiographs were obtained with the condyles superimposed. A marker was placed at the height of the femoral shaft as a calibration device.
Radiographs revealed an atypical procurvatum deformity that was centred over the right distal femoral physis. The mediolateral view of the right femur showed distal metaphyseal flaring, with the right distal metaphysis measuring 33% wider than the left. Additionally, there was sclerosis of the caudal aspect of the right distal metaphysis and a solid periosteal reaction over the cranial mid to distal diaphysis. The right distal femoral physis was indistinct and distorted caudally. Mediolateral views of the right femur showed that it was 18% shorter than the left. Additionally, the intercondylar fossa of the right distal femur was distorted and measured 19 millimetres (mm) deep. The medial condyle of the right distal femur appeared to show signs of hypoplasia (). An accurate evaluation of a frontal plane deformity was not possible as a true craniocaudal radiograph of the affected femur was not obtained. A torsional deformity of the affected femur was not suspected as the patella could not be luxated. Obvious joint effusion was present in the right stifle with displacement of the infrapatellar fat pad. The muscular atrophy was confirmed on radiographs.
The centre of rotation of angulation (CORA) method was used to define the sagittal plane deformity and plan the corrective osteotomy from the mediolateral radiographs (Fox & Tomlinson ; Kara et al. ; Kim & Lewis ; Raske et al. ). First, the distal femoral joint orientation line (yellow line) was defined as a line connecting the points where the distal femoral physeal scar exited cranially and caudally. Next, the anatomical axis of the distal femur (red line in , green line in ) was defined as the line bisecting the distal diaphysis and metaphysis of each femur. This allowed the anatomical caudal distal femoral angle (aCdDFA) to be calculated as the angle formed between the distal femoral joint orientation line and anatomical axis (). The aCdDFA was calculated as 86° on the left and 63° on the right.
To define the CORA of the deformity, the anatomical axis of the normal left distal femur (red line) was placed at an angle of 86° to the distal femoral joint orientation line (yellow line) of the abnormal right femur. Careful measurement ensured that the anatomical axis of the left distal femur intersected the distal femoral joint orientation line at the same distance caudal to the cranial exit of the physeal scar on both femurs. The CORA of the deformity was defined as the location where the distal femoral anatomical axes (red line and green line) intersected each other when superimposed on the abnormal right femur (). In this case, it was located at the most cranial aspect of the right distal femoral epiphysis and measured 23°. The transverse bisecting line and transverse angles were not calculated as the CORA was located too far distally to allow the corrective osteotomy to be performed at this level. A cranially based closing wedge of 23° was planned in this case (). The base of the triangle was situated over the cranial cortex and measured 1 cm. The apex converged on the caudal cortex of the distal femur.
The patient was premedicated with acepromazine hydrochloride (Aceprom, Bayer, Isando, South Africa) at 0.01 milligrams per kilogram (mg/kg) subcutaneous (SC) and morphine (morphine sulphate, Fresenius PF, Port Elizabeth, South Africa) at 0.4 mg/kg SC approximately 30 minutes (min) prior to induction. Anaesthesia was induced using propofol (Propofol Fresenius vial, Fresenius Kabi, Midrand, South Africa) at 6 mg/kg intravenous (IV) to effect. An endotracheal tube was placed to allow anaesthetic maintenance with isoflurane (Forane, Abbott Laboratories, Johannesburg, South Africa). Cefazolin sulphate (Zefkol 1 g injection, Aspen Pharmacare, Durban, South Africa) was administered at 22 mg/kg IV 30 min preoperatively, then every 90 min intraoperatively. Morphine (morphine sulphate, Fresenius PF) was continued at 0.3 mg/kg IV every 120 min intraoperatively. An epidural block was aseptically performed by administering morphine (morphine sulphate, Fresenius PF) at 0.2 mg/kg and ropivacaine at 1 mg/kg (Naropin; AstraZeneca Pharmaceuticals, Johannesburg, South Africa) into the lumbosacral epidural space. The patient was aseptically prepared for surgery and placed in left lateral recumbency. A routine surgical approach was performed to the right distal femur and stifle joint through a lateral incision (Paatsama ). Exploration of the stifle joint revealed a shallow trochlear groove with fibrous adhesions to the trochlear sulcus and osteophytes on the lateral and medial trochlear ridges. The cranial cruciate ligament was intact. A cranially based closing wedge ostectomy was planned using an oscillating saw. Two 2.0 mm Kirschner wires were placed as alignment aids in a craniocaudal direction, with one on either side of the proposed osteotomy site to allow a more orthogonal osteotomy to be performed (Addison et al. ). The level of the wedge ostectomy was such that it allowed an adequate size of the distal fragment for placement of a 3.5-mm supracondylar bone plate. Preoperative planning dictated that the cranial base of the wedge was 10 mm and the apex converged on the caudal aspect of the distal femur. The wedge ostectomy margins were reduced and stabilised with three divergent 1.6-mm Kirschner wires placed in a normograde fashion. Once stabilised a 3.5-mm supracondylar bone plate was contoured to the lateral aspect of the distal femur. Four bicortical screws were placed in the proximal fragment. One bicortical and three monocortical screws were placed in the distal fragment. Placement of bicortical screws in the distal fragment was hindered by the distorted anatomy of the intercondylar fossa and fear of iatrogenic damage to the cruciate ligaments. Screws were angulated to avoid the ostectomy site. A trochlear block recession was performed (Fox & Tomlinson ), followed by routine closure of the surgical site.
Post-operative radiographs revealed adequate implant positioning. Determination of the post-operative aCdDFA was not possible as the implants obscured the necessary landmarks. Subjectively, the operated limb was still markedly shorter but not worse than preoperatively.
The patient was admitted to an intensive care unit and maintained on intravenous Ringer’s lactate solution (Sabax Ringer’s lactate, Adcock Ingram Critical Care, Johannesburg, South Africa) for 48 h. The operated limb was placed in a protective bandage for 96 hours (h). The analgesic protocol included morphine (morphine sulphate, Fresenius PF) administered at 0.2 mg/kg – 0.4 mg/kg IV every 4 h for 48 h. Additionally, firocoxib (Previcox, Merial, Midrand, South Africa) was administered at 5 mg/kg per os PO (by month, once daily) for 10 days. Cephazolin (Zefkol 1 g injection, Aspen Pharmacare, Durban, South Africa) was administered at 22 mg/kg IV bid for 24 h and then cephalexin (Ranceph, Rabaxy SA [Pty] Ltd, Centurion, South Africa) was continued at 20 mg/kg PO twice daily for a further 5 days. The patient was discharged 1 week later with instructions to restrict exercise, allowing only short leash-walks, and to continue passive range of motion exercises. At this time, the patient was placing the paw with each step but not bearing full weight. Moderate weight-bearing lameness continued in the recovery period.
Follow-up radiographs 6 weeks after the operation showed good healing of the ostectomy site with all surgical implants in their original position ( and ). The patient was consistently bearing more weight on the operated limb when compared to preoperative use. Additionally, approximately 50° of motion was gained in stifle extension, but approximately 35° was lost in flexion when compared to preoperative values. At this stage, the activity level was gradually allowed to increase and more rigorous physiotherapy was administered.
At follow-up evaluation 10 months post-operatively, no clinical lameness was evident on the right hindlimb at a walk, and the range of motion of the right stifle had stayed constant when compared to the values determined at follow-up evaluation 6 weeks post-operatively. Obvious crepitus was still palpable over the patella. Radiographs revealed that the ostectomy site had healed fully and that joint effusion had subsided in comparison to preoperative views.
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pmc-6295965-1
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A 46-year-old female patient with RA, known to the Charlotte Maxeke Academic Hospital’s rheumatology outpatient department, presented with a one-week history of fever (> 38 °C) and a generalised skin rash requiring hospitalisation. She gave a history of starting sulfasalazine two weeks prior, for the management of RA. She had no known allergies. On past medical history, she was also HIV-positive with an absolute CD4+ count of 411 cells/µL and a lower than detectable viral load. Other chronic medications (for > 3 months) included hydroxychloroquine for RA, risperidone for psychiatric manifestations of HIV, and antiretroviral therapy, namely tenofovir, lopinavir with ritonavir, and lamivudine. On examination, she was found to have significant (> 1.5 cm) bilateral cervical and left submental lymphadenopathy associated with severe periorbital oedema. On skin and mucosal examination, her palms and soles were indurated, her lips showed superficial mucosal erosions and there were widespread urticarial papules and target lesions on her face, trunk and extremities. A differential diagnosis including erythema multiforme major, vasculitis and acute drug eruptions such as Steven-Johnson Syndrome and toxic epidermal necrolysis were considered.
Baseline laboratory investigations were performed (). The full blood count (FBC) revealed a leucocytosis with a lymphocytosis and eosinophilia. The peripheral blood smear (PBS) demonstrated 31% atypical lymphocytes and plasmacytoid lymphocytes (). A lymphoproliferative neoplasm associated with HIV infection was considered. Flow cytometry of the peripheral blood was performed. Immunophenotypic analysis revealed a population of 20% – 25% reactive plasma cells with a range of CD138 (dim to +++) expression () and no light chain restriction (). In addition, there were ~26% – 28% reactive T-cells and ~8% polyclonal B-cells (). Polymerase chain reaction analysis for the immunoglobulin heavy-chain gene rearrangement studies was polyclonal. These findings demonstrate no evidence of a B-cell lymphoproliferative disorder.
Further laboratory and radiologic investigations supported the diagnosis of DRESS Syndrome (). The chest X-ray revealed bilateral interstitial lung infiltrates in keeping with pneumonitis. The liver function tests (LFT) were abnormal (). Serology for hepatitis studies was negative. Additional viral studies and a skin biopsy were not performed, at the discretion of the treating physician.
Sulfasalazine was immediately discontinued. Administration of promethazine, montelukast as well as intravenous and topical hydrocortisone led to a dramatic improvement. The clinical manifestations resolved and the patient was discharged. On outpatient follow-up, laboratory investigations, namely FBC, PBS and LFT, had returned to baseline.
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pmc-6296019-1
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The patient was a 55-year-old woman who visited the emergency room in the morning complaining of headache and fever. She was able to perform her daily activities independently and lived with her infant grandchild. She had no medical history of pneumonia and no history of pneumococcal vaccination. She received treatment for diabetes mellitus. The rapid influenza test result was negative, but blood samples were taken for culture test after which the patient was sent home with supportive therapy. However, because the headache continued to worsen, she returned to the emergency room later that evening and was hospitalized. The results of the blood test taken at this stage are presented in Table . Gram-positive cocci were detected in the blood culture taken during the initial visit, and treatment was initiated with 2 g ceftriaxone every 24 h combined with 1 g vancomycin every 12 h. Lumbago occurred on hospital day 2. A plain lumbar T1-weighted MRI scan showed a low signal intensity in the vertebral body endplate of the 4th and 5th lumbar vertebrae, and a short-tau inversion recovery image showed a mildly hyperintense signal in the region dipping below the posterior side of the 5th lumbar vertebra (Fig. ); consequently, purulent spondylitis and epidural abscess were diagnosed. The results of other tests such as the spinal fluid test, head MRI, thoracoabdominal contrast CT, and transesophageal echocardiography did not indicate infection. Pneumococcus was detected on blood culture, and the antimicrobial drugs were changed to 2 g ampicillin (ABPC) every 6 h from hospital day 3. The blood culture result on hospital day 3 was negative. To normalize the white blood cell count, CRP level, and blood sedimentation rate and to improve CT findings, antimicrobial drug treatment was administered for a total of 9 weeks.
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pmc-6296019-2
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The patient was a 60-year-old man who was the husband of the patient described above. He experienced lumbago on the same morning his wife was hospitalized. Fever and disturbance of consciousness occurred in the evening, and he visited the emergency room at another hospital. He had completed the course of neoadjuvant and adjuvant chemotherapy and radiation for glioblastoma 6 years ago, and was able to carry out his daily activities independently. He had no medical history of pneumonia or a history of pneumococcal vaccination. Although right lumbar pain was observed, the origin of fever was unknown; antimicrobial treatment was initiated with 4.5 g piperazine/tazobactam every 8 h. The results of the blood test taken at hospitalization are shown in Table . Pneumococcus was detected in his blood culture as well, and the regimen was changed to 2 g ABPC every 6 h. There were abnormal findings in the lumbar MRI scan taken on hospital day 2. Nonetheless, the results of the spinal fluid test, head MRI, thoracoabdominal contrast CT, transesophageal echocardiography, did not reveal presence of infection at other sites. Because lumbago persisted, MRI was performed again on hospital day 9; the consequent MRI results revealed purulent spondylitis (Fig. ). The patient was transferred to our hospital on hospital day 9. To normalize white blood cell count, CRP level, and blood sedimentation rate and to improve CT findings, antimicrobial drug treatment was carried out for a total of 9 weeks.
Both patients tolerated the antimicrobial treatment well, and recovered completely. A 13-valent pneumococcal conjugate vaccine was administered initially, and a 23-valent pneumococcal polysaccharide vaccine was administered 1 year later in both patients. More than 1 year has elapsed since the completion of treatment, and there has been no recurrence.
In the bacterial strain analysis (Table ) performed on the samples from both patients, the capsule serotype was 12F identified by the capsule quelling reaction using rabbit antisera (Statens Serum Institute, Copenhagen, Denmark). Drug sensitivity test was performed using a dry plate Eiken (Eiken Chemical Co., Tokyo, Japan), and was performed in accordance with CLSI M100-S-18 (hemosupplemented Mueller–Hinton broth, 22-h culture). The drug sensitivity in both strains was similar. As the next step, we performed a sequence typing match using the defined genetic sequence of the pneumococci was determined (aroE, gdh, gki, recP, spi, xpt, ddl) according to the method described in /, and it was compared with the sequence information present in the existing databases. Both strains matched completely.
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pmc-6296023-1
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A 12-year-old African Ethiopian girl presented with bilateral neck swelling with purulent discharge and skin ulceration of 3 months’ duration. She had dry cough, low-grade fever, decreased appetite, and drenching night sweats, and she had lost a significant amount of weight. She had a global throbbing type of headache with occasional projectile vomiting of ingested matter starting 6 days before her visit. She had never been vaccinated and had no known contact with any person diagnosed with TB or with any chronic cougher. She had not received any treatment for the complaints prior to her current visit. She had no known medical problem, and her family and psychosocial history were unremarkable.
Her physical examination revealed a conscious, emaciated, and wasted child. Her admission vital signs were pulse rate 80 beats/min, respiratory rate 20 breaths/min, blood pressure 90/60 mmHg, and axillary temperature 37.3 °C. Matted bilateral anterior cervical and postauricular lymphadenopathy with pus-draining sinus was noted. Crepitation over the anterior and posterior lower right chest, multiple skin ulcers with purulent drainage over the left lateral neck, anterior left chest, and left axilla were documented (see Figs. and ). Nuchal rigidity was positive, but no neurologic deficit was present.
The results of complete blood count, urinalysis, and biochemical analysis were normal, except for mild anemia (see Table ). The result of an antibody test for human immunodeficiency virus was negative. The patient’s erythrocyte sedimentation rate was 65 mm/hr in the first hour. Cerebrospinal fluid analysis showed 105 cells with 65 lymphocytes, and no organism was detected on Gram stain and acid-fast bacilli stain. Right upper and middle lobe ill-defined air space opacity was noted on a chest x-ray (see Fig. ). Discharge analysis from the skin revealed gram-positive diplococci in chain, and Mycobacterium tuberculosis was detected using the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA). Fine-needle aspiration cytology showed only caseous necrosis and no granuloma, and smears from ulcerated lesions showed mixed inflammatory cells, predominantly polymorphs. Tuberculous scrofuloderma was diagnosed on the basis of skin biopsy with a section showing mature squamous cell-lined skin tissue composed of epithelioid cell granuloma, multinucleated giant cells, caseous necrosis, and mixed inflammatory cells (see Figs. and ). Brain computed tomographic scans showed multiple precontrast hyperdense randomly distributed supra- and infratentorial lesions with mild perilesional edema. Rim enhancement on postcontrast images (caseating granulomas) on some lesions and a solid pattern of enhancement (noncaseating granulomas) were evident on other lesions. Dense basal cistern exudate seen on precontrast images with avid postcontrast basal leptomeningeal enhancement was observed. Severe bilateral lateral third- and fourth-ventricle dilation was noted (see Figs. , and , Table ). A tuberculin skin test (TST) could not be done, owing to unavailability of the service.
Routine care and medical treatment was provided as per World Health Organization (WHO) guidelines for severe acute malnutrition. Antituberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol as per weight (four tabs per day), prednisolone 2 mg/kg/day, and pyridoxine 25 mg/day was started. Wound care was also given. After a 1-month hospital stay, the patient was discharged for outpatient directly observed antituberculosis therapy in a nearby health center after acute complications were treated and once the skin lesion had started to dry or heal. She received antituberculosis therapy for 12 months. No drug-related side effects were seen or reported during admission or follow-up. Follow-up visits (including 6 months after completion of therapy) demonstrated a patient who had recovered well with no major neurologic problems and with healed skin lesions.
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pmc-6296042-1
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A 69-year-old man was referred to our Emergency Department for resting dyspnea after 2 months progressive shortness of breath, 2 years after transcatheter aortic valve replacement (TAVR).
In 1994 he underwent aortic valve replacement with a 23 mm Biocor™ valve (St. Jude, MN, USA) for native valve endocarditis. Eleven years later (2015) he was re-operated for structural valve deterioration. In that occasion – due to the presence of extreme calcification of the aortic annulus and root – we had to replace the prosthesis with a 23 mm Edwards Sapien 3 transcatheter valve (Edwards Lifesciences, Irvine, CA) under direct view, as previously described [].
The patient revealed anticoagulants discontinuation due to excessive bleeding after surgery for a chordoma of the nose within the last 2 months (he was on anticoagulant after an episode of atrial fibrillation). He took Aspirin 100 mg/day with a good compliance. He had no history of hyper-coagulation state or previous documented thrombosis.
The transthoracic echocardiogram showed increased trans-valvular gradients (mean left ventricular outflow tract/aorta gradient of 62 mmHg with 0,43cm2 of valvular area) and ipo-echogenic images evocative of intra-valvular thrombosis. A thoracic computed tomography (CT) confirmed the presence of valvular thrombosis (Fig. ) in the presence of diseased-free coronary anatomy. After discussion in the Heart Team setting it was decided to attempt systemic anticoagulation with heparin to achieve dissolution of the thrombus. After 1 week of systemic anticoagulation a control CT did not show any evidence of improvement, so we planned a surgical re-intervention. The day before the scheduled surgery the patient suddenly experienced thoracic pain and electrocardiographic signs of myocardial ischemia. An urgent coronary angiography was performed while the clinical and hemodynamic state worsened. He had a cardiac arrest during the procedure; an immediate cardio-pulmonary resuscitation (CPR) was performed while a peripheral extracorporeal membrane oxygenation (ECMO) support was instituted and the patient transferred into the operating room for an emergent surgery.
After cardioplegic cardiac arrest and transverse aortotomy the thrombosed transcatheter valve was excised and a new 23 mm Edwards Sapien 3 valve was deployed in an off-label fashion under direct view with good echocardiographic result (Fig. ). The valve thrombosis was confirmed once excised (Fig. ).
Unfortunately he developed an incoercible cardiogenic and septic shock and finally died on the 10th postoperative day.
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pmc-6296056-1
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A 23-year old female was hospitalized due to limb numbness, muscle weakness for one month, recurrent tetany and palpitation for 10 days. She visited the local hospital and was found to have a decreased plasma potassium (2.24 mmol/l) and calcium (1.6 mmol/L), while plasma magnesium was unknown because of limited conditions at the hospital. Her condition seem to have improved after treatment with “potassium chloride” and “calcium gluconate”, however, symptoms recurred after discharge, so she visited our hospital. She denied having any other diseases or taking any medication prior to her visit to the hospital. Her two children and her father were healthy without any similar symptoms. Her mother and her only sister however, had passed away at the age of 30 years old and 1 year old, respectively, with unclear diagnosis. Her parents were from the same town but denied of consanguineous marriage.
Physical examination on admission showed normal vital signs, except for her relatively low blood pressure, which fluctuated between 88 and 108/56-78 mmHg. She had a height of 158 cm and body weight of 46 kg. The lower limb muscle strength was decreased, accompanied by diminished tendon reflexes. The Trousseau’s sign was positive. Other signs of physical examinations were normal.
Laboratory test results are shown in Table .
Her thyroid function tests and glucocorticoid level were within the normal range, and autoimmune antibodies were negative, while the 25(OH)VD3 was 17.08 ng/mL (reference value: > 20 ng/ml). The PTH was 11.2 pg/ml (reference value: 15-65 pg/ml) at the local hospital, and returned to the normal range 2 days later. At our hospital the value was 32.66 pg/ml. Her chest X-ray and abdominal ultrasound were normal and the dual-energy x-rays showed osteopenia (T value was − 1.8). Laboratory results suggested hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and secondary hyperaldosteronism. These characteristics indicated GS. We also tested the serum electrolytes of the patient’s father and children, which showed normal results.
After obtaining informed consent from the patient and family members, genomic DNA was extracted from peripheral blood for SLC12A3 and other related genes of Bartter syndrome whole genome sequencing in the Changsha Kingmed Center for Clinical Laboratory. Genomic DNA was extracted via centrifugal column method, with Qiagen kit. Gene sequencing was performed as referred [].
We found that the patient was positive for SLC12A3 gene homozygous mutation (exon 17: nucleic acid mutation: c.2039delG, amino acid mutation: p.Gly680AspfsTer20). It was a frameshift mutation in exon 17, which began from the glycine in the No.680, mutated into aspartate, and leading to premature termination of NCCT protein in the No.700 amino acid (terminator codon TGA). To exclude the possibility that the c2039delG is heterozygous mutation with deletion of the other allele at this locus, we performed copy number variation (CNV) analysis using next-generation sequencing data, the result is shown in Additional file : Figure S1, confirming the c.2039delG is bi-allelic homozygous mutation. A heterozygous mutation in the same site was observed in the sequences of the patient’s father and her two children. C.2039delG was a novel mutation and has not been reported in SNP databases such as Exome Aggregation Consortium and 1000Genome. We also tested SLC12A1, KCNJ1, CLCNKB, BSND, CLCNKA/CLCNKB related to Bartter syndrome, showing negative results. Pedigree analysis was shown in Fig. , and the sequence map is shown in Fig. .
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pmc-6296059-1
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An obese 42-year-old African American male with diabetes mellitus, hypertension, heart failure with reduced ejection fraction, coronary arterial disease, and atrial fibrillation presented with new onset right-sided chest pain and a palpable right chest mass. Ultrasound showed an anterior right chest, well-demarcated 7.5 × 6.5 × 4.8 cm, intramuscular mass, 0.6 cm deep to the skin. CT demonstrated a 9x9x9cm necrotic mass arising from the pectoralis major. CT-guided core biopsy was positive for high-grade spindle cell neoplasm (positive for smooth muscle actin, desmin, S100, and CD31; negative for CD34, PAX8, and beta-catenin) and verified by two independent pathologists.
Unfortunately, the patient was lost to follow up after referral to Oncology and Thoracic Surgery. He presented to oncology clinic with progressive symptoms including a rapidly enlarging chest mass, increasing pain, and new onset chest wall numbness. A repeat CT showed that the mass increased in size to 21.4 × 17.8 × 13.7 cm without evidence of metastatic disease over course of two months. MRI was consistent with 23 cm mass within the right pectoralis major without vascular or bony invasion. The patient chose to undergo neoadjuvant chemotherapy given his multiple comorbidities. He was hesitant to pursue resection and elected to attempt to shrink the tumor before resection.
Patient underwent neoadjuvant chemotherapy with gemcitabine and docetaxel for 2 cycles followed by radiation therapy (50Gy over 2 months to tumor bed + 3 cm margins). Restaging CT showed a stable tumor at 23 cm without any evidence of local or distant metastases.
The patient returned to Thoracic surgery clinic to discuss options for resection and reconstruction. He then underwent wide local surgical resection for definitive therapy. Tumor was removed en bloc with resection to the intercostal fascia including pectoralis major and minor (Fig. ). There did not appear to be any violation of the intercostal investing fascia and no entry into the thoracic cavity was made. Negative pressure dressing was used until post-operative day 7 when Plastic Surgery performed advancement flap coverage and skin grafting to the > 1,000cm2 defect (Fig. a, b).
Final pathology demonstrated 38x20x18 cm tumor with 70% gross necrosis and R0 resection. Microscopic examination confirmed high-grade sarcoma with smooth muscle differentiation (Fig. ). Final pathologic staging based on AJCC 7th edition was Stage III G3 pT2bNxMx.
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pmc-6296101-1
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This was a 34-year-old man, grower and farmer residing in the commune of Tchaourou. A Christian, he is married to two women and has seven children. He was hospitalized on 18 January 2018 with bloody and febrile diarrhea.
The beginning of symptomatology would date back to 10 January 2018 (approximately 1 week before admission) and was marked by the start of diarrhea, made up of soft, yellowish, sometimes mucusy, blood-ribbed stools, emitted three or four times a day, associated with a constant unquantified fever. The patient consulted on January 12, 2018 at his local health center where he received outpatient treatment consisting of: paracetamol 1 g × 2 per day, quinine 300 mg × 3 / day, metronidazole 500 mg × 2 / day, ciprofloxacin 500 mg × 2 / day, diazepam 5 mg in the evening, albendazole 400 mg in single dose. No paraclinical investigation has been conducted at this stage. Under this treatment, the course was marked by an improvement in symptoms for about 2 days but with the persistence of an unquantified low grade fever. Faced with the resumption on 16 January 2018 of the initial symptomatology and the appearance of two episodes of bilious vomiting, odynophagia, intense headaches and generalized aches, the patient was taken by his parents on 18 January 2018 to the Emergency Department of the Regional and Teaching Hospital of Borgou which referred him to the Internal Medicine Department for further management.
At admission, the interview did not note any particular medical history. The patient was non-smoker and would occasionally take alcohol.
Initial clinical examination revealed a temperature of 39 °C, tachycardia at 86 beats per minute, polypnea at 30 cycles per minute and blood pressure at 130 / 100 mmHg. Palpebral mucosas were well colored. There was no jaundice or edema of the lower limbs. Examination of the digestive tract revealed inflammation of the palatal tonsils covered with a whitish coating and pain in the right iliac fossa, which was not very intense and without radiation. The rectal exam noted a tonic anal sphincter and the finger came back with mucus. The cardiovascular examination noted a deafening of the heart sounds. Otherwise, the physical examination did not reveal any anomalies. The paraclinical check-up carried out at admission was as follows: a thick drop for trophozoites of negative plasmodium, red blood cells at 4.53 106 / mm3, hemoglobin at 15.33 g/dL, hematocrit at 41.6%, platelets at 123 109/L, leukocytes at 6.6 109 cells/L with neutrophils at 70%, lymphocytes at 27%, eosinophils at 1% and monocytes at 2%, azotemia at 0.65 /L, creatininemia at 14.13 mg/L, natremia at 135.7 meq/L, kalemia at 4.08 meq/L, blood chloride at 115.4 meq/L, alanine aminotransferases (ALT) at 82 IU/L, aspartate aminotransferases (AST) at 62 IU/L. HIV status was negative.
In front of this clinical presentation, the diagnosis of severe sepsis was retained and the treatment instituted was ceftriaxone 2 g daily, metronidazole, intravenous (IV), 500 mg two times daily, gentamycin 3 mg/kg once daily, tramadol injection 100 mg two times daily, serum glucose 5%, saline 9‰ and oxygen therapy.
The course of this treatment was marked by persistent signs with fever ranging from 36.3 °C to 40.1 °C. Figure shows core temperature (°C), pulse and respiratory rates (per minute) measured every 12 h throughout the hospitalization period for the patient. The occurrence on the third day of hospitalization of melena, facial puffiness and conjunctival hemorrhage gave rise to suspicion of viral hemorrhagic fever. Then, an insistent interrogation noted a regular consumption of rat. The patient was isolated and a blood sample was taken and sent to the national laboratory of viral hemorrhagic fever on 22 January 2018. He was given ribavirin 30 mg/kg IV (maximum, 2 g) loading dose to be followed by 15 mg/kg IV (maximum, 1 g) every 6 h for 4 days, vitamin K1, transfusion of two isogroup isorhesius blood bags, and oxygen therapy.
On 23 January 2018 (the sixth day of hospitalization), the patient died after repeated convulsions with bradypnea and then cardio-circulatory arrest.
The blood test result returned on 24 January 2018 and confirmed Lassa hemorrhagic fever by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) assay. A safe burial was organized. An investigation team has been set up to look for and follow up contact subjects under the supervision of the Epidemiological Surveillance Unit of the Borgou’s Departmental Health Office. Each contact subject was provided with a thermometer allowing him to take morning and evening body temperature and to communicate it to the focal point of the epidemiological surveillance for a total duration of 21 days as from the date of the contact with the case. All contact subjects gave their oral consent to participate in the follow-up. The data resulting from this follow-up were treated confidentially and anonymously. No associated cases were observed among contact subjects.
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pmc-6296120-1
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A forty-year-old psychotic and intravenous-drug-addicted Caucasian male was cared by prehospital service for coma due to drugs overdose. In this emergency situation, without any intravenous access available, an IO device (EZ-IO™; Teleflex Medical, Research Triangle Park, NC, USA.) was promptly inserted by the emergency medical technician (EMS) on scene in the upper portion of the left tibia to administer therapeutics and initiate mechanical ventilation. Hospitalization in the intensive care unit of the University Hospital of Tours (France) with close monitoring lasted three days. Several attempts to establish another IV catheter were unsuccessful and no central catheter was used as the need for infusion was expected to be short due to a rapid clinical improvement. The IO catheter was removed at Day 1, with report of local inflammation around the insertion site. An erysipelas was diagnosed. Treatment with oral amoxicillin-clavulanic acid (1gx3/day) was introduced. The patient reported psychiatric problems with schizophrenia, multiple intravenous-drug intoxications with coma, and regular cocaine and heroin use. He left the hospital against medical advice three days after IO device removal.
Three months later, he asked for a consultation in the same hospital because of fever and bone pain in the left leg and was hospitalized again. Other complaints were chills and inability to walk normally and to bear weight on his left leg. Redness, warmth, point tenderness and swelling on the site of the IO access were present (Fig. a, arrow). He was afebrile, without hemodynamical instability. Laboratory results were only significant for leukocytosis at 12.4.109/L and C reactive protein at 51.2 mg/l. Blood cultures were negative. Routine radiographs revealed an ill-defined osteolysis of the metaphysis and the epiphysis with a condensed area and blurred periosteal appositions (Fig. b). The magnetic resonance showed an important marrow edema with T1-weighted hyposignal (Fig. c) and fat-saturated-T2-weighted hypersignal (Fig. d) extending in the left tibia, measuring twenty-one centimeters. Soft tissues were infiltrated. No abscess was visualized but the radiologist could not achieve gadolinium injection because IV access was lacking. MR imaging was compatible with the diagnosis of osteomyelitis.
An open biopsy of the left tibia revealed Gram positive cocci with focal signs of acute osteomyelitis, bone remodeling and marrow fibrosis containing polymorphic inflammatory infiltrate comprising neutrophils, foamy macrophages, lymphocytes and plasma cells. Treatment with piperacillin-tazobactam and vancomycin was initiated. Culture from the surgical site grew methicillin-susceptible Staphylococcus aureus (MSSA). An oral switch with levofloxacin 750 mg/day and rifampin 900 mg/day for six weeks was introduced. A favorable outcome was noted eighteen months later.
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pmc-6296127-1
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A 25-year-old man, who had a history of diabetes mellitus with poorly controlled blood sugar levels for 7 years, was admitted to a local hospital for fever and right upper quadrant abdominal pain. A computed tomography (CT) scan of his abdomen showed a low-density area of 4.6 cm × 2.9 cm in the caudate lobe of the liver, and he was diagnosed with a liver abscess after magnetic resonance imaging (MRI) with gadolinium enhancement. The patient received intravenous antibiotic without aspiration or drainage of the abscess, and no ophthalmological examination was performed at that time. Detailed information about bacterial cultures and antibiotic treatment in the local hospital was unavailable. One week later, the fever and abdominal pain had resolved. However, visual acuity of the right eye decreased significantly 3 days after relief of the initial symptoms. Therefore, the patient was transferred to our hospital for further ophthalmic examination. On admission, a complete blood cell count (CBC) analysis did not show any change, and a white blood cell (WBC) count of 6700/μl (62.5% segmented neutrophils, 25.6% lymphocytes and 10.9% monocytes) was recorded. However, the blood analysis did reveal an increase in C-reactive protein (60 mg/L) and fasting serum glucose reached 14.53 mmol/L. The patient’s visual acuity in the right eye was light perception only. Slit-lamp examination showed moderate conjunctival injection, corneal infiltrate, along with hypopyon in the affected eye. A presumed diagnose of endophthalmitis was made. Empirical treatment of intravenous imipenem (0.5 g given every 6 h [Q6H]) and intravitreal injection of imipenem, vancomycin and dexamethasone were started immediately. Culture of the vitreous fluid grew a K. pneumoniae strain, named KP587. However, blood cultures yielded negative results. Four days later, a pars plana vitrectomy with silicone-oil injection was performed. Imipenem was continued for a total of 16 days and then switched to oral moxifloxacin (0.4 g given daily, [QD]) for another 14 days after discharged. Because symptoms were relieved and the size of the liver abscess was decreasing after antibiotic treatment, percutaneous needle aspiration was not performed based on the judgment of the hepatobiliary surgeon. At a two-week follow-up, the patient’s visual acuity in the affected eye had improved to FC/40 (the patient could count the number of fingers at a distance of 40 cm from his eyes).
The K. pneumoniae strain KP587 demonstrated hypermucoviscosity, as determined by a positive string test. Antibiotic susceptibility testing was conducted using the broth microdilution method. The minimum inhibitory concentrations (MICs) were determined in accordance with the breakpoints defined by the Clinical and Laboratory Standards Institute []. For tigecycline, the result was interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria (version 7.1, ). In contrast to the wide-susceptibility profile of most HVKP, this strain was resistant to aztreonam, amikacin, gentamicin, ceftazidime, ceftriaxone and piperacillin-tazobactam, while susceptible to cefepime, imipenem, ciprofloxacin, levofloxacin and tigecycline, as shown in Table .
Genomic DNA was extracted and sequenced using the HiSeq 2000 platform (Illumina, San Diego, CA, USA) with a 2 × 125 bp paired-end strategy. De novo assembly using Velvet version 1.2.07 produced 108 contigs with an N50 length of 272,305 bp []. Using Glimmer version 3.0, 5550 genes including 48 RNA genes and 5502 protein-coding genes were identified []. The overall genetic information is listed in Table . We then assigned hypothetical or putative functions to 1329 protein-coding genes with the NCBI nucleotide sequence database using NCBI blastn and annotated the genome using the RAST (Rapid Annotation using Subsystem Technology) server []. We also categorized 3014 genes into COGs (Clusters of Orthologous Groups of proteins) functional groups []. The detailed distribution of genes into COG categories and SEED subsystems for this isolate is shown in Fig. . The whole-genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession PETA00000000. The version described in this paper is version PETA01000000.
Analysis of the wzi locus indicated that KP587 had a K1 capsular antigen, and 7-gene multilocus sequence typing (MLST) showed that this strain belonged to a novel sequence type, ST2922, a single-locus variant (loci tonB with one base difference) of ST23, the most predominant sequence type causing invasive community-acquired infections []. Pairwise single nucleotide polymorphisms (SNP) analysis for KP587 and 14 other whole genomic sequences of HVKP available in GenBank using the CSI Phylogeny 1.4 pipeline found that the core genome of KP587 differed from five publicly available ST23 K1-serotype K. pneumoniae strains only by a few SNPs (n < 100) []. We then performed a comparative chromosome sequences analysis of these strains. The circular map generated using BLAST Ring Image Generator (BRIG) showed that KP587 contained several fragments missing in other ST23 stains [], as shown in Fig. . The plasmid replicons of this strain were determined using PlasmidFinder (). IncR, IncFIB and IncHI1B were identified with 95% identity, suggesting the existence of three plasmids. The virulence factors were annotated with the existing database () and the resistant genes were investigated using the web-based tool ResFnder (). Together with additional PCR, we found that KP587 harbored rmpA and magA genes, which are the main regulators of the mucoid phenotype and are often associated with K1 and K2 capsular types []. KP587 possessed the genes coding for siderophores, such as iucABCDiutA for aerobactin, ybtAPSTUX for yersiniabactin and iroBDN genes encoding salmochelin. It also carried the mrkABCDHIJK genes encoding type 3 fimbriae. The allABCDRS (allantoin utilization) and kfuABC (iron acquisition system) gene clusters were present in the genome of this isolate as well. In contrast to most HVKP strains without antibiotic resistance genes, KP587 was found to harbor the ESBL gene blaCTX-M-14, and the plasmid-mediated AmpC β-lactamase gene, blaDHA. Additionally, the 16S rRNA methylase gene for aminoglycoside resistance, armA, and the plasmid-mediated quinolone resistant gene, qnrB, were also detected. Overall, the genomic features of KP587 were consistent with a multidrug resistant hypervirulent strain as previously described [].
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pmc-6296136-1
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A 28-year-old female Chinese patient presented with the onset of acute continuous right abdomen pain, nausea and vomiting at the emergency department. On admission, abdominal dynamic computed tomography (CT) with a multislice detector row CT scanner showed several air-fluid levels in the enteric cavity, and the diagnosis was considered to be ileus.
The patient was diagnosed with BD four years ago. She had received medications regularly, including immunosuppressive therapy with oral prednisone (60 mg/day) and cyclophosphamide (100 mg/day).
The patient first presented with abdominal pain at the hospital. A computed tomographic angiography (CTA) was performed, which (Fig. ) indicated an aneurysm of 5.67 cm*5.28 cm*0.97 cm located in the left junction of the thoracic aorta and abdominal aorta. An approximately 0.8 cm segment was found to block the starting part of the celiac trunk. Subsequently, a graft stent was implanted. Follow-up CTA (Fig. ) showed no residual aneurysm. However, six months after the intervention, a rapidly growing mass was found in the lower abdomen, and the patient presented with nausea, vomiting, progressive and intermittent pain in the abdomen which radiated to her back. Before being admitted to the intensive care unit (ICU), the patient underwent CTA, which showed that there was a haematoma of approximately 6.0 × 4.8 cm in the abdomen. The extravasation of contrast agent was located in the opening of the renal artery, with a mixed soft tissue mass of 3.7 cm (Fig. ) in the haemoperitoneum. The haemoglobin concentration decreased to 4.36 g/dL with abrupt hypotension (60/43 mmHg). The critical condition of the patient prompted the cardiac surgeons to perform open surgical repair (OSR) rather than a more conservative treatment. The patient was transferred to the ICU after the operation. Three days later, after her vital signs were stable, she was transferred back to the general ward. No recurrence of pseudoaneurysm was found during a follow-up of 15 days (Fig. ). She continued receiving immunosuppressive therapy as usual. This course of treatment was decided based on previous studies showing that use of immunosuppressive therapy with cyclophosphamide and corticosteroids before and after surgical intervention could help prevent BD activation [, ].
Ten months later, after the implantation of artificial vascularization in the thoracic and abdominal aorta, doppler-ultrasound indicated deep venous thrombosis in the left popliteal vein (Fig. ). Therefore, the patient was treated with anticoagulant therapy using hypodermic injections of low-molecular-weight heparin at a daily dose of 4100 U.
One month later, the patient suffered from persistent right abdominal pain with nausea and vomiting accompanied by oral aphtha and genital ulcer. Abdominal CT showed the occurrence of an air-fluid level in part of the ileum and colon (Fig. ). The diagnosis was determined to be an incomplete intestinal obstruction, which may have been caused by the previous aneurysms. Mesenteric artery angiography showed that the root of the celiac trunk and superior mesenteric artery were stenosed (Fig. ). Then, conservative treatment was administered, such as fasting, gastrointestinal decompression and enema. Approximately 20 days later, the patient recovered well and was discharged from the hospital.
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pmc-6296145-1
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A 16-year-old boy without systemic disease had come to our attention in October 2012 with a diagnosis of bilateral JOAG and high myopia (− 8.0D). Although he was treated with dorzolamide 2%, latanoprost 0.005%, brimonidine 0.2%/timolol 0.5% fixed combination, and oral acetazolamide 500 mg/day at another hospital, his IOP was approximately 25 mmHg and was poorly controlled in both eyes by full medication. Several months before this visit, he had ceased treatment with anti-glaucoma medication. His BCVA was 20/20 in both eyes in 2012, though it gradually deteriorated to 20/400 in both eyes in 2017. Gonioscopy revealed a normal iridocorneal angle; pachymetric measurements were 611 μm in the right eye and 614 μm in the left eye. The axial length of the right eye was 27.56 mm and that of the left eye was 27.46 mm. Fundoscopic examination revealed bilateral enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in the left eye (Fig. ). Optical coherence tomography angiography (OCTA) revealed retinal nerve fiber layer (RNFL) thinning over the temporal upper and lower quadrants and nasal upper quadrant of the right eye and RNFL thinning at the temporal quadrant and nasal upper quadrant of the left eye (Fig. ). The vascularity of the peripapillary capillaries was 43.6% in the right eye and 49.15% in the left eye. Both eyes revealed a decrease in the sectoral division of the temporal regions (Fig. ). A VF of 30–2 Swedish interactive thresholding algorithm standard (30–2 SITA standard) was characterized by progressive central scotoma in both eyes (Fig. ). Due to the presence of bilateral progressive central scotoma, further examinations were arranged. The electroretinogram (ERG) result was subnormal in both eyes, and there were more decreased amplitudes in the right eye than there were in the left eye. However, no obvious implicit time delay was noted. The pattern visual evoked potential (VEP) and pattern ERG showed extinguished responses in both eyes (Fig. ). A brain MRI revealed an incidental finding of a 0.8 mm non-enhancing nodule in the pituitary gland. Furthermore, the genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON. High-dose ubidecarenone (240 mg/day) was prescribed by the neurologist. However, under high-dose ubidecarenone therapy, the patient’s IOP was still poorly controlled and his visual acuity gradually decreased to less than 20/400 in both eyes after one year of ubidecarenone treatment.
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pmc-6296145-2
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A 15-year-old boy, the first younger brother of Patient 1 who was diagnosed with bilateral JOAG in 2010, attended our clinic in October 2012. He denied having systemic disease, but he had a family history of glaucoma and LHON (Fig. ). After taking medication, including dorzolamide 2%/timolol 0.5% fixed combination, latanoprost 0.005%, and brimonidine 0.15%, IOP was controlled in both eyes. His BCVA of both eyes remained at 20/20 during the follow-up period. Gonioscopy revealed a normal iridocorneal angle, and the pachymetric measurements were 592 μm in both eyes. Fundoscopic examination revealed bilateral mildly paled optic disc with enlarged cupping and reduction of the neural rim in both eyes (Fig. ). OCTA revealed RNFL thinning at the nasal upper quadrant of the left eye (Fig. ). The VF (30–2 SITA standard) was normal in both eyes during the follow-up period. The pattern VEP showed no delay, and the pattern ERG revealed decreased N95 amplitudes in both eyes (Fig. ). The genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON. High-dose ubidecarenone(240 mg/day) was prescribed as well. During the course of high-dose ubidecarenone treatment, the patient’s IOP, visual acuity, and visual field remain stable.
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