_id
stringlengths 7
16
| description
stringlengths 55
95.2k
|
|---|---|
pmc-6159248-1
|
A 26-year-old male presented to Accident and Emergency following assault with a baseball bat. His past medical history consisted of longstanding Hepatitis C infection only, he was on no regular medications nor had any known allergies.
On admission, the patient had complained of bilateral pleuritic pain on inspiration with visible, tender bruising to the posterior thoracic region bilaterally. There were no urinary, bowel or neurological symptoms reported and no open wounds were visible on examination. The anterior abdomen was soft and non-tender to palpation.
A CT scan of chest (performed at 30s post i.v. injection) showed acute fractures of left 10th/11thand right 8th/9th ribs, but no evidence of pneumothorax or lung contusion. A splenic laceration was not suspected clinically and the timing of the scan, optimized for the chest, only showed subtle splenic changes which were not identified by the original reporter ().
Later that day, the patient complained that their pain had spread from the chest down to the right and left flanks. This prompted a CT scan of abdomen/pelvis (performed at 70 s), which demonstrated a contained splenic laceration with no evidence of capsular breach (). Both the rib fractures and splenic injury were treated conservatively with bed rest and analgesia.
The patient abruptly deteriorated becoming hypotensive and tachycardic in keeping with hypovolaemic shock. A further CT scan showed splenic capsular rupture, active bleeding and large-volume intraperitoneal haemorrhage ().
This was managed urgently with endovascular embolisation. While the patient gave informed consent for the procedure he indicated that he was unlikely to be compliant with some aspects of his aftercare and likely to self-discharge very soon after completion of the procedure.
Following local anaesthesia an ultrasound guided puncture of the right common femoral artery was performed and the splenic artery selectively catheterized with a Sim 1 catheter (a reverse angled catheter). Angiography revealed three pseudoaneurysms, two arising from a second order upper pole branch and one from a third order equatorial branch (). These were then superselectively catheterized and embolized with a series of 3, 4 and 5 mm microcoils (Nester & Vortex, Nester = Cook Medical, Bloomington, IN, USA, Vortex = Boston Scientific, Watertown, MA, USA), delivered through a microcatheter. This abolished filling of the pseudoaneurysms but there was more devascularisation of the upper half of the spleen than envisaged when the decision to perform superselective embolisation was made. The right common femoral artery was then closed with a Starclose vascular closure device (Abbott Medical).
The decision to perform superselective embolisation was made with the intention of achieving definitive haemostasis in a patient who was likely to leave hospital at the earliest possible opportunity and not comply well with the procedural aftercare (). There was no further bleeding.
Day 1 post-procedure, the patient developed a post-embolisation syndrome (PES) characterized by fever, nausea and left abdominal pain. A fourth CT scan was performed. This showed splenic necrosis, parenchymal and intravascular gas, which is an expected appearance post-embolisation. No fluid collection was demonstrated. Conservative resuscitation was initiated with i.v. fluid and antibiotic administration.
There was no indication for surgical drainage at this point as the CT scan showed only splenic necrosis, with no evidence of abscess formation. The patient’s temperature and clinical features were also settling, further reassuring stabilisation of his condition ().
The patient recovered from this episode a few days later, and deemed medically fit, was subsequently discharged home.
3 weeks later, the patient presented to Accident & Emergency once again; this time with episodes of frank haemoptysis. He had an associated fever, and left upper quadrant (LUQ) pain.
Blood tests showed elevated inflammatory markers, suggesting an infection, thought to be of likely respiratory origin at this time.
|
pmc-6159249-1
|
A 40 year-old immunosuppressed male diagnosed with AIDS presented with complaints of cough and fever. Initial chest X-ray showed nodular opacities in bilateral lung fields (). Plain CT scan showed multiple small (<2 mm) nodules distributed in the bilateral lung fields. On further analysis of the distribution of nodules they were predominantly seen along the peribronchovascular interstitium and subpleural (perilymphatic) regions (). Multiple enlarged lymph nodes were seen in the mediastinum and axillary regions (). Image-guided fine needle aspiration cytology of the axillary node was performed and the diagnosis of cryptococcal infection was made () based on the histopathological findings, which demonstrated capsulated organisms. The patient was started on antifungal therapy and dramatically improved clinically.
|
pmc-6159249-2
|
A 30-year-old immunocompetent female patient came with complaints of fever and headache for 1 month associated with vomiting. The patient was evaluated for immune-suppressed states such as diabetes mellitus, AIDS and hepatitis B and C virus infections, and was negative. In view of the fever and headache, a provisional diagnosis of meningoencephalitis was made and CT brain scan with contrast was ordered. CT brain scan with contrast showed multiple ring-enhancing lesions. MRI brain spectroscopy was performed, which showed ring-enhancing lesions with surrounding oedema (). These lesions were reported to be tuberculomas based on the imaging findings and MRI spectroscopy findings.
CT thorax scan was performed with administration of intravenous contrast, which showed consolidation with cavitation in the left upper lobe ( and ). There was associated soft tissue extension along the left hilum encasing and narrowing the left pulmonary vessels and left bronchus with features of fibrosing mediastinitis (). Enlarged mediastinal lymph nodes were seen. In view of the brain lesions and the lung findings the possibility of tuberculosis was raised. CT-guided biopsy of the thick-walled cavity was performed and histopathological and microbiological findings showed features of cryptococcus pneumonia. The patient was started on antifungal therapy and he improved symptomatically.
|
pmc-6159249-3
|
A 5-year-old boy on immunosuppressive therapy after bone marrow transplantation presented with cough. In view of the persistent symptoms, CT thorax scan (plain) was performed. CT thorax scan showed a mass in the right lower lobe with mild irregular margins simulating a malignant mass lesion (). In view of the suspicious features, CT-guided biopsy was performed. A diagnosis of cryptococcal infection was made based on the histopathological features. The patient was started on antifungal therapy but succumbed owing to widespread sepsis.
|
pmc-6159250-1
|
A 50-year-old male presented to the emergency department with sudden onset right upper quadrant (RUQ) abdominal pain. It was described as a colicky sharp stabbing pain, which progressed to a constant dull discomfort, worse with coughing and deep inspiration. This was preceded by a 1 week history of productive cough with yellow sputum. His past medical history included absence of trauma, undifferentiated immunodeficiency, idiopathic thrombocytopaenia (ITP) with splenectomy, a previous possible stroke, and paroxysmal atrial fibrillation on warfarin. He had multiple courses of antibiotics in the past for recurrent lower limb cellulitis and respiratory tract infections post splenectomy.
The patient weighed 152 kg, with a body mass index of 45. His vital signs were stable. There was pain in the RUQ on palpation. Blood test revealed a platelet count of 232 × 109 l−1, mildly elevated white cell count of 13.8 × 109 l−1 and C-reactive protein of 12.7 mg l−1. Liver function tests were normal. International normalized ratio (INR) was elevated at 3.8. Lactate was elevated at 2.7 mmol l−1. Possible differentials included acute cholecystitis and right lower lobe pneumonia with associated pleurisy.
The patient’s body habitus was deemed unsuitable for a reliable abdominal ultrasound; therefore, the patient underwent a CT abdomen and pelvis with oral and intravenous contrast. Portal venous phase and 10 min delayed phase were obtained. The study revealed a well-defined ovoid mass of 37 × 27 mm with Hounsfield Unit (HU) of 51 (both in portal venous phase and delayed phase) with no washout, suggestive of an adrenal lesion (). The left adrenal was of normal “Y” shape in appearance. There was no evidence of cholecystitis. There was patchy consolidation in the right lower lobe. The patient was commenced on intravenous antibiotics for a lower respiratory tract infection.
Over 12 h the pain had migrated from the RUQ to the left flank. The patient underwent a further non- contrast CT scan of abdomen and pelvis with portal venous phase (). The study showed persistent right adrenal mass of 40 × 31 mm with a HU of 36. There was a new enlargement in the left adrenal gland measuring 34 × 24 mm with a HU of 25. The sudden enlargement of the left adrenal gland strongly suggested acute haemorrhage. To further evaluate this adrenal finding, an adrenal CT protocol was carried out with pre, arterial, portal venous and 10 min delayed images, 1 week after the initial scan. There was no discrete adrenal mass and densities of adrenals were consistent in all phases, measuring 40 HU.
|
pmc-6159251-1
|
A 67-year-old male initially underwent contrast-enhanced multidetector CT of the abdomen in Sept 2014 at another hospital, which showed an incidental 4.2 × 3.9 cm mass in the upper abdomen. This was interpreted as a head of pancreas mass causing portal vein compression. The patient was asymptomatic; physical and laboratory examinations were all unremarkable.
The patient was lost to follow-up and did not receive any further investigation or treatment. Although still asymptomatic, he re-presented 12 months later for a repeat MDCT, which showed that the mass had increased in size to 4.8 × 5.0 cm. Cavernous transformation of the portal vein was also observed. The patient underwent exploratory laparotomy, which showed a tumour at the upper border of the pancreas and duodenum compressing the portal vein. A 1-cm lesion in the subcapsular aspect of segment II of the liver was also seen. The presumed pancreatic tumour was deemed unresectable and multiple biopsies were taken. The liver lesion was resected and the histology of both samples showed spindle cell tumour. The patient also underwent a positron emission tomography-CT, which showed the lesion to be hypermetabolic with SUVmax of 7.3. No metastatic disease was identified.
The patient was then referred to the hepatobiliary team in Queen Mary Hospital in Hong Kong for further assessment. The patient remained asymptomatic clinically with normal laboratory results including liver biochemistry (bilirubin 4 μmol l–1, alkaline phosphatase 54 U l–1, alanine aminotransferase 29 U l–1 and aspartate aminotransferase 23 U l–1). A repeat MDCT 2 months later showed that the lesion had a soft tissue density on non-contrast scans. The mass now measured 5.3 × 5.9 × 6.4 cm, extending from the superior mesenteric vein/splenic vein confluence to the porta hepatis. It exhibited heterogeneous enhancement with feeding vessels seen on the arterial phase, both within and around the mass. On the portal venous phase, numerous collaterals were seen surrounding the mass with a sharp interface between the mass and opacified portion of the main portal vein at the porta hepatis giving the appearance of a “beak” (). The pancreatic duct was mildly dilated and measures 3 mm. The biliary tree was not dilated. There was splenomegaly measuring 13.5 cm craniocaudally. No gastroesophageal varices or ascites was appreciated. Based on these MDCT and histological findings, a preoperative diagnosis of primary leiomyosarcoma of the main portal vein was made.
The patient underwent Whipple’s procedure and portal vein reconstruction using cadaveric graft. Intraoperative findings confirmed the tumour arising from inside the portal vein and confined to the lumen with no macroscopic evidence of disease spread. Histological examination of the tumour showed spindle cells with enlarged, pleomorphic, hyperchromatic nuclei and abundant eosinophilic cytoplasm. Patchy coagulative necrosis was also seen. Mitotic figures were at 8 per 50 high power fields, and atypical mitotic figures were found. There was focal infiltration into adjacent pancreatic parenchyma. Immunohistochemical stains showed the tumour was positive for actin, h-caldesmon and desmin but negative for myogenin, c-kit and S100 protein. The final histological diagnosis was of a primary LMS of the portal vein (). The patient made an uneventful recovery and no adjuvant radiotherapy or chemotherapy was given. He was followed up for 4 months in our institute with no complications.
|
pmc-6159253-1
|
A 53-year-old male patient (hepatitis B carrier), who had been suffering for 3 months from HCC with multiple lung metastases, was admitted complaining of headache. A brain MRI scan that was performed to identify brain metastasis showed a solid mass occupying the left nasal cavity (3.7 × 1.8 × 2.8 cm). The mass showed iso-signal intensity on T1 weighted image, high signal intensity on T2 weighted image, and heterogeneous well enhancement on Gd-T1 weighted image (). Gradient-echo images showed small foci of low signal, suggesting haemorrhage in the mass. Restricted diffusion was not noted in the mass on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) map. Metastasis of HCC was suggested, as the nasal cavity was normal on a positron emission tomography CT scan that had been performed 3 months ago. The patient had developed left nasal obstruction, clear rhinorrhea and left facial pain. A CT scan that was performed for excisional biopsy (17 days after the MRI scan) showed that the mass had rapidly increased in size (6.2 × 2.2 × 3.4 cm) with involvement of the ostium of the nasolacrimal duct and the lateral wall of the anterior nasal cavity (). There was no calcification in the mass on the pre-contrast CT scan. A punch biopsy was performed. Histological examination revealed tumour cells with enlarged nucleoli and clear cytoplasm arranged in trabecular cords and glandular arrays, consistent with metastatic HCC (). The tumour was grade 2 (moderately differentiated). While the patient was awaiting resection of the tumour, his general condition declined and he was transferred to another hospital owing to his location.
|
pmc-6159257-1
|
A 24-year-old previously asymptomatic male presented to his primary care physician with a complaint of focal penile irritation related to sexual intercourse. The irritation originates from a lesion along the midline on the dorsum of his penile glans. He was referred to a urologist for further evaluation.
The patient reported noticing a small dimple along the midline on the dorsum of his glans for as long as he could remember. The lesion had not previously caused him any discomfort, nor did he report a history of discharge, including urine, semen, blood or pus from the orifice. In recent months, the patient has become more sexually active and he has become aware that during and after intercourse the site is painful and inflamed for a short period of time. The patient wants to make sure there is not something wrong with his anatomy and seeks a solution.
The patient had no significant past medical history. There is no family medical history of relevance, specifically no one has reported any genital malformation. Physical examination by a urologist demonstrated a well-developed adult male. A small midline opening was present on the dorsum of the penile glans. There was no focal erythema or discharge present at the time of examination. Manipulation of the opening demonstrated a thin lumen that appeared to continue proximally along the dorsum of the penile shaft. The most likely aetiology was determined to be urethral duplication. Imaging was necessary for confirmation and to delineate the particular anatomic presentation in order to plan treatment. Demonstration of communication with the urethra or bladder would require more extensive surgical intervention to eliminate the sequelae of discharge accumulation in the lumen causing infection, cyst formation or recanalisation of the accessory orifice. The patient was referred to radiology for urethrography.
Since no urine, semen or other discharge had ever been noted to exude from the accessory urethra, a retrograde urethrogram (RUG) was performed (). A 5F paediatric catheter was advanced 3 cm through the dorsal accessory meatus. Simultaneously, a 6F Foley catheter was inserted into the orthotopic urethral meatus and the retention balloon inflated in the fossa navicularis. Cystografin contrast was manually instilled into both catheters. Opacification of the accessory meatus demonstrated a hypoplastic urethra traversing the dorsum of the penis and terminating blindly at the level of the levator musculature. No contrast was visualized refluxing into either the orthotopic urethra or the bladder. Contrast injected into the orthotopic urethra demonstrated a normal appearing urethra terminating at the sphincteric musculature. There was 2 mm of distance separating the terminal blind end of the accessory urethra and the orthotopic urethra. Based on the radiographic evidence a Type 1-A urethral duplication was diagnosed.
After confirming a Type 1-A urethral duplication the patient was offered and consented to operative reconstruction. A short rigid ureteroscope was used to inspect the main urethra and bladder demonstrating the appearance of normal verumontanum and sphincteric mechanisms confirming the ventral urethra as the functional urethra. The ureteroscope was then used to evaluate the accessory urethra and passed through to the blind-end. The accessory urethra was cauterized as the ureteroscope was withdrawn.
The patient tolerated the procedure well without any reported postoperative complications. At follow-up the patient did not report recurrent irritation during sexual intercourse and was pleased with the cosmetic result.
|
pmc-6159259-1
|
A 48-year-old male presented with a paraspinal mass seen on preoperative chest X-ray obtained for knee arthroscopy. He reported relatively constant sharp left axillary pain radiating to the anterior chest wall for about 8 months.
|
pmc-6159261-1
|
Mr JA, a 59-year-old active doctor with no significant medical history, presented with a 4-month history of right-sided hip pain radiating to the groin following minor trauma incurred by a jump from a wall. Conservative measures such as rest, non-steroidal anti-inflammatory medication and physiotherapy provided minor relief but failed to resolve the pain. Clinical examination suggested impingement and a labral tear as the source of the pain. The patient went on to have an MRI of the hip, which demonstrated a small synovial herniation pit within the anterior aspect of the superolateral femoral head and neck junction measuring 5 mm with a mild amount of surrounding bone oedema and subtle lateral femoral head–neck junction contour abnormality suggestive of early cam-type impingement morphology. There was no fracture evident and the articular surfaces, labrum and the remainder of the pelvis were normal ().
Flouroscopically guided intra-articular steroid injection of 8 mg dexamethasone mixed with 2 cc of 0.25% bupivacaine was performed resulting in symptom improvement immediately following the procedure. Within 6 days the symptoms had completely resolved.
Follow-up MRI 1 month later demonstrated complete resolution of the bone oedema surrounding the herniation pit (). At 1-year follow-up the patient remained asymptomatic.
|
pmc-6159262-1
|
A 43-year-old female with dyspnoea was transferred to our emergency department for further treatment. She had dyspnoea and cough about 6 months ago. No sputum or haemoptysis was observed. She worked as a farmer for about 10 years, and such symptoms had never happened. Occupational poison contact was denied. Her parents were healthy, with no similar family history or medical history. Empiric anti-infective therapy and antituberculosis therapy were given in the last few months at a local hospital, but the symptoms of dyspnoea worsened. Plain CT of the chest revealed a mass with well-circumscribed soft-tissue attenuation, which measured about 25 Hounsfield units (HU) on the lateral wall of the trachea (). It was about 2 × 1 × 1 cm3 in size. Contrast-enhanced CT revealed marked homogeneous enhancement (), with the highest density of 122 HU in the arteries that declined gradually to 85 HU at 120 s after injecting the contrast medium. No metastatic lymph nodes or infiltration into nearby structures was observed. No similar lesions were found in the lungs, mediastinum or abdomen. Tracheotomy was arranged. Macroscopically, the mass was about 2 × 1 × 1 cm3 with a distinct border and smooth surface. No enriched vasculature was observed. Microscopically, the lesion was composed of a large amount of lymphatic tissue and hyperplastic vascular and lymphoid follicles, with atrophy of the germinal centre (). Immunohistochemical staining of the specimen confirmed the diagnosis of Castleman’s disease (CD). The specimen was CD20(+)/CD79(+) in B lymphocytes and CD3(+)/CD5(+) in a few T lymphocytes. Plain CT of the chest 3 months after the surgery excluded relapse or residual lesions in the trachea. The patient was then under regular follow-up, and her physical condition was quite good.
|
pmc-6159263-1
|
A 63-year-old female presented in 2016 with pain in her left clavicle while out walking her dog. She had a history of grade I, node negative, triple receptor negative ACC of the left breast, which was treated with mastectomy in 2003. Eight years later she was diagnosed with a new primary tumour in the contralateral (right) breast. This was a grade III, 3/17 node positive, ER positive/HER2 negative invasive ductal carcinoma, which was treated with mastectomy, axillary node clearance, chemoradiotherapy and letrozole (Femara, Novartis, UK). The patient had been disease free up to the latest presentation in 2016. The clavicular pain initially settled spontaneously but recurred and prompted further investigations. Clinical examination revealed a mass involving the left clavicle measuring 5 cm in transverse diameter. A radiograph of the left clavicle showed evidence of an expansile destructive lesion at its medial end (). This finding, in addition to the soft tissue invasion, was confirmed on CT (), bone scintigraphy () and PET-CT (). Given the atypical nature of this lesion on a background of breast cancer, a bone biopsy was performed. Histology showed cores of bone invaded by a tumour with a biphasic pattern of epithelial and myoepithelial cells forming cribriform and tubular structures containing eosinophilic secretions (). There were no solid areas to indicate high grade disease and no perineural invasion was seen. Immunohistochemical staining was positive for keratin 7 but negative for ER/PR/HER2, keratin 20, gross cystic disease fluid protein-15 and thyroid transcription factor-1. The histology from the original breast carcinoma was reviewed and this showed a similar histomorphological pattern. In the absence of an additional radiological primary site, the bone lesion was reported as primary metastatic ACC in keeping with the previously diagnosed left breast cancer and recommended for multidisciplinary team discussion. The patient underwent surgical resection of the lesion and clavicle. Macroscopic examination showed an expansile tumour in the clavicle with probable extension into soft tissues (). In concordance with the biopsy, histology revealed a tumour with classic ACC features invading bone and confirmed soft tissue extension. The patient is now undergoing adjuvant radiotherapy to the area.
|
pmc-6159265-1
|
A 72 year old female, with no significant past medical history, was sent to our hospital by her primary care physician for vague abdominal pain and dyspepsia. The patient had no history of alcohol abuse neither abdominal operation. We performed an abdominal ultrasonography, which revealed a large and well-defined mass of mixed echogenicity (iso-hyperechoic), with posterior attenuation, in the left lobe of the liver (). The maximum axial diameter of the mass was about 10 cm, and a colour Doppler modality has been used to study the lesion showing a perilesional vascularisation (). Gallbladder lythiasis was detected, with no dilatation of biliary system; there were no signs of cholecystitis. There were no splenomegaly or ascites. Laboratory studies including the blood cells count and liver function tests were within the limits, only triglycerides and glucose were altered, with a body mass index of 30.8. Hepatitis serology and tumour markers (e.g. alpha-fetoprotein, protein induced by vitamin K absence/antagonist II, carcinoembryonic antigen and carbohydrate antigen 19.9) were negative.
|
pmc-6159268-1
|
A 32-year-old female at pregnancy week 22 was admitted to the haematology department with bilateral supraclavicular swelling, diffuse itching and right shoulder pain. Ultrasound imaging showed pathological bilateral supraclavicular enlarged lymph nodes, which were biopsied. A diagnosis of nodular sclerosis Hodgkin’s lymphoma (HL) was made.
Fetal ultrasound screening was normal. In view of the patient’s desire to proceed with the pregnancy, a multidisciplinary follow-up (by haematologists, gynaecologists, radiologists and neonatologists) was scheduled.
Combined fludeoxyglucose positron emission tomography (FDG-PET)/CT scan was not performed before the delivery because of the risk of radiation exposure during pregnancy.
It was decided to stage the disease through ultrasound and whole-body MRI (WB-MRI), which showed right cervical, bilateral supraclavicular and mediastinal lymph node involvement without a bulky mass (axial diameter 4.7 × 4.1 cm), indicating Stage IIA disease, according to Ann Arbor classification ().
The multidisciplinary team decided to start chemotherapy only if clinically necessary. Accordingly, the patient was followed up with ultrasound, WB-MRI, haematology consults and gynaecological examinations. Furthermore, therapy with steroid and paracetamol was started to slow down the progression of disease, and treat the itching and shoulder pain.
At pregnancy week 27, WB-MRI demonstrated a slight progression of the disease, seen as an enlargement of the lymph node packages, the largest was in the mediastinum with an axial diameter of 5.4 × 4.5 cm.
At pregnancy week 29, the clinical conditions got worse and the patient presented with coughing, night sweating, numbness and pain radiating across the shoulder down the arm. An ultrasound examination showed enlargement of a right axillary lymph node and the internal jugular vein thrombosis that was treated with enoxaparin, which allowed complete recanalization in just a week. Thus, it was decided to start chemotherapy.
WB-MRI was performed at pregnancy week 30, before the beginning of chemotherapy, confirming the progression of disease with right axillary involvement and further enlargement of the supraclavicular and mediastinal lymph nodes (the largest lesions with axial diameters of 5.8 × 4.7 cm), but without the involvement of extranodal or subdiaphragmatic sites; so the disease stage had not changed ().
The patient received two courses of chemotherapy (adriamycin, bleomycin, vinblastine and dacarbazine) and showed an improvement in her clinical status a few days after the beginning of therapy, with disappearance of the coughing and sweating, and a decrease in the cervical swelling, numbness and pain.
At pregnancy week 38, the patient gave birth to a healthy child, with a weight of 3.110 kg, via spontaneous delivery. A week after delivery, the patient presented with worsening of clinical symptoms, the reappearance of sweating and asthenia, signs of increased cervical swelling, and she received another course of adriamycin, bleomycin, vinblastine and dacarbazine. Ultrasound and WB-MRI were then performed to assess the response to treatment and showed progression of the supraclavicular lymphadenopathy and an enlargement of the longest axial diameter of the spleen from 11 to 14.5 cm, concluding that the disease was a resistant lymphoma ().
After WB-MRI, the patient underwent FDG-PET/CT scan that confirmed the MRI findings ().
After confirming the findings, the haematologists decided to change the chemotherapy regimen and thus the patient received three courses of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone and three standard bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone.
After chemotherapy, the patient underwent WB-MRI and FDG-PET/CT, which showed disappearance of the nodal locations of the disease and normal splenic size ().
|
pmc-6159271-1
|
We report a case of a 40-year-old female (gravida 5 para 4, gestational age 32 weeks) who attended the obstetrics and gynaecology outpatient clinic in our institute. She complained of repeated episodes of vaginal bleeding. Abdominal examination revealed a disproportionately high uterine fundal level that was not matching her corresponding gestational age. Abdominal ultrasound examination showed a viable, single intrauterine 32 weeks fetus. On screening the adnexal regions, bilateral highly vascular complex adnexal masses were identified, measuring 8 × 6 cm² on the right side and 12 × 8 cm² on the left side (). Transvaginal ultrasound imaging showed an additional highly vascular polypoidal mass projecting in the upper vagina, indistinct from a rather bulky cervix. Solid peritoneal deposits were also identified in the Douglas pouch (). Further evaluation of the pelvis by MRI was requested and a non-contrast study was performed at the same institute after a 1-week interval, which was interpreted by a different set of readers. T2 weighted images showed findings matching those of the preliminary pelvic ultrasound imaging (). Functional data concerning the cellularity and integrity of the cell membranes of the adnexal and vaginal masses was provided by the diffusion-weighted MRI (DWI) sequence. On the DWI sequence, the masses showed restricted diffusion in the form of persistent bright signal intensity and low apparent diffusion coefficient (ADC) values, which strongly favoured likely malignant pathology (). Laboratory data were within normal limits apart from a raised CA-125 level. Corticosteroids were administered to ensure fetal lung maturity. The pregnancy was terminated by an elective caesarean section at 34 weeks gestation via a midline subumbilical incision. A 2.5 kg living normal fetus was extracted. The abdomen was explored and the bilateral complex adnexal masses were identified, together with the multiple omental metastatic nodules and bloody ascites. The right ovarian mass was attached to the posterior abdominal wall and was inseparable from the sacral promontory. Debulking of the ovarian lesions, panhysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed. Minimal tumour residue that was adherent to bone could not be removed. Vaginal exploration was also performed to remove the polypoidal vaginal component, which was grasped and totally excised. It was completely separable from the cervix. Pathological examination revealed an undifferentiated ovarian adenocarcinoma (grade 3), metastasizing to the upper vagina with clear cervical margins. The patient is now undergoing chemotherapy.
|
pmc-6159274-1
|
A 56-year-old female with metastatic (liver, bones and brain) breast cancer treated with mastectomy and systemic chemotherapy underwent a restaging total-body CT scan. She was receiving a scheme of chemotherapy, including lapatinib, capecitabine, zoledronic acid and steroids (to reduce cerebral oedema). CT examination revealed a moderate amount of pneumatosis in the mesentery and pericolic fat, and intramural gas along the caecum and ascending colon (), with the absence of other worrisome CT findings. The patient did not have abdominal pain or fever and had no history of any recent operative procedure or endoscopy. The oncologist, warned by the radiologist about the situation, decided to discontinue the steroids and follow a conservative approach, with clinical and radiological surveillance. The patient remained asymptomatic and follow-up imaging showed a slow resolution of PI.
|
pmc-6159274-2
|
A 52-year-old female with breast cancer underwent left mastectomy and axillary dissection, and then received local radiotherapy. During the following 2 years, the cancer progressed, with metastases to the lymph nodes, bone and brain. For brain metastasis, she was treated with whole brain radiotherapy.
The patient was admitted to hospital to rule out injury following a minor trauma while she was being given systemic chemotherapy with docetaxel, trastuzumab and zoledronic acid in association with steroids to reduce cerebral oedema. A CT scan excluded any abdominal injury, but showed a moderate amount of PI along the caecum, and ascending and proximal transverse colon. On clinical examination, there were no signs of peritonism or sepsis, hence the surgical consultant recommended close conservative observation with supportive care alone. 5 days later, a follow-up CT scan of the abdomen showed an increase in the amount and extent of PI (). Again, there were no other worrisome gastrointestinal findings on the CT and the patient was asymptomatic, thus steroids were discontinued and a conservative approach was followed. A CT scan performed a month later documented resolution of the PI.
|
pmc-6159274-3
|
An 80-year-old male was found to have a pulmonary nodule that turned out to be an adenocarcinoma. The patient did not undergo surgery owing to the comorbidities he was suffering from, which included chronic obstructive pulmonary disease (COPD), diabetes and heart disease. He underwent stereotaxic radiotherapy with little benefit; indeed, the cancer progressed giving rise to lymph node and lung metastases bilaterally. He underwent several cycles of chemotherapy with vinorelbine, while receiving corticosteroids for COPD-related dyspnoea.
A CT scan of the chest performed to evaluate worsening cough and dyspnoea showed a large amount of gas in the adipose tissue along the caecum, and the ascending and transverse colon (). The CT examination was extended to the abdomen and documented no other signs of bowel wall distress or perforation. The patient had no abdominal pain or fever; thus the surgical consultant suggested close observation alone. An abdominal plain film () taken a week later documented the persistence of PI along the right and transverse colon. As the dyspnoea improved, the oncologist decided to gradually discontinue steroids and proceed with vinorelbine. A follow-up CT scan performed 4 months later showed improvement in the condition with a PI of minimum extent, limited to the caecum.
|
pmc-6159274-4
|
A 57-year-old female underwent anterior rectal resection and subsequent radiation therapy for colorectal cancer. A year later, owing to a locoregional recurrence of malignant disease, she underwent further surgery and radiotherapy, and was then started on systemic chemotherapy with 5-fluorouracil and oxaliplatin. Afterwards, she received capecitabine, then fluorouracil, folinic acid and irinotecan, and cetuximab. A subsequent restaging total-body CT scan showed moderate PI involving the caecum and the ascending colon () in the absence of other gastrointestinal worrisome findings. The patient had no signs of peritonism or sepsis. The surgical consultant recommended close observation with supportive care. The oncologist suspended cetuximab. A CT scan of the abdomen performed 3 days later showed a worsening of PI.The patient was still asymptomatic, thus a conservative approach was followed. Follow-up imaging documented a slow decrease of PI during the subsequent 2 months. The patient remained asymptomatic.
|
pmc-6159275-1
|
A 64-year-old female with newly diagnosed Stage 1B pancreatic adenocarcinoma was treated by neoadjuvant gemcitabine chemotherapy and radiation, followed by a Whipple procedure at an outside institution 1 month after the completion of neoadjuvant therapy, resulting in a substantial weight loss of 40 pounds (18 kg). The patient was admitted to our institution with dizziness and hypotension.
A contrast-enhanced CT scan of the abdomen was performed with a 16-slice multidetector CT scanner (Somatom Sensation 16, Siemens Medical Solutions, Forchheim, Germany) using a routine single-phase abdomen and pelvis protocol in the portal venous phase after administration of 125 ml of iohexol 350 mg ml−1 (Omnipaque 350, GE Healthcare, Milwaukee, WI) at a rate of 3 ml s−1 with 5 mm slice thickness and 120 kV. The contrast-enhanced CT scan revealed an incidental solid enhancing mass measuring 2.5 cm in diameter in the lower pole of the left kidney, which was suspicious for renal cell carcinoma (RCC; ). On comparison with pre-treatment imaging performed 9 months earlier, the mass corresponded to a 3.0 cm lesion () that demonstrated regions of negative attenuation (−39 Hounsfield units), characteristic of intratumoral fat and consistent with angiomyolipoma (AML). The subcutaneous fat thickness seen on the post-chemotherapy CT scan was 1.0 cm, compared with 2.5 cm on the pre-treatment CT scan, and consistent with the substantial reported weight loss. Several CT and MR examinations of the abdomen were subsequently performed for various reasons unrelated to the AML, demonstrating continued decrease in the size of the mass, reaching a size of 2.0 cm. The intratumoral fat component remained imperceptible on imaging, including an MR of the abdomen performed more than 2 years after the initial CT () and an unenhanced CT that had shown minimal hyperattenuation of the mass compared with the surrounding parenchyma ().
|
pmc-6159278-1
|
A 27-year-old Asian female presented to the surgical outpatient department with complaints of perineal swelling. The swelling was noticed by the patient 6 months ago in the right perineal region; it was approximately the size of a lemon and did not show noticeable increase in size over this time period. It was painless and not associated with changes in the overlying skin colour or texture. The patient was referred for an MRI examination with the clinical query of a possible lipoma in the soft tissues.
MRI of the perineum was carried out before and after administration of intravenous gadolinium contrast. The examination revealed a well-encapsulated lesion measuring 36 × 26 × 24 mm in the subcutaneous soft tissues of the perineum on the right side, appearing as a low signal intensity on T1 weighted images (), intermediate signal intensity on T2 weighted images () and heterogeneous high signal intensity on proton density fat-saturated images (). The lesion showed restricted diffusion, appearing as low signal intensity on apparent diffusion coefficient images and as high signal intensity on diffusion-weighted images (). Post-contrast images demonstrated subtle enhancement of the lesion wall, with no abnormal internal enhancement (). Based on the MRI features, the clinical diagnosis of lipoma was ruled out and epidermoid cyst was suggested as the alternative diagnosis.
1 week later, surgical excision of the swelling was performed and the specimen sent for histopathology, which subsequently confirmed it to be an epidermoid cyst, without any evidence of malignancy.
|
pmc-6159280-1
|
An 82-year-old Indian male presented to the surgical outpatient department with complaints of non-specific left flank pain. During the course of the investigations, a non-contrast CT scan was performed, which was unremarkable except for the liver. The liver appeared to be malrotated in
situ, with the inferior surface and the gallbladder facing anteriorly (). The left lobe appeared to be atrophic and the right lobe showed physiological hypertrophy. The situs of the patient was normal. The left atrium, spleen and stomach were located on the left () and the right atrium and liver on the right side, with the cardiac apex pointing towards the left side (). No evidence of polysplenia or asplenia was seen. There was a single spleen, which was normal in size and position (). Another interesting finding was the abnormal position of the inferior vena cava, which was not seen on the right side of the abdominal aorta (). No contrast was given as the patient was old. He was subsequently lost to follow-up.
|
pmc-6159285-1
|
A 68-year-old female was referred to the haematology clinic with left-sided above-knee DVT, which was essentially unprovoked as per the obtained clinical history. Her medical history included osteoporosis, osteoarthritis and sciatica. She had undergone a subtotal colectomy with ileorectal anastomosis for large bowel obstruction due to a histologically proven benign stricture secondary to colonic diverticular disease 16 years ago.
Although she was a non-smoker, she had been consuming 20–30 units of alcohol per week for the past many years until 4 years ago, when her daily intake increased by an additional 10 units. She often indulged in binge drinking, mainly for the pain associated with her musculoskeletal and rheumatological comorbidities. There was no clinical history to suggest any liver abnormality (e.g. jaundice, pedal oedema, ascites, encephalopathy, gastrointestinal bleeding) or symptoms suggestive of cardiac overload such as shortness of breath or history of cardiac ischaemic disease.
Haematological and liver function tests (LFTs) revealed asymptomatic mild thrombocytopenia that had been ongoing since 2006. Mild derangement of the LFTs was also noted ().
A portovenous phase CT scan was performed by the haematologist to look for any possible underlying malignancy as the cause of the DVT. The scan showed bulky enlargement of the left thyroid lobe with multiple nodules. There was neither any supraclavicular, thoracic or axillary lymphadenopathy nor any focal lung lesions. The gallbladder, pancreas, spleen, adrenal glands and kidneys were also unremarkable.
However, there was an incidental finding of an extrahepatic portosystemic connection, with an enlarged vein arising from the portal vein just superior to the confluence of the superior mesenteric and splenic veins. This was seen to anastomose with an engorged left adrenal vein and ultimately drain into the left renal vein. The hepatic portal vein was evidently patent. The appearance of the liver was consistent with fatty infiltration but was otherwise unremarkable ().
The radiologist reporting the CT scan recommended a hepatology clinic referral, which was subsequently organized. During the clinic visit, a full assessment, including physical examination, was conducted. Contrary to any plausible clinical expectations, no central or peripheral signs of cardiac or chronic hepatic disease were identified. There were neither audible murmurs on auscultation nor any evidence of hyperdynamic circulation. The liver was not palpable, and there was no free fluid in the abdomen. There was, however, a mildly enlarged spleen, about 2 cm below the left costal margin; this was also confirmed on the CT images.
The patient, however, was still asymptomatic with a Type II Abernethy malformation, and her previous surgical history did not seem to qualify as an iatrogenic cause for this shunt. Therefore, further investigations were conducted. These included a non-invasive liver screen with immunoglobulins, autoimmune and viral hepatitis (hepatitis B and C) markers; a fibroscan with a view to proceed to liver biopsy; and an endoscopy to look for portal hypertension and varices.
On her subsequent review by the hepatology team, the fibroscan showed a median liver stiffness measurement value of 5.5 kPa (normal healthy adult < 7.0 kPa, median 5.3 kPa), which was within the normal range to exclude liver fibrosis. Additionally, a subsequent non-invasive liver screen was also negative. The platelet count on the most recent pathology test was normal (platelet count 154). Given these results, chronic liver disease and portal hypertension were deemed unlikely and the most likely cause of her shunt was believed to be a long-standing congenital anomaly, hence a liver biopsy was not indicated.
Given the above findings in the absence of any local and/or systemic complications, she was discharged back to the care of her general practitioner without any further follow-up planned.
|
pmc-6159285-2
|
A 56-year-old male was brought in by the regional ambulance team to our trauma centre (level 1) after being involved in a high speed road traffic accident. His past medical history included schizophrenia. Otherwise, he was fairly fit and well, with no significant comorbidities.
He was seen and assessed by the trauma team and had a series of investigations and imaging studies, which included performing a CT scan to evaluate the traumas. He was found to have acute multiple traumatic injuries, all right-sided, with several fractures of the right upper and lower limbs, and the right hemipelvis.
The CT scan revealed an abnormal enhancing and distended extrahepatic portosystemic communication between the left renal vein/inferior vena cava and the splenic vein. A markedly hypoplastic portovenous system was also noted, likely due to considerable flow diversion into the systemic veins without any intrahepatic shunts identified. The findings suggested an incidental Type II CEPS, draining into the left renal vein ().
His LFTs on admission were normal, as detailed in . Following his management, he spent a significant amount of time in high dependency care and was repatriated to his base hospital for further management.
There were no findings on history taking or physical examination to suggest any relevant symptomatology, and thus a full hepatological screen (viral screen, immunoglobulins, neutrophil cytoplasmic antibody level and antinuclear antibody level) was not carried out owing to the circumstances.
|
pmc-6159295-1
|
A 72-year-old female was referred for ultrasound evaluation of the liver secondary to worsening liver function tests. The patient’s history included obesity, for which she had undergone sleeve gastrectomy 2 months ago. Her liver function tests had been slightly elevated in 2012, but had progressed by the time of current presentation ().
Ultrasound examination demonstrated a right hepatic lobe hypoechoic solid mass measuring 5.6 cm in transverse diameter. Further evaluation with contrast-enhanced CT scan showed a mildly nodular hepatic surface contour with two heterogeneously enhancing or hyperdense masses containing central areas of diminished attenuation within segments 6 and 7 of the right hepatic lobe (). The larger lesion measured 5.3 × 5.7 × 5.1 cm. The portal vein was noted to be diminutive (abnormal for early cirrhosis) with a transverse diameter of 9 mm. A large tortuous complex shunt was noted (maximum transverse diameter of 2.0 cm) to arise from the portal vein bifurcation with connections to the left renal vein and descending along the aorta to communicate with the inferior vena cava at the level of the L2–3 vertebrae ( and ).
Review of the patient's chart showed that she had a CT examination performed 10 years ago. Upon review of images from that examination, the liver surface was again noted to be mildly nodular, but without any discrete mass being present. The portal vein was normal in calibre (maximum transverse diameter of 1.5 cm). The described portosystemic shunt was present; however, it was significantly smaller in calibre compared to the current examination, measuring 9 mm in the transverse diameter ().
The patient underwent CT-guided biopsy of the larger mass, with pathology results consistent with hepatocellular carcinoma (HCC). The patient is currently undergoing treatment for her disease. The final outcome is yet to be determined.
|
pmc-6159296-1
|
A 44-year-old male was admitted with dyspnoea that had progressively worsened 3 days earlier. He complained of recent chest pain in the midsternum, and left arm oedema and weight loss for 4 months. Vital signs at presentation were blood pressure of 100/80 mmHg, pulse of 98 beats min−1, temperature of 36.6°C and oxygen saturation of 100%. There was no known underlying disease.
A chest radiograph showed mediastinal widening, nodular consolidation in the left lower lobe and pleural effusion ().
Blood urea nitrogen/creatinine level was elevated at the time of analysis (79.9/4.7), so a CT scan was performed without contrast enhancement.
The CT scan showed a huge lobulated mass involving the oesophagus, mediastinum and lower neck with enlarged lymph nodes ().
The analysis revealed a large amount of pericardial effusion and extraluminal air bubbles along the pericardium, suggesting pneumomediastinum () and pneumopericardium ().
Echocardiography and pericardiocentesis were performed, resulting in the drainage of 300 ml of pus-like light brown fluid.
An endoscopic study revealed a huge oesophageal ulcer encircling the oesophageal lumen at 20–30 cm from the incision ().
The stomach showed multiple erythematous plaques and erosions, and mild atrophic changes of the mucosa but no definite mass lesion.
Endoscopic biopsy was performed of the oesophageal lesion and histological analysis of the biopsies suggested small cell carcinoma (SCC; –). On immunohistochemistry, the tumour cells stained positive for CD56 and synaptophysin (endocrine markers) and were negative for p63 and leukocyte common antigen, excluding squamous cell carcinoma and lymphoma.
An enhanced CT scan study performed 4 days after presentation () showed residual pericardial effusion with thin diffuse pericardial enhancement and a huge mass encircling the oesophagus, mediastinum and lower neck with metastatic lymphadenopathy.
Small nodules in the left lower lobe with pleural effusion suggested pneumonia or metastasis to the lung.
Positron emission tomography/CT scan was performed on the same day, and very high uptake was noted by the mediastinal mass and lymph nodes ().
The patient was treated with chemotherapy with cisplatin and etoposide, which markedly decreased the size of the mediastinal mass and improved the dyspnoea and left arm oedema ().
Antibiotic treatment was administered and improved the pneumonia in the left lower lung.
After eight cycles of chemotherapy, the masses showed partial response; however, multiple brain metastases developed 7 months after the initial diagnosis. A poor prognosis is expected.
|
pmc-6159297-1
|
A 70-year-old female with no significant past medical history, Eastern Cooperative Oncology Group performance status 0 and no prior incidence of hypersensitivity reactions, was incidentally found to have a small nodule in the proximal right posterolateral vaginal wall after presenting with post-menopausal bleeding. Subsequent biopsy demonstrated a 9 mm invasive melanoma and the patient underwent wide local excision with confirmed negative margins. 4 months later, she developed a right periclitoral mass. Positron emission tomography/CT scan at that time demonstrated focal uptake in this area but no regional/distant metastases (). Excision demonstrated a large submucosal mass of atypical epithelioid cells with evidence of melanin synthesis, consistent with malignant melanoma. Breslow depth was 9 mm (3 mitoses/mm2) with a positive deep margin, and there was no evidence of lymphatic invasion. Her case was presented at a multidisciplinary tumour board and either additional surgery or radiation therapy was recommended to the patient. Owing to the significant morbidity anticipated with additional surgery, the patient opted for radiation therapy. Given the high risk of both local and regional/distant failure, concurrent chemotherapy was proposed. Owing to the historically poor response rates with standard chemotherapy, an immune pathway targeted agent was considered. This non-standard approach was actually initially proposed by the patient. After being thoroughly explained the current standard of care, in addition to the pros and cons of pursuing concurrent radiation and immunotherapy, the patient chose to proceed with combination immunotherapy and radiation treatment. Several studies have demonstrated that local radiotherapy primes and/or enhances an immune response through cytotoxic T lymphocytes. Concurrent immunotherapy may then further enhance the activity and/or duration of the downstream immune response. Given the historically low efficacy of our current treatment paradigms in this disease, as well as the preclinical/clinical rationale to combine radiation and immunotherapy, a strategy of pursuing a combination of ipilimumab with radiation was felt to be reasonable.
Radiation was planned with intensity-modulated radiation therapy (IMRT) to the vulva and vagina (no elective nodal radiation to the groin) to an initial dose of 45 Gy (1.8 Gy/fraction over 25 fractions), and was to be followed by an electron boost to a total dose of 63 Gy (1.8 Gy/fraction over 10 fractions) at the site of the positive margin (). A thermoluminescent dosimeter was placed on the vulva at the start of treatment to measure the skin dose and read as 1.78 Gy [95% confidence interval (1.66–1.90)], confirming that the planned dose was accurate on the skin. The patient received her first cycle of ipilimumab (3 mg kg−1) 7 days after the start of radiation, and the second cycle was delivered 3 weeks later when the patient was at a dose of 36 Gy. Around this time (3 weeks post ipilimumab cycle 1), she began to develop non-painful erythema in the vulvar and perianal area, as well as a pruritic, grade 2 cutaneous eruption that morphologically showed distinct erythematous papules that coalesced into thin plaques over the upper arms, chest, back and face/ears (all toxicities were graded using Common Terminology Criteria for Adverse Events version 4.03). She did not experience any fevers or other systemic symptoms. By 48.6 Gy dose (10 days post ipilimumab cycle 2), the patient developed a grade 3 skin reaction () that was characterized as a moist desquamation with significant oedema, erythema and pain in the vaginal/vulvar/perianal region and was restricted to the radiation field (). A timeline of these events is illustrated in . After proper consent, a 4 mm punch biopsy of the affected skin was performed and histopathological examination demonstrated spongiotic and interface dermatitis with a perivascular inflammatory infiltrate consisting of numerous eosinophils, consistent with a fixed drug eruption.
Radiation and ipilimumab were held given the severity of the moist desquamation, and the patient was referred to a dermatologist for evaluation of the ipilimumab-associated cutaneous eruption. It is noted that the patient had no existing risk factors or hypersensitivities predisposing her to an enhanced skin toxicity. The patient was started on 0.1% topical triamcinolone cream along with a methylprednisone dosepak. Given only mild improvement after 1 week, she was started on prednisone 60 mg daily (tapered over 7 days) with oral diphenhydramine for pruritus as needed. This resulted in significant improvement in her cutaneous eruption and pruritus. She then received a third cycle of ipilimumab (4 weeks after cycle 2) and resumed her periclitoral radiation boost without further issues after a 1-month break from radiation treatment. She went on to receive a fourth cycle of ipilimumab after completion of radiation without any complications.
At follow-up 8 months post completion of radiotherapy, she had complete resolution of the in-field toxicity and improvement of her ipilimumab-associated cutaneous eruption (). Clinical examination and positron emission tomography/CT imaging 10 months after completion demonstrated no evidence of disease recurrence. Most recently, at her 15-month follow-up, she remains disease- and symptom-free ().
At each follow-up visit, the patient has repeatedly expressed satisfaction with her decision to pursue immunotherapy rather than standard chemotherapy to complement her radiation treatment. She admits the initial side effects and intensity of the treatment course were difficult, although she is very pleased with the outcomes and would make the same decision if asked to do so again.
|
pmc-6159299-1
|
A 73-year-old female was referred to our Trust by her general practitioner with a 5-month history of a painless vaginal mass, which extruded from the introitus on straining, but was otherwise asymptomatic. This was originally thought to be a vaginal prolapse; however, examination revealed a soft, well-defined pink mass occupying the upper vagina and an MRI of the pelvis was requested for further characterization.
MRI was performed using a 3.0 T system utilizing axial T1 weighted fast spin echo; small field of view axial, coronal and sagittal T2 weighted fast spin echo; and T1 weighted fat-saturated sagittal images before and after gadolinium contrast administration, obtained in the arterial and portal venous phases. Diffusion-weighted imaging was also acquired. The images demonstrated a 47 × 40 × 44 mm well-circumscribed, oval mass in the upper vagina. On the T1 weighted images, the signal intensity of the abnormality was intermediate, similar to that of the skeletal muscle (). However, on T2 imaging, there were discrete zones within the lesion; the anteroinferior aspect was of high T2 signal with no enhancement, whereas the posterosuperior aspect was of low T2 signal with avid enhancement (–). There was no restricted diffusion. The posterior wall of the retroverted uterus was demonstrated to abut the superior surface of the lesion and the vaginal lumen was deviated anteriorly. Normal vaginal wall was seen to extend around the lesion’s anterior and posteroinferior surfaces. The lesion appeared to be arising within the left posterolateral vaginal wall and there were areas of loss of definition of the outer margin of the vagina. There was no involvement of the rectum, urethra or bladder; however, there were hazy low T1 and T2 signal changes in the left paravaginal fat.
Through a MDT discussion, it was agreed that owing to the suspicious imaging features of enhancement and tissue inhomogeneity, a staging portal venous phase CT scan was required to look for evidence of metastatic spread. Again, the vaginal lesion demonstrated fluid and soft tissue attenuation areas with regions of enhancement (). Significantly, there was no evidence of distant spread or lymph node enlargement. After further MDT discussion, the mass was still thought to be suspicious for malignancy and the patient underwent surgery.
The uterus, ovaries, cervix and upper vagina were removed en bloc and macroscopic examination revealed a well-circumscribed 45 mm polypoid mass arising from the paracervical upper vaginal tissue. The cut surface of the lesion was fleshy grey and white in colour, and was mainly solid in nature.
Microscopic examination () revealed an unencapsulated lesion with a spindle cell morphology arranged occasionally in fascicles. Beneath the surface epithelium, there was a grenz zone. The spindle cells were set within finely collagenized stroma and were bland in nature, with no conspicuous mitoses identified. Areas of oedema and myxoid change were also present, with no evidence of haemorrhage or necrosis.
Immunohistochemistry demonstrated that the lesional cells expressed desmin, vimentin, oestrogen and progesterone receptors. The Ki67 proliferation index was low. Immunohistochemistry for MNF116, alpha smooth muscle antigen, smooth muscle myosin, h-caldesmon, S100 and CD34 were negative in the lesional cells.
The morphological and immunohistochemical profile was considered consistent with a superficial cervicovaginal myofibroblastoma, which is also known as superficial myofibroblastoma of the lower female genital tract.
|
pmc-6159301-1
|
A 36-year-old Japanese female presented at a local hospital with a 6-day history of throbbing headache, tinnitus and blurred vision. The next day, she was referred to our hospital with positive meningeal signs and cerebrospinal fluid (CSF) lymphocytic pleocytosis. Her past medical history was unremarkable, and she had no history of ocular trauma or surgery. Her vital signs were normal, and laboratory findings were unremarkable, except for the CSF test (). Goldmann perimeter showed a central scotoma in the right eye. Fundus photography revealed serous retinal detachment in the posterior pole of both eyes (). Optical coherence tomography demonstrated subretinal oedema and macular detachment in the right eye. Auditory examination revealed no hearing loss. There were no dermatological findings, such as poliosis, alopecia, and cutaneous vitiligo. VKH was diagnosed based on the presence of meningeal irritation, serous retinal detachment, and lack of past history of ocular trauma or surgery.
|
pmc-6159302-1
|
Patient aged 32 years, gravida 3 para 3, abortion nil, with a history of amenorrhoea of 7 months duration reported to the department of radiodiagnosis for routine antenatal ultrasound.
Obstetric evaluation of the patient revealed no specific complaints. Her general condition was good. Blood pressure was 120/80 mmHg; pulse 76 min–1, regular; temperature was normal; body weight 49 kg. Menstrual history, 3–4/28–30-day cycle, regular.
Abdominal examination revealed 26 weeks size fundal height of the uterus. Blood examination revealed haemoglobin 11.8 g dl–1; total leukocyte count 9900 mm–3; differential leukocyte count, neutrophils 77%, lymphocytes 18%, monocytes 2%, eosinophils 3%, basophils 0%. Total red blood cells 5.31 million mm–3, packed cell volume 36.4%, platelet count 2.25 million mm–3; blood urea 14 mg%, serum creatinine 0.64 mg dl–1. Human immunodeficiency virus/venereal disease research laboratory/hepatitis B surface antigen were non-reactive; blood group “A” Rh positive; bleeding time and clotting time were normal. Urinalysis was normal.
Ultrasound examination revealed a single live intrauterine foetus in the cephalic position of 24 weeks gestational age (GA), while GA by last menstrual period was 31.2 weeks. Foetal movements and cardiac pulsations were present. Amniotic fluid was normal. Placental position was fundal, posterior with maturation grade 0. Estimated foetal body weight was 649 g (50th percentile). The umbilical cord was a three-vessel cord with absence of coiling (). Colour imaging revealed an uncoiled umbilical cord ().
|
pmc-6159302-2
|
Patient aged 24 years, gravida 4, normotensive, no history of diabetes mellitus, ultrasound examination at 32 weeks GA revealed hypocoiled cord, estimated foetal weight (EFW) 2000 g ().
|
pmc-6159302-3
|
Patient aged 28 years, primigravida, normal blood pressure, no gestational diabetes, revealed hypocoiled cord near term pregnancy (39 weeks GA by ultrasound), EFW 2545 g ().
|
pmc-6159302-4
|
Patient aged 22 years, gravida 2 with normal blood pressure, no diabetes mellitus, nothing significant in past obstetric history, ultrasound examination at 36 weeks GA revealed hypercoiled cord; EFW 2250 g ().
|
pmc-6159303-1
|
A 66-year-old female was found to have an abnormality in the lower outer quadrant of her left breast on screening mammogram. Core biopsy showed infiltrating ductal cancer. Her medical history was significant for smoking, Type 2 diabetes and transient ischaemic attacks.
She underwent left partial mastectomy and sentinel node biopsy. Pathological examination revealed moderately differentiated infiltrating ductal cancer, pT1c (16 mm), N1mi(sn) (0.5 mm); oestrogen and progesterone receptor positive, human epidermal growth factor receptor 2 negative; and Oncotype DX score 21. Post-surgical staging CT scan (node-positive disease) revealed bilateral lung masses: left upper lobe measuring 1.2 cm and right lower lobe measuring 1.8 cm, and both were proven to be positron emission tomography (PET) fludeoxyglucose avid (). An MRI of the brain and a bone scan showed no evidence of metastases.
Differential diagnosis included three synchronous primary cancers or metastatic disease. Transthoracic core biopsy of the lung lesions revealed adenocarcinoma acinar type, positive for thyroid transcription factor 1 and Napsin; negative for oestrogen receptor, anaplastic lymphoma kinase, and epidermal growth factor receptor.
The case was discussed at the multidisciplinary tumour board. Histology suggested three distinct curable primaries: T1N1 breast cancer and bilateral T1N0 lung cancers. Management of the breast cancer included partial mastectomy with sentinel node sampling; adjuvant tangential whole breast irradiation (WBI) with regional nodal irradiation (RNI); and an aromatase inhibitor (letrozole). The bilateral lung primaries were planned to be treated with stereotactic ablative radiotherapy (SABR).
The patient underwent four-dimensional CT simulation, with immobilization by abdominal compression for the SABR plans, and free-breathing CT simulation for the breast and regional nodal plans. CT images were fused with those from the PET scan. Gross tumour volumes, clinical target volumes, bilateral lung internal target volumes, planning target volumes, organs at risk and axillary nodal regions were defined as per local policy.
The left and right lung tumours were each treated with 48 Gy in 4 fractions prescribed to the isocentre of each lung lesion, using SABR with volumetric modulated arc therapy technique. A pair of clockwise and counterclockwise partial arcs was utilized, with the collimator set at 30 and 330 degrees to avoid the contralateral lung. A 6 MV photon beam was used.
The breast and regional nodes (supraclavicular and axilla levels I, II and III) were treated to 50 Gy in 25 fractions using a field-in-field technique in a four-field beam arrangement. The breast fields were delineated so that the target (whole breast) was covered by 95–107% of the prescribed dose. Fluence maps were extended 2 cm outside the breast skin to accommodate the respiratory motion of the chest. 6 and 15 MV photon beams were used to achieve adequate dose coverage and dose uniformity for large separation.
It was planned to treat all three sites concurrently. In the composite plan, all doses and dose coverage were within tolerance limits, despite a region of increased dose in the upper left breast, owing to the contribution from the SABR plan (). and show the dosimetric parameters for individual plans and shows the equivalent dose in 2 Gy fractions for individual plans and the composite plan. Three safe and deliverable treatment plans were developed.
The left and right lung were concurrently treated with 48 Gy in 4 fractions, delivered with abdominal compression, treating each side on alternate days, for a total 8-day course. Patient position was verified with daily cone-beam CT pre- and post-treatment. Each daily lung treatment, including patient setup and beam delivery, was completed in a 15-minute slot with intensity-modulated radiotherapy.
Following completion of lung treatments, the breast and regional nodes were treated to 50 Gy in 25 fractions, delivered 5 days per week, without breathing control. Field position was verified using kV–kV imaging.
The patient completed all her treatments without toxicity. She developed dyspnoea and cough 5 weeks post lung radiotherapy and within 1 week of completing breast radiotherapy. She did not feel her symptoms warranted therapy, and given her diabetic history, steroids were withheld. Her CT scan was consistent with post-radiotherapy changes. Pulmonary function tests showed mild restrictive defect, forced expiratory volume in 1 s/forced vital capacity = 56% (compared with 66% pre-radiotherapy). Repeat CT scan 6 months post radiotherapy showed stable lung findings. Examination of the breast skin revealed excellent cosmetic results.
|
pmc-6159306-1
|
A 34-year-old Caucasian female, who had originally undergone an uneventful laparoscopic adjustable gastric band 4 years ago, presented to the bariatric surgery clinic with inability to tolerate solids. A work-up revealed that the laparoscopic band remained in good position but the patient had oesophagitis and gastritis, causing swelling of the mucosa at the band site. The fluid was removed from the reservoir, and the patient was treated conservatively with anti-reflux medication and a full liquid diet. After 2 weeks of treatment the patient’s symptoms improved. After careful consideration, she wished to undergo revisional surgery converting the laparoscopic adjustable gastric band to a laparoscopic vertical sleeve gastrectomy. The patient moved through the appropriate multidisciplinary team approach and was found to be an appropriate candidate for surgery. She underwent laparoscopic removal of the adjustable gastric band and conversion to a laparoscopic vertical sleeve gastrectomy without complications. Her post-operative course was uncomplicated and she was discharged on post-operative day 3.
On post-operative day 12, the patient was readmitted to an outside tertiary care hospital for lightheadedness and shortness of breath and was found to have leukocytosis, with white blood cell count of 18,000 cells μl–1. The work-up included a CT scan with intravenous contrast of the chest, abdomen and pelvis, and the patient was diagnosed with a pulmonary embolism. The patient was immediately transferred to our centre for definitive care. When the patient arrived at our centre, the CT films from the outside hospital were reviewed by our radiologists and there was concern that there was air and a faint suggestion of oral contrast outside of the suture line (). Given this finding, an UGI evaluation was ordered. During the early phase, no leak was observed, owing, in part, to the slow passage of 30 ml oral non-ionic contrast (). Some residual contrast from the outside hospital CT was present in the transverse and descending colon. Only after delayed imaging and with administration of additional non-ionic contrast for a total of about 65 ml (approximately 2 h after the start of the fluoroscopic examination) was there a faint suggestion of extravasated contrast, best seen below the left hemidiaphragm (). Follow-up CT scan with oral contrast confirmed the obvious leak ().
The patient was treated definitively with endoscopic stent placement and clipping using an Ovesco clip (Ovesco Endoscopy AG, Tubingen, Germany) to close the leak. After an extended hospital course, she was discharged and is presently doing well.
|
pmc-6159334-1
|
A 62-year-old woman was referred to the authors' hospital for evaluation of a corneal ulcer in her left eye. With the patient's consent, a review of the clinic record was conducted. Ten years previously she received an allogeneic hematopoetic stem cell transplant for treatment of myelodysplasia syndrome. Her course was complicated by the development of cGVHD affecting the liver, skin, esophagus, mouth, and eyes. Severe keratoconjunctivitis sicca had been treated with a PROSE lens for more than 2 years prior to developing this corneal ulcer. Her medical status was compromised by systemic steroid dependence and by steroid induced diabetes mellitus.
After presenting with a corneal ulcer in her left eye, the patient was empirically treated with topical 0.5% moxifloxacin (Vigamox, Alcon) that was applied 6 times a day (once before the PROSE lens was inserted in the morning, 4 times during the day inside of the PROSE lens reservoir, and once again at night after the PROSE lens was removed). After failure to improve on 4 days of this treatment, she was referred to Massachusetts Eye and Ear Infirmary for additional corneal ulcer evaluation, culture and modification of treatment. Upon presentation, the central cornea was opaque and neovascularized with tissue loss of approximately 60% of the corneal thickness. There was an epithelial defect that measured 2.5 mm by 1 mm, with an underlying 2 mm by 1 mm infiltrate. Microbiological smears and cultures were performed with the specimen from corneal scraping. No bacteria or fungi were evident with Gram stain or Calcofluor white stain. At the time, frequency of application of topical moxifloxacin was increased to every 2 hours while awake (approximately 8 times per day), delivered as one drop added to the PROSE reservoir after removal and cleaning reinsertion of the device and replenishment of the reservoir with preservative free saline (B).
Four days after culture and modification of antibiotic delivery regimen, the corneal ulcer resolved, with re-epithelialization of the cornea surface and resolution of the infiltrate. A strain of E. coli cultured from the lesion in 5% sheep blood agar media exhibited resistance to fluoroquinolones, trimethoprim/sulfamethoxazole and ampicillin and ampicillin-sulbactam according to breakpoints set by the Clinical Laboratory Standard Institute-CLSI (). The strain carried multiple single point mutations in the quinolone resistance-determining region (QRDR) of gyrA (Ser83Leu, Asp87Asn), parC (Ser57Thr, Ser80Ile) and parE (Leu416Phe) genes. These mutations were correlated with varying levels of resistance to the fluoroquinolones: ciprofloxacin (MIC 256 μg/mL), levofloxacin (8 μg/mL) and moxifloxacin (16 μg/mL), as determined by reference broth microdilution.
|
pmc-6159344-1
|
A 57-year-old male presented to his General Practitioner with 15 months history of progressive fatigue, dyspnoea and numbness over the soles of his feet. Test results showed evidence of hypothyroidism. His chest x-ray showed significant global cardiomegaly, and he was subsequently referred to a cardiologist for the management of his myopericarditis, which necessitated drainage of pericardial effusion. Electrocardiogram showed sinus rhythm rate 80 beats per minute with low voltage complexes in the limb leads and voltage criteria for left ventricular hypertrophy (LVH). Post-drainage echocardiogram appeared characteristic of an infiltrative process. There was moderate concentric LVH with septal hypertrophy (IVSd 1.6 cm) and moderate global hypokinesis of the left ventricle, and an ejection fraction of 25–30%. The right ventricle was moderately dilated, with mildly reduced systolic function. Both atria were mildly dilated. Cardiac MRI showed high normal left ventricular (LV) size with severely increased LV mass, global hypokinesis and moderate hypertrophy with no inflammation or oedema on short-tau inversion recovery (STIR). In addition, there was impaired biventricular systolic function, moderate bi-atrial dilatation, normal native myocardial T1, mildly raised extracellular volume (ECV) 0.36 and diffuse subendocardial late gadolinium enhancement. Moreover, perfusion scan showed severe circumferential inducible ischaemia and transmural fibrosis in the lateral wall at basal and mid ventricular level post-godolinium. An abnormal appearance of the liver and spleen were also noted incidentally; suggestive of iron overload, and there was extensive mediastinal and bi-hilar lymphadenopathy. Coronary angiography, undertaken four months later, showed 70% stenosis over the left anterior descending artery.
These findings were initially attributed to amyloidosis; however, this diagnosis was not supported by further evalautions. Serum amyloid P component (SAP) scintigraphy showed no visceral amyloid uptake. Technetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) scintigraphy showed no cardiac uptake (ruling out transthyretin cardiac amyloidosis). Additionally studies did not reveal evidence of plasma dyscrasia, and skeletal survey, and bone marrow and trephine biopsy were normal. Ultrasound studies showed diffusely enlarged thyroid glands, thick isthmus with no lymphadenopathy. Fat pad and myocardial biopsies were negative for infiltrative disease; although there were signs of myocyte hypertrophy and patchy fibrosis.
Past medical history revealed perforated right eardrum, two previous varicose veins surgeries and bilateral hip osteoarthritis. He had a ceramic-on-ceramic right total hip replacement 10 years prior to presentation, with revision to a metal-on-polyethylene prosthesis eight years later. Over a period of two years thereafter he began to develope fatigue, poor memory and inattention, increased dizziness and incoordination, nausea, deterioration in vision and hearing, vertigo and tinnitus, pain and numbness over his lower extremities. The complexity of clinical presentation and lack of a unifying diagnosis prompted a referral to the Inherited Metabolic Diseases Unit (IMDU) for investigations. There was no family history of note.
Prior to IMDU referral, patient was also evaluated independently for polycythaemia; and testing was negative for JAK2 mutations. Blood film showed mild persistent eosinophilia with degranulation. RBC (6.30 × 1012/L; reference range 4.50–5.50), haemoglobin (189 g/L; 13.0–18.0), and haematocrit (0.572 L/L; 0.400–0.500) were elevated. Autoimmune screen was negative, apart from elevated antinuclear antibody of 320 titre (<80) with a speckled pattern. Anti-double stranded DNA was 10 (elevated). The significance of these findings was uncertain. Evaluations for polyneuropathy also failed to disclose the underlying cause. Nerve conduction studies showed evidence of severe motor-sensory axonal/demyelinating polyneuropathy involving the lower extremities. The upper extremities showed normal conduction velocities with a degree of mild carpal tunnel syndrome on the right.
Physical examination revealed significant peripheral neuropathy, impaired joint-position sense and absent tendon reflexes on his lower limbs. Abdominal examination showed palpable liver and spleen edges with firm consistency. He had hepatosplenomegaly, bilateral sensorineural hearing loss and bilateral visual impairment.
Biochemistry test results showed serum lactate of 3.8 mmol/L (0.5–2.2 mmol/L). Urine organic acid screen showed mild increases in excretion of tricarboxylic acid cycle intermediates and 2-ethylhydracryllate; suggestive of primary or secondary mitochondrial dysfunction. There were also slight increases in excretion of 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate suggestive of liver dysfunction. Serum amino acid profile was normal. Acylcarnitine profile showed slight increase in hydroxybutyrlcarnitine and tetradeceneoylcarnitine that may reflect ketosis. Serum Brain Natriuretic Peptide was 141 ng/L (<135). Creatine kinase was 61 IU/L (44–272 IU/L) and lactate dehydrogenase was raised at 325 IU/L (120–220 IU/L).
Molecular genetic analysis for suspected mitochondrial disease was undertaken and negative for 3243A > G mutation.
Patient developed further visual problems, which led to a referral to the Ophthalmology Unit. Eye electrophysiology showed poor macular and central retinal function evidenced by absent pattern retinal electrogram (PERG) response, consistent with a mild cone/rod dystrophy or macular dystrophy with mild pan-retinal involvement. There was no evidence of cataract.
Subsequently, he presented to the Emergency Department with severe right sided hip pain and inability to weight bear Right hip X-ray reported high density material surrounding the right hip joint and overlying the right iliac bone, possibly representing extruded orthopedic cement. CT of his right hip showed significant volume of high density homogenous material in the right iliopsoas bursa, anterior to the acetabulum and surrounding the greater trochanter. Small bony bodies and free air were noted. In comparison to the CT scan performed 7 months previously, the observed extrusion into the right iliopsoas bursa was new. Pelvic MRI was performed and confirmed high density collection lateral to the right proximal part of the femur, and medial to the right ilium suggesting metallic content. CT-guided right periprosthetic fluid drainage was undertaken, with 150 ml of black fluid aspirated within the right ilipsoas muscle collection and another 100 ml of black fluid aspirated from the right greater trochanter collection. A total of 300 ml of black fluid was aspirated from around the right hip arthroplasty.
The diagnosis of metallosis was considered. Preoperatively, plasma cobalt concentration (903.32 μg/L; reference range 0.1–0.4) and chromium (71.32 μg/L; <0.5) were found to be markedly elevated. Six months post right hip prosthesis removal the concentrations had declined but were still above the threshold recommended by Medical Health Regulatory Authority; cobalt concentration was 61.72 μg/L and chromium 23.97 μg/L. However, patient reported feeling better, without further deterioration of his vision and peripheral neuropathy. Hearing test showed a severe sensorineural hearing loss that stabilised.
Two years later his repeat plasma lactate, plasma acylcarnitines and urine organic acids were unremarkable.
|
pmc-6159349-1
|
A 32-year-old woman was admitted to our hospital with progressive edema. She had a history of photosensitivity, malar rash, and oral ulcers from childhood. She presented with amenorrhea 6 months after normal childbirth. A home pregnancy test was positive and she visited a local hospital 2 months prior to her admission. She was diagnosed with a miscarriage by sonography that showed no fetal sac. She developed progressive edema from 1 month (weight gain of 4 kg) prior to her admission. The clinical course after admission is shown in .
On admission, her body temperature was 36.9 °C, blood pressure 138/89 mmHg, and the pulse rate 99 beats/minutes with a regular rhythm. A physical examination showed no malar rash or oral ulcers. There were moderate edemas on the face and both legs. No crackles were audible in the chest, and the heart sounds were normal. The liver and spleen were not palpable.
Her erythrocyte count, hemoglobin level, leukocyte count (lymphocytes 6.2%), and platelet count were 479 × 104/µL, 14.2 g/dL, 14,000/µL, and 18.2 × 104/µL, respectively. Urinalysis showed proteinuria with mild hematuria. Total urinary protein level for 24 hours was 4.0 g. Her serum total protein was 4.5 g/dL, albumin 2.1 g/dL, blood urea nitrogen 16.1 mg/dL, creatinine 0.46 mg/dL, lactate dehydrogenase 245 U/L, haptoglobin (2-1 type) 172 mg/dL, C3 94 mg/dL, C4 11 mg/dL, and CH50 44 U/mL. Tests for antinuclear and anti-dsDNA antibodies were negative, but the concentration of anti-cardiolipin IgG antibody was 23.4 U/mL (normal < 10 U/mL). Serological tests for rheumatoid factor, human immunodeficiency virus, hepatitis B virus, and hepatitis C virus were negative.
Computed tomography (CT) revealed bilateral pleural effusion, ascites, and swelling of the uterus with low-density areas.
Due to the presence of nephrotic syndrome, a renal biopsy was performed. Light microscopy showed thickened glomerular capillary walls with lumina occluded by thrombus-like structures and a double-contour appearance along the glomerular capillary walls (A, B). There was mild mesangial expansion and proliferation. Tubulointerstitial structures were preserved, and there were no apparent vascular changes. Immunofluorescence microscopy showed 2+ staining for IgM, IgA, and fibrinogen, 1+ staining for C1q, and 0.5+ staining for IgG, κ, λ, and C3 along the glomerular capillary walls (C). Electron microscopy showed large aggregates in the glomerular capillary lumina as well as expansion of the glomerular subendothelial space with amorphous electron-dense aggregates, but no deposits in the mesangial area. There were no alterations of the podocyte foot processes (D).
Considering her previous history that consisted of lymphopenia, renal disorder, and positive anti-cardiolipin IgG antibody, an initial diagnosis of systemic lupus erythematosus was made according to the 2012 SLICC criteria [8]. Since renal biopsy showed a thrombotic microangiopathy (TMA)-like glomerular lesion, antiphospholipid syndrome (APS) was suspected. She was initially treated with prednisolone, beraprost sodium, and warfarin. Although the progressive edema decreased, proteinuria (~ 2 – 3 g/day) persisted.
Based on the abnormal CT findings of the uterus, her serum human β-subunit of chorionic gonadotropin (β-hCG) level was measured. The results showed that the level had increased to 289.2 mIU/mL (normal < 0.5 mIU/mL). Endometrial cytology showed proliferation of intermediate trophoblasts with abnormal cell nuclei. Endometrial curettage was performed, and methotrexate therapy was initiated. Since the pathological diagnosis was an exaggerated placental site and her serum β-hCG level had decreased to 87.9 mIU/mL, she was followed up at our outpatient clinic 1 month after chemotherapy.
However, follow-up imaging studies revealed abnormal uterine findings suggestive of a trophoblastic tumor. Total hysterectomy was performed 9 months after her first admission. A pathological examination showed that the tumor was primarily composed of a population of intermediate trophoblastic cells. The tumor cells that had invaded the myometrium and vessels were strongly positive for human placental lactogen, but weakly positive for hCG. Thus, she was diagnosed with PSTT. Two months after the hysterectomy, her proteinuria disappeared and her serum β-hCG level normalized.
Eight months after the hysterectomy, a follow-up renal biopsy was performed. Light microscopy revealed the disappearance of the TMA-like glomerular lesion (Figure 2E, F). Furthermore, immunofluorescence studies showed negative staining for immunoglobulins, complements, and fibrinogen.
|
pmc-6159545-1
|
An 83 years old female was admitted in 2012 to the Peruvian Naval Hospital, Centro Médico Naval ‘Cirujano Mayor Santiago Távara’ (CEMENA), in Lima, Peru, with complaints of low back pain, vomiting and intestinal obstruction. The patient had a history of high blood pressure, type 2 diabetes mellitus, chronic renal disease and multiple urinary tract infections. In addition, she had a prolapsed bladder with a prior history of hysterectomy. At the time of admission, the patient was taking loperamide, amlodipine and ranitidine.
As part of her initial work-up, a midstream urine sample was collected and sent to the local CEMENA laboratory for routine urine culture. P. aeruginosa was isolated and initial antibiotic susceptibility testing showed it to be sensitive to imipenem. The clinicians started a course of meropenem at 500 mg IV q12h based on her renal function, but the patient did not improve. After 5 days, a second urine culture was performed, isolating P. aeruginosa that was now resistant to imipenem. She was then changed to renaldosed fosfomycin at 0.8 g IV q12h with noted improvement and clearance of her infection.
The second P. aeruginosa isolate was sent to the Naval Medical Research Unit No. 6 (NAMRU-6) in Callao, Peru (coded as MIS1668) for confirmation and further molecular characterization. The isolate was confirmed as P. aeruginosa by routine biochemical algorithms and antimicrobial susceptibility testing (AST) was performed using the automated Phoenix System (BD Diagnostics). MIC results were interpreted using the Clinical Laboratory Standards Institute guidelines (CLSI M100-S23) []. The isolate was found to be resistant to all antibiotics on the NMIC/ID-124 Phoenix panel (). Additional antibiotic susceptibilities were tested using the disk diffusion test (DDT) for colistin 10 µg, imipenem 10 µg, and ticarcillin–clavulanic acid 75/10 µg, with only sensitivity to colistin exhibited, thus meeting the criteria for an extensively drug-resistant (XDR) isolate according to the international guidelines [].
Since the MIS1668 isolate was carbapenem-resistant, we used the modified Hodge test (MHT) assay to screen for carbapenemase activity with Klebsiella pneumoniae ATCC 700603 []. A P. aeruginosa harboring the blaIMP-16 gene and P. aeruginosa ATCC 27853 were also used as positive and negative controls, respectively. Surprisingly, MIS1668 was determined to be negative for carbapenemase activity by MHT (a). Thus, we subsequently characterized the isolate using the disk diffusion synergy test (DDST) using EDTA disks with imipenem, meropenem and ceftazidime disks placed 15 mm center-to-center of each disk using the method described by Radice et al. []. Although MHT was negative, DDST showed synergy when subjecting the isolate to all disks (b), indicating the presence of an MBL enzyme being inhibited by chelation of the metal ion required for activity by the added EDTA. Synergy between imipenem and ceftazidime was observed only in the presence of the EDTA disk, a pattern similar to activity exhibited by the GES enzyme (c) [].
To further characterize the carbapenem-resistance activity, we performed a combination of multiplex PCR to detect bla genes with primer sets for the MBLs (IMP, VIM, NDM), serine-carbapenemase KPC, and for other beta-lactamases (TEM, SHV, OXA, GES, VEB, PER and CTX-M) using the primers listed in . The series of multiplex PCRs clearly demonstrated positive bands for blaVIM, blaGES and blaOXA-1-like from the P. aeruginosa MIS1668 isolate with band sizes consistent with those of the controls (). Subsequently, we used Sanger-based sequencing (Applied Biosystems) of the amplicons followed by blast search of the sequences to confirm the blaVIM-2, blaGES-1 and blaOXA-1 gene variants (Table S1 available in the online version of this paper). Finally, we used the Diversilab Rep-PCR method (Biomerieux) to detect homogenous DNA regions in the bacterial genome to the reference strain ATCC 27853 and found the MIS1668 isolate to be 94.1 % homologous.
|
pmc-6159546-1
|
A 4 year-old female fiery-shouldered conure (Pyrrhura egregia) was submitted to the diagnostic service at the Faculté de médecine vétérinaire for post mortem examination in September 2015. The animal was bought in December 2014 from a breeder located in Ontario, Canada. The animal travelled by air to Montréal, Québec, Canada, where quarantine was established for 30 days. The new owner noted brittle feathers, but the overall behavior was normal. The new owner’s farm consisted of breeding pairs from different species (conures, amazon parakeets). The animal was housed in a controlled environment with adequate ventilation and temperatures. Cages were cleaned every 4 days with a mixture of water and vinegar. Recycled paper was used as litter. Birds had unlimited access to water and dry food (Roudy Bush). Couscous, fresh fruits and fresh vegetables were available 5 h a day. The animal was newly introduced in the owner’s farm with a male from the same species previously purchased in Québec, Canada. No breeding was reported before death. Overall, the animal health surveillance program was minimal and consisted mainly of weighing the animal twice a year. No significant weight loss of the bird was reported prior to its sickness. The owner reported that the animal was drowsy and presented labored breathing when resting over a period of one week and it died before its physical examination could be conducted or a blood sample could be collected.
The animal’s body was in good condition with ruffled feathers on the head, back and distal third of the wings. In the coelomic cavity, the liver was enlarged, with irregular edges and multiple adhesions to the coelomic wall. The liver contained numerous irregular, slightly elevated, white nodules measuring between 0.1 and 0.3 cm in diameter, which were randomly distributed in the parenchyma (). Similar nodules were observed at the surface of the air sacs. The lungs and kidneys were congested.
Tissues were fixed in 10 % buffered formalin, paraffin embedded and cut at 3 µm thickness for microscopic evaluation. The liver was severely infiltrated by macrophages and multinucleated giant cells, forming numerous round, irregular foci which were often centered around eosinophilic material and cellular debris (granulomas) (a, b). The macrophages were large with abundant eosinophilic cytoplasm. There was a mild and multifocal periportal fibrosis with mild biliary duct hyperplasia and lymphohistiocytic infiltration. The liver capsule was slightly edematous and thickened by fibrin. Ziehl–Neelsen staining revealed the presence of numerous intracytoplasmic, acid-fast bacilli in the macrophages and multinucleated giant cells (c). Similar granulomas were also observed in air sacs, kidneys and, rarely, in the vascular walls. Additional lesions included lymphohistiocytic infiltration of the pericardium and peribronchiolar tissue.
Liver tissue was submitted to the molecular diagnostic laboratory of the Faculté de médecine vétérinaire of Université de Montréal for further characterisation of the mycobacterium specimen. First, DNA was extracted from a liver tissue homogenate using the QIAamp DNA mini kit (Qiagen) with the Qiacube apparatus following the manufacturer’s instructions. Thereafter, a polymerase chain reaction (PCR) assay was conducted based on an adapted protocol from Hashimoto et al. which was designed to sequence the 16S ribosomal RNA gene, allowing for the identification of a broad range of mycobacterial species []. The obtained PCR amplicon was sequenced and this sequence was submitted to GenBank’s Basic Local Alignment Search Tool (blast) for comparison. The sequence demonstrated 100 % homology to M. xenopi sequences.
Tissue samples (liver, kidneys and lungs) were submitted for routine bacterial culture. The samples were cultivated on Columbia agar 5 % sheep blood at 35±2 °C with 5 % CO2 to evaluate the possibility of a bacterial infection. Fungal culture was also performed on Sabouraud agar at 30 °C for 21 days. No growth was observed overall.
Frozen sections of the liver, lungs and digestive tract were also submitted to the Laboratoire de Santé Publique du Québec (LSPQ) for mycobacterial isolation to confirm the presence of M. xenopi in the affected lesions. Liver and lung samples were processed at Hôpital Honoré-Mercier’s microbiology laboratory in St-Hyacinthe prior to submission to the LSPQ. Ground pieces of digestive tract (3 ml) were incubated with 0.9 % hexadecylpyridinium chloride (HPC) (Sigma Chemical) at 37 °C for 24 h and then centrifuged at 900 for 30 min. The pellets were collected and re-suspended in sterile water (1 ml). Liver, lung and treated digestive tract samples were incubated in liquid Bactec MGIT 960 system (Becton Dickinson Microbiology Systems) and solid Middlebrook 7H10 agar and Löwenstein–Jensen medium.
Pure and confluent mycobacterial cultures were obtained for the liver and digestive tract samples. Mixed culture was observed for lung tissue containing slow-growing mycobacteria with few Gram-negative bacteria. DNA was extracted using the BioRobot M48 (Qiagen) as per laboratory protocol. Identification was performed by 16S ribosomal RNA (rRNA) gene sequencing. Sequence alignment has shown a 100 % identity with the sequence of the type strain M. xenopi ATCC 19250.
The final diagnosis was consistent with disseminated avian mycobacteriosis due to M. xenopi.
In the four months following the diagnosis, four other birds from the owner’s farm that had died were sampled. PCR assays were conducted on different samples (liver, digestive tract, lungs) for mycobacteria and these were negative.
|
pmc-6159547-1
|
A 70-year-old sexually active African American male with a past medical history of untreated hepatitis C, erectile dysfunction treated with vardenafil, hypothyroidism and hypertension presented to the Louis Stokes Department of Veterans Affairs Medical Center emergency department with a 1 week history of dull, aching pain in the right testicle that had increased in severity the day prior to admission after doing yard work. He denied erythema or pain of the contralateral testicle or penile discharge. He reported haematospermia three times in the preceeding 4 weeks. He reported urinary urgency and frequency the night prior to admission, but had no dysuria, difficulty initiating a stream or haematuria. He also denied pelvic pain or rashes. He had protected intercourse regularly with a healthy single female partner. He reported a remote history of unspecified sexually transmitted infection (STI) that was treated.
On admission, vital signs were relevant for tachycardia to 107 beats min−1. On physical examination, his right testicle was swollen and tender, but non-erythematous with no abnormal masses. His prostate was non-tender and non-enlarged. He had no inguinal lymphadenopathy, no inguinal hernias and no penile discharge. His examination was otherwise unremarkable. His complete blood count was notable for a white blood cell (WBC) count of 40 000 with neutrophil predominance (89.5 %). Prostatic Specific Antigen (PSA) was 6.4 ng ml−1, elevated from 1.0 ng ml−1 1 year prior. Urine culture grew 10 000 c.f.u. normal urogenital flora, while urinalysis showed 13 WBCs per high power field small leukocyte esterase and negative nitrites. PCR identification tests for chlamydia and gonorrhoea from a first-voided urine specimen were negative. Testicular ultrasound showed right epididymitis and orchitis with bilateral hydroceles. The patient developed fever to 39 °C during the admission.
The patient received ceftriaxone, 1 g (to cover community acquired Gram-negative rods and Neisseria gonorrhoeae), and azithromycin, 1 g (to provide double coverage against N. gonorrhoeae as well as Chlamydia trachomatis). Coverage of STIs was given due to a higher STI risk in the veteran population []. The antibiotic regimen was later changed to ciprofloxacin (400 mg iv every 12 h), assuming epididymo-orchitis secondary to enteric organisms. Despite antibiotics, the patient remained febrile. Blood cultures turned positive on hospital day 2, with both sets showing Gram-positive cocci in clusters on Gram staining. The antibiotics were changed to vancomycin (dose adjusted for trough level of 15 mg dl−1) and ceftriaxone (1 g every 12 h), and the fever resolved, while the testicular swelling persisted. A chest x-ray and computed tomographyscan of the abdomen and pelvis were unremarkable. Meanwhile, the WBC count down trended to 22 000 and resolved after 48 h antibiotic therapy. The final microbiology result was of S. haemolyticus sensitive to vancomycin. The patient received intravenous vancomycin for 2 weeks, followed by oral clindamycin (300 mg every 6 h) for 1 week. Repeat blood cultures were negative. A repeat testicular ultrasound prior to discharge demonstrated continued evidence of right epididymo-orchitis, which resolved on follow up ultrasound 3 weeks after discharge.
|
pmc-6160044-1
|
A 60-year-old male who had a history of liver cirrhosis was referred for evaluation of a pain, swelling, and erythematous changes of the anterolateral aspect of his left leg. His symptoms started a month ago without any specific trauma. He had a history of open reduction and internal fixation performed for a tibial plateau fracture that occurred when his left knee was pinned under a tree 18 years ago. He had sciatic nerve injury at the time of the fracture. He had an open reduction and internal fixation as well as a stent insertion in the femoral artery 8 years after the initial trauma due to a distal femur fracture and femoral artery rupture. At that time, a widespread radiopaque mass was observed on plain radiographs of left leg, and obstruction of popliteal artery with abundant collateral circulation was observed on angiography. The patient had no difficulty with his daily life functions until the aforementioned symptoms appeared, except for limited motion in the ankle and toes and sensory reduction in his foot owing to the sciatic nerve injury.
After admission, the patient maintained with a long leg splint. Two weeks after the admission, the erythematous changes in the left leg localized to the anterior aspect in the middle of the leg and formed a fluid-filled, erythematous mass. A draining sinus had developed on the erythematous mass spontaneously and a thick fluid with a chalk-like material was discharged through the shiny skin via the sinus. The range of motion of the knee was 0 degrees to 100 degrees of flexion; ankle dorsiflexion was 0 degrees, ankle plantar flexion was 5 degrees, and all of the toes had clawing deformity. As for the motor strength of the ankle, the dorsiflexion was grade 0 and plantar flexion was grade 3. He had no sensation in the first web space and on the medial aspect of the foot, and had sensory reduction in the lateral, dorsal, and plantar aspects of the foot, in order of decreasing sensation.
The radiographs of the left leg taken 10 years ago (8 years after the initial trauma) showed a large, fusiform-shaped, radiopaque soft tissue mass in the space between the tibia and fibula that spanned from 5 cm below the proximal tibio-fibular articulation to just above the distal tibio-fibular articulation. The medial cortex of the middle third of the fibula and the posterior cortex of the distal third were sclerotic. Ten years later (18 years after the initial trauma), the patient's radiographs showed a large, fusiform-shaped soft tissue mass with extensive plaque-like and amorphous calcifications, similar to those seen in the radiographs taken 10 years earlier (Fig. ). Furthermore, we observed that calcification within the fusiform mass and in the distal part of the deep posterior compartment had increased in comparison to that seen in the radiographs taken 10 years earlier. The erosion of the medial and posterior parts of the distal two-thirds of the fibula had also increased, and a sclerotic change in the lateral cortex of the middle third of the tibia was newly observed. We performed a computed tomography (CT) scan to examine the pattern and distribution of the calcifications more closely; peripherally distributed calcification was found in the anterior compartment and in the distal part of the deep posterior compartment, and sclerotic changes were found in the tibial and fibular cortex (Fig. ). There was evidence of increased uptake between the tibia and fibula in the delayed bone phase on 3 phases of bone scan, which was determined to be caused by calcification.
Laboratory investigations revealed that the erythrocyte sedimentation rate (ESR) was 69 mm/h and the C-reactive protein (CRP) level was 5.80 mg/dL with no fever. Serum calcium, phosphorous, and alkaline phosphatase levels were all within the normal limits.
We performed an incisional biopsy to differentiated soft tissue sarcoma and no viable, malignant cells were found. A thick fluid with a chalk-like material continued to be discharged through the sinus opening. We performed an extensive debridement of the anterior and deep posterior compartments to ensure definitive treatment. Intraoperative findings showed that the deep fascia was thickened, and that the tibialis anterior, extensor hallucis longus, and extensor digitorum longus muscles had become necrotic and changed into a whitish, toothpaste-like material (Fig. ). Hard calcific materials resembling rice grains were spread within the necrotic muscle. Furthermore, we observed an erosion of the cortex without intramedullary involvement on the lateral tibial surface and medial fibular surface. After an en-block resection of the anterior compartment, we approached the posterior compartment through the interosseous membrane. When we opened the interosseous membrane, the turbid fluid was drained, and we found that the flexor hallucis, flexor digitorum, and tibialis posterior muscles formed a twig-shaped, hard calcification in the direction of the muscle fibers, unlike in the anterior compartment (Fig. ). Upon performing extensive debridement, we inserted a drain tube and performed primary closure. As Pseudomonas aeruginosa was identified in the intraoperative culture, we used antibiotic treatment (piperacillin-tazobactam, intravenously for 6 weeks and then ciprofloxacin, orally for 4 weeks). The fluid continued to be discharged through the drain even after the surgery; delayed wound healing occurred four weeks following the surgery, and there was no recurrence and the patients were satisfied with the result of the operation at follow-up conducted 2 years later (Fig. ).
Pathologic evaluation revealed that the anterior compartment specimen had acute and chronic inflammation with dystrophic calcification, and the posterior compartment specimen had fibrosis with dystrophic calcification; the tibial periosteum had acute and chronic inflammation with dystrophic calcification, and the tibial bone was fibrotic. These findings led to the diagnosis of calcific myonecrosis.
|
pmc-6160050-1
|
Case 1 is a 44-year-old male with no significant medical history before being diagnosed with HCV genotype 1b in 2014 (Table ). Before starting our treatment, his viral load was 10,400,000 IU/mL. The strategy SOF+RBV+PEG-IFN was given. The course of treatment was 12 weeks. He had a rapid virological response (RVR) with undetectable viral load at week 4 that remained undetectable for the remainder of 10 weeks of SOF-based triple therapy. The strategy SOF+RBV+PEG-IFN was stopped after the 12-week therapy. A sustained virologic response (SVR) was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-2
|
Case 2 is a 40-year-old female with Hashimoto thyroiditis before being diagnosed with HCV genotype 6 in 2014 (Table ). This patient was previously taken no treatment. Before starting our treatment, his viral load was 17,000,000 IU/mL. For the consideration of uncontrolled Hashimoto thyroiditis, PEG-IFN was not suitable for her. The strategy SOF+RBV was given for 24 weeks. She had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 20 weeks of SOF+RBV therapy. The strategy SOF+RBV was stopped after the 24-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-3
|
Case3 is a 44-year-old male with no significant medical history before being diagnosed with HCV genotype 1b in 2007 (Table ). Before starting our treatment, his viral load was 1,970,000 IU/mL. The strategy SOF+RBV+PEG-IFN was given. He had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 10 weeks of SOF-based triple therapy. The strategy SOF+RBV+PEG-IFN was stopped after the 12-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-4
|
Case 4 is a 24-year-old female with hypothyroidism before being diagnosed with HCV genotype 1b in 2014 (Table ). Before starting our treatment, her viral load was 828,000 IU/mL. The strategy SOF+RBV was given. Her had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 20 weeks of SOF+RBV therapy. The strategy SOF+RBV was stopped after the 24-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-5
|
Case 5 is a 49-year-old male with hyperthyroidism before being diagnosed with HCV genotype 1b in 2013 (Table ). Before starting our treatment, his viral load was 2,790,000 IU/mL. The strategy SOF+RBV+PEG-IFN was given. He had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 10 weeks of SOF-based triple therapy. The strategy SOF+RBV+PEG-IFN was stopped after the 12-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-6
|
Case 6 is a 29-year-old male diagnosed with HCV genotype 1b in 2014. He was a patient with hyperthyroidism in March 2015 (Table ). When after the treatment I131, he became hypothyroidism. Before starting our treatment, his viral load was 14,000,000 IU/mL. The strategy SOF+RBV was given. Her had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 20 weeks of SOF+RBV therapy. The strategy SOF+RBV was stopped after the 24-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-7
|
Case 7 is a 59-year-old male with diabetes II. He was diagnosed with HCV genotype 2 in 2015 (Table ). Before starting our treatment, his viral load was 99,400 IU/mL. The strategy SOF+RBV was given. Her had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 10 weeks of SOF+RBV therapy. The strategy SOF+RBV was stopped after the 12-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-8
|
Case 8 is a 69-year-old female with no significant medical history before being diagnosed with HCV genotype 1b in 2007 (Table ). Before starting our treatment, her viral load was 15,000,000 IU/mL. The strategy SOF+RBV+PEG-IFN was given. He had a RVR with undetectable viral load at week 4 that remained undetectable for the remainder of 10 weeks of SOF-based triple therapy. The strategy SOF+RBV+PEG-IFN was stopped after the 12-week therapy. A SVR was observed. The viral load remained undetectable until SVR24 (Table ).
|
pmc-6160050-9
|
Case 9 is a 61-year-old female with hypertension and cirrhosis. She was diagnosed with HCV genotype 1b in 2014 (Table ). This patient received no treatment previously. Before our treatment, her viral load was 2,990,000 IU/mL. The strategy SOF+RBV+ PEG-IFN was given for 12 weeks. She had a RVR with undetectable viral load at week 4 that remained undetectable for the rest of 12 weeks of therapy. But the virus relapsed in SVR4 and was still uncontrolled in SVR12 (Table ). The treatment failed. The patient quitted our research and turned to another therapy.
|
pmc-6160055-1
|
A 43-year-old female patient underwent skin-sparing mastectomy (Fig. ). A pedicled TRAM flap was performed to reconstruct the breast mound, and a modified C-H flap was used for the 1-stage nipple reconstruction. No complications were observed. The final height of the reconstructed nipple was similar to that of the contralateral nipple.
|
pmc-6160055-2
|
A 46-year-old female patient underwent skin-sparing mastectomy (Fig. ). A pedicled TRAM flap was used for the breast mound reconstruction, and the nipple was reconstructed with a modified C-H flap in 1 stage. No complications were observed. The height of the reconstructed nipple 1 year postoperatively was similar to that of the contralateral nipple.
|
pmc-6160058-1
|
A 35-year-old woman presented with a 1-year history of a progressively growing painless mass in the left temporal area. Physical examination revealed a firm, nontender palpable mass in the left temporal area just superior to the zygomatic arch. The lesion exhibited no superficial ulceration or cutaneous erosion. All laboratory data were normal. Initial work-up with ultrasound (US) (Accuvix XG; Medison, Seoul, Korea) revealed a somewhat ill-demarcated, lobulated hypoechoic mass 3.0 × 2.5 × 1.5 cm in dimensions located subcutaneously in the left temporal region (Fig. A). Color Doppler US revealed moderate internal vascularity, without pulsatility (Fig. B). To further evaluate the lesion, the patient was examined using a 3.0-Tesla MR scanner (Verio; Siemens, Erlangen, Germany) 10 days later. The mass yielded a hypointense-to-isointense signal relative to that of the adjacent muscles on T1-weighted imaging (Fig. A), and a heterogeneous mixture of isointense and hyperintense signals (with a central dark spot) on T2-weighted imaging (Fig. B). After intravenous administration of gadolinium contrast material, the mass exhibited heterogeneous intense enhancement with the nonenhancing portion indicating internal necrosis (Fig. C). The mass was located in the left temporal scalp, between the temporal fascia and the temporalis muscle, and had a multilobulated margin. T2-weighted and contrast-enhanced imaging revealed diffuse, high-level signaling abnormalities extending from the mass into the surrounding soft tissue, spreading along the temporal fascia and the temporalis muscle. However, there was no evidence of bone or bone marrow involvement.
On the basis of the clinical and radiological characteristics, the lesion was considered to be a malignant tumor originating from soft tissue. An incisional biopsy was performed. Histologically, the tumor cells were aggregated in nodules exhibiting central necrosis, thus appearing pseudogranulomatous in nature (Fig. A). The tumor cells were epithelioid, with abundant eosinophilic cytoplasm, vesicular chromatin, and small nucleoli (Fig. B). Immunohistochemical analysis showed that the tumor cells stained positive for both mesenchymal markers [smooth muscle actin (Fig. C) and cluster of differentiation (CD) 34 glycoprotein (Fig. D)] and epithelial markers [cytokeratin (CK) (Fig. E) and epithelial membrane antigen (EMA) (Fig. F)]. The tumor cells were not immunoreactive for CD 31, S-100 protein, Melan-A, MyoD1, desmin, or CD 68. The lesion was pathologically diagnosed as an epithelioid sarcoma.
18F-fluorodeoxyglucose positron emission tomography/CT (18FDG-PET/CT) (Biograph Truepoint 40; Siemens, Berlin, Germany) was used to stage the tumor and revealed focally intense FDG uptake (Fig. ) but no regional lymph node or distant metastasis. The patient underwent total surgical resection of the tumor followed by postoperative irradiation. In cross-section, the tumor was a pale gray solid mass containing hemorrhagic and necrotic portions. There was no evidence of recurrent disease during the follow-up period of 18 months. The present study was approved by the institutional review board of Chonbuk National University Hospital and written informed consent for the publication of the case was obtained from the patient.
|
pmc-6160060-1
|
A 77-year-old man presented with an 11-day history of back pain, bilateral lower extremity pain, and numbness at the back of the right foot. He was transferred to our hospital by ambulance because of exacerbation. He had received anticoagulant and antiplatelet therapy after extrasystole and brain infarction for 2 years. There was no history of trauma or any invasive procedure. Walking gait was stable with the use of a stick. Neurological examination showed no abnormality except for a positive result in the straight-leg-raising test for the right leg. Laboratory data did not indicate coagulopathy-related diseases. We used a previously published protocol for differential diagnosis (Table ).[ Magnetic resonance imaging (MRI) was performed 7 days after the first medical examination, and it showed a spinal SDH extending from L4 to S1 (Fig. ). The hematomas showed high signal intensity on T1-weighted imaging and low signal intensity on T2-weighted imaging 18 days after symptom onset. The patient was treated conservatively as his neurological symptoms were not severe. We stopped anticoagulant and antiplatelet therapy, and his pain and numbness gradually improved However, 30 days after the onset of lumbar symptoms, he began experiencing tinnitus and optical illusions. Brain computed tomography (CT) showed a chronic cranial SDH and midline shift (Fig. ). Burr-hole evacuation was performed, and his condition improved. Forty days after the surgery, brain CT showed SDH recurrence at the same location. He thus underwent another burr-hole evacuation. At 5 months of follow-up, there was no recurrence of the spinal or intracranial SDH (Fig. ). The patient has provided informed consent for publication of the case.
|
pmc-6160082-1
|
A 40-year-old woman working as bank clerk was admitted to the Hematological Medicine division of our hospital. She presented with oral cavity and nose mucosal bleeding and muscle hematoma on both legs associated with homolateral painful knees that had lasted for 14 days. She denied any prior personal or family history of bleeding or clotting disorders. She had 2 artificial abortions, and one abdominal delivery without significant bleeding. Three days prior to the appearance of bleeding, she had been prescribed cephalosporin and proton pump inhibitors for 2 days due to abdominal pain and diarrhea. Upon admission, coagulation tests showed a severely prolonged activated partial thromboplastin time (aPTT) (107.4 seconds; reference value: 24.9–36.8 seconds) with normal prothrombin time (PT) and thrombin time (TT). Laboratory investigations revealed severe anemia (HGB: 49 g/L) and thrombocytopenia (PLT: 31 × 109/L). Plasma bilirubin levels were normal and reticulocyte percentage was 1.4% (reference value: 0.5%–1.5%). Serum B12 and red cell folate concentrations were both within normal limits. Additional tests revealed that FVIII:C was 1% (reference value: 50%–150%), FIX:C was 130% (reference value: 50%–150%), FVIII inhibitor (FVIII:I) was 210 BU/ml (reference value: <0.6). The direct antiglobulin (Coombs) test was negative, platelet associated antibody IgG is positive, and Lupus anticoagulants (LAC) were negative. Complement levels were reduced (C4: 0.06 g/dL; reference value: 0.16–0.38 g/L, C3: 0.70 g/L; reference value: 0.79–1.52 g/L). Because this patient was a woman of child-bearing age who was likely to contract connective tissue disease (CTD), we also suspected she might be a CTD patient, particularly systemic lupus erythematosus (SLE). Therefore, we performed an autoimmune screen for CTD, including antinuclear antibodies, antidouble stranded antibody, extractable nuclear antigen (ENA) polypeptide antibody, antineutrophil cytoplasmic antibodies, antiphospholipid antibody and antithyroid antibody, all of which were normal. Virology tests for HIV, HPVB19, EBV, CMV, and hepatitis virus were all negative. A pectoral-abdominal computed tomography (CT) scan did not detect infection or tumor. In the end, the patient was diagnosed with AHA along with immune thrombocytopenia and blood-loss anemia. For treatment, the patient was initially transfused with packed red-blood cells to improve anemia, as well as with fresh frozen plasma (FFP) and human prothrombin complex concentrate (hPCC) to complement clotting factors. No additional hemorrhaging was observed; however, aPTT remained severely prolonged. As soon as the patient was diagnosed with AHA, she was administered intravenous immunoglobulin (IVIG) at a total dose of 2 g/kg over 5 days and started with oral prednisone at a dose of 1 mg/kg/day. Although the previous bleeding had subsided, and platelet counts gradually rose to near normal level after 2 weeks of treatment, the aPTT of this patient did not appear to shorten. Next, we administered intravenous cyclophosphamide (2.0 mg/kg/day) and continued oral prednisone at 1 mg/kg/day. While the aPTT of this patient remained severely prolonged, platelet counts reached a normal level. At week 3 of cyclophosphamide combined with prednisone treatment, the patient presented with moderate pain in the right shoulder region. An emergency CT was performed which showed the presence of a right shoulder joint hemarthrosis. We suspected the treatment effect of cyclophosphamide combined with prednisone was not satisfactory. We then administered intravenous anti-CD20 monoclonal antibody (Rituximab) treatment at 375 mg/m2 each week with tapering of the prednisone dose to 0.8 mg/kg/day. Following 2 weeks of anti-CD20 monoclonal antibody therapy, the prolonged APPT of this patient began to shorten and her shoulder joint bleeding gradually ceased. After 4 weeks of anti-CD20 monoclonal antibody therapy, both APTT and plasma FVIII were normalized, and the FVIII:I titer became undetectable. The duration of the course of anti-CD20 monoclonal antibody at 375 mg/m2 each week was 4 weeks. Prednisolone was gradually reduced at 10 mg each week until it was discontinued and the duration of prednisolone treatment was approximately 4 weeks. The patient remains in good medical status. There was no relapse during the 3-year follow-up period.
|
pmc-6160237-1
|
A 60-year-old male from Jamalpur district was admitted in Surja Kanta Kala-azar Research Center (SKKRC), Mymensingh with the complaints of progressive non-itching hypomelanotic macular lesions for the last five years. He had a previous history of Visceral Leishmaniasis (VL) 11 years back and was treated with Cap. Miltefosine (50mg) twice daily for 28 days. His general and systemic examinations revealed no other abnormalities. The skin sensation was intact on the affected sites. Both microscopic examination and qPCR of the skin following a positive rK39 test confirmed the presence of LD body and DNA respectively. The patient was then prescribed to take Cap. Miltefosine (Miltefos, Popular Pharmaceuticals Ltd., Batch No.–SGJ02), 100 mg, in two divided doses for 84 days as per national guideline. After taking the drug for 33 days the patient experienced mild pain, increased lacrimation and redness of the left eye followed by photophobia and marked dimness of vision. He was advised to stop the medicine as soon as he contacted SKKRC and was referred to Department of Ophthalmology, Mymensingh Medical College and Hospital (MMCH), where they diagnosed him as a case of Mooren’s ulcer on the basis of visual acuity 3/60, matted eyelashes, congested conjunctiva and 360° peripheral corneal infiltration with ulceration. He was treated with topical antibiotics, steroid and lubricant eye drops. He was eventually treated with multi-dose LAmB without facing any adverse events, after his eye condition went back to normal. On 6 month after treatment follow up, his skin qPCR for LD-DNA was negative and there was no ophthalmic complaint.
|
pmc-6160237-2
|
An 18-year-old male from Fulbaria, Mymensingh district came to SKKRC with progressive maculo-nodular lesions for the last two years. He gave a history of suffering from VL 4 years back for which he was treated with single Dose LAmB. In the beginning, there were only macular lesions on the face and arms, but later nodular lesions started to appear on his chin, cheek, lip, tongue and both hands, feet, and buttock. General examinations revealed no abnormality except the skin lesions over the above-mentioned sites. No hepato-splenomegaly was found and the lesions were non-itching with intact sensitivity. His diagnosis was confirmed through rK39 strip test followed by microscopic examination of skin biopsy confirming the presence of LD bodies. He was also treated with Cap. Miltefosine (Cap. Miltefos, Popular Pharmaceuticals Ltd., Batch No.–SGJ02) following the same protocol as case 1. About a month after having Cap. Miltefosine the patient developed pain and red coloration of the left eye. At first, he went to the local Upazilla health complex (secondary health care facility at the Sub-district level in Bangladesh) where the doctors treated him as a case of conjunctivitis but the condition was not improved and was eventually referred to SKKRC. The doctors at SKKRC stopped his medication and referred him to department of ophthalmology, MMCH. His ophthalmic examination revealed visual acuity—4/60, photophobia, congested conjunctiva, peripheral corneal infiltration extending up to 2 mm of corneal tissue from limbus, involving all the layers of the cornea and he was diagnosed as Marginal keratitis (left). He received specific treatment under the supervision of National Institute of Ophthalmology & Hospital (NIO&H), Dhaka. As soon as he felt better, he was treated with multi-dose LAmB at SKKRC. On 6 month after treatment follow up, his skin qPCR for LD-DNA was negative and there was no ophthalmic complaint.
|
pmc-6160237-3
|
A 16-year-old male from Bhaluka, Mymensingh was admitted to SKKRC with non-itching macular skin lesions all over the body for a year. He had a history of VL seven years back and was treated with Cap. Miltefosine (50mg) twice daily for 28 days and was cured. On examination, the patient was non-febrile, non-anaemic and no hepato-splenomegaly was found. Laboratory investigations revealed he was rK39 positive and LD bodies were found under direct microscopy of skin biopsy. His qPCR for LD-DNA of skin biopsy was also positive. After confirming the diagnosis he was treated as a PKDL case with Cap. Miltefosine, (50mg), (Cap. Impavido, Endo Venturex Limited, Batch No.– 2K5312A) two capsules daily for 84 days. About one and a half month after medication he developed painful, red eye and dimness of the vision along with a white spot in the left eye. He was initially treated by village doctor and continued to take Miltefosine. As the condition worsened, he went to a local eye consultant who diagnosed him as a case of corneal ulcer and treated accordingly. Despite having no progress regarding his complication, he did not contact SKKRC and came for his scheduled follow up after completing the full dose of Miltefosine. The physician at SKKRC immediately referred him to MMCH ophthalmology department for further management. After examination, they found visual acuity 1/60, congested conjunctiva, and peripheral corneal infiltration with ulceration which extends towards the center and presence of hypopyon and was diagnosed as a case of Peripheral ulcerative Keratitis with secondary bacterial infection. Unfortunately it was too late for a recovery and doctors had to go for the evisceration of the eye with baseball implantation. He was further approached to take treatment for PKDL with LAmB but he refused to take any treatment.
|
pmc-6160237-4
|
A 15-year-old male from Gafargaon, Mymensingh was admitted to SKKRC with non-itching papulo-macular skin lesions all over the body for 7 months. He had a history of VL 2.5 years back and was treated with single dose LAmB and got cured. On examination, the patient was non-febrile, not- anemic and no hepato-splenomegaly was found. His rK39 RDT was positive and direct microscopy of skin biopsy showed LD bodies. qPCR for LD-DNA was also positive. After confirming the diagnosis he was treated as a PKDL case with Cap. Miltefosine, (50mg), (Cap. Miltefos, Popular Pharmaceuticals Ltd., Batch No.–SLL 21) two capsules daily for 84 days. About 7 weeks later he developed painful, red eye with watery discharge and dimness of vision along with marginal white discoloration of the left eye. Despite the instructions, he didn’t stop taking the medicines for another two weeks and then contacted the physicians at SKKRC. The physician at SKKRC immediately stopped his medication and referred him to ophthalmology department, MMCH for further management. After examination, they found visual acuity 3/60, congested conjunctiva, and peripheral corneal infiltration which extends towards the center and presence of hypopyon and was diagnosed as a case of Marginal Keratitis. He was treated with topical antibiotics in addition to steroid and lubricant eye drops. He was administered LAmB at SKKRC after recovery from eye complications. On 6 month after treatment follow up, his skin qPCR for LD-DNA was negative and there was no further ophthalmic complaints.
|
pmc-6160237-5
|
34-year-old male from Gafargaon, Mymensingh was admitted to SKKRC with non-itching nodulo-macular skin lesions all over the body for 5 years, with a history of VL 8 years back and was treated with SSG. He was previously treated twice for PKDL by multi-dose AmBisome, but his condition had not improved. On examination, the patient was non-febrile, slightly anemic and no hepato-splenomegaly was found. Laboratory investigations revealed he was rK39 positive and LD-DNA was found by qPCR of skin biopsy. After confirming the diagnosis he was treated as a PKDL case with Cap. Miltefosine, (50mg), (Cap. Miltefos, Popular Pharmaceuticals Ltd., Batch No.–SLL 21) two capsules daily for 84 days. About 3 weeks later he developed a painful, red eye with watery discharge. He immediately contacted physicians at SKKRC and was advised to stop taking the medication and was given steroid eye drops. After a week he recovered from his complications and was treated with multidose LAmB at SKKRC without further complication. On 6 month after treatment follow up, his skin qPCR for LD-DNA was negative and he had no similar ophthalmic complaint.
|
pmc-6160243-1
|
The healthy 31-year-old Japanese woman had suffered from fever (≥38°C) that had lasted for 2 to 3 days along with arthralgia since May 2017. These recurrent attacks completely coincided with the start of her menstrual periods. In September 2017, she presented with a high fever and arthralgia that had occurred at the initiation of her menstruation. The fever attack disappeared once approximately 48 hours after the onset of fever, but the next day she presented a high fever again and was admitted to our department for the evaluation of fever of unknown origin.
On admission, her body temperature was 36.8°C, her blood pressure was 97/68 mm Hg, the heart rate was 97 beats/min, and the pulse oximetric saturation (SpO2) was 98% (room air). On physical examination, she had mild arthralgia without heat and swelling at the joints of both shoulders, elbows, and knees. She had no symptoms suggesting peritonitis or pleuritis, or erysipelas-like skin lesions.
Laboratory investigations showed the following results: white blood cell count 3600/μL (neutrophils 72.8%, lymphocytes 18.9%), hemoglobin (Hb) 12.0 g/dL, platelets 18.6×104/μL, C-reactive protein (CRP) 9.53 mg/dL, ferritin 51 ng/mL (normal range 6.0–138 ng/mL), and serum amyloid A (SAA) 884.5 μg/mL. The serum complement level was normal. No abnormalities were revealed by a urinalysis, and no liver or renal dysfunction was detected.
The following immunologic and serologic results were all negative: rheumatoid factor, antinuclear antibody, proteinase-3 antineutrophil cytoplasmic autoantibodies (PR3-ANCAs), and myeloperoxidase antineutrophil cytoplasmic autoantibodies (MPO-ANCAs). The results of assays of β-d-glucan, T-SPOT.TB, and human parvovirus B19 were all negative. The results of assays of both cytomegalovirus and Epstein–Barr virus showed a pattern of her past infection.
A thoracico-abdominal enhanced computed tomography examination and gallium-67 (67G) scintigraphy revealed no abnormalities. She did not present a high fever after her admission to our department. Her arthralgia also disappeared spontaneously on the 1st hospital day, and the CRP level had decreased rapidly to the normal range. We suspected FMF based on the recurrent and self-limiting fever attacks, and we administered 1.0 mg/d of colchicine for 5 days immediately after the start of her next menstrual period. After this treatment, no further febrile attacks were observed. We finally diagnosed typical FMF on the basis of the Tel Hashomer criteria.[ A subsequent genetic analysis of exons 1, 2, 3, and 10 of the MEFV gene revealed the G304R heterozygous mutation in exon 2 of the MEFV gene.
We excluded other autoinflammatory diseases such as hyperimmunoglobulinemia D with periodic fever syndrome, cryopyrin-associated periodic syndrome, and tumor necrosis factor receptor-associated periodic syndrome based on the patient's medical history, physical findings, and laboratory findings. Her remission has been maintained by intermittent colchicine therapy (1.0 mg/d of colchicine for 5 days at the start of each menstrual period) for over 6 months as of this writing (Fig. ).
We investigated the presence of subclinical inflammation in our patient's case by analyzing her serum cytokines at the attack and remission before the initiation of colchicine. Her levels of IL-1β, -4, -6, and -17 and TNF-α were higher than normal not only at the attack but also at the remission (Table ). Although we recommended a daily continuous administration of colchicine to her to regulate subclinical inflammation, she refused to accept it because intermittent colchicine had improved her symptoms.
|
pmc-6160294-1
|
We report unique wrong implant error occurred during bilateral total knee replacement procedure in 71-year-old woman, known to have bilateral knee osteoarthritis that has failed conservative treatment. Patient reports severe pain in both knees with decreased walking distance. Examination showed full range of motion for both knees, preoperatively. X-ray showed severe bilateral tricompartmental osteoarthritis (
). Patient underwent bilateral sequential total knee replacement (PS, Sigma) in 2013. Postoperative radiographs showed well-fixed femoral, tibial, and patellar components; however, right femoral implant was placed in the left knee instead of left femoral component (
). Postoperative examination showed painless full range of motion 0 to 125 degrees. There was no patellar maltracking. No popping was heard. The patient was informed about this error. She has been following up in the clinic for 5 years. She complains of mild occasional pain but otherwise is functioning well. Knee Society score was 75. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 84 (
).
|
pmc-6160296-1
|
A previously healthy 75-year-old woman presented to her local hospital with a fractured right hip after suffering a fall at home. She was neurologically intact before the fall and denied any history of syncope or lower limb weakness. The following day (Day 2), a right hip hemiarthroplasty was performed. The procedure was uneventful. Soon after the surgery, the patient experienced deterioration of her respiratory status which required biphasic positive airway pressure (BiPAP). Chest X-ray was unremarkable. The patient was noted to have a urinary tract infection on admission and given ceftriaxone. Doxycycline was added empirically for possible community-acquired pneumonia. The following morning (Day 3), the patient was noted to have decreased responsiveness for which she was transferred to the intensive care unit (ICU). Dilaudid was discontinued in light of this worsening drowsiness. Magnetic resonance imaging (MRI) of the brain revealed subacute ischemia in the left basal ganglia and chronic small vessel ischemic disease (Day 3).
An electroencephalogram (EEG) on Day 4 demonstrated focal slowing with sharp bitemporal spikes. Levetiracetam (Keppra, UCB, Brussels, Belgium) was initiated for seizure prophylaxis. The following morning (Day 5), she had worsened to become unresponsive to painful stimuli. The patient was then intubated and transferred to our hospital for further management. Continuous electroencephalogram (EEG) monitoring was initiated. Antibiotic coverage escalated to include acyclovir, ampicillin, and vancomycin. Intravenous (IV) ceftriaxone and IV Keppra were continued. Lumbar puncture revealed normal opening pressure and clear cerebrospinal fluid (CSF). CSF protein and glucose were within normal limits, at 22 mg/dL and 91 mg/dL, respectively. There were no cells seen on CSF microscopy. An increased creatine kinase of 493 U/L and increased thyroid-stimulating hormone (TSH) level of 6.150 mcunit/mL were found on Day 5. She was started on 25 mcg levothyroxine. IV thiamine 500 mg was initiated for chronic alcoholism.
Continuous EEG monitoring did not reveal any seizure activity. Antibiotics were reviewed after the CSF analysis to discontinue vancomycin and acyclovir (Day 6). Her pupils were 3 mm in diameter in the right eye and 2 mm in diameter in the left eye, which prompted a repeat computed tomography (CT) of the head, which did not reveal any new findings (Day 6). Brain MRI was repeated on Day 7 and revealed multiple punctate foci of diffusion restriction in the gray-white junction (Figure ). Magnetic resonance angiography (MRA) was significant for chronic occlusion of the right internal carotid artery with distal middle cerebral artery reconstitution. Cerebral fat embolism (CFE) syndrome was suspected. Brain oxygen partial pressure (PbtO2) monitoring via Licox (Integra LifeSciences, Plainsboro, NJ, US) was initiated to optimize cerebral perfusion (Day 8). Subdural bolts were placed for continuous intracranial pressure monitoring via Camino (Integra LifeSciences, Plainsboro, NJ, US). Transthoracic echocardiogram (TTE) revealed no thrombus or a patent foramen ovale (Day 9). Patient’s sensorium improved with the eye opening in response to painful stimulus and was extubated (Day 9). She required bronchodilator therapy after extubation. Modified barium swallow demonstrated impaired pharyngeal clearing (the patient required 3-5 swallows to clear each bolus) and she was kept nil per os (NPO) (Day 12). She required 2L/min oxygen via nasal cannula to maintain saturation. Intracranial pressure monitoring and PbtO2 monitoring were discontinued once cerebral oxygenation and intracranial pressure were within physiological limits. She remained drowsy post-extubation. She opened her eyes to verbal stimuli but did not speak coherently. Her sensorium improved gradually and passed modified barium swallow (Day 15). She was discharged the following day (Day 16).
|
pmc-6160297-1
|
A 68-year-old gentleman with a 20-year history of idiopathic Parkinson’s disease with bilateral subthalamic nucleus deep brain stimulation (left 2-, 1+ amplitude=2.0mV, pulse width=60 microseconds, frequency=130Hz, right 11-, C+ amplitude=1.0mV, pulse width=60 microseconds, frequency=130Hz) was evaluated for Duopa due to worsening dyskinesia. His medications included amantadine 100 mg three times a day and carbidopa-levodopa four to six tablets crushed and infused three times a day over four hours through a G-tube. He had a history of idiopathic sensorimotor axonal polyneuropathy (baseline pain in his feet 3/10 on a visual analog scale). A nerve conduction study done two years ago showed right sural amplitude 2.5 uV, left sural amplitude 2.0 uV (normal > 5 uV), radial sensory 38.0 uV (normal > 15uV), peroneal motor 2.0 mV (normal > 2.5 mV). Neuropathic pain was managed with 300 mg gabapentin once daily. Work-up for neuropathy at that time included vitamin B12 levels, which was 600 pg/ml (Mayo Clinic normal values 200-900 pg/ml), folic acid 10 ng/ml (Mayo Clinic normal 2-20 ng/ml), methylmalonic acid 0.2 nmol/ml (Mayo Clinic <= 0.4nmol/ml), and homocysteine 4 mcmol/L (Mayo Clinic < 13 mcmol/L). The hepatitis profile was negative, HbA1c was 5.5%, serum protein electrophoresis did not show an M spike (monoclonal spikes). The thyroid profile, liver function, fluorescent antinuclear antibody (FANA), and renal functions were also normal. A repeat vitamin B12 and folic acid levels at the time of starting therapy were also normal. The patient was taking vitamin B12 and folic acid supplementation at the time when Duopa was initiated.
At the initial visit, Duopa pump settings were: lock level 1, continuous infusion rate 3.0 cc/h, lockout two hours, extra dose 1.5 ccs, and morning dose nine ccs. The patient developed severe neuropathic pain within 24 hours of initiating Duopa characterized by burning and stinging in his feet (10/10 on a visual analog scale). He had no symptoms after he had morning bolus but four hours after starting the maintenance dose, these symptoms started acutely. The neurological exam was unchanged from before (baseline: absent ankle reflexes and sensory gradient to pinprick at mid-shin level). The continuous rate was reduced to 2.5 cc/h, which did not relieve the symptoms. The gabapentin dose was increased to 600 mg two times a day, and he developed severe dizziness. Duloxetine at 30 mg two times a day made him irritable. Topical lidocaine cream (5%) did not provide any relief. Hydrocodone-acetaminophen 5/325 mg caused him nausea. The continuous infusion rate was brought down to 1.4 cc/h (with series of titrations). The neuropathic pain started to improve (4/10 on a visual analog scale) four hours after reducing the dose to 1.4 cc/hour. He has been using extra dose boluses to manage off periods. The boluses have not resulted in the development of acute neuropathic pain.
|
pmc-6160379-1
|
The patient was a 70-year-old man. He was admitted to our hospital because of a hepatic disorder that was discovered during a routine health examination. Blood tests showed aspartate aminotransferase 48 U/L (normal range, 13 to 33 U/L), alanine phosphatase 66 U/L (normal range, 8.0 to 42 U/L), alkaline phosphatase 263 U/L (normal range, 115 to 359 U/L), gamma-glutamyl transpeptidase 100 (normal range, 10 to 47 IU/L), total bilirubin 0.5 mg/dL (normal range, 0.2 to 1.2 mg/dL), carcinoembryonic antigen 4.4 ng/mL (normal range, < 5.0 ng/ml), and carbohydrate antigen 19-9 10.4 U/mL (normal range, < 15 U/mL). Abdominal ultrasonography showed an 8 × 7-mm solid mass at the gallbladder fundus and several stones in the gallbladder (Fig. ). Enhanced computed tomography (CT) showed that irregular wall thickening at the gallbladder fundus and the boundary between tumor and the liver was indistinct (Fig. ). T2-weighted magnetic resonance imaging (MRI) showed a high-intensity nodule inside the thickened wall at the gallbladder fundus (Fig. ). According to these findings, we diagnosed the lesion as suspicious of malignancy and decided to perform surgery. During surgery, a tumor of approximately10 mm was found at the gallbladder fundus and color change of the liver bed floor adjacent to the tumor was detected. We performed laparoscopic cholecystectomy and liver bed resection. The macroscopic findings of the resected specimen showed a 15 × 10-mm milky yellow mass at the gallbladder fundus, and its cut surface showed papillary lesions (Fig. ). The tumor mucosal surface was smooth, and its form was similar to that of a submucosal tumor. Histopathological findings showed papillary tumors with cyst formation, and the tumors represented mucin secretion (Fig. ). Additionally, the Rokitansky-Aschoff sinus (RAS) was formed, and the smooth muscle became hyperplasia in the stromal tissue surrounding the papillary tumors (Fig. , ). Within the epithelial cells, nucleus chromatin increased, karyotype was irregular, and nuclear body became clear. There was no invasion into the stromal tissue. These findings demonstrated ICPN with low-grade dysplasia (Fig. ). There was neither dysplasia nor biliary intraepithelial neoplasia on the background mucosa. Immunohistochemical analysis of the mucosal characteristics showed that MUC1, MUC5AC, and MUC6 were positive, whereas MUC2 was negative (Fig. ). According to the predominant pattern on morphology and the mucin expression form, it was diagnosed as biliary type. Additionally, because Ki67 index was a little less than 10%, it was denied that the tumor was malignant. The postoperative course was good, and the patient was discharged 9 days after the operation. A recurrence has not been detected for 3.5 years.
ICPN was first described as gallbladder lesions of IPNB in the 2010 WHO classification and was classified as premalignant lesions of biliary system in the same category as adenoma, biliary intraepithelial neoplasia, and mucinous cystic neoplasm []. IPNB is defined as biliary tumors with an exophytic nature exhibiting papillary mass which can be detected macroscopically within the bile duct lumen, characterized by intraluminal growth []. It is associated with mucobilia due to excessive mucin secretion and is more commonly found in the hepatic biliary system [].
The histopathological characteristics of ICPN are equivalent to IPNB. Four histological subtypes exist, including biliary type, gastric type, intestinal type, and oncocytic type according to IPMN. The mucus glycoprotein expression form is different depending on each histological subtype; that of early biliary carcinoma differs from ICPN [, ]. About biliary type, Adsay et al. reported 68% of those represented cancer in situ and 69% included infiltrating cancer []. Correlation between mucin expression form and prognosis about several tumors has been studied. The current study showed that MUC1 immunohistochemical staining is a poor prognostic marker for IPNB []. Although there are few reports on ICPN, it is considered that this case should be followed closely.
ICPN shows various degrees of dysplasia from low- to high-grade and finally to invasive carcinoma, and the histological findings are often mixed []. This variation of dysplastic degree demonstrates the adenoma-carcinoma sequence while papillary adenocarcinoma is assumed to arise through de novo carcinogenesis. Therefore, from the perspective of carcinogenesis, ICPN is distinguished from papillary adenocarcinoma and it is related to the difference of each tumor prognosis. ICPN rarely infiltrates and metastasizes, and the prognosis for ICPN is typically much better than that for gallbladder adenocarcinoma. The 5-year survival rate for ICPN is 60% if including invasive carcinoma and 78% if excluding the invasive region. In contrast, the 5-year survival rate for gallbladder adenocarcinoma is 30% []. Therefore, it is important to diagnose ICPN correctly.
However, the concept of ICPN remains unclear about several points.
First, it is difficult to distinguish ICPN, including widespread infiltrating cancerous regions, from gallbladder carcinoma, including papillary tumor regions. It is important to distinguish both for selecting an appropriate treatment strategy. If ICPN is diagnosed preoperatively, simple cholecystectomy can be performed without lymphadenectomy. Second, management for tubular components in ICPN is controversial. There is no clear description about it in the 2010 WHO classification. Adsay et al. defines ICPN as an exophytic intramucosal gallbladder mass greater than 1 cm and composed of dysplastic cells forming a lesion distinct from the neighboring mucosa []. According to their definition, the existence of tubular components is not important if the condition mentioned above is satisfied. Additionally, it is considered that macroscopic papillary lesions are not essential for diagnosis.
In the present case, the tumor’s mucosal surface was smooth and its form was similar to a submucosal tumor. Although the macroscopic findings were atypical, histopathological examination showed papillary tumors with low-grade dysplasia and mucin secretion and ICPN was diagnosed. The RAS was formed, the smooth muscle became hyperplastic in the stromal tissue, the tumors arose into the RAS, and the adenomyomatous hyperplasia was merged with ICPN. Thus, the tumor formed like a submucosal tumor.
Although histopathological findings showed papillary tumors with cystic formation, preoperative CT showed only wall thickening and did not show cystic formation findings. It was considered that because the cysts were involved in hyperplastic smooth muscles, the imaging could not detect the cystic formation. On the other hand, the high-intensity punctiform lesions were detected by T2-weighted MRI. It was considered that the finding demonstrated the tumors rise into the RAS, and the cysts were formed.
Although gallbladder adenocarcinoma or ICPN rising in RAS have been reported, to our knowledge, this is the first case of ICPN with adenomyomatous hyperplasia []. It is necessary to consider the possibility of tumor lesions within adenomyomatous hyperplasia. As in this case, coexistence of fundal-type adenomyomatous hyperplasia makes diagnosis difficult. In cases of adenomyomatous hyperplasia with irregular wall thickening and sequential changes, it is necessary to follow closely about the merger of the neoplastic lesion.
|
pmc-6160622-1
|
This study was approved by the Ethics Committee of Orthopedic Surgery Department, Imam Khomeini Hospital, Tehran, Iran and a written consent was signed by the parents.
A 7-yr-old boy, the only child of otherwise healthy parents was referred the Pediatric Orthopedic Clinic, Imam Khomeini Hospital, Tehran, Iran on July 2018 with the diagnosis of CP. The reason for referral was the parents’ concern about the increasing severity of disease despite regular occupational therapy.
On physical examination, the patient was developmentally delayed, unable to walk or stand, with obvious cognitional and gross and fine motor retardation. Flexion contractures were noted in elbows, wrists, knees, and hips. There was bilateral equinovarus deformity of feet and increased popliteal angle. Plantar reflexes showed extension response and DTRs were exaggerated. Spastic response of muscles was recorded after continuous stretching. Sitting balance was extremely unstable ().
The patient was the result of a consanguine marriage and normal pregnancy. Birth weight was 2950 gr and head circumference and height were 35 and 47, respectively. The few first months of his life showed normal weight gaining and development. He was able to hold his head in 5 months and roll over at 7 months age. The first time the parents had been told about the possibility of an abnormality was in a routine screening at 5 months age. The pediatrician noticed a decreased head circumference growth. Further investigation showed the head circumference reached a plateau (40 cm) in its growth around 12 months age (). His general and developmental condition seemed to experience a sudden pause with progressive delay in growth and development since then. He lost his ability to rolling over and never gained any gross motor milestones. His face became expressionless and his eyes started to sink into the orbits (). Other findings were: apparent cachectic dwarfism, microcephaly, loss of facial adipose tissue, pigmented retinopathy, thoracolumbar kyphosis, multiple joint contractures, senile appearance, photosensitivity, and thin and dry hair.
Although physical examination had a lot of similarity to a patient with CP, the history was inconsistent with the diagnosis of CP in its almost all aspects. This made us reevaluate the diagnosis. After a thorough history taking, some clues were added to our knowledge which was critical to the correct diagnosis. These include rapid regression of all motor functions, regression of language and fine motor functions and facial changes which are not compatible with CP.
At 7-yr-old age, he was in a cachectic dwarfism condition. The progeroid appearance narrowed our differential diagnosis.
Our first diagnosis based on clinical findings and progression of the disease was Cockayne syndrome. The diagnosis was later confirmed by molecular analysis for Cockayne syndrome. The patient was homozygous for ECCR6 gene (genotype: c.2551 T>A /p.W851R- c.2551 T>A /p.W851R). The parents were also heterozygous for the same gene. This was also true for the patient’s only sister.
|
pmc-6160624-1
|
An 11-year old girl was admitted Mofid Children’s Hospital, Tehran, Iran in 2015 and we took her family informed consent form template for case report studies. She had high-grade fever, severe headache, and vomiting since four days before admission. She had been diagnosed with meningitis in another hospital and had received dexamethasone and antibiotics including ceftriaxone and vancomycin. No improvement had been seen in her status, and her high-grade fever had remained uncontrolled. The patient was referred to Mofid Hospital with complaints of high-grade fever, severe headacheand photophobia. Her mother reported that she had a history of common cold, sinusitis and pharyngitis few days before her first admission.
In addition, she had a history of right knee arthritis last year; she also had a congenital occipital mass with occasional purulent discharge. It had been manipulated by her father because of pain and edema 2 weeks before her admission leading to oozing of pus.
On physical examination, the patient was lethargic; vital signs included body temperature of 39 °C, blood pressure120/80 mm Hg, pulse rate 90/min, and respiratory rate 25/min. Meningeal irritation was present (positive nuchal rigidity, Kernig and Brudzinski signs) with photophobia; pupils midsize and were reactive to light. Erythematous occipital mass (1×2 cm) was palpated in the midline, with no discharge. The range of motion of right hip was decreased with tenderness without erythema, warmth and edema. The rest of the physical examination was normal.
Because of continuation of fever despite antibiotic administration, lumbar puncture was done. CSF analysis in previous hospital admission showed; WBC=132(p=70%,L=28%), Glucose=10, Protein=27, RBC=180 and with a gram-negative bacilli (Enterobacter) in CSF culture.
Laboratory evaluations showed WBC=17000/mm3 (PMN=87%), Hemoglobin=12.6 g/dl, and Platelets=197000/mm3. Biochemistry tests including Na, K, P, amylase, lipase, and LDH were normal and serology for hepatitis b, hepatitis Cand CMV viruses was reported as negative. The erythrocyte sedimentation rate, (ESR) was 67 mm in the first hour and CRP 124 mg/l. NBT, Immune Globulins (Igs) and CD flow cytometry were also in normal range. Mild TR, Mild AIand Mild PI were reported in echocardiography without any vegetation. Audiometry also was normal.
CSF analysis in our hospital showed WBC=1000/mm3 with 90% PMN and 10% lymphocyte, Glucose=18mg/dl, Protein=30 mg/dl, RBC=10/mm3and CSF culture was negative.
Antibiotics were changed to vancomycin and meropenem in our hospital. After 3 days, the patient was not responding and had leukocytosis and fever, so chloramphenicol was added to vancomycin and meropenem. Five days later, CSF analysis showed WBC=100/ mm3 with 80% PMN and 20% lymphocyte, Glucose=25 mg/dl, Protein=18 mg/dl, RBC=60/mm3Blood culture was negative. Vancomycin and meropenem were discontinued and intrathecal amikacin was added to chloramphenicol. After five days, CSF analysis showed WBC=30/mm3with40% PMN and 60% lymphocyte, Glucose=29mg/dl, Protein=95mg/dl, RBC=10/ ml. The second CSF culture 8 days after admission showed gramnegative bacilli Enterobacter by BACTEC (Becton Dickinson Microbiology Systems, Model No. B9120). According to the antibiogram, microorganism was sensitive to chloramphenicol and cotrimoxazole and resistant to ampicillin- sulbactam, amikacin, gentamicin and cefepime. Therefore, antibiotics were changed based on antibiotic sensitivity test (Amikacin was discontinued, chloramphenicol continued and cotrimoxazole added). Patient responded to the new antibiotic therapy clinically and CSF culture became negative.
Brain CT scan with and without contrast was performed for the patient which showed an extra-axial hypo dense relatively round lesion in posterior mid aspect of posterior fossa along with calcified foci in its superior aspect. A subcutaneous lesion was also noted in the overlying scalp. After contrast administration, rim enhancement was seen in both intracranial and subcutaneous lesions (). The lesion was suspected to be an infected intracranial and subcutaneous dermoid cyst with a connecting tract through the occipital bone, Brain MRI with and without contrast was performed subsequently which revealed CSF signal in the lesion and rim enhancement as well as prominent restriction in DWI sequence (Diffusion weighted imaging) which confirmed the diagnosis in the CT scan ().
She was referred to the Neurosurgical Department for removal of the infected dermoid cyst. After neurosurgery, Brain CT revealed an evidence of posterior craniotomy in occipital bones with mild pneumocephalus. Small subdural effusion was detected in the right side of the posterior fossa with normal ventricle sulci; no infarction, hemorrhage, mass, midline shift or herniation was seen.
The histopathology findings of brain mass showed a cyst lined by keratinized squamous epithelium containing hair shafts and keratinous material. Severe mixed inflammation and foreign body type reactions well as foci of calcification with hyalinization and congestion in the periphery are seen with no evidence of malignancy. It confirms the diagnosis of an infected dermoid cyst ().
She was discharged with final laboratory results of normal CBC, CRP=23and ESR=60. Her final CSF analysis showed negative smear and culture. Meningitis was treated by chloramphenicol and cotrimoxazole. Patient responded to our treatment and was well on discharge and on follow-up one month after discharge with normal CBC, ESR and CRP.
|
pmc-6160712-1
|
The first patient, a white 9 months-old girl born at term and small for gestational age (2.300 g), was referred at the outpatient clinic of Hospital das Clínicas of University of Sao Paulo, with atypical external genitalia noticed at birth, characterized by microphallus (2.5 cm), perineal hypospadias and absence of palpable gonads. The karyotype was 46, XY. No Müllerian derivatives were found at pelvic ultrasonography and retrograde uretrocistography showed a blind vagina. At 2 years of age, a human chorionic gonadotropin (hCG) stimulation test was performed (two doses of 2,000 U) and no testosterone increase and steroid precursor accumulation was found. Since childhood, the patient showed a male behavior and after psychological evaluation, changed to male social sex at 5 years of age. He had a normal mental development. At 10 years of age he was submitted to exploratory laparotomy which disclosed bilateral atrophic testis that were removed. Anatomopathological data showed dysgenetic testes characterized by immature tubules with Sertoli cells only and a few atypical spermatogonias. No Leydig cells were identified in the interstitium. By 17 years of age, he started androgen replacement with testosterone esters. At this time his penile size was 12 × 3 cm, serum LH level was 16 U/L, FSH level was 54 U/L, and testosterone level was 230 ng/dl 14 days after exogenous testosterone (NV LH: 1,4–9,2 UI/L; FSH: 1,0–12 UI/L. Total testosterone: 271–965 ng/dL).
|
pmc-6160733-1
|
The patient was a 16 year-old Kenyan male with severe aplastic anemia resulting in transfusion dependence. He sought care in India where he was treated with horse anti-thymocyte globulin (h-ATG) and cyclosporine. The patient was unresponsive to treatment and had several hospitalizations for disease-related complications. During this time he accumulated multiple risk factors for MDRO carriage including frequent antibiotic and healthcare exposure. He was transferred to the NIH for enrollment in a research study involving a potential haplo-cord transplant, but arrived septic with vancomycin-resistant Enterococcus fecium (VRE) and MDR E. coli-positive blood cultures. The source was identified as a large superinfected presacral hematoma, thought to have resulted from chronic rectal tube trauma. Given the patient's pressor requirement, severe pancytopenia and advanced debilitation, deep surgical resection of the infected hematoma was deemed impractical. The clinical strategy shifted to gaining sufficient control of the infection to enable hematopoietic reconstitution via stem cell transplant.
Expanded susceptibility testing for the two MDR E. coli isolates from the blood showed highly resistant organisms with in vitro susceptibility to colistin/polymyxin B and tigecycline only. Borderline susceptibility to imipenem was detected in one of the two isolates. Three MDR isolates detected on peri-rectal screening (one isolate of Klebsiella pneumoniae, two isolates of E. coli) showed susceptibility to colistin/polymyxin B, tigecycline and ceftazidime-avibactim. The VRE isolate showed susceptibility to daptomycin and linezolid. Consequently, the patient was treated with an antibiotic regimen that included daptomycin, imipenem, ceftazidime-avibactim, colistin and tigecycline. This combination was formulated to accommodate the differing antibiotic sensitivities among the gram-negative isolates and to apply aggressive pressure to a large inoculum of polymicrobial MDROs poised to continue seeding the patient's bloodstream. In this setting of extensive rectal fistulization and severe immunocompromise, antifungal therapy was added empirically.
Following initiation of antibiotics the patient's fever defervesced, his blood cultures cleared and his hemodynamic instability improved. However, a direct hyperbilirubinemia developed between Week 1 and Week 3 of admission, reaching a peak total bilirubin level of 26.3 mg/dl. Transaminases remained normal. No signs of cholestatic obstruction were observed by imaging. There was concern that imipenem may be contributing to cholestasis as has been reported previously for beta-lactam antibiotics, particularly carbapenems (). However, there was also concern that discontinuation of imipenem could compromise control of the patient's MDROs. The preservation of hepatic function being imperative, it was decided that the patient would be trialed on a carbapenem-sparing regimen.
To identify the most suitable alternative antibiotic combinations, a “real-time” HTS combinational drug screen was performed. Three MDROs were isolated from the patient on admission: one Klebsiella pneumoniae (KP11) and two Escherichia coli (Ec1A and Ec2B). These strains were tested for sensitivity to a total of 8 drugs (gentamicin, colistin, rifabutin, imipenem, ceftazidime, meropenem, tigecycline, and auranofin) in 9 unique combinations and 14 total combinations. Each sample was tested in quadruplicate, amounting to a total of 2,304 samples which were run on three 1,536-well plates using clinically-relevant drug concentrations (Figures –). None of the tested drugs was able to completely suppress the growth of all three strains as monotherapy. Notably, colistin was the only solo drug that mediated >50% inhibition of each strain. It exerted a greater inhibitory effect on Ec1A and Ec2B than KP11. The other antibiotics demonstrated negligible activity against these three strains (<20% inhibition).
For the three-drug combinations, #9 (gentamicin+colistin+rifabutin) successfully suppressed > 90% growth of all three strains (Figure ). #10 (colistin+imipenem+rifabutin) and #11 (meropenem+tigecycline+colistin) were less effective, inhibiting 54–90% of all three strains. In the four-drug combination tests, #12 (meropenem+tigecycline+colistin+ceftazidime) and #13 (meropenem+tigecycline+colistin+rifabutin) inhibited 22–83% of all three strains.
Next, we studied the three-drug combination (gentamicin+colistin+rifabutin) against KP11 at various drug concentrations (Figure ). Colistin was tested as a single drug at 0.5 or 2 μg/ml. Either 1 or 4 μg/ml gentamicin was added into colistin as two-drug combinations. 0.06 μg/ml rifabutin was added into the mixture of colistin and gentamicin to form three-drug combinations. Addition of 4 μg/ml gentamicin into 2 μg/ml colistin improved growth inhibition from 29 ± 7% to 59 ± 20%. However, growth inhibition was not enhanced with addition of 1 μg/ml gentamicin, suggesting dose-dependent synergy. Addition of 0.06 μg/ml rifabutin into 4 μg/ml gentamicin and 2 μg/ml colistin further improved growth inhibition to 93 + 5%.
Verification of the inhibitory effect of these drug combinations in an accredited clinical laboratory by traditional methods could not be performed in real-time, prior to the decision about therapy, due to time constraints. The additional testing was performed retrospectively to validate the selected drug combinations for this report. Colistin and gentamicin as single agents and in combination with each other were tested against KP11 in the broth microdilution assay recommended by the CLSI. Neither 0.25 μg/ml colistin nor 8 μg/ml gentamicin as single therapy was fully inhibitory. The combination of 0.25 μg/ml colistin and 8 μg/ml gentamicin was inhibitory in all but one of six replicates (Figure ). The significance of this finding is unclear but may be related to the poor reproducibility of colistin, which is well known to interfere with methods of MIC testing (). Additionally, a relatively low density of MDRO was inoculated in the HTS assay, while a higher density of MDRO was inoculated in the broth microdilution assay. This may contribute to the differing degree of inhibition observed for colistin between these two methods.
Infection with MDROs in this case proved difficult to treat due to the extensive drug resistance and the potential liver toxicity. We continued colistin as the “backbone” of the antibiotic regimen based on the initial MIC data generated by conventional susceptibility tests and successful clinical microbiological control. Imipenem was discontinued and replaced with piperacillin-tazobactam plus gentamicin, the former to maintain broad spectrum coverage for the infected hematoma and the latter for synergy based on the HTS data. Rifabutin was eschewed secondary to an adverse side effect profile and problematic drug-drug interactions. Beginning 2 days after the change in antibiotic therapy and continuing over the next 3 weeks, total bilirubin levels steadily declined to 2.2 mg/dl and the MDR E. coli and K. pneumoniae remained controlled with negative blood cultures, which allowed reinstatement of the patient's aplastic anemia therapy that included eltrombopag (contraindicated with severe liver toxicity) prior to transplant. The patient subsequently received a haplo-cord transplant but died 4 months after presentation due to disseminated infection with a resistant Scopulariopsis mold. MDROs did not appear to be a source of systemic infection at the time of his death. The patient's direct hyperbilirubinemia was, in the end, ascribed to imipenem toxicity given the tight temporal correlation between increasing/decreasing bilirubin levels and imipenem exposure, as well as the lack of convincing evidence for other etiologies.
|
pmc-6161185-1
|
A 13-year-old boy from Jimba in Watamu, Malindi Kenya was playing with his friends in a bushy area surrounding their homestead. Suddenly, he was bitten on his right leg by a snake which was described by onlookers as long and brown in colour. Upon noticing the bite, he rushed home where a black stone was tied at the site of the bite and prayers were invoked. Soon after, he started frothing at the mouth and had labored breathing. A cousin rushed him to the nearest health facility (Gede dispensary in Watamu), where they were immediately referred to Bio-Ken Snake Farm. They arrived at Bio-Ken Snake Farm about an hour after the bite had occurred. Once at Bio-Ken, he was immediately driven by Sanda Ashe, a director at Bio-Ken to Watamu Hospital, a journey which took less than 10 min. On arrival, two bite marks could be seen on his right mid-shin with no signs of edema. He was sweating profusely, hypersalivating with severe ptosis, and his pupils were non-responsive to light (). His blood pressure was unrecordable, his heart rate was 100 beats per minute but thready, and body temperature was 35.5 °C. He was semi-comatose (Glasgow Coma Scale: 9/15) and oxygen saturation was 83%. Evaluation of the respiratory rate and ECG were not performed.
Suction was initiated to clear the secretions and oxygen administered via an ambu-bag. Two ampoules (20 mL) of South African Vaccine Producers (SAVP) polyvalent antivenom was administered to the patient by rapid IV push. Furthermore, two other ampoules (20 mL) were given in a 500 mL IV infusion of 0.9% w/v normal saline. Extra IV lines were run at 10, 15, and 20 min intervals. In total, four vials of antivenom were used. About 10 min after antivenom infusion, the patient developed severe urticaria for which adrenaline 0.5 mL was administered subcutaneously. Ambu-bagging was the only means of resuscitation available and the victim was bag ventilated over a period of two hours with oxygen via an oxygen cylinder ().
A clinical officer, a nurse, a nurse assistant, and the physician all took turns hand-ventilating the patient. In the course of ambu-bagging and IV infusion of antivenom, the victim went into cardiac arrest on two occasions. There were no cardiac sounds on auscultation and his pulse could not be detected. Similarly, no readings could be observed on the screen of the pulse oximeter. Chest compressions lasting 3–5 min were then immediately initiated on both occasions to complement artificial ventilation. This was stopped when cardiac sounds could be heard on auscultation, and readings could be observed on the screen of the pulse oximeter. At this point, his pulse was fluctuating and, thus, presumed post-resuscitation hemodynamic instability was corrected using IV infusion of Ringers lactate and normal saline (three litres over 24 h) until his pulse stabilized at 95 BPM. Ambu-bagging was continued for a further five and a half hours until pulse oximeter readings stabilized at 95–98% and a strong pulse could be felt. At this time, his temperature was 36.5 °C, BP was 110/70, pulse was 88/min (and strong) and oxygen saturation was 99%. He was then weaned off oxygen and admitted for further monitoring. Over the course of the next day, he could breathe on his own and had no neurological impairment. (). He could recall all the events leading up to his arrival at the hospital and was also able to identify members of his family who had visited him at the hospital. Bio-Ken later confirmed the snake to be a black mamba. Given the remarkable progress made by the patient, the absence of neurological impairment or any other organ dysfunction, the decision was made not to refer the patient.
It is worth noting that Watamu Hospital is a small private hospital with a capacity of eight beds. The facility is located 422 km southeast of Nairobi (3.3622° S, 40.0017° E) in a rural area on Turtle Bay Road in Watamu. The hospital has a basic laboratory and the bite occurred on a day (Sunday) when the hospital operates with minimum staff. Moreover, the nearest referral hospital (Malindi County Hospital) is 25 km away and lacks appropriate antivenom. Therefore, the main focus of this intervention was resuscitation of the patient. Apart from what we have highlighted, it was not possible to do more. Thankfully, the patient had no neurological impairment or any organ dysfunction. He is currently volunteering at the Bio-Ken Snake Farm where he assists in the care of the captured snakes.
|
pmc-6161216-1
|
The patient was a 65-year-old man with recurrent oral cavity squamous cell carcinoma who underwent a composite resection of the floor of mouth, the mandible from angle to angle, and the entire chin pad (). The defect was addressed by designing a left fibular free flap with skin paddle 15 cm in length and 14 cm in width (ie, mid-calf: from the border of the lateral tibia to the mid-posterior line of the calf). Once an anterior incision was made, an anterior-lateral perforator supplying the skin paddle was encountered (). This was skeletonized through the anterior compartment of the leg down to the anterior tibial artery and vein and prepared as a separate pedicle. The fibula was then harvested with one posterior-lateral septal perforator to the skin paddle. Four osteotomies were made in the fibula to reconstruct the angle-to-angle bony defect. The skin paddle was then draped over the bony reconstruction, with the area of de-epithelialization between the 2 perforators. The anastomoses of the peroneal artery and its 2 venae comitantes were done to the right facial artery, the right external jugular vein, and the right common facial vein, respectively. The pedicle to the anterior tibial perforator was then sewn to the distal ends of the peroneal artery and of one of the venae comitantes (ie, flow-through technique) (). The peroneal perforator was centered in the skin paddle for the floor of mouth reconstruction, and the tibial perforator was centered in the skin paddle of the chin ().
|
pmc-6161313-1
|
An 82-year-old female with a previous medical history (PMH) of type 2 diabetes mellitus, chronic atrial fibrillation, and several cardio-embolic lacunar strokes on chronic therapy with apixaban was admitted to the emergency department with a six-day history of a fever, chills, and general malaise. Her general practitioner prescribed her empiric therapy with amoxicillin-clavulanic with no improvement. She was vaccinated against Influenza and Pneumoccocus every year, but she had never received a BCG (Bacillus Calmette-Guerin) vaccine. She lived alone, and nearest family members were asymptomatic.
At admission, she was febrile (39 °C), eupneic with oxygen saturation 99%, a blood pressure of 125/85 mmHg, with a pulse rate of 86 bpm, arrhythmic, and a breath rate of 14 bpm. Physical exams revealed no abnormalities. At emergency department evaluation, laboratory work-up results were as follows: 6300 leukocytes with 80% neutrophils, erythrocytes count, platelets count, electrolytes and biochemistry tests were normal except for glycemia: 155 mg/dl, natremia: 123 nmol/L and C-reactive protein: 87 mg/dl. Urine analysis: 100 leukocytes and 10 erythrocytes per high-power field. Chest X-ray: normal without pulmonary infiltrates ().
A urinary tract infection (UTI) was suspected in this patient besides hyponatremia, and ciprofloxacin was prescribed. On the fourth day, the patient continued with fever and meropemen was administered instead of ciprofloxacin. All microbiological studies at that moment were negative including blood and urine cultures, Mantoux test, PCR for influenza virus and respiratory syncytial virus and TSH: 1.8 µU/mL and plasmatic cortisol: 25.5 µg/dl. Echocardiogram and abdominal ultrasound were also normal.
Three days later, the patient started with progressive dyspnea with productive cough. Arterial blood gas analysis showed PO2: 67 mmHg, PCO2: 39 mmHg and SatO2: 94% and a new chest X-ray () presented bilateral interstitial infiltrate. Sputum culture and acid-fast stain were negative. Urinary Legionella antigen was also negative.
Chest CT scan revealed an extensive pulmonary parenchymal involvement consisting of irregular septal thickenings with ground-glass areas and centrilobular nodules with a peri-lymphatic distribution, which had a predominantly central distribution although it affected the entire parenchyma of both hemithorax without apico-basal gradient ().
A fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBBX) were performed. Cytology from BAL revealed inflammatory cells. Microbiological studies: negative culture, Ziehl-Neelsen stain negative, IFA (immunofluorescence assay) for P. jirovecii negative. TBBX showed no positive histopathological or microbiological results. Serology was negative for HIV (Human Immunodeficiency virus), Cytomegalovirus (CMV), Herpes Virus 6 (HV 6), Epstein Barr virus (EBV) and Coxiella burneti.
After bronchoscopy, steroids were administered (methylprednisolone 0.5 mg/kg) but respiratory distress increased () and the patient died five days later.
Shortly after her demise, results from her sputum mycobacterial culture in Lowenstein-Nielsen medium; on day seventh, they tested positive for Mycobacterium tuberculosis. Some weeks later, results from BAL and TBBX mycobacterial cultures were also positive in both samples.
The complete necropsy was performed to detect cause of death and pulmonary pathology. Macroscopic appearance showed multiple white-yellowish lesions 1 to 4 mm in diameter that resemble millet or rice seed, affecting lungs, liver, spleen, kidney, lymph nodes, pancreas, and adrenal glands ().
Microscopic studies revealed all those white-yellowish nodules contained central caseating granulomas with several acid-fast bacilli on Ziehl-Neelsen stanning (). There were also granulomas inside bone marrow and in some arterial walls. Miliary lesions were not found in the necropsic study of the central nervous system.
|
pmc-6161374-1
|
A 40-year-old Asian woman who had been in her usual state of good health was incidentally found to have a small nodule in the lower lobe of her right lung during a regular medical checkup. The patient was seen in the department of medicine of our hospital for further evaluation. The patient’s family history was noncontributory, and a physical examination revealed no abnormalities. The results of laboratory studies were either within normal limits or negative. A computed tomographic (CT) scan revealed a lytic lesion of the fifth lumbar vertebral bone, as well as a small nodule (1.2 cm in diameter) in the lower lobe of the right lung (Fig. ). The vertebral lesion was situated on the left transverse process and was separated from the spinal canal (Fig. ). Biopsy specimens of both lesions were histologically similar and showed spindle cell neoplasms with a bland appearance; however, we could not make a definitive diagnosis, owing to the small size of the samples. The patient was placed under close observation with suspicion of multiple metastases from an unknown primary tumor.
Five years later, a CT scan indicated that the pulmonary nodule had slightly increased in size. Magnetic resonance (MR) imaging also revealed an increase in the size of the lytic lesion in the left transverse process of the fifth lumbar vertebra. To evaluate both the pulmonary and vertebral lesions, video-assisted thoracic surgery for the pulmonary lesion and curettage of the lytic bone lesion were performed. The orthopedic surgeons found that the tumor of the fifth left transverse process was exposed on the posterior surface but not on the anterior surface. They also found that the vertebral lesion was completely confined within the vertebral bone and was not connected to the spinal canal. During the clinical course (105 months), no significant findings other than the pulmonary and vertebral lesions were found, even with imaging examinations, including CT and MR imaging. The patient made good postoperative progress and remained free of disease at 41 months after the operation.
The resected specimen of the lung contained a well-circumscribed solid lesion 13 mm in diameter. It was composed of fascicular architecture of bland spindle or polygonal cells (Fig. ). Neither necrotic foci nor mitotic figures were observed. The tumor was immunopositive for epithelial membrane antigen (Fig. ), D2-40, progesterone receptor, vimentin, and S100 but negative for alpha-smooth muscle actin. Although curettage specimens from the vertebral bone were fragmented, the morphological and immunohistochemical findings were identical to those of the pulmonary lesion (Fig. ). The tumor was shown to be a transitional meningioma on histological examination, including immunohistochemical analyses (Table ).
|
pmc-6161403-1
|
A 73-year-old woman visited our hospital with the complaint of coughing up blood for three days. She had experienced massive haemoptysis the previous year, but no disorder could be identified during her follow-up examination. The patient had a significant past medical history of hypertension, hyperlipidaemia, and atrioventricular block with an implanted dual chamber pacemaker and a negative smoking history. On examination in the emergency room, her blood pressure was 146/72 mmHg, pulse was 86 beats/min (regular), temperature was 36.6 °C, respiratory rate was 20/min, and blood oxygen saturation level was 95% on room air. Her physical examination was unremarkable, without coarse crackles on the right lung field, and laboratory test results were within the normal limits. Her chest radiograph showed a homogenous, flat opacity along the right heart border in the lower lung field (Fig. A). Chest computed tomography (CT) demonstrated only a consolidation due to a collapsed right lower lobe and a diaphragmatic hernia (Fig. B). A chest CT performed five years ago showed an expanded bronchus in the small right lower lobe; these findings suggested pulmonary hypoplasia of the right inferior lobe (Fig. C). In the dynamic CT angiography, we could not detect the extravasation of blood on arterial and venous phase; however, bronchoscopic examination demonstrated that the right inferior lobar bronchus was filled with blood clots (Fig. D). The bronchial artery angiography confirmed the expansion and meandering of the bronchial arteries and the growth of the reticular artery from the diaphragm arteries (Fig. E). We performed two arterial embolizations and also plugged an endobronchial Watanabe spigot into her right inferior lobar bronchus but failed to stop the haemoptysis. Therefore, we were forced to perform a thoracoscopic right lower lobectomy. The excised surgical specimen presented a small hypoaerated, atrophied, and occluded right inferior lobe. The bronchus was underdeveloped and irregular throughout its running (Fig. F). Microscopic examination demonstrated extensive small epithelial nests surrounding the blood and fibrosis in the bronchial mucosa. These multiple micronodular hyperplastic foci were smaller than 5 mm in diameter (Fig. A). These tumorlets were detected around the erosional mucous membrane of bronchus. The nodules were composed of a relatively uniform population of atypical cells with moderate amounts of scant cytoplasm and oval nuclei without mitotic activity and exhibited necrosis beneath the bronchial mucosa (Fig. B). There were no histological features to suggest malignancy. Immunohistochemical markers stained positively for Grimelius and chromogranin A, CD56, and vascular endothelial growth factor (Fig. C–F). These findings led us to the diagnosis of pulmonary tumorlets on a hypoplastic right lower lobe. The postoperative course was uneventful, and the patient was eventually discharged.
|
pmc-6161445-1
|
A 19-year-old female, with no underlying medical illness presented acutely to the Emergency Department with massive hemoptysis. Upon arrival, she was noted to be in asystole. Pupils were 4 mm bilaterally, non-reactive. CPR was commenced, and continued for 20 min until she was revived. Urgent blood work revealed a hemoglobin of 2.3 g/dL (normal range 12–15 g/dL), normal coagulation profile, and arterial blood gases indicative of metabolic acidosis. She was intubated for airway protection, and transferred to the ICU for further management. An urgent CT angiography of the thorax showed a right sided pulmonary AVM, with evidence of active bleeding (hemothorax) (Fig. ). Non-contrasted cranial CT revealed cerebral edema (Fig. ). At this juncture, a decision was made to embolize the bleeding pulmonary AVM, should cerebral resuscitation show improvement. On day 3 of admission, repeat cranial CT showed dense basal cisterns and subarachnoid spaces (Fig. ), with marked worsening of the initially seen cerebral edema. A neurological consult was sought at this point, to assess the brain function, anticipating a possibility of brain death. The brain stem reflexes were absent, compatible with brain death. Additionally, the deep tendon reflexes were depressed, and the Babinski’s response was up-going. An electroencephalography was not pursued. Taking into account the previous history of resuscitation, worsening cerebral edema with a clinical diagnosis of brain death, stable hemoglobin level post transfusion, as well as fixed and dilated pupils (7 mm bilaterally), this is recognized to be a pseudo-SAH. Combined with the worsening cerebral edema and loss of grey-white matter differentiation, findings are suggestive of hypoxic-ischemic injury. The family was counselled, and decided to discontinue life support. Patient subsequently passed away.
|
pmc-6161456-1
|
A 7-year-old, 32 kg, neutered female Briard dog presented with inspiratory dyspnoea and an audible inspiratory wheeze particularly during exercise and after eating. The symptoms had been gradually worsening for a period of 3 months. There had been no cough or nasal discharge.
Mild inspiratory dyspnoea and increased inspiratory sounds during tracheal and laryngeal auscultation were noted at rest. Symptoms progressed to moderate to severe inspiratory dyspnoea under stress and an audible inspiratory wheeze became evident. Serum biochemistry revealed raised alkaline phosphatase activity (144 μ/L; reference interval < 95); other values were within normal range.
Left lateral cervical projection radiograph and radiographs of the thorax (right and left lateral and dorsoventral projections) were obtained. The dorsoventral projection included the caudal cervical trachea. In the left lateral cervical radiograph, a soft tissue opaque crescent shaped mass with long side dorsally was identified in the tracheal lumen at the level of the 5th and 6th cervical vertebrae (Fig. ). The mass measured 14 mm × 32 mm, and the tracheal diameter was reduced at the site. The mass was not visible in the dorsoventral projection. The cervical and thoracic parts of oesophagus were markedly dilated and air-filled, most likely due to dyspnea. Otherwise the thoracic radiographs were unremarkable.
Tracheoscopy and bronchoscopy were performed under light anaesthesia with butorphanol (Torpudor, Richter Pharma AG) and propofol (PropoVet Multidose, Fresenius Kabi AB) with a 4.9-mm flexible endoscope (Olympus GIF-N180). An approximately 3 cm long intraluminal mass originating from the dorsal membrane of the trachea was detected approximately 11–12 cm from the larynx (Fig. ). The base of the mass seemed to extend slightly to the left side of the dorsal membrane. FNA of the mass was performed using an endoscopic needle (Olympus NM-401L-0423, size 23G, diameter 0.6 mm and length 4 mm). Cytology of the samples revealed a scarce population of benign monomorphic mesenchymal cells. No signs of inflammation or malignancy were noted.
The surgery was performed 9 days later. The dog was pre-medicated with morphine (Morphin; Takeda Austria GmbH) and acepromazine (Plegicil; Pharmaxim) and anaesthesia was induced with propofol (PropoVet Multidose, Fresenius Kabi AB), ketamine (Ketaminol; Intervet) and midazolam (Midazolam Accord; Accord Healthcare Limited). Anaesthesia was maintained with a constant-rate infusion of fentanyl (Fentanyl-Hameln; Hameln Pharma Plus Gmbh). Intubation was performed under endoscopic guidance and an endotracheal tube was placed such that its cuff was distal to the mass. Cefazoline (Kefzol; Eurocept) was given intravenously 30 min before incision and every 90 min thereafter.
The dog was placed in dorsal recumbency and neck in extended position. Before the incision, the surgical area was infiltrated with lidocaine (Lidocain 20 mg/mL; Orion Oyj Orion Pharma). The cervical trachea was approached via ventral midline approach. The centre of the incision was approximately 10 cm from the larynx. The dissection was continued along the left side of the trachea as the endoscopic examination suggested that the mass extended more to the left side of the dorsal membrane. Oesophagus, nerves and vessels were avoided during the dissection. A stay suture was placed around the tracheal cartilage to facilitate rotation of the trachea to the right. The tracheal mass was localised using palpation and a longitudinal incision was made to the dorsal membrane next to the tumour margin. On the right side, the mass was attached to the dorsal membrane and on the left side to the site where the dorsal membrane joins cartilage. The tumour was resected from the dorsal membrane with narrow margins of healthy looking tissue. The right-sided dorsal membrane was sutured to the cartilage edges and annular ligaments on the left side using simple interrupted 3-0 polydioxanone (PDS, Ethicon) appositional sutures placed 2–3 mm from the wound edge. The last sutures were preplaced before tightening. Closure of the wound was performed in a routine fashion. On macroscopic evaluation the mass resembled fat tissue. The mass was formalin fixed and processed for histology at which it was identified as a lipoma (Fig. ).
The dog was hospitalised for 24 h after surgery for postoperative observation. Respiratory signs were relieved immediately after surgical removal of the tumour and postoperative recovery was uneventful.
At the control visit 6 weeks after the operation, the dog was free of symptoms and there were no abnormal findings on physical examination. In the control endoscopic examination, the surgical area had healed well with minimal scar tissue formation and no tracheal stenosis (Fig. ). The owner was contacted by telephone 9 months after the surgery and reported the dog to be asymptomatic.
|
pmc-6161600-1
|
A 43-year-old woman was diagnosed with cancer in the right breast during health screening. Magnetic resonance imaging (MRI) showed a 70 × 40 × 36-mm non-mass-like enhancement from the exterior of the right breast to the nipple region. Ductal carcinoma in situ (DCIS) was diagnosed on core needle biopsy; thus, mastectomy was considered necessary. As the patient desired to undergo immediate breast reconstruction, she was referred to our department. She underwent nipple-sparing mastectomy (NSM), sentinel node biopsy (SNB) performed by a breast surgeon and breast reconstruction with a de-epithelialized DIEP flap using thoracodorsal vessels as recipient vessels performed by a plastic surgeon (). The cancer was pathologically diagnosed as DCIS. Postoperative hormone therapy was continued at a nearby medical facility. At an outpatient visit three years and eight months after surgery, a tumor measuring 5 mm was detected by palpation at the lower right region of the right breast and a tumor shadow was identified on ultrasound. Fine-needle aspiration cytology indicated the possibility of C4 local recurrence. Thus, we performed enucleation of the lesion, and a subsequent pathological examination confirmed that the tumor was invasive ductal carcinoma (IDC) with the ductal spread. In addition to the enucleated tumor, a contrast-enhanced lesion extended from the upper exterior area to just below the nipple on MRI. The patient was diagnosed with multiple cancer recurrences in the reconstructed breast. As the patient desired to undergo autologous breast reconstruction again, extensive extirpation of the nipple-areola, breast skin including the buried DIEP flap and initial breast reconstruction with an anatomical tissue expander (TE) were performed at another hospital (). We did not give an irradiation to the breast in this case because surgical margins were free from cancer by the intensive pathological examination with 5-mm serial sectioning on the surgical specimen. At one year and eight months after insertion of the TE and postoperative adjuvant therapy with tamoxifen and leuprorelin, we extracted the TE and simultaneously performed breast reconstruction with a right S-GAP flap using internal thoracic vessels as anastomotic vessels. There has been no recurrence at two years and five months (four years after the surgery for the recurrence) postoperatively. We performed areola and nipple reconstruction through transplantation of a part of the contralateral nipple and use of a full-thickness skin graft from the proximal thigh. We have been monitoring for four years and currently, continue to monitor the patient every three months on an outpatient basis, each time giving an adjuvant therapy with leuprorelin and anastrozole. Although the right reconstructed breast appeared both upper pole fullness and lower pole skin shortage, the patient did not desire further surgery ( and ).
|
pmc-6161981-1
|
The following case was observed in 2015, a few months after the publication of the EMA document.
A 52-year-old woman had been treated with lithium carbonate, haloperidol and risperidone for schizoaffective disorder since 1997. The patient also received benzodiazepines. From 1998 to 2004, carbamazepine was added as a second mood stabilizer. Lithium doses varied throughout the years from 600 to 1050 mg/day, in order to keep serum concentration within the therapeutic range (0.6–0.8 mmol/L). No episodes of lithium intoxication occurred. Comorbidities included increased body mass index, repeated findings of abnormally high fasting plasma glucose, hypertension (treated with amlodipine, 5 mg/day). Over the last 10 years, her estimated glomerular filtration rate (eGFR) had gradually declined to 40 ml/min/1.73 m2, which falls into the category G3b [moderately to severely decreased chronic kidney disease (CKD)] according to KDIGO (kidney disease improving global outcomes) (KDIGO ). She developed a multinodular goiter that eventually caused dysphagia and dyspepsia. After an ultrasound scan, she underwent a medical workup in September 2015. Computer tomography scans showed abnormal thyroid images, multiple pulmonary metastasis, increased adrenal gland, a renal mass in the left kidney (maximum diameter, 38 mm), and multiple hyperdense nodules in the contralateral kidney (maximum diameter, 13 mm). She underwent thyroidectomy and the histological examination was consistent with the presence of two different tumors. A papillary thyroid carcinoma within adenomatous goiter tissue was identified within the left lobe, whereas an epithelial, sarcomatoid-like tumor was found in the right lobe. The latter was consistent with renal origin according to immunohistochemistry. A subsequent renal biopsy led to the diagnosis of oncocytoma, stage IV (M1). The patient died in May 2016 for respiratory failure due to pulmonary metastases.
We reported the case to the national pharmacovigilance agency in April 2016. The adverse reaction was codified as severe (life threatening). The causality assessment, evaluated by the Regional Centre of Pharmacovigilance according to the Naranjo algorithm (Naranjo et al. ), was considered “possible” based on the chronological criteria (18 years of lithium treatment), and the presence of objective evidence and previous conclusive reports. In fact, the ADR renal tumor has been included in the package leaflet since the 2015 EMA document.
|
pmc-6162192-1
|
A 16-year-old boy with phimosis underwent elective circumcision at an outside hospital. Anesthesia was performed via dorsal penile nerve block (DPNB) (15 mL of 0.25% bupivacaine). On the first postoperative day, he was referred to our hospital due to pain, black discoloration, and swelling of the glans. Voiding was possible. On clinical examination, the distal glans showed severe ischemia (
). All laboratory results including blood count, lactate, D-dimer, and clotting profile were within normal limits. Color Doppler ultrasound of the penis showed good cavernosal artery flow to the glans. After transferral to our pediatric intensive care unit, a caudal block was performed to reduce sympathetic tone and improve arterial blood flow. Five hours after admission, the patient underwent digital subtraction angiography (DSA) under sedation. After overwiew of the pelvic arteries and the left internal iliac artery, the internal pudendal artery was explored selectively via microcatheter (Progreat 2.7F, Terumo) but no vasospasm or thrombus was detected. A sufficient arterial perfusion as well as normal venous drainage of the glans was confirmed (
and
). To use all therapeutic options, intra-arterial spasmolysis with a bolus of 5 µg alprostadil and 150 µg nitroglycerine was sequentially given. Eight hours after admission, systemic therapy with sildenafil (1 mg/kg orally once a day), L-arginine-hydrochlorid (0.1 mg/kg/hour), and unfractionated heparin (15 units/kg/hour, up to 20 units/kg/hour depending on partial thromboplastin time) were initiated and given for 3 days.
After 3 days of systemic vasodilatative therapy, the darkish color of the glans changed to a brownish appearance. A surgical intervention was not necessary and ischemia resolved completely. The boy was discharged on the seventh postoperative day without adverse events (
).
|
pmc-6162389-1
|
A 6-year-old female child approached the pediatric outpatient department with a swelling under her left ear that had been present for the past one year. The swelling had gradually increased to its present size and was well-defined, multilobular, 5 cm × 4 cm in diameter, and erythematous. The left ear was slightly everted as shown in . On palpation, the swelling was firm, non-tender, and affixed to the surrounding structures. Lymph node palpation and facial nerve palsy was absent. Magnetic resolution imaging (MRI) of the lesion was done. T2-weighted images exhibited a 40 mm × 34 mm sized, well-defined, high-intensity, heterogeneous mass arising from the superficial lobe of the left parotid, which had displaced the surrounding soft tissue. The deep lobe of the parotid and the facial nerve were not involved. Fine needle aspiration cytology (FNAC) was consistent with pleomorphic adenoma. Other routine blood investigations were within normal range. A clinical diagnosis of pleomorphic adenoma of the parotid was made. The patient subsequently underwent superficial parotidectomy with preservation of the facial nerve under general anesthesia. No recurrence has been observed in six months of follow-up.
|
pmc-6162468-1
|
An 18 year-old female patient reported to our dental outpatient unit with a fractured and discolored tooth in the maxillary anterior region three years before. The patient gave a history of trauma five years back with occasional pus discharge from the gingiva in relation to maxillary right and left central incisor tooth #11 and tooth #21. Medical history was noncontributory. Clinical examination revealed an enamel fracture in relation to tooth #11 and a discolored tooth with enamel–dentin–pulp fracture in relation to tooth #21 (a). As the prognosis of tooth #21 was guarded and the regenerative procedure was attempted in tooth #11, this case report will further describe about tooth #11 only. The tooth was not tender to palpation and percussion tests. Sensitivity tests with cold and electric pulp testing was negative. There was no evidence of swelling or a sinus tract. The mobility was within the physiological limits. Radiographic evaluation of tooth #11 revealed an immature apex with thinned out root dentin near the apex of the root with periapical radiolucency (b,c). A cone beam computed tomography (CBCT) Promax 3D (Planmeca, Helsinki, Finland) with a limited field of view (FOV) of 3 × 3 cm was taken to aid in diagnosis and treatment planning. By using an inbuilt software program (Planmeca Romexis software V3.5.1, Planmeca, Helsinki, Finland), various linear dimensions were recorded in millimeters. The root length was 7.4 mm. The root dentin thickness in the axial section measured 1.2 mm labially, 0.8 mm mesially, 0.8 mm lingually, and 0.8 mm distally, respectively (a,b). The volume of periapical lesion was measured using a Volux–Horos viewer for Mac (V2.0.2, Nimble Co., LLC d/p/a Purview, Annapolis, MD, USA), and a CBCT periapical index (CBCTPAI) score of 5D was assigned to tooth #11 (f,h,j,l). A diagnosis of an immature tooth with pulp necrosis and asymptomatic apical periodontitis in relation to tooth #11 arrived.
A regenerative procedure was planned for tooth #11 using HAM as scaffold. The patient was explained about the extensive use of HAM in clinical scenarios [] and its use in a root canal is off-label. Written informed consent was obtained from the patient after a thorough explanation of treatment procedure. Tooth #11 was anesthetized with 2% lidocaine with adrenaline (Xylocaine, AstraZenecaPharma India Pvt. Ltd., Bangalore, India) and isolated with rubber dam (Dental Dam, Coltène Whaledent, Langenau, Germany). The tooth #11 was accessed with round bur (Dia-burs, Mani Inc., Tochigi, Japan). The working length was determined by electronic apex locator (Root ZX; J Morita MFQ, Kyoto, Japan) and confirmed by taking a digital periapical radiograph (Satelec India Pvt Ltd., Acteon Group, the Hague, the Netherlands). Minimal instrumentation of the root canal was performed by circumferential filing with #80 K file in relation to #11. The canals were gently irrigated with 20 mL of 1% sodium hypochlorite (NaOCl) (Parcan; Septodont, Saint-Maur, France) using EndoVac (Discus Dental, Culver City, CA, USA). The canal was dried with sterile absorbent points (Dentsply Maillefer, Baillaigues, Switzerland). The interappointment medication of calcium hydroxide (Prime Dental products, Mumbai, India) was placed inside the canal and then temporized with cavit (3 M, St Paul, MN, USA).
The patient was recalled after four weeks and was asymptomatic in relation to #11. The access cavity was reopened under rubber dam isolation. Calcium hydroxide was removed with saline using passive ultrasonic irrigation (Satelec, Acteon group, Merignac, France). Final disinfection was performed with 20 mL of 1% NaOCl and 20 mL of 17% ethylenediamine tetraacetic acid (EDTA) (Dent Wash, Prime Dental products, Thane, India) using EndoVac. The canal was dried with sterile absorbent points. The commercially available processed freeze-dried irradiated human amniotic membrane (ACTREC, Tata memorial hospital tissue bank, Mumbai, India) was cut into small pieces and moistened with saline. The membrane was packed inside the canal incrementally with finger plugger in the apical portion of the canal. ACTREC is the first tissue bank in India to use radiation for the sterilization of biological tissues with an ISO 9001:2000 Certified Quality Management System. The processing of amnion tissue in Tata Memorial Hospital is carried out according to the guidelines of the American Association of Tissue Banks []. BiodentineTM (Septodont, Saint-Maur, France) was then placed in the coronal third of the root canal and the access was sealed with glass ionomer cement (Fuji IX, GC, Tokyo, Japan) and resin composite (d,e).
The patient was asymptomatic when reviewed after 15 days in relation to tooth #11. At the three-month follow up, the patient was asymptomatic with no signs of swelling or sinus tracts in relation to #11 (f). The patient was lost to follow up and returned to the clinic at 19 months. The patient was assessed at 19 months (g) and at 36 months (h) wherein the patient continued to be asymptomatic in relation to tooth #11. The patient responded to electric pulp vitality and cold testing methods, which was reproducible multiple times. The intra oral radiographic examination revealed healing of periapical lesion, thickening of dentinal walls as well as a mineralized dentin bridge formation over Biodentine™ (f).
A postoperative CBCT was performed for the evaluation of treatment outcome. The post-operative reduction of volume of periapical lesion was assessed using a Volux—Horos viewer for Mac (V2.0.2). The CBCT images of #11 revealed a reduction in size of periapical radiolucency, a thickening of the root canal wall and deposition of the mineralized layer in close approximation to Biodentine™ (c,d,e,g,i,k,m).
|
pmc-6162540-1
|
A 62-year-old male was diagnosed with CLL (Binet B) in 2006. He was initially treated with fludarabine alone, then with FCR (Flu, cyclophosphamide, Rituximab), and kept in partial remission. In February 2015, a rapidly growing systemic lymphadenopathy was observed, and laboratory findings revealed elevated levels of lactate dehydrogenase (LDH) (414IU/L) and C-reactive protein (5.40 mg/dL), as well as very high levels of soluble IL-2 receptor (8387 U/mL). The bone marrow (BM) aspirate showed a massive infiltration of small lymphocytes (>65% of total BM cells), and flow cytometry (FCM) analysis revealed that most of the small lymphocytes in the peripheral blood (PB) and BM were positive for CD5, CD19, CD20, CD23 and IG light chain, resembling the phenotypic feature of the original CLL cells. These small lymphocytes displayed a normal karyotype and had no deletions of p53 according to a fluorescence in situ hybridization (FISH) analysis. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis revealed 2300 copies of Epstein-Barr Virus (EBV) DNA per ml of whole blood at that time. In addition, the CLL cells were negative for Zeta-chain-associated protein kinase 70 (ZAP-70), a tyrosine kinase family normally expressed on T-cells and natural killer cells, whose expression on B-CLL served as a prognostic marker and an indicator for unmutated IGH variable regions of the CLL cells [].
A fluorodeoxyglucose-positron emission tomography (FDG-PET) showed increased fluorodeoxyglucose (FDG) uptake in various lymph nodes, with a maximum standardized uptake value (SUVmax) higher than 8.5 in cervical, mediastinal and paraaortic lymph nodes. The right cervical lymph node was surgically excised, because SUVmax of the lesion was equivalent to that of the other lymph nodes and a histopathological analysis showed scattered Hodgkin/Reed-Sternberg (HRS) cells in the background of diffuse proliferation of small lymphocytes. Immunohistochemistry studies revealed that the HRS cells were positive for CD15, CD30 and epstein-barr encoded RNA (EBER). In contrast, the small lymphocytes around the HRS cells were positive for CD2, CD3 and CD5 but were negative for CD10, CD20 and CD23, consistent with the phenotype of normal T lymphocytes. In addition, CD5/CD20/CD23-positive small lymphocytes were intermingled, indicating B-CLL involvement (). The patterns of rearranged IGH bands were the same amongst samples from the lymph node, the PB, and the BM by Southern blot (SB) analysis.
To elucidate whether HRS cells were clonally related to the original B-CLL clone, laser capture microdissection and semi-nested PCR studies of immunoglobulin heavy chain (IGH) were performed. Surprisingly, sequencing patterns of the germline CDR3 region of the IGH gene showed that the HRS cells were indeed clonally unrelated to those of B-CLL cells. Since the HRS cells were composed of five separate and distinct clones, a genetic diagnosis of de novo lymphocyte-rich classic Hodgkin lymphoma with small lymphocytic lymphoma (SLL) as made (). However, because of rapid lymphoma progression with B symptoms, the patient was clinically diagnosed with CHL-RS.
Two courses of combination chemotherapy with doxorubicin, bleomycine, vinblastine, dacarbazine (ABVD) were unsuccessful, with a persistently high number of circulating B-CLL cells being documented in the PB, despite chemotherapy. In addition, the patient developed febrile neutropenia that required broad-spectrum antibiotics. Computed tomography studies indicated disease progression and therefore, salvage therapy with BR (90 mg/m2 Bendamustine on days one and two, 375 mg/m2 Rituximab on day one) was started. After six cycles of BR, complete remission was confirmed in both SLL and classic Hodgkin LPDs by FDG-PET, which has continued for more than one year so far.
|
pmc-6162695-1
|
We present the case of a 4-year-old boy with onset of AML with fever, abdominal pain, a very enlarged spleen palpable on transverse umbilical line, and hyperleukocytosis. The first evaluation of disease revealed a massive invasion of the bone marrow (50% of myeloid leukemia cells) with absence of invasion of the central nervous system. The karyotype analysis revealed a monosomy of chromosome 7 without translocations of prognostic impact at fluorescent in situ hybridization analysis. The child was therefore treated with European protocol LAM 2013/01 but showed no response to induction treatment with the persistence of 30% of blast cells at bone marrow aspiration. The bone biopsy, after induction phase, showed dysmorphic and dysplastic precursor myeloid cells of the three lineages, allowing diagnosis of acute myeloid leukemia with myelodysplasia-related changes (AML-MDC). Resistance to induction, monosomy 7 and the condition of AML-MDC categorize the disease as a high-risk AML, requiring the achievement of remission and bone marrow transplantation. The boy received two cycles of idarubicin, cytarabine, and etoposide and one cycle of fludarabine and high-dose cytarabine as salvage therapy without response. At the end of therapy, peripheral blood immunophenotypic analysis showed a persistence of CD34+ CD117+ CD33− blast cells (14% of leukocytes, 435 cell/μL). Because of the disease severity, we chose to continue the program of HSCT and started conditioning treatment.
The boy received high doses of ARA-C (4 g/m2/die) for 5 days prior to transplant on day 0, L-PAM (200 mg/m2) and antithymocyte globulin (6.3 mg/kg/die for three days). Despite the high-dose ARA-C treatment, at day −3, peripheral blood flow cytometric analysis still showed presence of blast cells (13% of leukocytes; 21 blast cells/µL). At day −2, we administered a dose of 240 µg/kg of plerixafor, an inhibitor of CXCR4, to mobilize staminal CD34+ leukemic cells from bone marrow. After 8 h and 1/2 from the subcutaneous injection of plerixafor, we analyzed all CD34+ cells in peripheral blood, finding the expected massive mobilizing effect with 493 CD34+ cells/μL (85% of blast cells on peripheral white blood count). At the same time, we started the administration of L-PAM 200 mg/m2 in an hour. The conditioning regimen was well tolerated without any adverse effect ().
Restudying the peripheral blood cells by immunophenotyping, after 8 h from the administration of L-PAM, we found a blast cell absolute number of 1.3 cells/μL and a very low overall white blood cell count of 20 cells/μL (). On day 0, before transplant, we did not find any cells identifiable with flow cytometric analysis and with qPCR.
We infused 6.6 × 108 total nuclear cells/kg from the 10/10 HLA matched unrelated donor, AB0 mismatched. Tacrolimus and mycophenolate mofetil were used as graft-versus-host disease (GVHD) prophylaxis. An engraftment was successfully achieved, confirmed by peripheral blood full donor chimerism analysis at day +32.
During the engraftment, we monitored minimal residual disease (MRD) with flow cytometric analysis without finding any statistically significant sign of relapse. We outlined a protocol to detect simultaneous expression of several markers (CD34, CD33, CD117, CD13, HLADR, CD11b, CD16, CD66b, CD14, CD45) on AML blast cells by multiparametric flow cytometry. The combination of these markers can monitor MRD at a sensitivity of 10−4.
The post-transplant period was complicated by early and immediately severe GVHD grade IV that necessitated a combined therapy with methylprednisolone (3 mg/kg) and one dose of methotrexate (13 mg/m2) without a significant response. Intestinal damage was still symptomatic, causing a diffuse thickening of the ileum and colic walls with mesenteric herniation at the abdomen ultrasonography. Because of GVHD steroid refractoriness, the boy was treated with anti-Tumor necrosis factor-α therapy with infliximab (10 mg/kg/dose weekly) with a good response immediately after the first administration. The cutaneous symptoms still remained only partially controlled and, due to a new serious reactivation, on day +41 the patient received a single dose of fludarabine with a progressive and stable remission of the signs of disease.
During the post-transplant period, the boy was affected by a systemic infection caused by human herpesvirus 6 and cytomegalovirus and by a BK polyomavirus-related hemorrhagic cystitis, without any consequences and a good response to the therapy. Liver biopsy confirmed a mild cholestatic hepatitis due to almost complete ductopenia, which was treated with ursodesossicolic acid. After 12 months from transplant, the boy was still in complete remission, validated by both the bone biopsy, which showed only a hypocellular bone marrow with a normal myeloid series, and the immunophenotypic and MRD analyses of bone marrow cells, which showed complete remission. With no severe morbidity and a complete engraftment with a normal function of B-cells, the boy was able to return to the vaccination calendar with inactivated vaccines.
Informed consent for publication was obtained and is available for review by the Editor.
|
pmc-6162813-1
|
A 33-year-old male presented with a painful scrotal ulcer of two weeks’s duration. Initially, an ulcerative papule occurred over scrotum and enlarged rapidly. He had a history of Evans syndrome diagnosed by autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), since seven years ago. A bone marrow study showed a hypercellular pattern without malignancy. The long time medication of predinsolone was given to control the AIHA and ITP. An intermittent blood transfusion with blood and platelets was also performed during a recurrent acute episode, with a poor control of anemia and thrombocytopenia. Six months before this admission, the patient discontinued medication of steroids by himself. On examination, a 5-cm painful destructive ulcer with an irregular margin and erythematous edges on the anterior scrotal wall was found (). He did not have any joint or eye complaints and has never had sexual intercourse. The skin pathergy test was negative. No other skin or muscosal ulcer was found. Laboratory data showed a white blood cell count of 8500/mm3, platelet count of 36,000/mm3, hemoglobin of 7.3 g/dL, and serum C-reactive protein of 9.5 mg/dL. The features of hemolysis, including a low hepatoglobin level, elevated lactate dehydrogenase, bilirubin levels, and direct antiglobulin test, were positive. Rheumatoid factor, anti-neutrophilic cytoplasmic antibodies, anti-cardiolipin antibody, anti-dsDNA, and anti-nuclear antibody were negative. No monoclonal gammopathy was detected on the protein electrophoresis. The microbiological tissue cultures for bacteria, fungi, and mycobacteria were negative. A biopsy of the scrotal ulcer was done and showed the ulcer with necrotizing inflammation, with a focal lymphocytic thrombogenic vasculopathy ( and ). PG was impressed and the patient received intravenous methylprednisolone 120 mg daily for four days. The scrotal ulcer was improved progressively, and the C-reactive protein was decreased (1.1 mg/dL) after one week. He was then given the medication including prednisolone 20 mg twice daily and azathioprine 50 mg daily. After two weeks of immunotherapy, a significant reepithelialization of the ulcer was found. One month after the initial presentation, the scrotal ulcer of PG was totally healed ().
|
pmc-6162841-1
|
A 53-year-old female with a history of type 2 diabetes mellitus, hypertension, and hypothyroidism presented with increasing diplopia and nausea for six days. The patient experienced an unintentional weight loss of 10 pounds in the preceding two weeks. Physical exam revealed bony tenderness localized to the ribs as well as a right CN VI palsy manifesting as impaired right eye abduction. Remainder of the exam was unremarkable.
Hemogram with differential was remarkable for white count of 10,700 k/µL (3.7–10.3 k/µL), with absolute neutrophil count of 7.5 k/µL (1.6–6.1 k/µL). Absolute lymphocyte count was within normal limits (2.42 k/µL (1.6–6.1 k/µL)). Blood chemistry was remarkable for: serum Ca2+ of 15.8 mg/dL (8.9–10.2 mg/dL), ionized Ca2+ of 7.7 mg/dL (4.6–5.1 mg/dL), and glucose of 254 mg/dL (90–120 mg/dL). Parathyroid hormone was <10 pg/mL (12–72 pg/mL) and parathyroid hormone related peptide was 1.3 (normal). Urine analysis and urine protein electrophoresis was unremarkable without evidence of Bence-Jones protein. The calculated protein gap between total protein (6.8 g/dL) and serum globulin (2.8 g/dL) was 4.0 g/dL and the albumin/gamma globulin ratio was elevated at 2.4 (0.8–2.0).
Serum protein electrophoresis revealed faint monoclonal immunoglobulin. Serum immune-quantification showed IgG 1150 mg/dL (720–1598 mg/dL), IgA 200 mg/dL (75–400 mg/dL), and IgM 41 (35–225 mg/dL). Kappa light chain was 108.18 mg/L (3.30–19.4 mg/L), lambda light chain 445.32 mg/L (5.71–26.30 mg/L), with a kappa/lambda free light chain ratio of 0.24 (0.26–1.65). Bone marrow biopsy results demonstrated hypercellular bone marrow involved by plasma cell neoplasm (50–60% aberrant lambda restricted plasma cells). Fluorescence in situ hybridization studies found evidence of CCND1/IGH gene fusion and gain of chromosome 1q. Flow cytometry of bone marrow aspirate demonstrated a small population of aberrant lambda restricted plasma cells positive for CD38, CD56, moderate CD45 and Lambda, and negative for CD19.
Computed tomography (CT) of the chest/abdomen revealed multiple osteolytic lesions in the appendicular and axillary skeleton throughout the thoracolumbar vertebral bodies, and pelvic bones; a healing non-displaced fifth anterior lateral rib fracture was present on the right. CT and magnetic resonance imaging (MRI) of the head showed multiple bone lesions, with a well-defined lesion measuring 12 × 15 mm within the right side of the clivus adjacent to Dorello’s canal ( and ). Bone survey showed lytic lesions in the left proximal fibular diaphysis ().
The patient’s hypercalcemia was treated with IV normal saline, calcitonin, and pamidronate. Pain was controlled with acetaminophen and tramadol with oxycodone for breakthrough pain. The patient was evaluated by the hematology-oncology service and received external beam radiation therapy to the clivus, alleviating her CN VI palsy. Her disease was then managed with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) chemotherapy. With treatment her symptoms resolved. Three months into therapy, her repeat laboratory testing demonstrated good response to treatment. The lambda light chain had decreased to 13.1 mg/L (5.71–26.30 mg/L), with a normal kappa/lambda free light chain ratio of 1.0 (0.26–1.65). Furthermore, a repeat bone marrow biopsy was obtained, which showed no morphologic evidence of multiple myeloma.
|
pmc-6162860-1
|
The patient was a 49-year-old Caucasian male, a professional driver, who underwent a dental examination in which bruxism was detected [,,]. He underwent several laboratory tests (in order to assess metabolic and hormonal functions), whole-night video-polysomnography (vPSG) adjusted to evaluating bruxism and parasomnias. PSG was evaluated in 30 s epochs, according to standard sleep criteria. Pathological events were evaluated according to the standards of the American Academy of Sleep []. The patient was also examined with a battery of scales and questionnaires: Athens Insomnia Scale (AIS), Epworth Sleepiness Scale (ESS), Berlin Questionnaire, STOP BANG questionnaire, Beck Depression Inventory (BDI), WHO Quality of Life–BREF (WHO QOL-BREF), Pittsburgh Sleep Quality Index (PSQI), Headache Impact Test–6 (HIT-6), Oral Behavior Checklist, Paris Arousal Disorder Severity Scale (PADSS) and Perceived Stress Scale-10 (PSS-10).
Medical history was positive for hypertension, psoriasis and Barrett’s esophagus. The patient reported a history of common nightmares and sleep terrors. He was also a long-term smoker. Medications included pantoprazole (40 mg), nebivolol (5 mg) and ramipril (5 mg). At presentation he complained of snoring, daytime fatigue, clenching and grinding of the teeth (during the day as well as night), pain located bilaterally in masseter muscles and area of temporomandibular joints, perceived increased masseter muscle tension and dissatisfaction with his quality of sleep. He identified his bruxism as one of the main causes of his subjectively reduced sleep efficiency.
Dental examination confirmed malocclusion (Angle’s class II), dental crowding, excessive overbite, teeth midline deviation and high Tooth Wear Index. During the examination, according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) guidelines, we found pain in both masseters and pain of both temporomandibular joints and also clicks in both temporomandibular joints during opening and closing of the mouth and during lateral and protrusive movements []. The Oral Behavior Checklist showed that the patient presented behaviors strictly connected with bruxism, such as bracing or thrusting of the mandible during the daytime. The patient knew about his bruxism and noticed an increased number and frequency of episodes after changing to a more stressful job. Dental examination together with Oral Behavior Checklist confirmed the high probability of severe sleep and awake bruxism.
Physical exam was within normal limits (WNL), apart from increased BMI (29.3). ESS score was 11 (mild daytime sleepiness). STOP BANG (patient scored 5 points) and Berlin questionnaires confirmed increased risk of Obstructive Sleep Apnea Syndrome (OSAS). PSS-10 indicated a higher level of perceived stress (21 points); BDI score of 9 was in the non-depressed range. Laboratory tests revealed only lowered concentration of HDL cholesterol, slight hypertriglyceridemia and slightly increased fasting glucose levels with normal levels of hormones and other metabolic parameters.
V-PSG confirmed the diagnosis of severe SB (Bruxism Episodes Index = 10.1/h, Bruxism Bursts Index = 12.8/h), with total count of 64 episodes lasting from 1.8 s up to 21.5 s (mean = 6.5 s). They often triggered EEG arousals. Suspected OSAS was not confirmed (AHI = 4.8/h, average SpO2 = 92.5%, Oxygen Desaturation Index = 5.5/h, average desaturation drop = 2.9%). Total Sleep Time (TST) was 379 min, Sleep Latency (SL) was 31 min and REM Latency (RL) was 160 min. Sleep stage distributions: N1 = 6.9%; N2 = 60.1%; N3 = 10%; REM sleep = 23%. Sleep moisturance is presented in . Periodic limb movements (PLMs) were not evaluated due to technical limitations. PSG report is presented in .
The most unexpected and striking result was observed with the video recording. The patient had several episodes (total count = 8) of sexual activity, lasting from a few up to over a dozen seconds, which appeared during most sleep stages (N1, N2, and REM). The patient performed masturbation with his hand or with friction moves by pushing his loins against the quilt while lying in the prone position or on his side. The episodes were short, mostly lasting less than 20 s, and did not result in ejaculation. Notably, each of these sleep masturbation episodes was preceded by a bruxism episode with EEG arousal lasting for at least a few seconds. In most of the episodes, SB lasted throughout the whole sexsomnia episode. After awakening from all of these episodes, there was never any recall by the patient. There were no spontaneous arousals from N3 or N2 sleep, and REM-atonia was preserved. However, an episode of intermittent non-periodic myoclonic activity was recorded in N2, lasting 21 min and about 40 myoclonic movements in the left arm and hand were recorded. This episode ended with SB and an awakening. Mentioned episodes are presented in the .
The patient was offered various treatments, including manual therapy jaw massages and an occlusal splint for the lower teeth arch with the goal of relaxing the masticatory muscles and decrease the number of SB/AW episodes, but he refused. When informed about the SB-triggered sexsomnia episodes, he confirmed that he was unaware and added that he would always ask for a single room in hotels.
|
pmc-6162860-2
|
The patient was a 38-year-old Caucasian male, who underwent a thorough dental examination in which bruxism was detected [,,]. He underwent several laboratory tests (in order to assess metabolic and hormonal functions), whole-night vPSG adjusted to evaluating bruxism, OSAS and parasomnias. PSG was evaluated in 30 s epochs, according to standard sleep criteria. Pathological events were evaluated according to the standards of the American Academy of Sleep []. The patient was also examined with the same battery of scales and questionnaires that were mentioned in Case 1. Medical history was positive for masseter muscles hypertrophy and severe teeth damage. The patient reported a history of common nightmares and muscle cramps during sleep. He was also a long-term smoker. At presentation, he complained of loud snoring, daytime fatigue and massive teeth wear.
Dental examination confirmed bilateral hypertrophy of masseter muscles and teeth wear of 4th stage in Tooth Wear Index ().
Physical examination revealed enlarged palatine tonsils, apart from this examination was WNL, with Body-Mass Index 25.3. The ESS score was 16 and confirmed severe, excessive daytime sleepiness. STOP BANG confirmed high risk of OSAS, same with Berlin Questionnaire (2 categories positive). PSS-10 indicated a level of perceived stress within normal limits (19 points); BDI score of 7 was in the non-depressed range, while the PSQI score of 6 points confirmed a slightly decreased sleep quality. Laboratory tests revealed only lowered concentration of 25-hydroxycholecalciferol.
V-PSG confirmed the diagnosis of severe SB (Bruxism Episodes Index = 11.4 episodes/h, Bruxism Bursts Index = 3.1/h), with a total count of 69 episodes lasting from 2.4 s and up to 19.8 s (mean = 8 s). Most of the registered bruxism episodes were associated with respiratory events and spontaneous arousals. Also, the suspected OSAS was confirmed and evaluated as severe with the AHI = 33.5/h, average SpO2 = 92.2%, Oxygen Desaturation Index = 35.7/h, average desaturation drop = 6.1% and percentage of sleep time with blood oxygen saturation below 90% = 13.4%. Apnea to Bruxism Index = 7.6/h. Desaturations often triggered spontaneous arousals, with a total count of 57 arousals on the Arousal Index = 9.4. Total Sleep Time (TST) was 363.5 min, Sleep Latency (SL) was 10.5 min, and REM Latency (RL) was 59.5 min. Sleep stage distributions: N1 = 9.4%; N2 = 50.5%; N3 = 18%; and REM sleep = 22.1% (). Pulse rate reached values between 60 and 103, with average = 75.6. Periodic limb movements (PLMs) were not evaluated due to technical limitations. PSG report is presented in .
In the video recording, we observed repeated episode of OSAS, SB and sexsomnia overlapping. There was a single period lasting about 17 min divided into several repeatable and similar episodes. The first episode started with hypopnea during the N2 stage in a supine position. When the patient reached a blood oxygen saturation level of 88%, spontaneous arousal occurred lasting 5 s and was accompanied by a mixed bruxism episode lasting 15 s. After 3 s of bruxism activity, the patient started to move his left arm and then masturbated with his dominant left hand. The whole motor activity of the arm lasted about 20 s and ended suddenly, right before the beginning of apnea episode. PSG recording with EEG of this event is presented in the . It started with blood oxygen saturation of 95% and lasted 35 s, during which the patient desaturated down to 86% and the apnea ended with the patient’s sudden gasp, accompanied by tonic bruxism episode (10 s) and again sexual motor activity lasting few seconds. There was a total period of 22 s of breathing and snoring, and then the next apnea appeared, lasting 33 s. Respiratory registration on the first two events are presented in the . We observed next 14 episodes which looked similar—first apnea/hypopnea appeared, during which saturation went down to about 89% and then breathing occurred with a desaturation drop, still decreasing down to 85–87%. During this desaturation drop bruxism and sexual activity appeared, but lasted only until the patient reached a saturation of 89–90% again. Then the activity stopped with the continuation of breathing for a few seconds until the next episode of apnea appeared. What is striking about this vPSG recording is the recurrence of these very similar episodes, each event happening within the same scheme, although during the last set of episodes normal breathing decreased between apneas and became shorter and shorter, from 28 s down to 9–10 s. After the last episode, the patient changed his position to non-supine and breathed normally, with no bruxism or sexsomnia until the next change of position. However, during the rest of the sleep time, no sexual activity was observed. Sexual activity was not leading to ejaculation, and it mostly appeared during the N2 stage or N1 stage, which was present after some spontaneous arousals evoked by respiratory events, similar to SB episodes. For the most of the time of sexual activity also the bruxism activity was present. The patient did not remember the episode. Respiratory registration of the whole described episode is presented in the .
The patient was offered treatment with continuous positive airway pressure (CPAP) according to the recommendations of the American Academy of Sleep Medicine. The first night with treatment resulted in a good response to treatment. Tonsillectomy was also advised. Dental treatment could be performed after OSA treatment and sleep bruxism management.
Both of the cases describe the coexistence of bruxism and sexsomnia. The mechanism of comorbidity of these both sleep disorders cannot be accurately determined because there are no other similar published clinical cases and what is more important, the mechanisms for generating sexsomnia instead of other parasomnia behaviors is still unknown. We suspect that the SB arousal can trigger sexual behaviors. However, these two cases (adult males, 39 and 49 years old) present the typical profile of sexsomnia that is more often connected with the male gender (approx. 75% in published cases), while there are notably no gender differences in SB, so that could have created a bias for sexsomnia episodes induced by SB arousals. Accordingly the presented cases, SB can be added to comorbid with sexsomnia sleep disorders, and the problem of comorbidity of these two issues should be studied more precisely.
|
pmc-6162877-1
|
A 71-year-old woman without any significant medical history presented to the emergency room (ER) of our hospital with slight drowsiness. The hepatitis B surface (HBs) antigen and elevated transaminase levels were detected on a blood examination, revealing chronic hepatitis. The patient contracted the HB virus while receiving transfusion during a cesarean section. Head computed tomography (CT) revealed a subarachnoid hemorrhage (SAH) with a right temporal hematoma and an aneurysm on the right M1-M2 bifurcation (Fig. ). The SAH was believed to be caused by a right middle cerebral artery (MCA) aneurysm that was classified as World Federation of Neurosurgical Societies Grading of SAH (WFNS) Grade II and CT Fisher Group III. We maintained her systolic blood pressure (SBP) under 120 mmHg and mildly sedated the patient in the ER. Subsequently, a procedure to clip the ruptured aneurysm was performed. After the craniotomy and dural incisions, subdural and massive temporal hematomas with severe brain swelling were detected. Massive bleeding occurred before we could properly reach the aneurysm, implying that the aneurysm reruptured before or during the operation. A temporary clip was quickly set on the right M1 trunk. Following this, a permanent clip was appropriately applied to the aneurysmal neck to close it (Fig. ). The removal of the temporary clip took 15 min. One day after surgery, the follow-up CT showed low density in almost the entire right MCA territory, suggesting an infarction. One month after surgery, the patient gradually recovered through rehabilitation, although she had hypoalbuminemia due to malabsorption and cirrhosis.
On day 38, she suddenly developed high fever (40.3 °C) at midnight. However, the following morning, i.e., on postoperative day (POD) 39 (Fig. ), her blood test showed acceptable levels of white blood cell (WBC) and C-reactive protein (CRP) (5250 cells/μL and 2.72 mg/dL, respectively) (Fig. ). As her fever reduced, it was believed that the fever was caused by central nervous system (CNS) damage. We immediately completed a general culture workup of the sputum, urine, and blood to understand the origin of the fever. Thus, we intentionally postponed antibiotic administration till the culture workup was completed. However, her SBP gradually declined to 70 mmHg on POD 40. A on-call doctor started vasopressor drugs administration and stabilized her SBP to approximately 100 mmHg. Though WBC and CRP levels were 8810 cells/μL and 6.56 mg/dL, respectively (Fig. ), the number of platelets was extremely low (less than 10000/μL) and the fibrin/fibrinogen degradation product (FDP) level was 62.1 μg/mL, suggesting disseminated intravascular coagulation (DIC). Although the spinal tap showed no evidence of meningitis, two sets of blood culture revealed the existence of gram-negative rod bacteria, strongly indicating a septic shock. Although we inserted a central venous catheter (CVC) in a sterile manner, the central line catheter seemed to be contaminated by traces from stools or urine (Fig. ). Thus, we immediately removed the catheter and started treatment with cefepime, a fourth-generation cephem type antibiotic. Only two hours after antibiotic administration, her SBP reduced dramatically and she became unresponsive to high dose vasopressor (epinephrine). The patient died at 11:00 a.m. on POD 40, one and a half days after fever onset. After her death, the causative agent was confirmed to be Klebsiella pneumoniae, as observed by blood culture and catheter analyses. These findings imply that CRBSI might have occurred, inducing a rapid decline in the patient’s condition and resulting in death in a stroke patient with additional organ failure.
|
pmc-6162896-1
|
A 20 year-old man presented with a 1-month history of impaired vision, binocular horizontal diplopia and metamorphopsia. There was no history of headache, vomiting, fever, or trauma. He denied any history of hematological or neurological diseases, and was not on any medication. Notable in his past medical history was that he had undergone surgery for mastoiditis 8 years previously.
On presentation, the patient appeared in clear consciousness. Vital signs were stable, with blood pressure 121/82 mmHg, pulse 88 bpm and a body temperature of 37 °C. Best corrected visual acuity was 0.15 (Decimal Fraction) in both eyes. Ocular motilities of both eye were normal. Ophthalmoscopy revealed significant bilateral optic disc swelling with peri-papillary hemorrhages (Fig. ), but the eyes were otherwise normal. Fundus fluorescein angiography (FFA) showed hyperfluorescent leaking defects at the optic discs (Fig. ). Humphrey automated perimetry (HAP) revealed bilateral inferior arcuate scotomas (Fig. ). Optical coherence tomography (OCT) showed bilateral papilledema, but the macular morphology was normal (Fig. ). Flash visual evoked potentials (FVEPs) showed normal peak time of the P2 wave (Fig. ). The electroretinogram (ERG) also showed normal retinal function. Routine hematological and biochemical tests showed no significant abnormalities. Unenhanced brain and orbital magnetic resonance imaging (MRI) showed neither abnormal signals nor any signs of increased intracranial pressure, such as enlarged ventricles or mid-line shift, partially empty sella, flattening of the globe, or enlarged optic nerve sheaths (Fig. ). The patient was examined by neurologist, and no positive neurological signs were found. Considering the poor vision of both eyes, he was administrated with systemic steroids, but the visual acuity did not improve afterwards.
Given the patient’s manifestation and ophthalmological and systemic investigations, primary optic neuropathies, including optic neuritis and ischemic optic neuropathy, were basically ruled out. Specialized investigations for intracranial pathology were therefore performed. Magnetic resonance venography (MRV) showed a loss-of-signal void in the right sigmoid sinus (Fig. ). LP at the time showed an elevated cerebrospinal fluid (CSF) opening-pressure of over 40 cm H2O (normal, 18–20 cm H2O). CSF protein, glucose, and cell counts were all within normal limits. After neurological consultation, a digital subtraction angiography (DSA) was performed, which showed a filling-defect in the right sigmoid sinus (Fig. ). The patient was diagnosed with right sigmoid sinus thrombosis, and was referred to the neurology department for conservative treatment. At 6 months follow up, the visual acuities improved to 0.2 in right eye and 0.3 in left eye.
|
pmc-6162896-2
|
A 72 year-old man presented with visual loss in his left eye for 7 months and decreased vision in his right eye for 8 months. He had been diagnosed with multiple lacunar cerebral infarctions and non-arteritic anterior ischemic optic neuropathy (NAAION) in the neurology department, but no positive neurological signs were found. He was given oral steroid therapy for several months, but with no improvement in vision. The patient had no history of hypertension or diabetes and no history of systemic or local infection.
The patient came to the ophthalmology outpatient department for further investigation. On presentation, he was in clear consciousness. Best corrected visual acuity was 0.3 (right) and no light perception (left). Relative afferent pupillary defect was present in the left eye. Mild lens opacity was observed in both eyes. In the right eye, the optic disc was slightly edematous (Fig. ). In the left eye, the optic disc was slightly pale in color (Fig. ). Signs as gliosis of peripapillary retinal nerve fiber layers, optociliary shunt vessels, or refractile bodies were not found. FFA showed hyperfluorescence of the right optic disc, and hypofluorescence in the left optic disc (Fig. ). HAP revealed superior and nasal scotomas (Fig. ). OCT revealed that both macula had normal morphology (Fig. ). FVEP showed a mild decrease in amplitude of the P2 wave in the right eye, and a severe decrease in the left eye (Fig. ). The ERG was relatively normal bilaterally. In the neurology department, he had previously undergone a contrast-enhanced CT-head (Fig. ) and CTA (computed tomographic angiography), which showed no abnormalities (Fig. ). An unenhanced MRI brain showed multiple lacunar cerebral infarctions and mild cerebral atrophy. Laboratory tests ruled out any blood disorders or infections. To further investigate for intracranial conditions, an MRV was performed, which demonstrated superior sagittal sinus thrombosis (Fig. ). LP showed an elevated cerebrospinal fluid (CSF) opening-pressure of 30 cm H2O. CSF protein, glucose, and cell counts were all within normal limits. The patient was referred back to the neurology department for endovascular intervention and stent placement. The best corrected visual acuity of right eye improved to 0.4 at six months following treatment.
|
pmc-6162896-3
|
A 20 year-old woman presented with a 1-month history of deteriorating vision. There was no history of eye pain, headache, vomiting, fever, or trauma. She denied any history of infection or surgery, and was not taking oral contraceptives, or any other medication. There was no notable past medical history.
On presentation, the patient’s best corrected visual acuity was 0.9 (right) and 0.5 (left), and she had normal pupil diameter and pupillary reflexes. Ophthalmoscopy revealed significant bilateral optic disc swelling and peri-papillary hemorrhages, but no other abnormalities (Fig. ). The papilledema was surprisingly severe given her moderate visual impairment. The intra-ocular pressure (IOP) of both eyes was normal. Examined by neurologist, the patient showed no positive neurological signs. FFA showed hyperfluorescence of both optic discs and dilated peri-papillary capillaries (Fig. ). There was no other abnormal fluorescence observed. OCT showed bilateral papilledema but normal macular morphology (Fig. ). HAP showed non-specific bilateral inferior nasal scotomas (Fig. ). Pattern VEPs (PVEPs) indicated a nearly normal amplitude of the P100 wave in the right eye (visual acuity of 0.9) and a decreased amplitude with normal peak time of the P100 wave in the left eye (Fig. ).
Blood tests showed no evidence of systemic infection or biochemical abnormalities. No abnormalities were seen on an unenhanced MRI of the brain (Fig. ). An LP demonstrated an elevated CSF opening pressure of 29 cm H2O. To further investigate for intracranial conditions, an MRV was performed, which showed a narrowed right transverse sinus, but no other abnormalities (Fig. ). From this imaging, the patient was diagnosed with right transverse sinus stenosis and referred to the neurosurgery department for further investigation of venous anatomy, prior to treatment. At 6 months follow up, the visual acuity kept unchanged. Due to personal reasons, the patient refused the ventriculoperitoneal shunt suggested by neurologists.
|
pmc-6162916-1
|
A woman in her 40s presented with acute onset of marked jaundice that had become progressively worsening over the course of 30 days, after taking ibuprofen intermittently for menalgia. The associated symptoms included profound fatigue and dark urine. No other symptoms were present. Twelve months prior to the onset of jaundice, she had menorrhagia after receiving the diagnosis of adenomyosis of uterus. She started only on ibuprofen 300 mg bid by mouth for 2–3 days each month with a total of six months when menalgia occurred. Her medical history included type II diabetic for one year on oral acarbose 50 mg TID and metformin 500 mg three times daily. She had no other medications. She had a surgical resection for a right ovarian cyst about 20 years ago. At the time, she was a non-smoker and did not consume any alcoholic drinks or recreational drugs. Clinical examination revealed normal vital signs and mental status. Although she has scleral icterus and a soft, non-tender abdomen with a surgical scare, neither signs of ascites nor hepatomegaly were presented. Her spleen was palpable at 3 cm below the left costal margin. There was no asterixis.
Laboratory testing revealed a normal completed blood count except Hb of 82 g/L (110–150); normal plasma thromboplastin antecedent and partial thromboplastin time; deranged liver function tests (alkaline phosphatase 1598 U/L, alanine transaminase 207 U/L, aspartate transaminase 247 U/L, total bilirubin 103 umol/L with direct bilirubin 75 umol/L, and albumin 30 g/L); abnormal lipid profile (total cholesterol 43 mmol/L, triglyceride 3.6 mmol/L, high-density lipoprotein cholesterol 6.4 mmol/L, low-density lipoprotein cholesterol 35 mmol/L Apolipoprotein-A1 0.6 g/L, Apolipoprotein-B 1.2 g/L); and normal electrolytes except potassium of 3.1 mmol/L. Viral serology was negative for hepatitis A, B, C, and Epstein-Barr virus. Antibody tests for hepatitis E, ASMA, RO-52, LKM, AMA, AMA-M2, SLA, and gp210 were negative. Her ceruloplasmin, ferritin, and iron were normal. The titers of cytoplasmic type and nuclear membrane type of ANA were 1:100 and 1:320, respectively. Her IgG level was 15.9 g/L and cytomegalovirus (CMV) PCR was negative although CMV IgG was > 500.00 U/ml. The patient was admitted and ibuprofen was discontinued. Further investigations included the followings: an MRCP revealed stones in the gallbladder without intrahepatic or extrahepatic bile duct dilatation; a computed tomography scan with contrast on day 10, which showed a few small enhanced patchy lesions on the left hepatic lobe likely due to the abnormal perfusion, mild splenomegaly, but no vascular abnormalities or intraperitoneal free fluid. However, three follow-up MRI exams with contrast on days 100, 185 and 260 showed a normal size of the spleen and normal diameters of both intra/extra-hepatic ducts. There were no signs of lymphoma. On the day of first evaluation, the Roussel Uclaf Causality Assessment Method score (RUCAM) was 6 (R = 0.32, grade III liver injury). A liver biopsy was performed on day 28 from the onset of her jaundice. The pathology slides were presented in Fig. , which revealed biliary injury and absence of small terminal bile ducts around hepatic arteries affecting over 50% of sampled portal tracts. In addition, Bile salt deposition was visible among peripheral hepatocytes with no evidence of steatohepatitis or significant fibrosis. The Ishak grading showed necroinflammatory activity score of 5 and fibrosis score of 2. The findings were consistent with DILI and VBDS.
This 40-year-old woman, who had a history of taking ibuprofen, became acutely ill with a rapid progressive jaundice and high cholesterol followed by profound fatigues that developed over a 4-week period. The differential diagnosis included drug-induced liver injury, viral hepatitis, marker-negative autoimmune hepatitis, non-alcoholic steatohepatitis, overlap syndrome, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC). Her initial presentations were consistent with intrahepatic cholestasis. She had laboratory evidence of acute hepatic injury and liver biopsy suggested drug-induced liver injury. Moreover, the histological features also suggested VBDS. Thus, further differential diagnosis for VBDS was needed, which includes not only aforementioned drug-induced liver injury, [] viral hepatitis, autoimmune hepatitis; but also biliary obstruction, idiopathic adulthood ductopenia, Alagille syndrome, PSC, PBC, lymphoma, and ischemic liver injury [].
As supported by the clinical data and the RUCAM score of 6, which indicated modestly probability of DILI with severe liver injury (stage III), her clinical diagnosis was an ibuprofen-induced liver injury resulting on persistent cholestasis and hyperlipidemia. The pathology diagnosis was DILI at the stage of IV. In addition, the features of bile duct injury and the loss of bile duct structures were consistent with VBDS. She has no hepatic duct dilatation or signs of lymphoma in MRI study on day 260. In addition, her negative test results of AMA-M2 and other autoantibodies did not support the diagnosis of PBC or PSC.
Due to further deterioration of liver function tests despite the cessation of ibuprofen, the patient was hospitalized and received supportive care with intravenous therapy of polyene phosphatidylcholine 930 mg daily. Her oral medication included silibinin capsule at the dose of 200 mg daily, glutathione 2.4 g daily, and weight-based ursodeoxycholic acid at the dose of 250 mg three times a day. In addition, she continued on acarbose and metformin for her diabetic. Although she had progressively worsening jaundice over the first 7 days, the patient’s fatigue and biochemistry were subsequently improved with her total bilirubin decreased from167 umol/L to 130 umol/L. She had normal prothrombin time (PT) during her hospital stay. She was discharged on day 47 and followed up in outpatient’s clinic with the last visit on day 315. Her hyperbilirubinemia persisted with normal PT during the period of her outpatient visits, although the levels were slowly trending down from over 100 umol/L to 30 umol/L. The changes in biochemistry parameters including bilirubin and alanine aminotransferase (ALT) are shown in Fig. . Her ALT levels fluctuated at the range of 70–180 U/L. In addition, the patient had persistent hyperlipidemia during the entire observational period. Her total cholesterol and triglyceride levels both remained at levels above 10 times higher than normal, whereas the low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were always below 10 mmol/L (Fig. ). Owing to the persistent elevation on the serum levels of bilirubin and ALT, a second liver biopsy was performed on day 213. Pathology report indicated again the absence of small terminal bile ducts, interstitial fibrous tissue hyperplasia, bile salt deposition in the peripheral liver cells, and visible lymphocytes with small amount of plasma cell infiltration; Ishak necroinflammatory activity score of 4 and fibrosis score of 2; keeping with a diagnosis of acute VBDS but some features of autoimmune hepatitis (Fig. ).
|
pmc-6162942-1
|
A 57-year-old man was admitted to our institution with repeated attacks of high IOP accompanied with AU in left eye for 4 months in 2016. He had a history of Posner–Schlossman syndrome (PSS) in left eye with recurred several times 20 years ago. According to outpatient medical records (Figs. , and ; Additional files , and ), the maximum IOP is 36 mmHg and the best-corrected visual acuity (BCVA) is 20/25 with deep anterior chamber, fine pupillary light reflex and a few anterior chamber inflammations during 4-month follow up period. Examinations found significant thinned retinal nerve fiber layer (RNFL) at superior and nasal side corresponding to visual field defects in inferior temple quadrant for the infected eye on his first visit in our outpatient center in May 2016. Topical corticosteroids and anti-glaucoma agents were treated then while IOP elevated repeatedly.
On admission in September, his BCVA is 20/25 for right eye, and 20/200 for left eye. The IOP is 18 mmHg and 40 mmHg respectively. The main features in his left eye are cornea edema with bullous keratopathy, fine white keratic precipitates (KPs), deep anterior chamber, 2+ flare counts in aqueous and patched iris atrophy. Meanwhile, visual field defects and glaucomatous optic nerve defects were enlarged (Figs. and ). Quantitative PCR testing for CMV-DNA was immediately performed in samples from aqueous humor and serum. Human immunodeficiency virus (HIV) and other infection antibodies in serum were also tested. Results showed serum IgG for CMV but no IgM, HIV and other infectious diseases. The CMV-DNA in aqueous sample was positive (1800 copies/ml). Then the patient was treated with 2-week systemic antiviral therapy (ganciclovir 5 mg/kg twice a day intravenously for a week, followed by once a day for another week), topical 0.15% ganciclovir gel four times daily, 1% prednisolone acetate eye drops (Pred Forte) four times daily and local anti-glaucoma medications (brinzolamide and brimonidine). The IOP became normal 3 days later and the patient was asked to follow up.
However, 12 days after cessation of systemic use of genciclovir, the IOP in patient’s left eye reached to 33 mmHg with topical genciclovir gel, corticosteroid (Pred Forte) and NSAID (Pranoprofen) consistently used (Fig. ). The patient was readmitted because of the persistence of elevated IOP despite additional medication treatments for 20 days. After readmission, test showed that CMV-DNA was only 526 copies/ml in aqueous. But the IOP maintained a high level of 50 mmHg or above (Fig. ). To exclude corticosteroid glaucoma, NSAID were applied topically without steroid, accompanied with genciclovir gel and glaucoma medications. In addition, systemic therapies were administered for anti-virus (ganciclovir 5 mg/kg twice a day intravenously), anti-inflammatory (vein injection of methylprednisolone 80 mg per day) and anti-glaucoma (anterior chamber penetration, intravenous mannitol) in subsequent 15-day. Nevertheless, in view of the persistence of high IOP, corneal opacity with no cornea endothelial cells (CEC) could be measured and the development of glaucomatous damage (Figs. , , and ), trabeculectomy was operated for refractory glaucoma (Fig. ) of left eye in Nov. 2016. At this time, the test for CMV-DNA of the eye was negative (10 copies/ml) and the postoperative IOP has been controlled (8-13 mmHg) with BCVA of 20/25 a year later (Fig. ). However, the count of CEC in the infected eye has much lesser than that in the fellow eye after 6 months (Fig. ; Additional file ).
|
pmc-6162950-1
|
A 44-year-old Asian woman with type 2 diabetes and schizophrenia was being treated at our hospital. For type 2 diabetes, she received 1250 mg of metformin and 50 mg of sitagliptin phosphate hydrate a day and an intermediate-acting insulin 6 unit injection before bedtime. For schizophrenia, she received 8 mg of biperiden hydrochloride, 600 mg of valproic acid, 600 mg of carbamazepine, 15 mg of mirtazapine, 25 mg of clomipramine, 25 mg of chlorpromazine, 12.5 mg of promethazine, and 40 mg of phenobarbital. There was no other medical history. Her father had type 2 diabetes. She smokes two packs of cigarettes per day for 24 years, and drinks socially. After a quarrel with her mother, she attempted suicide by ingesting 10 tablets of 500 mg metformin and drinking about 600 mL of Japanese sake containing 15% alcohol.
She was transferred to our emergency department because of disturbed consciousness. On physical and neurological examination, her Glasgow Coma Scale was 3 (eye, 1; verbal, 1; motor, 1). Both pupils were 1.5 mm, and light reflexes were rapid. Her respiratory rate was 30 breaths per minute. Her heart rate was 120 beats per minute and blood pressure was 120/60 mmHg. She then received continuous intravenous administration of noradrenalin (0.13 μg/kg per minute) because she was in shock. Her body temperature was 35.5 °C. On auscultation, no crackles and wheezing were detected. There were no murmurs. Aspiration pneumonia was detected in both the lungs by computed tomography. Laboratory findings (normal ranges in parentheses) demonstrated aspartate transaminase level of 16 (7 to 35) IU/L, alanine transaminase level of 15 (7 to 40) IU/L, lactate dehydrogenase level of 273 (125 to 225) IU/L, creatinine level of 0.94 (0.60 to 1.20) mg/dL, and blood urea nitrogen level of 12.7 (8 to 20) mg/dL. Arterial blood gas analysis on 100% oxygen revealed a pH of 7.067, partial pressure of oxygen in arterial blood of 143 mmHg, partial pressure of carbon dioxide in arterial blood of 52.9 mmHg, bicarbonate of 14.5 mmol/L, base excess of − 16 mmol/L, lactate of 119 mg/dL (13.2 mmol/L), and blood glucose of 632 mg/dL. Serum metformin concentration was 1138 ng/mL (Table ). Serum osmolality and sodium concentration were 309 mOsm/kg and 135 mEq/L, respectively. No ketone bodies were detected in her urine.
She was diagnosed as having MALA worsened by alcohol. First, enforced sedation with midazolam was performed because of restlessness, tracheal intubation was carried out, and activated carbon and magnesium citrate were used for decontamination after gastric lavage. After 4560 ml of bicarbonate ringer (Na+ 135 mEq/L, K+ 4 mEq/L, Cl− 113 mEq/L, HCO3− 25 mEq/L) was administered, HFHV-iHDF (dialysate flow rate: 500 mL/min, substitution flow rate: 3.6 L/h) was carried out for 6 h using a polysulfone high-performance membrane (APS-15E, Asahi Kasei Medical, Tokyo, Japan) to treat metabolic acidosis and remove lactic acid and metformin. After that, her serum metformin concentration decreased to 136 ng/mL (Fig. ) and noradrenalin administration became unnecessary to maintain normal vital signs. On hospital day 2, HFHV-iHDF was carried out again, which improved her consciousness. On hospital day 10, she was extubated after aspiration pneumonia healed. On hospital day 12, she was moved to the psychiatry ward. She left the hospital 1 month after she moved to the psychiatry ward. When she left the hospital, she was discontinued from metformin administration. Although there is no recurrence of lactic acidosis, she was re-hospitalized into the psychiatry ward because she took an overdose of sleeping pills, 2 months after she left the hospital. Since then, she was in the hospital for the control of her schizophrenia and diabetes for more than 2 months.
|
pmc-6162954-1
|
The patient is a 34 year old healthy primigravida with spontaneous dichorionic diamniotic twins and likely bicornuate uterus, with one fetus in each horn, initially diagnosed at 12 weeks gestation by two-dimensional ultrasound. Magnetic resonance imaging at that time reported bicornuate unicollis uterine anatomy, with symmetrical myometrial thickness in both horns. The left cervical canal was noted to communicate with the right lower uterine segment and not directly with the vagina. A thin amniotic band was noted in the superior left uterine horn. Bilateral normal maternal kidneys were noted.
The patient subsequently presented at 17 weeks gestation with new onset significant pelvic pain. An MRI at an outside hospital demonstrated a thin myometrial wall (thickness not reported) in the left uterine horn without myometrial disruption, but with moderate pelvic free fluid (Fig. ). The patient’s hematocrit was noted to decline from 32 to 26%, and she was transferred to our tertiary care center for further management. Three-dimensional ultrasound at our institution revealed two separate uterine cavities, each with a live appropriately-grown fetus with normal amniotic fluid. The anatomy of the cervices was difficult to delineate, but a vascular connection was noted between the medial surfaces of each horn. The myometrium over the left horn was noted to be “markedly thinned” superiorly (Fig. ). Moderate hemoperitoneum was documented, with a 3.6 cm clot adherent to the thinnest portion of the myometrium of the left horn. Concern was raised for rupture of a rudimentary uterine horn. A severe cardiac anomaly was incidentally diagnosed in the fetus in the right unicornuate uterine horn.
Given these imaging findings and the patient’s ongoing pain, the decision was made to proceed with diagnostic laparoscopy and left hemi-hysterectomy with fetus in situ. The patient underwent ultrasound-guided selective reduction of the fetus in the left uterine horn using intracardiac potassium chloride. Immediately after this procedure, the patient underwent laparoscopy, at which point she was noted to have a right unicornuate uterus with a rudimentary left uterine horn, with 2 cm rupture on the superior surface with amnion protruding (Fig. ), and moderate hemoperitoneum. Due to intraoperative bleeding and suspected amniotic rupture during examination of the left horn, the procedure was converted to an abdominal hemi-hysterectomy. During this procedure, a fibrous but narrow band was noted between the uterine horns, which was ligated and transected using bipolar energy. The procedure and the patient’s recovery were uncomplicated.
The pregnancy in the right uterine horn continued postoperatively. At 19 weeks of gestational age, in the setting of a severe fetal cardiac anomaly and high likelihood of preterm delivery complicating surgical correction, the patient underwent laminaria placement and uncomplicated ultrasound-guided dilation and curettage of the right uterine horn.
The patient subsequently spontaneously conceived two singleton pregnancies. Normal anatomical surveys and fetal echocardiograms were noted in each. Both pregnancies were complicated by preterm contractions without cervical change. Eighteen months after her surgery, the patient delivered a healthy, small for gestational age (2,580 g) female infant, followed by a healthy 2,722 g male the following year.
|
pmc-6163120-1
|
A 55-year-old man was referred to our hospital for jaundice and pruritus. His laboratory tests showed elevated blood markers, with a γ-glutamyl transpeptidase (γ-GTP) level of 1330 U/L (normal range, 10–75 U/L) and a total bilirubin level of 2.5 mg/dL (normal range, 0.5–2.5 mg/dL). Additionally, his serum carcinoembryonic antigen level was elevated at 17.4 U/mL (normal range, less than 5.0 U/mL), although there was no elevation in serum carbohydrate antigen 19-9 level.
Computed tomography (CT) showed wall thickening in the second portion of the duodenum, dilation of the common bile duct, and swelling of the para-aortic lymph node (Fig. ). Upper endoscopy suggested a duodenal tumor (Fig. ). Although intraductal ultrasonography was performed, invasion of the tumor into the bile duct was not observed. For obstructive jaundice, an endoscopic retrograde bile drainage tube was placed at the common bile duct. Further imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated abnormal uptake in the tumor in the duodenum (Fig. ), in the para-aortic lymph nodes (Fig. ), and in a 10-mm metastasis in segment 8 of the liver (Fig. ). Based on the Union for International Cancer Control TMN staging, the clinical diagnosis was cT4N2M1, stage IV.
The patient was scheduled for combined chemotherapy with XELOX: 2000 mg/m2 capecitabine orally on days 1–15 and 130 mg/m2 oxaliplatin intravenously on day 1 of a 21-day cycle. The patient received six cycles and experienced no adverse events.
In order to address the effectiveness of chemotherapy, the patient received follow-up FDG-PET/CT or CT every 2 months. Last FDG-PET/CT confirmed disappearance of the metastatic liver tumor and nodal metastasis (Fig. ). The patient was considered a surgical candidate to be evaluated for complete response (CR) by FDG-PET/CT. Seven months after the initial diagnosis and after 6 months of chemotherapy, the patient underwent pancreaticoduodenectomy with lymph node dissection and partial resection of the liver for curative intent.
During the operation, peritoneal dissemination and ascites were not observed. D2 lymph node dissection, including resection of the para-aortic lymph node, which is based on the dissection range of pancreatic cancer, was performed. Regarding liver metastasis, we could detect it as a scar. The lesions in the duodenum, liver, and 43 lymph nodes were not visible in the surgical specimen. Postoperatively, the histological effect was determined to be grade 3, and the patient was diagnosed as having achieved pathological CR (Fig. ).
Although the patient suffered from grade A postoperative pancreatic fistula based on the International Study Group of Pancreatic Fistula definition, he was discharged from our hospital on postoperative day 32 without fatal complications. He received capecitabine orally for 6 months and has been disease-free for 14 months after the surgery with no evidence of metastatic lesion.
PDC is a very rare disease; the cancer accounts for less than 0.3–1% of all digestive organ cancers [] and 25–45% of primary small intestinal cancers. Aggressive surgical resection for PDC is thought to be the most effective treatment and only chance for a cure. The 5-year survival rate for patients who undergo curative resection is 50–70%. However, patients who present with unresectable disease receive palliative operation or endoscopic treatment with or without chemotherapy, and their prognosis remains poor, despite considerable research.
In recent years, advancements in chemotherapy have allowed conversion surgery to emerge as a new therapeutic option. It is expected to have beneficial effects for various cancers, including pancreatic cancer [] and gastric cancer []. However, there are very few reports of conversion surgery for unresectable PDC. Kanehira et al. reported a conversion surgery in which they achieved R0 resection for PDC with para-aortic lymph node metastasis using S-1 and cisplatin combination chemotherapy []. However, even the feasibility of chemotherapy for PDC is unclear. Also, the most effective regimens are controversial. Treatment with S-1 and cisplatin, which is a standard treatment for gastric cancer, and FOLFILI or FOLFOX, standard treatments for colon cancer, have been used [, ]. Xian et al. reported that a modified FOLFOX regimen, which consists of biweekly oxaliplatin in combination with continuous infusional 5-fluorouracil and leucovorin, had efficacy and safety in 33 patients with unresectable small bowel cancer, including 26 patients with duodenal cancer. They observed only one CR, and the 15 patients who achieved partial response received a median of nine cycles []. Although Tsushima et al. and Zaanan et al. recommended a platinum-based regimen, such as FOLFOX, for unresectable intestinal cancer [, ], none of the patients in these studies achieved CR, despite platinum-based regimens being common in unresectable PDC.
Our patient received XELOX with the aim of eliminating the liver and lymph node metastases or decreasing them to operable sizes. Fortunately, our patient was able to achieve pathological complete response (pCR). This case also demonstrates two important clinical issues. First, this combination therapy, which is a platinum-based regimen, is safe and effective for patients with colon cancer. Second, the tumor, including the metastatic lesions, disappeared rapidly without severe toxicity. Moreover, PET/CT was beneficial for therapeutic evaluation in our case, as has been previously shown by several investigators [].
Conversion surgery for PDC has some limitations. Even retrospective data are limited by the accuracy and completeness of the medical record, and the case studies reported in many previous studies have been collected over several decades. Therefore, there is no clear evidence that conversion surgery improves outcomes in patients with unresectable PDC.
Moreover, there is no clear evidence for dissection of para-aortic lymph node metastasis from digestive cancer including PDC. In 2014, Tsubraya reported the effectiveness of para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis including para-aortic lymph node metastasis after neoadjuvant chemotherapy []. Also, Arimoto reported that the 3-year overall survival was 41.2%, though the recurrence rate after para-aortic lymph node dissection for patients with colorectal cancer receiving neoadjuvant or adjuvant chemotherapy was quite high []. So, we considered that there may be a value in trying para-aortic lymph node dissection in such our case.
In terms of watch and wait strategy, it is the agenda that is needed to debate for patients who achieved complete response. Renehan et al. reported the effectiveness of the wait and watch strategy for rectal cancer. In fact, 3-year non-regrowth free survival and 3-year overall survival rate for patients who received wait and watch approach did not show no significant difference compared with patients who underwent surgical treatment. Moreover, patients who were managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years []. However, in terms of watch and wait approach for patients with duodenal carcinoma who achieved complete response, none of the reports has been published. So, we should carefully determine the surgical indication for those patients, and it is needed to debate this agenda with those accumulating cases.
|
pmc-6163291-1
|
Our case was a 53-year-old man who received a deceased donor kidney transplant 16 years ago, which was presumably due to hypertension. He presented with redness, pain and swelling of his left arm. He reported no trauma but was trimming shrubs and plants one week earlier. He also complained of intermittent fever and chills. There was no significant animal contact or recent travels. He took cyclosporine and mycophenolate for immunosuppression but had no recent use of corticosteroids.
Evaluation showed a temperature of 100.3 °F, heart rate of 99 beats/min, respiration of 20 cycles/min and blood pressure of 109/71 mmHg. Skin examination showed erythema, tenderness and swelling on the medial aspect of his left arm and forearm in a linear fashion (). There was also a wound on his left forearm, which was located distal to the sporotrichoid lesion, which he thought might have been due to an insect bite or an injury related to his recent gardening (). There was an old unused dialysis graft on the forearm, which appeared to be unaffected. There were no significant lymph node enlargement and the examination of the other systems was completely unremarkable.
Ultrasound imaging of the left arm showed hypoechoic, tubular type structures (the largest measuring 8 × 5 mm) in the subcutaneous fat, which is consistent with an abscess. Two views of the chest radiograph was normal.
The patient underwent incision and drainage of a long abscess tract, which measured approximately 35 cm. Frank purulent drainage was expressed from the tract and was sent for bacterial, fungal and mycobacterial cultures. In the meantime, the patient was started on empirical intravenous piperacillin/tazobactam and vancomycin while awaiting culture results. Sporotrichosis was considered as a strong differential but antifungal therapy was deferred until the culture results became available.
Significant laboratory findings include a white blood cell count of 12.2 × 109/L, blood urea nitrogen of 56 mg/dL and creatinine of 2.7 mg/dL from a baseline of 1.8 mg/dL. Blood cultures and culture of the distal left forearm wound were negative for any growth.
Pale, yellowish-white colonies were isolated from fungal cultures of the pus on Sabouraud dextrose agar without Chloramphenicol after 11 days ().
The gram stain of the colonies revealed aerobic, branching, gram positive rods, which were further identified by 16S ribosomal RNA (16S rRNA) sequencing as Nocardia brasiliensis. Susceptibility results showed that the isolate was sensitive to trimethoprim–sulfamethoxazole, linezolid, amoxicillin/clavulanate, moxifloxacin, amikacin, ceftriaxone and tobramycin; had intermediate sensitivity to doxycycline and minocycline; and was resistant to imipenem, ciprofloxacin and clarithromycin. The bacterial cultures did not grow and were discarded after 5–7 days per institution protocol. Mycobacterial cultures were also negative. Pathology of the excised abscess tissue revealed acute inflammation and abscess formation, which involved the dermis and subcutaneous tissue with dermal and fat necrosis. No bacterial or fungal elements were seen on appropriate stains. Due to his worsening kidney function, a renal biopsy of his transplanted kidney was obtained, which showed findings that were consistent with IgA nephritis, chronic allograft nephropathy and glomerulosclerosis.
He received amoxicillin/clavulanate 875/125 twice daily for 6 months for definitive treatment of his Nocardia infection. Three weeks post discharge, the sporotrichoid lesion significantly improved and the abscess wounds showed evidence of good healing (). At his 6-month follow up, he had made a complete recovery with no residual lesions.
|
pmc-6163449-1
|
A 65-year-old woman was checked out by a Computed Tomography (CT) examination in April 2015, which showed a left upper lung shadow that was found to be a lesion occupying the left upper lung space. The woman underwent a left upper lung sleeve resection in June 2015. After the operation, her postoperative pathology diagnosis revealed low differentiated squamous cell carcinomas in the upper left lung. From 28 June 2015 to 30 September 2015, she endured five rounds of chemotherapy, but there seemed to be no improvement after chemotherapy. In early January 2017, she developed symptoms of fatigue, consciousness disorder, and limb twitching without any obvious cause. In 6 February 2017, she underwent a Brain Magnetic Resonance Imaging (MRI) examination and the result revealed that she had multiple brain metastases.
With the previous treatment process that gave her hardship, the old woman was not willing to undergo surgery again and continue to undergo multiple radiotherapies. Under such complex conditions, it was hard for the attending physician to determine an optimal therapeutic schedule by himself. In the real word, the attending physician gave five optional therapeutic schedules, i.e., “Stereotactic Radiosurgery (SRS) ”, “Whole Brain Radiotherapy (WBRT) ”, “ALK-Targeted Therapies ”, “WBRT-SRS ”, and “Erlotinib or Gefitinib ”, and gathered five experts from Radiotherapy, Neurosurgery, Oncology, Pathology, and Imaging together to consult on an optimal therapeutic schedule for the old woman. Through a long consultation, the experts chose as the woman’s therapeutic schedule, and the eutherapeutic of the therapeutic schedule was confirmed by clinical observation.
|
pmc-6163764-1
|
Case 1: Vancomycin
The patient is a 64-year old male who was hospitalized 3 days ago while on vacation in Florida for an infection in a wound on his leg. Further evaluation revealed MRSA in the wound. In addition to home meds for hypertension and ischemic heart disease, patient was placed on vancomycin with peak and trough targets.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.