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pmc-6311819-1
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Our patient is a 38-year-old male who presented with right chest wall and shoulder pain after a weight lifting injury. The patient was performing a one-rep max bench press when he felt a pop in his right upper arm, accompanied by severe pain. There was no history of anabolic steroid use. He was initially treated with ice and a sling by a trainer and presented to the emergency department for further evaluation. Plain films were negative for fracture or dislocation and the patient was neurovascularly intact, so he was discharged home by ER staff in the sling. He presented to the orthopedic clinic the following day with moderate pain in the chest and arm. He denied numbness and paresthesia. On physical examination, there was a large amount of swelling and ecchymoses throughout the right upper arm extending into the pectoralis major muscle belly. Additionally, there was a large bulge in the anterior chest with loss of contour of the axillary fold (). The patient had full active range of motion of the elbow, wrist, and digits. He was sensory intact throughout the right upper extremity with a 2+ radial pulse. An MRI was scheduled to determine the extent of the injury and to aid in surgical planning. The patient was given oxycodone and valium to alleviate the pain and muscle spasms until surgery, which was scheduled after his MRI. The MRI demonstrated avulsion of the pectoralis major tendon from its insertion on the humerus with retraction as well as strain of the anterior deltoid (Figures and ). He was scheduled for surgery in five days. Two days later, the patient returned to our facility with severe worsening pain in the right upper arm. Intracompartmental pressure readings in the anterior compartment of the arm taken about the midpoint of the biceps at the point of maximal swelling were 37, 39, and 42 mmHg with a diastolic blood pressure of 71 mmHg (). Thus, with a diagnosis of compartment syndrome confirmed, we proceeded to the operating room for an emergency fasciotomy with repair of the pectoralis major tendon rupture.
An extended deltopectoral approach was used, and the deltopectoral and biceps fascia were released. Immediately, a large amount of hematoma was expelled and the muscle bellies visibly bulged from the incision sites (Figures and ). All muscles still appeared viable. No apparent vascular damage was noted. Upon further dissection, both heads of the pectoralis major were found to be avulsed from the proximal humerus (). After preparation of the footprint with curette and rongeur, three double-loaded 4.5 mm Mitek suture anchors (DePuy Synthes, Raynham, MA) were placed lateral to the bicipital groove for the repair of the tendon. The proximal and distal suture anchors were used such that one suture of each was run in a Krakow fashion along the superior and inferior aspects of the tendon, respectively. The remaining suture from each of those anchors was passed in a horizontal mattress fashion medial to the Krakow stitches. The middle suture anchor was used to place a horizontal mattress stitch with a medial ripstop stitch (). The wound was irrigated, and a negative pressure dressing was applied. The patient was made nonweightbearing and placed in a sling with a circumferential strap to ensure adduction of the arm. The patient returned to the operating room four days later to undergo irrigation and debridement with a tension-free primary wound closure. He was again placed into his sling and given strict instructions to avoid abduction and external rotation of the arm. The patient did well postoperatively and was discharged home in a stable condition that same day with a one-week follow-up appointment. He continued to do well and was instructed to remain nonweightbearing in his sling for a total of 6 weeks before beginning formal therapy. Gentle stretching and passive range of motion were then begun, followed by strengthening exercises at the 12th week mark. At his four-month follow-up, the patient had active forward flexion of the shoulder to 150°, abduction to 150°, and external rotation of 50°. His rotator cuff, biceps, triceps, wrist extensors, wrist flexors, and interossei all demonstrated 5/5 strength. There were no sensory deficits on examination. He continues to attend therapy for motion and strengthening and has a lifting restriction of <5 pounds at work.
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pmc-6311830-1
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The case is of a 67-year-old woman who was initially diagnosed at age 36 with early stage ER+ left breast invasive ductal carcinoma, treated with breast-conserving surgery followed by adjuvant radiation therapy. Unfortunately, she developed recurrence in the thoracic spine 16 years later which was treated with surgery and postoperative thoracic spine radiation followed by hormone therapy (letrozole and fulvestrant) and cytotoxic chemotherapy (capecitabine) over a four-year period. She recurred in the cervical spine and was treated with cervical spine radiation followed by liposomal doxorubicin and then paclitaxel. Since the initial occurrence of bone metastases, she was also treated with a bone modifying agent, initially pamidronate and then switched to denosumab due to worsening renal function.
Ten years after this, her disease progressed with multiple new bone metastases on PET/CT scan, and a decision was made to switch to palbociclib in combination with fulvestrant. Her other medical conditions included well-controlled type 2 diabetes mellitus, hypertension, obstructive sleep apnea, stage 3 chronic kidney disease, and recurrent urinary tract infections. Her baseline complete blood count (CBC) at start of treatment with palbociclib was notable for mild anemia with hemoglobin (Hb) range 8–9.5 g/dL (ref. 11.8–16 g/dL) but normal white blood cell (WBC) count 8.2 × 109/L (ref. 4–11 × 109/L) with normal differential and platelet counts 345 × 109/L (ref. 150–400 × 109/L). The initial palbociclib dose was 125 mg daily on days 1–21 of a 28-day cycle in combination with monthly fulvestrant 500 mg intramuscularly.
On routine clinic visit during cycle 3, week 2 of treatment, she was found to have new pancytopenia (WBC 3.9 × 109/L (with neutropenia and monocytopenia), Hb 6.9 g/dL, and platelet count 117 × 109/L). On examination, she had pallor but no icterus, hepatosplenomegaly, nor clinically palpable lymph nodes. Extensive review of her medication list did not reveal potential culprits for her pancytopenia. Routine blood tests for other causes of pancytopenia including vitamin B12, iron studies, folate, thyroid studies, hepatitis C, and HIV were normal. Serum erythropoietin level was appropriately elevated at 53.6 mIU/ml (ref. 2.6–18.5 mIU/ml). She was transfused with 2 units of packed red blood cells (PRBCs), and palbociclib was continued with dose modification.
Interval PET/CT scan done after cycle 3 showed stable bone disease with no new bone or visceral lesions. Tumor markers remained elevated but stable. Pancytopenia persisted with worsening leukopenia and thrombocytopenia (WBC dropped to 2.2 × 109/L with neutropenia and platelets 24 × 109/L). Reticulocyte count was inappropriately normal at 0.9% (absolute reticulocyte counts 30,000 cells/microliter). She continued to require red cell transfusions and developed bleeding gums with minimal trauma. Peripheral blood smear revealed mild anisocytosis with nucleated red cells (12 nucleated RBCs per 100 leukocytes), leukopenia with no dysplastic changes or blasts, and thrombocytopenia without clumping or giant platelets. Given these findings on peripheral smear and prolonged cytopenia, a bone marrow biopsy was performed to exclude a bone marrow infiltrative or leukemic process. Bone marrow biopsy/aspirate showed features consistent with severe aplastic anemia (few pockets of trilineage hematopoiesis accounting for about 2% of total cellularity and 98% fat) (Figures –). There was no evidence of marrow metastases, dysplastic features, or myelophthisis. Normal flow cytometry on bone marrow aspirate ruled out a leukemic process. Cytogenetic testing was normal (46XX in all 20 mitotic cells analyzed). Next Generation Sequencing for 42 somatic genetic mutations associated with myeloid disorders and neoplasms including myelodysplastic syndrome was negative.
Due to continued red cell transfusion dependence and persistent pancytopenia despite dose interruptions, palbociclib was discontinued after a total of 4 months. After discontinuation of palbociclib, her cytopenias improved significantly despite treatment of her progressing breast cancer with multiple other therapies. Her WBCs and platelets have now normalized, and her transfusion requirements are markedly decreased (from an average 1 unit red cells every 2 weeks to 1 unit every 6 to 8 weeks). At the time of this report, she had not received red cell transfusion in 2 months. The most recent CBC, 7 months after palbociclib was discontinued, is as follows: WBC 10.4 × 109/L (normal WBC differential), Hb 8.7 g/dL, and platelets 256 × 109/L. Interestingly, her mean corpuscular volume (MCV) at the initiation of palbociclib was 83 fL and went up to 95 fL by the 4th month and trended downwards after discontinuation.
Given the recovery in her blood counts and clinical improvement after discontinuing palbociclib, a bone marrow biopsy was not repeated as this is unlikely to alter management strategy. She is followed closely in the medical oncology clinic.
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pmc-6311835-1
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A 52-year-old male with a history of rheumatoid arthritis (RA) presented with 3 months of right-sided frontal-parieto-temporal headaches with associated fevers and weight loss. 2 weeks prior to admission, he developed dysarthria and left-sided hemiparesis. He was diagnosed with RA 10 years before and was on adalimumab at the time.
Physical exam revealed left-sided facial droop with ipsilateral upper and lower extremities weakness and sensory deficit, and multiple rheumatoid nodules were noted. Laboratory studies revealed leukocytosis with neutrophilia, normocytic anemia, and markedly elevated inflammatory markers. Computerized tomography of the head revealed a right frontal hypodensity (). Brain magnetic resonance revealed patchy leptomeningeal enhancement involving right frontal and temporal lobes associated with subcortical edema (). Cerebrospinal fluid (CSF) cytology revealed normal glucose with elevated proteins and white blood cells. Cultures from both, CFS and blood, were negative for typical and atypical bacteria, fungi, viruses, and parasites. Brain biopsy was obtained and showed microglial activation and gliosis, suggesting no microorganisms grew from brain tissue culture ().
At this point, RME was strongly suspected, so the patient was started on methylprednisolone. He was sent home with long-term steroid taper. On follow-up visits in the office, all signs and symptoms were noted to be resolved.
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pmc-6311840-1
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A 21-year-old man with history of uncontrolled hypertension and asthma presented to the emergency department (ED) with sudden onset substernal chest pain that started an hour before his arrival. Patient was walking down the stairs while at work and started having chest pain, sweating, and shortness of breath. Patient reported that he became dizzy and felt that his heart was racing. Although this episode of chest pain was unique and graded as severe, he previously had racing episodes that were not evaluated. No family history of cardiac disease was noted.
In ED, an ECG was obtained immediately at presentation (see , ECG 1). ECG showed evidence of supraventricular tachycardia (SVT) at 220 beats per minute consistent with short RP tachycardia. ECG also showed diffuse ST segment depressions. Before any manoeuvres were applied, patient converted spontaneously to normal sinus rhythm but was still complaining of the same crushing chest pain.
A second ECG was obtained which showed significant diffuse ST depressions in leads I, II, III, AVF, V3, V4, V5, and V6 and ST segment elevation in leads AVR and V1 (see , ECG 2). Although patient's rapid troponin test was negative, STEMI code pager was activated and the patient was transferred to cath lab emergently.
Heart catheterization showed normal coronary arteries. In addition, left ventricular ejection was estimated at 70% and his ascending aorta was normal without evidence of dissection. Troponin level hours later was positive and peaked at 10 ng·dL. On the next day, echocardiography was essentially normal with no wall motion abnormalities. Patient's electrolytes and thyroid function tests were within normal range. Patient was discharged on diltiazem. Later on, the patient underwent successful and uncomplicated slow pathway modification for the treatment of typical slow-fast AVNRT. No recurrence occurred at 6-month follow-up.
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pmc-6311860-1
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An 87-year-old female with a previous history of osteoarthritis and hypothyroidism presented to her primary care physician with concerns about a rapidly growing lesion of the medial orbit of the left eye and was referred to an ophthalmologist. She first noticed the lesion 3 weeks prior to presentation, and it had grown significantly since it was first discovered. On examination, she was found to have a medial orbital mass causing ectropion of the lower eyelid and symptomatic epiphora (see ). A CT of the orbits showed a 2.0 × 1.6 × 1.0 cm nonenhancing intraorbital soft tissue lesion abutting the nasal lacrimal duct, lateral and inferior to the globe, without definite osseous remodeling. There is no thickening of the lateral rectus muscle or inflammation. There was a moderate lateral displacement of the intraocular structures. The globe was intact (see ). An anterior orbitotomy with biopsy was performed 4 days after presentation. The pathology was initially read as positive for intermediate grade epithelioid carcinoma. The specimen was then sent for an outside consultation, and the diagnosis was edited to epithelioid sarcoma with rhabdoid features (proximal type). Immunohistochemical stains revealed the tumor to be AE1/AE3 strong positive, GATA3 strong positive, vimentin strong positive, EMA focal positive, calponin focal positive, myogenin negative, GFAP negative, P63 negative, CD68 negative, P40 negative, ER negative, desmin negative, CDx2 negative, CK20 negative, CK7 negative, S-100 negative, BerEP4 negative, SALL4 negative, and CD99 negative.
Due to the patient's age and the tumor histology, chemotherapy was not recommended by medical oncology. To complete her staging workup, a soft tissue neck CT showed no evidence of abnormal lymph nodes. The patient also had a chest/abdomen/pelvis CT that showed no evidence of metastatic disease in chest, abdomen, or pelvis. Thus, the disease was localized to the left orbit only.
Within one month of the biopsy, the patient underwent a left orbital exenteration with partial maxillectomy and partial ethmoidectomy. The final pathology was positive for ES with rhabdoid features of the left medial orbital wall, stage pT2 N0 M0 (see ). The tumor measured 2.2 × 2.0 × 1.2 cm, and necrosis was present at less than 50%. Surgical margins contained tumor cells closer than 1 mm to the medial margin, and no lymphovascular invasion was identified.
Epithelioid sarcoma describes a mesenchymal malignancy with epithelial features. “Proximal-type” epithelioid sarcomas possess dense intracytoplasmic eosinophilic inclusions and associated eccentrically placed nuclei, which can contribute to an epithelioid or even rhabdoid histology. Necrosis is a common feature. Both proximal and distal types of epithelioid sarcoma demonstrate cytokeratin and CD34 immunoreactivity. Loss of INI-1 reactivity is also a characteristic.
Her postsurgical course was complicated by the formation of a sinoorbital fistula which was repaired with a temporalis flap. Following complete healing from her surgery (see ), she met with a radiation oncologist to discuss postoperative radiation treatment options. In addition, her case was discussed at the regional multidisciplinary head and neck tumor board where the board's consensus decision was to recommend adjuvant external beam radiation with intensity-modulated radiation therapy (IMRT) to improve local control. Adjuvant chemotherapy was not recommended due to lack of published clinical benefit and patient age. The recommended treatment was an intensity-modulated radiation therapy (IMRT) plan to a total dose of 6600 cGy in 33 fractions of 200 cGy (see ).
To further determine if targeted therapies were a treatment option for this rare malignancy, the patient's tumor specimen was sent for Foundation Medicine genetic testing. For example, patients with cancers that express her2, potential treatment options include trastuzumab and afatinib. Overexpression of EGFR can potentially make myoepithelial carcinoma susceptible to cetuximab. Treatment with PD-1 inhibitors might be indicated if high PD-L1 or high tumor mutational burden is present. In our case, the only detected genomic alteration was SMARCB1 (SWItch/sucrose nonfermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1). At the time of this patient's diagnosis, there were no therapies that directly target SMARCB1 loss or inactivating mutations. Therefore, no systemic targeted therapies were offered to this patient.
She has recovered well from her prior treatment courses and continues to follow up at 3-month intervals with her ophthalmologist and radiation oncologist without evidence of recurrence of disease. She has retained excellent vision in her right eye. She denies any residual headache or retroocular pain. She has not had any difficulty with fevers or infections, and she has been able to return to all activities of daily living.
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pmc-6311861-1
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A 10-year-old Caucasian male was referred by a general dental practitioner (GDP) for the management of dental caries and tooth surface loss. He had no complaint, and his dental problem was asymptomatic. He was diagnosed with infantile choriocarcinoma at the age of three weeks old. He had undergone chemotherapy for nine months and multiple surgical operations under general anaesthesia (GA) to remove the tumors and is currently in remission.
The patient also had kidney and gastric reflux diseases since he was 6 years old. Initially, he was treated with proton pump inhibitors (PPIs), but it failed to control the symptoms despite being given large doses of PPI. Eventually, at the age 8 years old, he underwent an antireflux surgery (fundoplication), wrapping the distal oesophagus with the uppermost part of his stomach. The surgery was successful in reducing his symptoms, and he was required to take 10 ml omeprazole every night. Unfortunately, on his 12th visit to the dental clinic, the sutures of the gastric reflux surgery had ruptured because of prolonged vomiting during an episode of gastrointestinal infection, and a second surgery was planned in the future. The patient also had mild asthma, managed with salbutamol inhaler, and was known to have had an allergic reaction to vancomycin, Calpol®, and numerous “E” numbers food contents.
Diet history revealed diluted juice, isotonic drink, and flavoured water intake daily, and the patient frequently snacked on biscuits, chocolate, and sweets.
The clinical examination showed that most of his teeth were affected with caries (). His oral hygiene was poor, and the lower left central incisor was nonvital. There were signs of erosion on the upper central incisors affecting the mesial and palatal surfaces.
A full mouth rehabilitation was carried out, which consisted of a root canal treatment on the lower left central incisor, composite restorations on all the incisors, and extractions of all the first permanent molars. The patient's dietary intake and oral hygiene were regularly monitored. Since the patient's gastric reflux problem was not under control due to the ruptured sutures of the previous fundoplication surgery, it was decided that the composite build-up treatment on the teeth affected by erosions should proceed. The upper incisor teeth were restored using microfilled composites resins (Durafill® VS) using the celluloid crown forms (Frasaco®) (). A topical fluoride varnish application every 3-4 months was included in the treatment plan. In order to control the plaque formation, the patient was advised to brush his teeth using high fluoride toothpaste (more than 1350–1500 ppm fluoride) twice daily and to use a fluoride mouth rinse (FluoriGard® 0.05%NaF) daily at a different time apart from brushing. The patient was very cooperative throughout the treatment except during the first two visits whereby he required acclimatization and assurance. The patient was satisfied with the result of the treatment. The comparison between the preoperative and postoperative views of patient's dentition is shown in .
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pmc-6311861-2
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A 13-year-old Caucasian female was referred by a general dental practitioner (GDP) for the management of noncarious tooth surface loss of permanent maxillary anterior teeth. The patient did not complain of any pain or hypersensitivity and was asymptomatic.
His medical history revealed that the patient was diagnosed with hypoglycaemia when she was two years old. This rare condition, which was not related to diabetes, had caused her blood sugar to become low. She was on a daily carbohydrate supplement (Maxijul) and consumed HypoStop (concentrated glucose gel) whenever she had a hypoglycaemic attack. In addition, she had severe asthma that was managed with two puffs of salbutamol and steroid inhaler, twice daily, with a history of hospitalisation. The patient also had a migraine attack every other day, usually followed by vomiting and nausea since she was eight years old. She was under the treatment of a consultant paediatric neurologist and was managed with sumatriptan and Migraleve for her migraine and domperidone to prevent vomiting. She was also known to have an allergy to peanuts. She was a regular dental attendee and had experienced dental treatment and tooth extraction under local analgesia.
Her dietary history showed that the patient consumed excessive quantities of acidic beverages: Coca-Cola, Irn-Bru and diluted fruit juice. The diluted juice was mixed with Maxijul and was taken to bed at night, and the mixed juice was sipped throughout the night.
Clinical examination revealed generalised dental erosion that had severely affected the palatal surfaces of all the maxillary incisors and caused a fracture of the mesial surface of both the maxillary central incisors (). Several restorations were present on the posterior teeth.
The patient was very anxious during the first visit to the clinic. The clinical and radiographic examinations were completed after the patient was successfully coaxed and reassured. The impressions of the maxillary and mandibular teeth were made during the second visit. Acclimatization, reassurance, tell-show-do, and distraction were accomplished throughout the procedure because the patient had a pronounced gag reflex. Alginate impression materials of different tastes were used to encourage the patient's cooperation.
At subsequent visits, the patient was cooperative and happy to continue with the treatment. Consent was obtained for the central maxillary incisors to be restored under rubber dam isolation and local anaesthesia. The teeth were restored with microfilled composite resins (Durafill® VS) shade A1 with the used of celluloid crown forms (Frasaco®). Both the patient and her mother were happy with the results. Following that, the patient became more confident and displayed less anxiety. She was happy to proceed with the impression making procedures for the construction of the nickel-chromium palatal veneers for all the maxillary incisors, using heavy body polyvinyl siloxane impression material and light body polyvinyl siloxane impression material. The cementation of the nickel-chromium palatal veneers was done during the following visit using Panavia™ F2.0 resin cement (). The aesthetic and function were found to be satisfactory. The patient's diet and oral hygiene were regularly monitored posttreatment, and the applications of topical fluoride varnish were done every 3-4 months. She was prescribed a high fluoride toothpaste (2800 pm fluoride) to be used twice daily and was advised to use a fluoride mouth rinse (FluoriGard® 0.05% NaF) daily at a different time apart from the time of brushing her teeth.
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pmc-6311863-1
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A 74-year-old male presented with jaundice for one month associated with generalized pruritus, epigastric pain, anorexia, and weight loss. On clinical examination, the patient was thin built and icteric with palpable gall bladder.
Liver function test was consistent with obstructive jaundice with total bilirubin of 154 μmol/l, direct of 152 μmol/l, SGOT of 147 U/l, SGPT of 67 U/l, and ALP of 731 U/l.
Transabdominal ultrasonography revealed hepatomegaly, moderately dilated IHBD and CBD, and distended gall bladder.
Contrast-enhanced CT of the abdomen with pancreas specific protocol revealed enhancing soft tissue density in the distal common bile duct with upstream dilatation of the CBD, CHD, and IHBD.
With the diagnosis of distal cholangiocarcinoma, the patient underwent Whipple's pancreaticoduodenectomy. After dividing the common hepatic duct, two openings were appreciated indicating that the division of common hepatic duct occurred at the confluence. However, on further evaluation, it was appreciated that the confluence was intact and it was the septum in the CHD that was giving the false impression. On detailed evaluation of the resected specimen, a septum extending from the hilum with cystic duct opening on the right side () to the distal end of the bile duct was appreciated, suggesting duplication of the common bile duct. However, the septum was not extending up to the papilla ().
This anatomical variation was not appreciated in the imaging preoperatively. A retrospective evaluation of the cross-sectional imaging revealed an incomplete septum extending from the hilum to the distal end of the common bile duct (Figures and ).
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pmc-6311866-1
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A 27-year-old Thai female presented with a rapidly growing mass over her right thigh for 3 months. She had no underlying or previous surgery. She had pain when she walked. She had slightly limited her right hip function on flexion and abduction. Physical examination revealed a firm nonpulsatile mass over the right thigh measuring ~8 × 6 cm. in diameter (). No notable grossly skin involvement and the mass appears not fixed to bony structure. No sensory deficit was identified. Inguinal lymph node cannot be palpated.
The magnetic resonance imaging (MRI) scan demonstrated a 7.8 × 5.8 × 5.7 cm, in vertical × transverse × AP diameter of well-defined, thin rim, enhancing simple cyst with vascularity at the right anterior intermuscular fascia of the upper thigh, just inferior to the right inguinal region. The cyst was located between the pectineus muscle and sartorius muscle, accompanied with anterior bulging to subcutaneous fat. The right common femoral artery and vein and superficial artery and vein were displaced posteriorly ().
Percutaneous aspiration of cyst revealed clear yellowish fluid about 60 ml., and the cytological examination showed hypocellularity consisting of few small lymphocytes and foamy macrophages in background of few erythrocytes and concluded cystic fluid. The cyst disappeared for a few days and presented in the same size within one week.
The operation was performed on supine position under general anesthesia. Vertical incision was performed; the cyst was identified and found dense adherance to femoral artery. Carefully, dissection was done. Complete cystic removal with femoral artery preservation was successful with minimal leakage of cyst wall (). Cystic content had shown the clear, yellow fluid ().
Microscopic examination was demonstrated as . Hematoxylin-eosin staining (H&E staining) indicated that the wall of the cyst consisted of a single flattened cell lining. The cell lining was histologically supposed to be derived from endothelium or mesothelium by routine H&E staining (Figures and ). Immunohistochemical studies for D2-40, CD31, CD34, and calretinin were performed to define the nature/origin of the cystic cell lining. Immunohistochemical studies revealed the cell lining of the cyst was positive for CD34, CD31 (), and D2-40 () and negative for calretinin. The constellation of histology and immunohistochemistry demonstrated that the wall of the cyst was not derived from the mesothelium but from the lymphatic vessels. The final pathological diagnosis was a benign lymphatic endothelial-lining cyst of soft tissue. The cystic fluid was sent for cytology and revealed no malignancy. No postoperative complication was found.
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pmc-6311874-1
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A 16-year-old male patient was referred by the orthodontist after a radiolucent lesion on the mandible was discovered after a panoramic X-ray of the jaws during orthodontic treatment, with approximately 4 months of evolution (). At the extraoral physical examination, there were no signs of increased volume and/or facial asymmetry; at the intraoral examination, the lesion presented with lingual cortical expansion, mucosa with normal coloration, no dental displacement, and absence of painful symptomatology with negative aspiration puncture. At tomographic examination, the patient presented a multilocular hypodense image in the body region and right mandibular angle, associated with retained teeth 47 and 48, which was initially suggested to be an odontogenic cyst or another tumor. The patient did not present comorbidities and/or basic, nonsmoking, and nonalcoholic diseases. An incisional biopsy was performed on the affected area, and a histopathological report of low-grade intraosseous mucoepidermoid carcinoma was prepared (). Immunohistochemical analysis of the lesion was performed through the CK-7 marker to confirm the diagnosis. According to the pathologist, mucin staining was performed for histology.
The surgical planning was segmental resection through the right hemimandibulectomy with a safety margin, from the right submandibular access with extension to the lower lip (Figures and ). Subsequently, the patient was submitted to radiotherapy in order to mitigate the chances of the lesion. The patient was followed for 2 years and has had no clinical evidence of relapse and/or metastasis ().
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pmc-6311875-1
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An 80-year-old retired woman was referred to our cardiothoracic centre in February 2016 with an incidental finding of 1 cm lung nodule in the left midzone, after having presented to her local hospital with chest discomfort. Her past medical history included previous right nephrectomy for a nonmalignant lesion of the urethra, a previous transient ischaemic attack, polymyalgia rheumatica, hypothyroidism, hypertension, and osteoporosis. Positron emission tomography-computed tomography (PET-CT) showed a T1a N0 M0 left upper lobe cancer with small-cell lung carcinoma confirmed on CT-guided biopsy. The multidisciplinary team decision was for surgical management; therefore, she was admitted for elective lobectomy.
This was undertaken in March 2016 using a single-port VATS technique and included lymph node sampling. Sequential identification, dissection, and division of the pulmonary vessels and bronchi were performed as standard. The procedure was uncomplicated, and the patient was discharged 3 days later.
She then received adjuvant carboplatin/etoposide chemotherapy and was re-referred in December 2016 with a contralateral right lower lobe nodule found on surveillance CT. The patient underwent single-port VATS wedge resection of the nodule in February 2017, which was again uncomplicated. Interestingly, histopathological examination revealed the nodule to be an area of necrotising granulomatous inflammation with acid-fast bacilli, consistent with past tuberculosis, rather than a metastasis.
On postoperative day 1, the patient had a self-resolving episode of ventricular tachycardia following by bradycardia, with chest tightness on minimal exertion. Troponin T was performed which was <20 ng/L. She subsequently underwent a variety of cardiac investigations. Computed tomography coronary angiogram (CTCA) was performed the following day, which showed diffuse disease in all major epicardial vessels, with possible lesions in the left anterior descending (LAD) artery and right coronary artery (RCA), and a coronary calcification score of 1800. A 24-hour Holter investigation revealed bradycardia throughout with rare ventricular ectopics. A subsequent echocardiogram showed normal left ventricular size and function with an ejection fraction of 60–65%, and a myocardial perfusion scan showed an overall ischaemic burden of 7%. Finally, cardiac catheterisation on postoperative day 8 revealed 85% tubular stenosis of the distal left main stem (LMS) artery and minor irregularity in the dominant right coronary artery (RCA).
The patient was symptomatically managed on the ward, and the multidisciplinary team discussed the case. Bearing in mind the patient's comorbidities, a decision was made for Endo-ACAB, rather than conventional cardiac artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), which took place 18 days after the initial thoracic surgery. 3 ports were utilised to harvest the left internal mammary artery (LIMA), and a submammary incision was performed in the 5th intercostal space to enable anastomosis to the LAD. She developed no further complications and was discharged 17 days later. She is awaiting cardiothoracic follow-up.
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pmc-6311888-1
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A sixty-one-year old male, in otherwise good health, was referred to otorhinolaryngology emergency for a one-year history of progressive dysphagia and recent dysphonia and dyspnea.
Intraoral clinical examination revealed an enormous mass (80 × 55 mm in size) filling the oropharynx and surpassing the anterior pillars. The lesion was firm and tender and showed no fluctuation. Cervical lymph nodes were not palpable. The remaining clinical examination revealed pain in the right lower limb.
Upon arrival in the emergency room, a rescue tracheotomy was performed.
Magnetic resonance imaging (MRI) showed a voluminous process occupying and infiltrating the entire posterior tongue. The lesion was heterogeneous on T1 and T2 tissue signal. Imaging was enhanced after injection of GADO (measuring 75 × 55 × 39 mm along major axes). This process infiltrated the uvula and the tonsils (). No associated cervical lymph nodes were found.
Biopsy of the tongue showed a squamous mucosa whose chorion was massively infiltrated by tumoral proliferation with distinct plasmacytic differentiation. Immunohistochemistry showed positivity of CD138 and monoclonal expression of Lambda chains ().
To screen for other locations, we performed whole-body MRI which demonstrated a lesional process occupying the lower metaphysis of the right femur. The lesion was rounded with polylobed contours and had an intermediate signal in T1 with a central zone in hypersignal. It destroyed the inner cortical and measured 61 × 47 × 47 mm according to major axes (). Spine MRI did not demonstrate signal abnormalities of the vertebral bodies or the spinal cord.
Laboratory workup showed a 7.5 g/dl normocytic anemia and accelerated sedimentation rate. Calcemia and renal function were of normal range. There was no clear monoclonal peak in serum electrophoresis. The serum and urinary immunofixation revealed lambda chains confirmed with nephelemetric free light chains dosage. Beta2 microglobulin was slightly elevated.
Bone marrow aspiration showed 12% dystrophic plasma cell medullary infiltration, with presence of some plasma cells clusters (). Screening of prognostic genetic abnormalities by conventional cytogenetics and fluorescent in situ hybridisation (FISH) was negative.
The patient received VTD induction therapy according to local guidelines (bortezomib: 1.3 mg/m2 and dexamethasone: 40 mg both on days 1, 4, 8, and 11 and thalidomide 100 mg daily in a 21-day schedule).
After 4 courses, the patient was in complete remission (CR) according to International Myeloma Working Group (IMWG) criteria []. He then received autologous stem cell transplantation (ASCT) after conditioning with melphalan 200 mg/m2. Two additional VTD cycles were given posttransplant as consolidation. Patient then started maintenance treatment with bortezomib at a dose of 1.3 mg/m2 every 2 weeks for a planned total duration of 2 years.
Overall, treatment was well tolerated with no grade 3 or more side effects.
One year after ASCT, the patient is still on bortezomib maintenance, with good tolerance and no sign of relapse.
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pmc-6311898-1
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We report a case of an African baby girl, who died at 7-months old, who was first seen in our hospital during the first 6 hours of life; she presented with a generalized cracked skin all over her body. She was delivered at 37 weeks’ gestation by caesarean section due to breech presentation; she weighed 2.5 kg, her length was 51 cm, and head circumference was 35 cm. Her Apgar score was 8 and 10 at first and fifth minutes, respectively. During pregnancy, her mother received reasonable prenatal care including screening for HIV and syphilis, which were all negative; however, a prenatal ultrasound was not done. She had no history of taking alcohol, drug abuse, or use of other medicines apart from hematenics and malaria prophylaxis.
The baby is the first born to the 24-year-old mother and 27-year-old father; there is no history of consanguinity or similar dermatological condition in the family.
On examination she was alert, her temperature was 37 °C, she had no difficulty in breathing and she was saturating well in room air, her respiratory rate was 49 breaths/minute, and her heart rate was 123 beats/minute. She was noted to have a thick parchment-like skin all over her body with peeling and varying degree of fissures, eversion of eyelids (ectropion), her mouth was wide open like a fish (eclabium), and she had hypoplastic digits and nail dystrophy, and swollen feet and hands. She also had scaling alopecia and her ear canals were filled with glue-like material. She also had a restricted range of movement in her extremities especially extension of both upper and lower limbs. The rest of the systemic examination was essentially normal.
Initial baseline investigations taken 6 hours post admission revealed random blood sugar 8.4 mmol/dl, serum sodium 154mmlo/l, creatinine 138.3 μmol/l, and normal potassium. Laboratory tests repeated 2 days later revealed normal creatinine, blood glucose, and sodium. A sepsis workup was performed on the day of admission, a report from blood culture and swab from a fissure showed no bacteria growth, and C-reactive protein (CRP) as well as complete blood count (CBC) were normal. Genetic testing was not done because it is not available in our setting.
Empirical antibiotic therapy of Ampiclox (ampicillin and cloxacillin) 125 mg 12 hourly and gentamycin 12.5 mg once daily was initiated and was continued for 5 days while awaiting results of the sepsis screening test. In addition, intravenously administered fluid (dextrose normal saline) at 175 ml per 24 hours was administered on the first day; on the second day, orogastric tube feeding was started, the baby received 25 ml (increased by 1 ml/day) of expressed breast milk every 3 hours until her seventh day of life when she was able to suck from the breast.
In the first few days of life her eyes were covered by gauze soaked in normal saline and from the third day chloramphenicol eye ointment was applied twice daily to keep her eyes lubricated. Conservative skin management was started using Vaseline (petroleum jelly), which was applied to her skin every 3 hours; strict infection prevention control that included isolation was adhered to and the baby was monitored for signs of hypothermia, dehydration, and sepsis.
While the baby was still in our hospital, by the 24th day of life, a significant shedding of the collodion skin had taken place. During this time she was noted to have a constricted band on her lower limb necessitating band release (Fig. ).
A dermatologist, otorhinolaryngologist, ophthalmologist, and pediatric surgeon were consulted and provided their multidisciplinary expertise for both short-term and long-term management of this newborn. To allow for adequate chest expansion and to prevent respiratory insufficiency on the second day of life, a pediatric surgeon made an incision along the collodion membrane on the anterior chest wall (sternal region).
A multidisciplinary team reached a decision to discharge the baby on her 35th day of life. The family was advised that the baby should attend follow-up clinics: neonatal; ophthalmology; dermatology; physiotherapy; and ear, nose, and throat (ENT).
By the time she was discharged, there was some improvement in ectropion, eclabium, and there was relief in contracture of her fingers and toes; however, extension of knee and elbow joints were still limited (Fig. ).
The mother and family were given counselling about the diagnosis, which involved clinicians, nurses, and a social worker; this was started on the day of admission and continued throughout the hospital stay. In addition to the care provided in the hospital, during the hospital discharge, the mother was advised on the care of the baby at home including breastfeeding, skin care, eye care, and care of joints. The baby received initial vaccines before discharge; continuation with the remaining vaccines according to the immunization and vaccine development program in Tanzania was advised.
The baby’s weight initially decreased to 2.25 kg during the first 2 weeks, then she started to gain weight; on discharge she weighed 3.2 kg and 2 weeks later when she came for a follow-up clinic she weighed 3.4 kg. She continued attending follow-up clinic for the first 6 months; however, she suddenly died at home at 7 months of age.
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pmc-6311956-1
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A 58-year-old woman with history of liver cancer originating from chronic hepatitis B was admitted to Taipei Tzu Chi Hospital, Taiwan, in August 2010, with chief complaints of yellowish discoloration of the skin and tea-color urine for one week. She has received transcatheter arterial chemoembolisation (TACE) three months prior to admission to this hospital. Laboratory tests showed elevated serum total bilirubin (5.1 mg/dL), alpha-fetoprotein (182.7 ng/mL), and carbohydrate antigen 19-9 (70.5 U/mL) levels. The carcinoembryonic antigen (CEA) serum level was within the upper limit of normal. Computed tomography revealed a hypervascular mass in the liver hilum measuring 4 × 5 cm. The patient underwent left lobectomy, and pathology showed proliferation of spindle-shaped hepatocellular carcinoma cells. The patient has survived for 5 additional years without tumor recurrence as of this writing.
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pmc-6311956-2
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A 39-year-old man with a history of HBV-related cirrhosis was referred to Hualien Tzu Chi General Hospital, Taiwan, in May 2011, diagnosed as having liver cancer without any previous treatment for HCC. The alpha-fetoprotein serum level was 123.5 ng/mL. Both the carbohydrate antigen 19-9 and CEA serum levels were within the normal range. The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) showed a huge hypervascular tumor in the right lobe of the liver. The patient underwent liver resection. Histological examination revealed spindle-shaped sarcomatoid carcinoma cells with unclear trabecular and pseudoglandular structures. However, the tumor relapsed in the residual liver 5 months after surgery, and despite TACE therapy, the patient died one year later.
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pmc-6311956-3
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A 72-year-old woman was admitted to Hualien Tzu Chi General Hospital, Taiwan, and diagnosed as having liver cancer originating from chronic hepatitis C. The alpha-fetoprotein, carbohydrate antigen 19-9, and CEA serum levels were all within the upper limit of normal. Computed tomography showed a hypervascular tumor in the caudate lobe of the liver measuring 5 × 6 cm. She underwent segmentectomy, and pathology revealed spindle-shaped sarcomatoid carcinoma cells. One year after surgery, the tumors relapsed in the residual liver. The patient began with TACE therapy. Unfortunately, she died two years later.
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pmc-6312576-1
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An 82-year-old female patient is with a history of chronic arterial hypertension, ischemic stroke without sequelae, and hypothyroidism. She is hospitalized in our institution with a diagnosis of nephrotic syndrome, for study and management. Prednisone 1 mg/kg/day is started at admission. There was a torpid progression with multiple intercurrent infections, right renal infarction, and a progressive deterioration of kidney function, requiring the initiation of hemodialysis. In this context, after 3 weeks of hospitalization, she manifested multiple painful genital and inguinal ulcers, the largest one on the skin of the left labia majora, 1.5 cm in diameter, with a well-defined erythematous border and base with scarce fibrin. There was a rapid progression of the ulcers, with an increase in their size, number, and the extension to the perianal region, thighs, and right leg (). Dermatology department was consulted, and polymerase chain reaction (PCR) for herpes simplex viruses 1 and 2, Varicella zoster virus, Epstein barr virus, and Cytomegalovirus, in addition to HIV serology and VDRL, were performed, with negative results. Biopsies of the vulvar and right leg lesions were taken and, on the PAS staining of the latter, septate hyphae were found, some with ramifications at acute angles and with invasion of blood vessels (). Cultures of the lesions were negative. The patient presented with respiratory distress, and chest computed tomography showed a cavitated lesion in the upper segment of the left lower lobe, suggestive of aspergilloma. Galactomannan blood test came back positive, thus confirming the diagnosis of invasive aspergillosis. Intravenous antifungal therapy with voriconazole and caspofungin was initiated; however, the patient deteriorated rapidly, with multiorgan failure, and died despite intensive care and twenty days of antifungal treatment.
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pmc-6312603-1
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A 9-month-old girl was admitted to her local hospital because of increasing pallor and lethargy in conjunction with an upper airway tract infection. She had no diarrhea. On admission she had hematuria and blood tests showed hemoglobin 8.2 g/L (reference value 11.0-15.5 g/dL), platelet count 87 x 109/L (150-450 x 109/L), leukocytes 17 x 109/L (5-15 x 109/L), and creatinine 178 μmol/L (20-30 μmol/L). Due to gradual deterioration of her clinical condition, decreased diuresis, and worsening laboratory findings, hemolytic uremic syndrome (HUS) was suspected. She was transferred to Oslo University Hospital to undergo dialysis. On admission, blood tests confirmed the initial findings: anemia, thrombocytopenia, and kidney failure. Additional blood values showed lactate dehydrogenase (LDH) 2115 U/L (180-430 U/L), bilirubin 18 μmol/L (5-25 μmol/L), creatinine 193 μmol/L, albumin 31 g/L (36-48 g/L), haptoglobin < 0.10 g/L (0.4-2.1 g/L), and C3 0.5 g/L (0.7-2.00 g/L). Schizocytes were present in the peripheral blood smear. Low C3 supported the suspected atypical HUS diagnosis. Combined treatment was initiated with plasma exchange (PE) and hemodialysis was initiated, with a good clinical response and normalization of hematology and renal function. Thereafter, during the following months, she developed three relapses, which all resolved after PE. A gain-of-function C3 mutation previously described in aHUS was identified in exon 14: R592W (R570W without the signal peptide) [].
Use of the chimeric IgG2/4 monoclonal anti-C5 antibody eculizumab had recently been introduced []. Eculizumab treatment was started according to guidelines when the genetic results supported the diagnosis. Her weight at the start of treatment was 9.3 kg, with a starting dose of 300 mg in the first week, followed by another dose 2 weeks later and thereafter every third week until she reached 10 kg in weight. At a weight of 20 kg, it is recommended that the dose is increased to 600 mg every second week. Based on the complete inhibition of complement activity, we continued treatment with 300 mg every third week and followed the complement activity carefully. Complement activity assayed before each dose has shown complete suppression of the alternative and classical pathway Wieslab® assays, using the C5 dependent C5-9 complex as a readout (Complement screen kit, EuroDiagnostica, Malmö, Sweden), suggesting that the given dose was adequate during the entire six-year follow-up period ().
There have been no relapses of aHUS since the start of eculizumab treatment. At seven years of age, the patient has normal development, normal growth with a weight of 27 kg (50th percentile), and normal blood pressure. At the most recent visit, the laboratory hematology and biochemical values remained normal, and glomerular filtration rate measured by iohexol clearance was 84 ml/min/1.73m2. Urinalysis was normal with no hematuria or proteinuria.
The routine complement analyses are presented in . The low C3 values observed throughout the 6-year follow-up are consistent with continuous C3 consumption, due to the gain-of-function mutation. Importantly, this selective continuous increased C3 activation does not seem to affect her clinical or pathophysiologic condition adversely. This is consistent with blocking the terminal complement pathway with activation of C5 being responsible for the pathogenesis of this disease [].
Complement activity was completely inhibited during the 6-year follow-up, indicating that a sufficient amount of eculizumab was administered even if the dose interval was prolonged to every third week, instead of every second week as recommended. In addition, the dose was not increased to 600 mg when reaching 20 kg as recommended by guidelines. Further on, we investigated in more detail the degree of C5 blockade and the complement activity in the course of one treatment interval. Three samples were collected for this purpose (): (1) 1 hr before infusion, (2) 1 hr after infusion, and (3) between two infusions of eculizumab (7 days after and 15 days before the next infusion); eculizumab-C5 complexes (E-C5) were quantified in an ELISA assay as previously described []. Briefly, the plate was coated with a monoclonal anti-human C5, incubated with serum samples (a source containing E-C5 complexes) followed by conjugated mouse anti-human IgG4 antibody for detection of eculizumab bound to C5.
Three patient samples and a control pool of sera from 20 healthy adult donors were available with approval of the regional ethics committee and informed written consent from patient's guardians and the controls. Samples were incubated with increasing doses of eculizumab (0-100 μg/mL). No changes in E-C5 concentrations were observed in the three patient samples, whereas the pooled control sera exhibited a dose-dependent increase in E-C5 from zero to the levels corresponding closely to the patient samples, indicating that a maximum of E-C5 complexes were present in all three patient samples (). Thus, no free C5 was present to react with eculizumab.
We then investigated the effect of adding eculizumab (0-100 μg/mL) on the complement activity as measured in vitro using the Wieslab test. Eculizumab blocks cleavage of C5 to C5a and C5b, thus inhibiting the formation of the C5b-9 complex in the assay. The three patient samples were completely negative from time zero, consistent with full blockade, whereas the control sera displayed a dose-response inhibition from normal activity to zero at eculizumab concentrations of 50-100 μg/mL ().
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pmc-6312608-1
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A 76-year-old Caucasian male with a history of stage Ic prostate cancer, gleason 3 + 3, status after radiotherapy and antiandrogen therapy in 1998 (in remission), hypertension, and IgG2/IgG4 subclass deficiency presented with CMML-1 with deletion 7q (q22q32) in 11 of 20 cells (55%) diagnosed in December 2008. JAK 2 mutation analysis and quantitative RT-PCR for the BCR-ABL transcript were negative. He had an isolated thrombocytopenia at presentation, his diagnostic bone marrow biopsy demonstrated trilineage hematopoiesis without dysplasia and 1% blasts, and atypical intermediate-sized monocytoid cells increased at 20%–30% of the bone marrow cellularity. No systemic treatment was commenced at the time. His other comorbidities include gastroesophageal reflux disease, lumbar spinal stenosis (L3–L4), and lumbar neuroforaminal narrowing due to degenerative disc disease.
In early 2009, he started PLE in the form of papaya leaf tea, 4 grams once daily in the morning and one teaspoon of elixir at night. He also had IgG2 and IgG4 subclass deficiencies. For his IgG subclass deficiencies, he was treated with cimetidine 400 mg 2 times daily starting from October 2014. He also started DRE 520 mg capsules, two capsules once daily in early 2015. His bone marrow blasts peaked at 11% in October 2009 and have been less than 5% since March 2013. Of note, both the papaya leaf extract and DRE supplements were commercial products.
Prior to his diagnosis of CMML, he had been on numerous over-the-counter supplements (commercial products): pomegranate XT 1 mg daily; vitamin C 500 mg daily; L-carnitine, red yeast rice, niacin, vitamin B6, and omega-3 fatty acids (all started in the 1990s); nettle root daily, pyrroloquinoline 1 tablet daily, melatonin 1.5 mg daily, beta-glucan 400 mg daily, and ellagic acid (all started in 2000); and one red rooibos tea bag daily with the PLE tea. Following the diagnosis of CMML, he started numerous additional OTC supplements: vitamin K daily (2011); bio-curcumin daily and vinpocetine 10 mg daily (2011); inositol 500 mg daily (2012); resveratrol 1 tab bid, vitamin B12, folic acid, and boswellia 100 mg daily (2013); S-adenosylmethionine (SAM-E) (2014) and rice bran 500 mg bid (2014); and maitake mushroom elixir about 2–3 cc once daily (2017). A trend of his blood counts and bone marrow results are illustrated in .
The patient had no side effects and no worsening of comorbidities attributable to the supplements. He was hospitalized in June 2017 with acute hypoxemic respiratory failure and reactive airways treated with antibiotics and bronchodilators, which was not attributed to the supplements. Additionally, he was not neutropenic (ANC was always greater than 1200 cells/μL) during the hospitalization. Clinically, he continues to feel well and his hematological parameters remain consistently stable.
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pmc-6312620-1
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A 59-year-old male was admitted to the nearest hospital after a serious car accident. The patient complained of pelvic and abdominal pain and had signs of hemodynamic instability (hypotension and tachycardia). Voiding was not possible. Clinical examination revealed pelvic instability and blood loss per urethra. Hemodynamic resuscitation was started and an urgent contrast enhanced CT-scan was performed. An excretory phase was not performed due to the patient's clinical condition. The CT-scan revealed a small liver laceration and an unstable pelvic fracture. The kidneys were normal and the bladder was empty (). Immediate external fixation of the pelvis was performed. Postoperatively, the patient was transferred to the intensive care unit (4h after admission) for further resuscitation and monitoring. Urethral catheterisation was attempted but failed generating the 1st referral to urology. A suprapubic catheter was considered but the bladder could not be identified on abdominal ultrasound. The urologist decided to wait for adequate bladder filling and came back after 4 hours. The bladder was again not seen on ultrasound but free intraperitoneal fluid was demonstrated. A follow-up abdominopelvic CT-scan with excretory phase (14h after admission) demonstrated a nearly empty and upwards displaced bladder, with contrast extravasation into the peritoneal cavity (). The urologist decided to place an intraperitoneal drain (percutaneously). On days 2 and 3 after the trauma, a progressive clinical deterioration evolved with signs and symptoms compatible with sepsis. Therefore, the decision was taken to transfer the patient to an academic hospital with dedicated trauma facilities. On admission, the patient was disoriented with hypotension, tachycardia, tachypnea, and abdominal pain. Clinical examination revealed marked abdominal distension and guarding. Laboratory blood tests demonstrated a severe electrolyte imbalance, an elevated creatinine level, and anaemia (). After multidisciplinary trauma-team discussion, immediate hemofiltration was arranged, followed by laparotomy. Copious amounts of urine were drained, and a large laceration in the bladder dome extending towards the extraperitoneal anterior surface of the bladder wall was observed. Direct inspection, via the laceration, of the ureteric orifices and bladder neck revealed no further injury. A suprapubic catheter was inserted and the bladder was closed in 2 layers (mucosa, detrusor) with a running suture monocryl™ 3.0. An extraperitoneal drain was placed and the intraperitoneal drain was maintained. Despite clinical indication of concomitant urethral injury (combination urethral blood loss-pelvic fracture, displacement of the bladder, and failed urethral catheterization), a trial of urethral realignment was not performed because of the clinical condition of the patient. During the following days, a clear clinical and biochemical improvement was noticed (). Ten days after laparotomy, a cystography proved integrity of the bladder wall repair (). A flexible cystoscopy then revealed a complete urethral injury. Suprapubic drainage was maintained and combined retrograde and antegrade cystourethrography performed at 3 months showed a complete obliteration of the membranous urethra (). The bladder had descended in the pelvis and the patient could lie in the lithotomy position. Urethroplasty (elaborated perineal approach with excision of scar tissue and anastomotic repair) was performed. The postoperative course was uneventful, voiding cystourethrogram (2 weeks after urethroplasty) proved no urethral extravasation and the catheter was removed (). At present (27 months after the initial trauma), the patient is continent without voiding difficulties.
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pmc-6312620-2
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A 30-year-old male patient was run over by a lorry and immediately transferred to a dedicated trauma centre. Hemodynamic resuscitation was started and urgent contrast-enhanced CT was performed which revealed an unstable pelvic fracture together with large amounts of free fluid in the peritoneal cavity (). A transurethral catheter was passed without difficulty but blood-stained urine was noted after insertion. A conventional cystogram demonstrated massive extraperitoneal extravasation at the bladder neck (). Intraperitoneal extravasation was not noticed. The patient underwent immediate laparotomy and a large amount of urine was evacuated from the peritoneal cavity. Exploration revealed a large combined intraperitoneal and extraperitoneal tear of the bladder wall extending towards the bladder neck. The urethral catheter balloon was actually lying free in the pelvis outside of the bladder. The ureteric orifices were inspected and bilateral double-J stents were inserted. The bladder neck was repaired and the tear was closed with a 2-layer vesicorraphy. The urethral catheter was maintained, but additionally, a suprapubic catheter was inserted in the bladder. An abdominal and pelvic drain were left in place and the abdomen was closed. The postoperative course was uneventful and after 16 days, a pericatheter voiding cystourethrography demonstrated complete healing of the bladder wall (). However, minimal extravasation was seen at the midbulbar urethra. At 6 weeks, the transurethral catheter was removed followed by cystourethroscopy which confirmed healing of urethra, bladder neck, and bladder wall. The double-J stents were removed as well. Spontaneous voiding was then possible without substantial residual volume of urine, and the suprapubic catheter was removed 3 days later. Patient, now 13 months after trauma, is voiding without any problems and is fully continent.
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pmc-6312625-1
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In 2008, a 44-year-old woman was referred to our Unit for high blood pressure, moon face, excess hair growth, easy bruising, headache, and weight gain. She had a family history of diabetes type 2. The diagnosis of ACTH-dependent CS was confirmed by high serum cortisol with a lack of circadian rhythm and high serum ACTH. MRI showed a pituitary microadenoma. In June 2008, she underwent transsphenoidal surgery and the histological examination confirmed a basophil adenoma. Six months later, clinical and biochemical signs of cortisol excess significantly improved. Subsequently, in January 2009, patient reported fatigue, palpitations, and exophthalmos. A thyroid ultrasound showed whole increase of the gland. FT4 and FT3 levels and TSH receptor antibodies were high, whereas TSH was suppressed, suggesting diagnosis of Graves' disease. Patients underwent treatment with propranolol 40 mg/day and methimazole 15 mg/day, obtaining an acceptable control of the disease.
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pmc-6312625-2
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The second case was a 48-year-old woman referred for hypertension, moon face, buffalo hump, severe muscle wasting, and hair grown on the face. The diagnosis of ACTH-dependent CS was confirmed by hormonal analysis, and MRI detected a pituitary adenoma. She underwent transsphenoidal surgery in May 2007, and the histological examination confirmed microadenoma. Three months after surgery, her blood pressure and both PC and ACTH levels were normal.
However, after 8 months, she reported weakness and weight gain. The evaluation of thyroid function showed low FT4, TSH of 1.3 mIU/L, and positive TPO Ab (212 IU/mL, n.v. 1–50 IU/mL). Ultrasound imaging of the thyroid gland revealed a diffuse dyshomogeneous pattern, suggesting diagnosis of Hashimoto thyroiditis. She started therapy with levothyroxine 50 mcg once a day with clinical improvement.
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pmc-6312625-3
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In May 2013, a 52-year-old woman was referred with cortisol excess confirmed by high 24h-UFC values and an overnight 1 mg DXM test, bilateral adrenal gland lesions (right 26 mm; left 24 mm), and scintigraphic evidence of increased radionucleotide uptake by the left adrenal gland. The patient underwent left adrenalectomy, and histological evaluation confirmed an adrenal adenoma. During follow-up, both PC and 24h-UFC values were normal. In December 2013, she developed a skin disorder characterized by reddish or salmon-like, raised, scaly skin lesions in knees, buttocks crease, and ears. A dermatologist confirmed the psoriasis diagnosis and required a topical tacalcitol therapy.
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pmc-6312625-4
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A 38-year-old woman was diagnosed with CS, due to a 27 mm nodule of the right adrenal gland. She underwent right adrenalectomy, and histological examination confirmed an adrenal adenoma. Five months after biochemical and clinical resolution of hypercortisolism, she developed tremor of the hands, sweating, insomnia, weight loss, palpitations, anxiety, itch, and neck pain. Hyperthyroidism was suspected and confirmed by hormonal evaluation (TSH suppressed with elevated free fraction of T3 and T4 and the presence of anti-TSH receptor antibodies). Subsequently, methimazole 5 mg/day was administered with clinical improvement.
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pmc-6312625-5
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In January 2010, a 36-year-old woman with high blood pressure levels was evaluated in our specialized Unit. Plasma aldosterone, plasma renin activity, and 24h urinary metanephrines were normal. 24h-UFC excretion and PC at 8 am were higher with nonsuppression by an overnight 1 mg DXM test. MRI showed a left adrenal mass (40 mm). Three months later, left adrenalectomy was performed and histological examination confirmed an adrenal adenoma.
Two years after, the patient reported onset of oral aphthous ulceration in the hard palate, photosensitivity, symmetric arthralgias on wrists, fibromyalgia, and cutaneous vasculitis. Antinuclear antibodies (ANA) were positive, and p-Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and c-ANCA were negative, confirming SLE. Hydroxychloroquine 200 mg twice per day was prescribed with subsequent clinical improvement.
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pmc-6312625-6
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A 45-year-old man was diagnosed with CS due to a right adrenal gland lesion (60 mm). Subsequently, the patient underwent right adrenalectomy and histological exam revealed multinodular hyperplasia of the adrenal gland. Three months after surgery, both PC and 24h-UFC values were normal and PC was suppressible by an overnight 1 mg DXM test. Nine months after surgery, he started to complain fatigue, sensitivity to cold, weight gain and reduced appetite, arthralgia, and myalgia. Thyroid function and antibodies were investigated, with a final diagnosis of hypothyroidism secondary to Hashimoto thyroiditis. Levothyroxine was administered with clinical improvement.
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pmc-6312625-7
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In 2011, a 56-year-old woman presented to our center reporting a high blood pressure level, fatigue, hirsutism, weight gain (body mass index 29 kg/cm2), and buffalo hump. Laboratory tests showed high PC, not suppressible after an overnight 1 mg DXM test, and high 24h-UFC and plasma ACTH levels. The diagnosis of ACTH-dependent CS was confirmed by MRI that showed a small left mass in the adenohypophysis. In January 2012, she underwent transsphenoidal surgery and the histological examination revealed a pituitary adenoma. Seven months later, she began to suffer from myalgia, arthralgia (shoulders, knees, wrists, and hands), headache, and long-lasting morning stiffness. Afterwards, she reported insidious swelling and pain of the first and second metacarpophalangeal (MCP) joints of the left hand. ANA were negative, whereas rheumatoid factor (RF) and C-reactive protein (CRP) were highly positive. Therefore, she was diagnosed a rheumatoid arthritis. She started therapy taking methotrexate once a week, folic acid 4 mg twice a week, and methylprednisolone 4 mg/day.
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pmc-6312625-8
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A hypertensive 62-year-old woman was admitted for the evaluation of an incidentally discovered right side adrenal mass. CT scan shown a 7 cm mass in the right adrenal gland, and after careful examination, the patient was diagnosed with subclinical hypercortisolism (SH). Adrenalectomy was performed in March 2013, and histopathological examination showed an adrenocortical adenoma. Significant symptoms and signs appeared 5 months later (bilateral ptosis, double vision, and proximal muscle weakness in the arms bilaterally); during specific evaluation, chest CT showed a solid tissue mass in the mediastinum. The diagnosis of myasthenia gravis was performed; thus, patient started on pyridostigmine 180 mg/day and prednisone 25 mg/day, with no evident benefit. Subsequently, she underwent a sternotomy with excision of the tumor, which histologically proved to be a type 2B thymoma. During the 1-year follow-up in our Unit, patient reported complete regression of myasthenic symptoms, with normal electrodiagnostic tests. She remained well on pyridostigmine 120 mg/day and antihypertensive therapy (amlodipine and bisoprolol) with good control of blood pressure [].
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pmc-6312625-9
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A hypertensive 61-year-old woman with a right adrenal incidentaloma was studied in our specialized Unit. Both PC (at 8 a.m.) and 24h-UFC values were higher and not suppressible after an overnight 1 mg DXM test, suggesting CS diagnosis. In April 2013, she underwent right adrenalectomy and histological evaluation confirmed an adrenal adenoma. Four months later, she began to suffer from fatigue, mild headaches, bilateral aching, and stiffness of neck and shoulders. In September 2013, she went to emergency room, for right vision loss and severe headache. Ophthalmoscopy showed pale and swollen optic disc, dilated retinal veins, and several flame-shaped hemorrhages, such as an anterior ischemic optic neuropathy (AION). Intravenous methylprednisolone was administered. A cross-sectional biopsy showed transmural inflammation with mononuclear cells and giant cells infiltrating the media, compatible with temporal arteritis (Horton disease). After discharge, prednisolone p.o. 25 mg twice a day was administered with significant clinical improvement.
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pmc-6312710-1
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Patient
A 39-yr-old infertile man with infertility by three recurrent miscarriage, and 46, XY, t(2;8)(p24;p21)mat carrier was studied. Semen analysis revealed normozoospermia. The presence of recent illness, high fever, seminal hyperviscosity or primary hormonal abnormalities was discarded. The patient presented varicocele (8 years ago) treated by varicocelectomy. His wife (30 yr old) had a normal karyotype and no reproductive problems (son born in 1994 with another partner). Recently the couple had treatment of assisted fertilization; unfortunately, we lost contact with the patient.
For analysis of aneusomies and sperm DNA fragmentation, in healthy male controls, as it was not possible to include controls related to the case five healthy male donors (age range, 25-30 yr) with normozoospermia according to the criteria of the WHO 2010 () and normal karyotypes were included as controls. Ejaculated sperm samples were collected after 3-5 days of sexual abstinence. After liquefaction and washing with PBS (pH 7.4; Sigma-Aldrich, St. Louis, MO), sperm samples were fixed with a fresh fixative solution (methanol: acetic acid, 3:1 v/v, -20oC) and then stored at -20oC until further use.
Cytogenetic analysis
Karyotyping was performed from blood lymphocyte cultures using G-bands by trypsin/Giemsa (GTG) analysis. Fifty metaphases were analyzed ().
Slide preparation
Sperm samples were fixed with 3:1 methanol: acetic acid, spread onto slides and stored in a freezer at -20oC until the FISH procedure. The slides were incubated in a decondensation solution (NaOH 1N) for 2 min, rinsed in distilled water, passed through a series of ethanol 70%, 90%, and 100% for 1 min each and then air-dried. Next, the slides were incubated in formamide 70%, 72oC for 2 min, ethanol 70%, 90%, and 100% for 1 min each, and then air-dried. Fixed lymphocyte cultures were spread onto slides directly before FISH.
FISH
FISH was performed according to the manufacturer’s (Poseidon FISH DNA probe. Kreatech, Diagnostics. Leica Biosystems; Nussloch, Germany) protocol on lymphocytes and sperm cells using a set of fluorescent centromeric and subtelomeric probes. To determine the segregation type and nuclear chromosomal content of each sperm, we used subtelomeric probes of chromosome-2 pter (green) and chromosome-8 pter (red). The hybridization of centromeric probes of chromosome-8 (CEP 8) was marked in red (D8Z1, red), and of chromosome-8 was marked in green (D8Z1, green); results in yellow were used as internal control.
For analysis of the aneuploidy, we used centromeric probes of chromosome-8 (CEP 8, D8Z1 alfa satellite, red) and chromosome-Y (DYZ1, satellite III orange) (Vysis, Inc., Abbot Laboratories, Downers Grove, IL, USA). Probes were first tested on chromosomes using conventional cytogenetic and FISH techniques. The success of the FISH experiments was 97%. For analysis, 500 sperm cells /individual were assessed using a Zeiss AxioPhot microscope (Carl Zeiss, Göttingen, Germany) equipped with a proper filter set (DAPI/FITC/Red Texas/Triple) and 20× and 100× oil-immersion objectives.
The images were impressed using an AxioCam MRm Zeiss 16-bit black-and-white charge-coupled device in a 12-bit TIFF format. The same person performed the analysis.
Sperm DNA fragmentation
Three methodologies were used to evaluate DNA damage in sperm: SCD test, alkaline comet assay and DBD-FISH. In SCD test, fragmented sperm cells produce a characteristic halo, representing DNA loops after of extraction of nuclear proteins and acid denaturation. Non-fragmented sperm do not halo produce. The SCD test was developed as the Halosperm® kit according to the manufacturer’s (Halotech DNA, Madrid, Spain).
We analyzed 300 sperm cells per sample under a microscope with objective of 100×. Five categories of halos were considered according to Fernández and colleagues criteria (); (a) sperm with large halos and (b) medium-sized halos were considered as non-fragmented. Sperm cells with a very-small-sized halo (c) and, sperm cells without a halo (d) were considered as fragmented. Sperm cells without a halo, but weakly or irregularly stained were considered as severe DNA fragmentation or “degraded (e)” (see ). Sperm without these characteristics were excluded from the analysis.
The comet assay methodology was performing according with Singh and colleagues (). The slides were stained with propidium iodide (1 µg/mL) in Vectashield (Vector Laboratories, Burlingame, CA, USA), and length of the tails (in µm; Mean±SD) of one hundred cells/individual was obtained. DBD-FISH consists in DNA protein depletion and ssDNA formation by alkaline treatment. It allows evidence ruptures in alkaline labile sites and abasic sites. Subsequently these ssDNA are hybridized with specific probes labeled with fluorescence and quantified by image analysis software Image J (http://rsb.info.nih.gov/ij/)
DBD-FISH in sperm was performed according to Fernández and colleagues. When the DNA breaks increase, the alkali produces more single-stranded DNA and more probe hybridizes, increasing levels of fluorescence (). Samples were analyzed in Zeiss Axiophot fluorescence microscope (Carl Zeiss, Göttingen, Germany) with specifics filters (DAPI, FITC and Texas red). Image J (http://rsb.info.nih.gov/ij/) was used to analyze 50 sperm nuclei by sample.
Cytogenetic study
Chromosomal analysis of the infertile patient revealed a balanced translocation involving chromosomes-2 and -8; 46, XY, t(2;8)(p24;p21)mat karyotype. Partial karyotypes from GTG banding with ideograms of the chromosomes involved in the balanced translocation are shown in . FISH confirmed the presence of this translocation.
Segregation pattern
The meiotic segregation pattern () showed a schematic representation of the theoretically predicted tetravalent structure (pachytene stage of meiosis I) with a chromosome labeling system in the analyzed carrier. An analysis of meiotic segregation by FISH revealed that 61.6% of the sperm cells were genetically unbalanced. The following percentages were found in the different segregations: Alternate: 38.4%, Adyacent 1: 15.6%, Adyacent 2; 12.8%, 3:1: 24.8%, 4:0: 4% and others 4.4% (
shows representative examples of different spermatozoa FISH phenotypes that occurred because of the meiotic segregation patterns in the 46, XY, t(2;8)(p24;p21)mat carrier.
Sperm aneusomies
Analysis of the aneusomies of chromosome-8 (nullisomic and disomic) and chromosome-Y(disomic) in the t(2;8) (p24; p21) mat carrier revealed three- and 24-fold increases, respectively, in comparison with that of the control group (). All aneusomy frequencies were significantly higher according to the mean control values (p<0.01). Representative examples of aneusomic spermatozoa are shown in .
Sperm DNA fragmentation
Interesting observations were made during sperm DNA fragmentation evaluation in the t(2;8)(p24;p21)mat carrier. The three tests used (SCD, alkaline comet assay, and DBD-FISH) showed a significant increase compared with those used for the control group (). Interestingly, our patient showed a high percentage of sperm (20%) with severe DNA fragmentation (degraded) in comparison with controls (0.42%). Examples of sperm cells in the t(2;8)(p24;p21)mat carrier and controls after SCD test, the alkaline comet assay, and DBD-FISH are shown in .
Ethical consideration
All participants were notified of the purpose of the planned research, and written consent was obtained in accordance with to the guidelines of the Research Bioethical Committee, Centro de Investigación Biomédica del Noreste, IMSS. Patient consent was obtained for publication of this article and accompanying images.
Statistical analysis
Comparison of aneusomies (chromosome-8 and chromosome-Y) and DNA fragmentation of spermatozoa between the translocation carrier and control group was performed using the Mann-Whitney test. A value of p<0.05 was considered statistically significant. All analyses were performed using IBM SPSS for Windows 20.0 (Statistical Package for the Social Sciences, IBM Corp., Armonk, NY, USA).
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pmc-6312764-1
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A 41 years old male presented to the head and neck outpatient department with a complaint of a growth on the leftt side of the tongue that he noticed 25 days back. He also had dysphagia and difficulty in talking. He was a chronic smoker but there was no history of alcoholism. On local examination, an intraoral, submucosal, solitary mass of size 2 × 1.4 cm was noted on left anterolateral aspect of tongue (). It was initially small but has increased to the present size. There was no history of bleeding or any discharge from the growth or pain and sensory changes associated with it. Surface of the growth was smooth and erythematous with surrounding mucosa appearing normal. On palpation, the size and extent were confirmed. Growth was non-tender, firm in consistency, sessile, non-fluctuant, non-reducible, compressible and non-pulsatile. No evidence of blanching was observed on digital pressure. There was no history of bleeding on palpation. The ultrasonography of the lesion revealed a heteroechoic lesion of 2 × 1.4 cm with cystic change. Fine needle aspiration cytology (FNAC) of the mass was done which revealed round to oval benign epithelial cells embedded in dense eosinophilic chondromyxoid material (). Cytological features were suggestive of a benign salivary gland neoplasm favouring the diagnosis of pleomorphic adenoma. Subsequently, excision of the mass was performed under general anaesthesia. The histopathological examination of the specimen revealed a well encapsulated tumor composed of islands and trabeculae of epithelial cells in chondromyxoid stroma (). The postoperative period was uneventful and the patient was discharged on the 7th postoperative day and he is free of recurence till date.
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pmc-6312798-1
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A 49 year old woman complained of abdominal pain in November of 2015 with diagnosis of large uterine fibroid, a myomectomy from within the uterus was performed. No malignancy was associated with the specimens recovered. In December of 2016, the abdominal pain persisted and a mass was palpable on physical examination in the mid-abdomen on the right. Colonoscopy was performed and biopsy showed a moderately differentiated adenocarcinoma of the caecum.
CT was performed in December of 2016 and the primary right colon malignancy along with bilateral ovarian metastases were imaged. Percutaneous biopsy of the right ovarian mass showed well differentiated adenocarcinoma consistent with a colonic primary. From December of 2016 through December of 2017, the patient was maintained on chemotherapy. Initially, she was treated with FOLFOX. After four cycles, because of neuropathy, the oxaliplatin was stopped. The patient was maintained on 5-fluorouracil and bevacizumab.
In December of 2017, a CT documented marked regression of the primary tumor. It was not visible by CT. However, multiple lymph nodes within the mesentery of the distal small bowel were enlarged. Also by CT a pelvic mass showed that the right ovary had increased in size to 15 cm in greatest diameter despite the fact that the primary caecal malignancy was no longer visible by CT.
Over approximately one month the patient became rapidly more symptomatic with abdominal distention from ascites and an expanding right ovarian mass. On February 1, 2018 the patient underwent cytoreductive surgery and HIPEC in a specialized center for management of peritoneal metastases. At the time of surgery she underwent a greater omentectomy, hysterectomy, bilateral salpingo-oophorectomy, complete pelvic peritonectomy, right colon resection, and small bowel resection. She received HIPEC with mitomycin C and doxorubicin with systemic fluorouracil. In order to determine if the multiple enlarged lymph nodes within the small bowel mesentery were involved by cancer, individual lymph nodes were removed and subjected to histopathologic study by permanent sections at a later time. A portion of each of these lymph nodes was sent for pharmacologic analysis for doxorubicin content. shows the pharmacokinetics of intraperitoneal doxorubicin in peritoneal fluid, mesenteric lymph nodes, and plasma. Clearly, the lymph nodes have taken up large amounts of doxorubicin nearly equal to that which was seen within the peritoneal fluid. The increased amounts of doxorubicin within lymph nodes as compared to the plasma can be measured by the area under the curve ratio. The ratio of lymph nodal tissue concentration times time to plasma concentration times time was 40. The area under the curve ratio (AUC ratio) of peritoneal fluid to plasma was 80.
After the HIPEC chemotherapy and biopsies, an end-to-side coloenteric anastomosis was performed. The patient required a 3-week hospitalization and was discharged eating well and having normal bladder and bowel function. Pathology showed cancer in the right ovary and small amounts of cancer remaining at the primary site. No cancer was present in the mesenteric lymph nodes.
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pmc-6312798-2
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This 35 year old woman began noticing increasing fatigue in 2014. The fatigue and left lower quadrant pain became increasingly severe so that she went an emergency room. On 19 February 2018, a CT scan was performed that showed an infiltrate into the greater omentum and multiple nodules associated with small bowel mesentery. There was no ascites. Masses were present on both the right and left ovaries. On 14 March 2018, she was taken to the operating room where multiple biopsies were taken. Her left ovary and appendix were removed. Pathology showed a mature cystic teratoma and extensive malignant peritoneal mesothelioma. Multiple biopsies from omentum, surface of uterus, peritoneum from the abdominal wall, and peritoneum from the small bowel showed malignant peritoneal mesothelioma.
Repeat CT on 2 May 2018 showed malignant peritoneal mesothelioma infiltrating the omentum and accumulating as a diffuse mass in the pelvis. The small bowel mesentery showed multiple prominent lymph nodes. For definitive treatment of her malignant peritoneal mesothelioma, the patient was taken back to the operating room on 3 May 2018. At that time she had a greater and lesser omentectomy, cholecystectomy, pelvic peritonectomy with hysterectomy and right oophorectomy along with cytoreductive surgery of the small and large bowel surfaces. HIPEC was performed with cisplatin, doxorubicin, and systemic ifosfamide with Mesna (2-Mercaptoethanesulfonic acid sodium). During the HIPEC procedure Mayo scissor dissection removed a layer tumor from large and small bowel surfaces along with large and small bowel mesenteric surfaces []. In order to rule out disease within the mesenteric lymph nodes, six of these lymph nodes were harvested during the HIPEC chemotherapy []. Portions of the node were sent for histopathologic analysis and other portions were sent for pharmacologic analysis of the intraperitoneal drug, doxorubicin. The results of the doxorubicin within blood, peritoneal fluid, lymph nodes, and tumor are shown in . The area under the curve ratio of lymph node doxorubicin to plasma doxorubicin was 30. The area under the curve ratio of tumor nodules to plasma was 20 and from peritoneal fluid to plasma was 50.
Again in this patient the markedly increased levels of doxorubicin in lymph nodes as compared to plasma were documented.
The patient was hospitalized for 15 days and was discharged eating well. An intraperitoneal port was placed at the time of the cytoreductive surgery and will be used to deliver long-term intraperitoneal pemetrexed with systemic cisplatin. Six cycles of treatment are planned. Pathology of resected specimens showed malignant peritoneal mesothelioma; the lymph nodes were negative for cancer.
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pmc-6313426-1
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A 48-year-old male patient diagnosed with adenocarcinoma consistent with salivary duct carcinoma T4a (40 mm) N2 (multiple focal 1 cm right submandibular and retrocervical nodes) M0/stage IVA. Surgical excision was not recommended; the patient underwent Intensity-ModulatedRadiation Therapy with a curative aim for 44 days. After radiotherapy, the patient started to complain of pain, dysgeusia, and oral dryness, which persisted with time. Oral mucositis, dysgeusia, and oral dryness were diagnosed based on a meticulous clinical examination. No ethical committee approval was necessary for our research since the protocol used in this case report is well described in the literature. The patient signed a written informed consent before enrolling in the study.
Assessment of oral mucositis
The severity of oral mucositis was measured according to the World Health Organization scale for assessing oral mucositis. The patient presented erythema and ulcers but was able to eat solid foods; therefore, the severity of oral mucositis was Grade 2 ().
Assessment of dysgeusia
According to the International Standards Organization (ISO), dysgeusia test was used in order to assess the severity of the disorder. Before all taste tests, the patient was asked to stop eating, drinking, smoking or using any oral care products. The patient was also required to drink only water at least one hour prior to testing. Five 2-mm solutions that represent basic taste qualities—sweet, salty, sour, bitter and umami—were tasted in a single ‘sip and spit’ technique. The solutions and their corresponding concentrations were sucrose 300 mM, NaCl 200 mM, citric acid 5 mM, caffeine 10 mM, and MSG 200 mM. Perceived taste quality was identified by selecting one of seven choices. Correct responses were sweet for sucrose, salty for NaCl, sour for citric acid, bitter for caffeine, and savory for MSG. Further choices were none or metallic. Taste identification score was assigned as 0–5 correct choices. The test identification score was 3 out of 5. The mouth was rinsed with purified water 3 times before and after sampling and expectorating each solution ().
Assessment of oral dryness
For the assessment of oral dryness or hyposalivation, the quantity of the total resting and stimulated saliva (Q-sal, mL/min) was measured. The patient was asked to expectorate all saliva into a graduated test tube for a 10-min period before the citric acid stimulation and a 5-min period after the stimulation. The amount of saliva before and after stimulation was determined by the scale on the graduated tube. The quantity of saliva was respectively 0.05 and 0.11 for the resting and stimulating saliva []. After the assessment of the severity of oral mucositis, dysgeusia, and oral dryness, the treatment of choice was the therapeutic (curative) use of photobiomodulation (low-level laser therapy) for at least 5 times a week until there was an improvement in symptoms. Photobiomodulation dosimetry, applications, and treatment protocol was based on evidence derived from the literature and expert opinion that provided a guideline for the use of photobiomodulation in supportive cancer care for oral mucositis, dysgeusia and oral dryness [] ().
i. Treatment of oral mucositis
Intraoral application of diode laser is employed with a wavelength of 980 nm (FONA Laser Sirona Dental Systems GmbH, Germany) at energy density of 4 J/point and a time of 12 s per point in a continuous and contact mode on 4 points on the tongue and 2 on the oropharynx. Extraoral application of diode laser is achieved with a wavelength of 980 nm (FONA Laser Sirona Dental Systems GmbH, Germany), energy density of 4 J/point, and a time of 12 s per point on the following areas: lips, cutaneous surface corresponding to the buccal mucosae, and bilateral cervical lymphaphatic chain [] ().
ii. Treatment of dysgeusia
Intraoral application of diode laser is achieved with a wavelength of 980 nm (FONA Laser Sirona Dental Systems, GmbH, Germany) at 10 points on the dorsal and lateral tongue at an energy density of 3 J/cm2 for 12 s on each point. Each session was repeated 3 times for one week, within 48 h between each session [] ().
iii. Treatment of Oral dryness/hyposalivation
Extraoral application of diode laser 650 nm (LLLT Laser Bio:PDT: Soulagement de douleur par MG Consiliis) is attained with a total of 20 points (10 each side) at an energy density of 3 J/cm2 for 12 s in a continuous and contact mode targeting major salivary glands (parotid and submandibular glands) and minor salivary glands in each side [].
Five sessions of photobiomodulation were implemented for one week as follows: Monday Tuesday, Wednesday, Thursday, and Friday. After 24 h of each session, assessments of oral mucositis, oral dryness and dysgeusia were made according to the already mentioned scores and criteria. After each session, the severity of oral mucositis and oral dryness decreased, and taste perception improved. Oral mucositis decreased from grade 2 to grade 0 after five sessions of PBM. The patient scored 5 out of 5 on the taste identification score. The quantity of whole resting and stimulated saliva increased from 0.05 to 0.12 for the resting saliva and from 0.11 to 0.21 for the stimulated saliva. shows the results.
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pmc-6313494-1
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A 22-year-old male student visited the department of restorative and esthetic dentistry of National Taiwan University Hospital for a dislodgement of lower right posterior tooth restoration. He had received direct composite resin filling three years ago, but the old restoration was dislodged while eating popcorn two days earlier. Clinical examination revealed food impaction over the large mesial cavity of the lower right first molar with gingival inflammation (). The pulp vitality test was normal with no symptoms or signs. Radiographic examination revealed a large mesial decay in proximity to the pulp horn while no obvious abnormal apical findings were noted (). After oral hygiene reinforcement, we discussed with the patient that composite onlay might be a choice for his aesthetic and financial concerns, and further possibility of root canal treatment. A written informed consent was obtained before the treatment, and patient gave permission for the related pictures and radiographs to be published before submission.
At the next appointment, under block anesthesia using 2% lidocaine with epinephrine 1:100,000, caries was removed by low speed carbide burs and sharpened spoon excavator under rubber dam isolation (). The mesial gingival margin was located approximately 0.5 mm subgingivally. Therefore, gingival displacement was achieved using a retraction cord. The undercuts of the tooth cavity were blocked out with a nano-hybrid composite resin (Grandio, shade A3, Voco, Cuxhaven, Germany), which served as a base material. The cavity was prepared, and an alginate impression was taken after removal of the rubber dam. A self-cured bis-acrylic resin (Structur 2 SC, Voco, Cuxhaven, Germany) was used as a temporary filling material before the next cementation appointment. A fast-setting silicone die material (GrandioSO Inlay System, Voco, Cuxhaven, Germany) was injected into the alginate. During the inter-appointment period, the onlay restoration was fabricated incrementally with a light-cured composite resin (Grandio, shades A2, A3, and A3.5, Cuxhaven, Germany) (), and each layer was polymerized for 10 s with a light-emitting diode curing unit (Valo, Ultradent, South Jordan, UT, USA) with light irradiance of 1000 mW/cm2. For sculpting the occlusal morphology, we determined mesio-lingual cusp and trianglular ridge by referring to the existing distolingual cusp and neighboring teeth. In addition, the cast of the upper arch was used for adjusting the occlusion. The final occlusal anatomy was reconstructed and incorporated with a resin staining kit (Tetric color, Ivoclar Vivadent, Schaan, Liechtenstein), which was used for internal staining to mimic the fissures of a natural tooth. After finishing and polymerization, the composite onlay was removed from the silicone die and cured from the intaglio surface for 40 s.
At the next appointment, isolation was performed with rubber dam. Then, the onlay was tried in and the fitness was checked. Before cementation, the intaglio surface of restoration received airborne-particle abrasion with 50 μm alumina particles; subsequently, it was conditioned with 37.5% phosphoric acid gel (Gel Etchant, Kerr, Orange, CA, USA) for 15 s. After the etchant gel was rinsed, the composite onlay was cleaned with 75% ethanol in an ultrasonic bath for 3 min. Moreover, the tooth was selectively etched with 37.5% phosphoric acid gel (Gel Etchant, Kerr, Orange, CA, USA) for 15 s, rinsed with water spray, and air dried. The self-etching adhesive and dual-cured luting composite (Multilink N system, Ivoclar Vivadent, Schaan, Liechtenstein) were used for final cementation. Polymerization was performed for 40 s per surface (). After rubber dam removal, the occlusal contacts were adjusted and checked with articulating paper (). Finally, the restoration was finished by fine-grained diamond burs and polished by abrasive, silicon-impregnated rubbers (Jiffy, Ultradent, South Jordan, UT, USA) (). A bitewing radiograph was taken to examine whether any overhang existed at the gingival margin (). At the one-year recall, the restoration still maintained its esthetic and chewing function ().
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pmc-6313525-1
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A 58-year-old man presented to medical attention with atypical chest tightness with exertion. He has a history of hypertension, hyperlipidemia, and orthostatic dizziness/pre-syncope. He has no history of diabetes and is a non-smoker. He underwent investigations including an electrocardiogram (ECG) and an exercise stress test, which were both normal. Echocardiogram was unremarkable as well, revealing mildly concentrically increased left ventricular wall thickness and mild biatrial enlargement. Cardiac computed tomography demonstrated diffuse non-obstructive coronary artery disease (CAD). The right coronary artery (RCA) was shown to have a cylindrical aneurysmal dilatation over 38 mm with associated plaque and the proximal left anterior descending (LAD) artery had an ulcerated noncalcified plaque (25–49%) (). He has no specific family history for premature CAD, arrhythmia or sudden cardiac death.
As a result of these findings, he underwent coronary angiographic assessment to clarify his anatomy. At the cardiac catheterization laboratory, a right radial artery access was obtained and subsequent left heart catheterization and left ventriculogram revealed left-ventricular end-diastolic pressure (LVEDP) of 15 mmHg and normal left-ventricular ejection fraction (LVEF) with normal wall motion. Coronary angiography revealed a right-dominant system with ectasia involving the proximal RCA, LAD artery and left circumflex (LCx) artery with no obstructive lesions. The ectasia was thought to be most likely related to atherosclerosis. The patient was started on atorvastatin (10 mg/day), candesartan (4 mg/day), and aspirin (81 mg/day). No anticoagulant therapy was recommended.
Four months later, the patient experienced chest pain while playing squash. Vitals were unremarkable and only the blood pressure was mildly elevated at 141/103. ECG done in the field showed inferior ST-elevation myocardial infarction (STEMI) (). The cardiac catheterization laboratory was activated. The left heart catheterization and ventriculogram revealed normal LV ejection fraction with mild inferior hypokinesia. Coronary angiography revealed thrombus at the proximal RCA with occlusion of the distal right posterolateral branch and distal right posterior descending artery due to embolism, without associated stenotic lesions (). He was treated with intravenous (IV) eptifibatide (22.5 mL bolus × 2, 15 mL/h infusion) and heparin (2000 units), followed by aspiration thrombectomy. Stenting was deferred due to the ectatic nature of his vessels. Thrombectomy was performed on the lesion at the 1st right poster olateral segment. Using a 6FR Runway FR4 guiding catheter, BMW Balance Middle Weight wire was used to cross the lesion. Balloon angioplasty was performed using a Sprinter Legend RX 1.5 × 20 balloon, with 1 inflation at a maximum of 10 atm pressure. Two attempts of mechanical thrombectomy were performed, with a maximum duration of 56 s and a volume of 30 mL. Visible thrombus was retrieved but the distal branches remained occluded. Echocardiogram confirmed hypokinesis of the inferior wall. The patient was treated with IV eptifibatide for 24 h and IV heparin for 48 h before being discharged in a stable condition. He was discharged on Clopidogrel (75 mg/day) and Rivaroxaban (15 mg/day) in addition to his preadmission risk modifying medications. The patient was adherent to the medications and there were no reported adverse events. A follow-up cardiac CT (2 months later) revealed no residual coronary artery thrombus, high-grade stenosis or occlusion and the latest treadmill stress test (11 months later) was negative for ischemia as well.
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pmc-6313600-1
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Mrs. ET, a 54-year-old woman, was admitted to our unit with a two-week progressive history of dull aching pain over her right shoulder. Her symptoms had progressively worsened over the few days prior to admission. The pain was associated with fever and rigours and was aggravated by minimal shoulder joint movement. She was not diabetic, and there was no history to suggest immunosuppression, with hypertension being the only past medical history of note. Additionally, there was no history of any trauma preceding her symptoms.
On examination, she had a core body temperature of 37.9° Celsius with otherwise normal physiological parameters (i.e., within normal range). There was no history of a recent illness, and on systematic review her only complaint was a painful right shoulder. On inspection of the right shoulder, there was no obvious erythema, with a small amount of swelling and localised temperature change over the right shoulder joint. Her shoulder tenderness was vague and spanned from her scapula through to her sternoclavicular joint. She had a reduced amount of shoulder movement (in every direction) and was specifically tender on arm adduction against resistance.
Laboratory investigations revealed raised inflammatory markers, with a white cell count (WCC) of 9.62 × 109/L, neutrophils of 8.73 × 109/L, and a C-reactive protein (CRP) of 52 mg/L. Radiographs of the right shoulder were obtained (a,b), and were unremarkable.
Mrs. ET had a recorded episode of pyrexia in the department, and at that point had additional blood tests taken for culture and sensitivity. Equally, at this point, septic arthritis of the shoulder could not be excluded and thus two attempts at shoulder aspiration were made (with an anterior and then a posterior approach), with no success.
Blood cultures from Mrs. ET had grown Staphylococcus aureus which was found to be sensitive to flucloxacillin, and so, after discussion with the infectious diseases (ID) team, the patient was commenced on intravenous antibiotics. An echocardiogram was also performed soon after and was found to show no evidence of an infective endocarditis.
The following day, Mrs. ET’s episodic spikes in body temperature had not settled and at that moment in time, despite a dry tap from the shoulder, the working diagnosis was a septic arthritis of the shoulder. Consequently, preparations were made for Mrs. ET to head to theatre for an arthroscopic (or potentially open) aspiration and washout of the shoulder joint.
Prior to the operation, an MRI (magnetic resonance imaging) scan was requested to assess/confirm the presence of a collection within the joint. The MRI scan went on to demonstrate no collection within the shoulder joint; however, inflammation involving the right pectoral muscle approximately 8.8 cm in circumference was observed, suggesting pectoralis major pyomyositis (a–c).
Mrs. ET did not proceed to surgical intervention and, after further discussions with the ID team, was given a two-week course of intravenous antibiotics (Flucloxacillin 2 g, four times a day). Over the course of her hospital stay, the CRP fell to 19 mg/L and the patient’s episodes of pyrexia settled completely. After this two-week course, Mrs. ET was prescribed a four-week course of oral Clindamycin (300 mg, four times a day).
At six-week follow up, the patient’s symptoms had almost fully resolved, with near full range of movement in the shoulder joint and a further drop in her CRP to 5 mg/L. A repeat MRI scan of the shoulder confirmed complete resolution of the pyomyositis. After a course of shoulder physiotherapy, Mrs. ET did not require any further antibiotics and was discharged from follow up.
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pmc-6313638-1
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In May 2015, a 100-year-old Caucasian man was referred to our outpatient clinic complaining of chronic pain in shoulder and hip girdle pain with 4-h morning stiffness. Constitutional manifestations were not present. In the previous four months, several non-steroid anti-inflammatory drugs (NSAIDs) and painkillers associated with physiotherapy treatments gave no significant improvement in pain and self-care. He had an X-ray of the chest, shoulders and pelvic, revealing no pathologic findings. An abdominal ultrasound (US) showed mild hepatomegaly and renal cysts. He did not suffer from psoriasis; no ocular, intestinal or uninary manifestations were present. ESR was 21 mm/1st hour (normal values < 30) at the onset and 12 mm/1st hour at the time of our examination. C-reactive protein (CRP) was 4 and 3 mg/dL (normal values < 6), respectively. Other laboratory data were all negative. In particular, serum fibrinogen levels were equal to 350 mg/dL (normal values < 400 mg/dL); rheumatoid factor (RF) and anti-protein citrullinated antibodies (APCA) were in their normal range; hemoglobin was equal to 12.8 gr/dL (normal values > 12.0 gr/dL); transaminases, creatine phospho kinase (CPK), protein electrophoresis, antinuclear cytoplasmic antibodies (ANCA) were in their normal ranges. Occult blood research in the stool was negative and fecal calprotectin dosage was in the normal range. Antibodies to hepatitis C virus and Australia antigen were absent. An US examination showed bilateral long-head-biceps exudative tenosynovitis and subdeltoid bursitis in his shoulders () and trochanteric bursitis in his right hip. An 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) associated with total body computed tomography (CT) was performed () and excluded pathological findings in other sites. PMR was proposed. He started with 12.5 mg/day prednisone and there was a rapid improvement. After 10 days, he spontaneously stopped prednisone, but after 24 h, the manifestations reappeared, and he took it again. Prednisone tapering was made according to the schedule proposed by an international collaborative initiative [] and stopped after 10 months. The patient refused a control PET/CT. A new US evaluation of shoulders and hips, performed after three months, showed normal findings. During a 3-year follow-up, he never had constitutional manifestations; no clinical manifestations suggestive for an overlapping giant cell arteritis (GCA) were observed; no alternative diagnosis was possible. As for today, our patient is fine.
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pmc-6313740-1
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An eight-year-old Hispanic male presented to the Stony Brook Dental Care Center with a history of GSD type Ib. Oral manifestations of the GSD Ib disease were observed and recorded upon the dental and radiographic examination. Overall, the patient presented with extensive generalized inflammation of the gingiva, erythema, ulceration, and generalized deep periodontal pocketing with bleeding on probing (). Generalized severe horizontal bone loss was noted radiographically (). Informed consent for treatment was obtained.
Microbial samples were taken with sterile paper points at various primary and permanent teeth to demonstrate the periodontal pathogen distribution []. A blood sample was drawn in order to study systemic neutrophil migration. Peripheral blood neutrophils were isolated according to a standard protocol [] and suspended in HBSS + 10 mM HEPES (pH 7.4) and 1% BSA. A 48-well Boyden chamber apparatus (Neuro Probe, Inc., Gaithersburg, MD, USA) was arranged so that 20 nM of CXCL1 (R&D Systems, Minneapolis, MN, USA), 20 nM of CXCL8 (R&D Systems), or HBSS + 10 mM HEPES (pH 7.4) and 1% BSA was added as the chemoattractant or control in the bottom portion of the chamber. A 5-μm 35 cellulose nitrate filter (Neuro Probe, Gaithersburg, MD, USA) was placed between the two halves of the Boyden chamber. Neutrophils in a volume of 50 μL, at no more than 4 × 106 cells/mL, were loaded into the top chamber and allowed to migrate for 15 min at 37 °C. The filter was fixed in 100% 2-propanol, stained with Harris-type hematoxylin, clarified with xylene, and mounted for analysis. The distance that neutrophils traveled into the filter was measured using the leading-front method via bright-field microscopy. The microbial composition of the oral biofilm was characterized by multiplex PCR. 16S rRNA gene was used as the primers in PCR. Sterilized deionized water was used as negative control. Of the common putative periodontal pathogens, Tannerella forsythia was readily identifiable from the biofilm samples (, ). In addition, a deficient host response was observed by impaired neutrophil migration in response to the chemokines CXCL1 and CXCL8 (). Histological evaluation [] of the soft and hard tissues of the periodontally affected primary teeth showed a normal attachment apparatus, including bone, cementum, and periodontal ligament ().
Based on the clinical findings and the understanding of the disease, a treatment plan was developed collaboratively with the Departments of Orthodontics, Pediatric Dentistry, and Periodontology. All remaining primary teeth had a hopeless prognosis and it was elected to proceed with extractions after obtaining informed consent. No postoperative infections or bleeding were reported or observed. In order to preserve the space for the remaining succedaneous teeth, a nance appliance and lower lingual holding arch were fabricated for the maxillary and mandibular dentitions, respectively. A two to three month recall interval for dental examinations and preventative care has been recommended for this patient []. Patient was not followed up in this case report after immediate post-operative treatment course.
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pmc-6313756-1
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A 64-year-old woman with a past medical history of Grave’s disease presented to the hospital complaining of sudden onset of facial and bilateral arm swelling, as well as "bruising" in her neck, abdomen, and arms, all of which she developed over a few days. Further, the patient reported fatigue, neck tightness, and dyspnea on exertion. She denied any other symptoms and the remainder of the full review of systems, including weight loss, was negative. Social history was significant for 40 years of smoking. The patient was hemodynamically stable with good oxygenation on 2 L of oxygen by nasal cannula. Physical exam revealed swelling of the face, neck, and both arms, superficial varicosities on the neck, chest, back, and arms, as well as mild inspiratory stridor. Computed tomography angiography (CTA) of the thorax and neck showed a large central mediastinal mass occluding the pulmonary artery and extending into the right atrium, encasing the superior vena cava (SVC), abutting the trachea but not causing tracheal narrowing (A), as well as pulmonary emboli at the right lower lobe (B). Given the tobacco abuse history, lung cancer leading to SVC syndrome was suspected, although other malignancies such as lymphoma were in the differential. The patient was started on a heparin drip and the Pulmonary and Hematology-Oncology services were consulted, both of which agreed for the need for tissue diagnosis of the likely malignancy and rapid initiation of treatment.
A complicating factor in this patient’s care was her adamant belief that the swelling was an allergic reaction to one of the many over-the-counter herbal and homeopathic medications that she was taking to try to rid her body of the “flukes” which she claimed to have seen in her nasal secretions and stool. The patient soon moved on to express the belief that her mediastinal mass was caused by her parasites and demanded treatment for them rather than for the cancer. Review of this patient’s medical record did not yield any evidence for a documented psychiatric disorder or treatment thereof in the past. However, her significant other at bedside revealed that the patient had been preoccupied with the notion of having blood flukes for at least eight years.
After much discussion, the patient agreed upon undergoing biopsy of her mass as long as she was also tested and treated for the parasites. Fine needle aspiration of the right supraclavicular lymph node on day two of admission revealed metastatic small cell carcinoma. On that same day, the patient was transitioned to the ICU due to increasing oxygen requirements necessitating bilevel positive airway pressure ventilation. Radiation–Oncology was consulted and recommended starting radiation treatment; however, the patient was reluctant to do so until the final diagnostic confirmation of cancer on day four. Similarly, she stated that she would refuse to start chemotherapy until she could obtain a second opinion. Not surprisingly, the consulting services deemed it dangerous to postpone treatment initiation given the size and location of the mediastinal mass and the patient’s worsening respiratory status. Due to an enlarging pleural effusion, thoracentesis was performed on the right side on day five and the pleural fluid was negative for malignant cells. Further, a metastatic workup revealed a suspicious lesion at S1 on a nuclear medicine scan that was consistent with Paget’s disease as well as malignancy. An MRI brain scan could not differentiate between small vessel ischemic disease and a possible small metastatic lesion. In the meantime, ova and parasite studies of the patient’s stool, nasal secretions, and lymph node aspirate had returned negative, yet she remained adamant in her decision to refuse chemo-radiation until the parasites were treated. Although there was a plan for an Ethics consultation, it was postponed as the patient changed her mind and underwent the first chemotherapy cycle on days 8 (carboplatin), 9 and 10 (etoposide), and radiotherapy was started on day 10. Ethics was eventually consulted on day 10 and recommended avoiding treatment for unproven parasitosis. Repeat CTA of the thorax on day 12 demonstrated new pulmonary emboli in the left lower lobe, slight increase in the bilateral pleural effusions, and no significant change in the tumor burden. On day 14, the patient decided to change her code status from FULL CODE to DNR/DNI. On day 19, her blood pressure dropped and she required pressor support, was started on a five-day course of cefepime for neutropenic fever, as well as fludrocortisone and hydrocortisone for a few days until the shock resolved. Given her unstable state, further chemotherapy was not advisable. Another complicating factor in the patient’s care were her poor nutritional status, her repeated attempts to drink water despite the danger for aspiration, as well as her increasing agitation and lack of cooperation with the hospital staff. The use of anxiolytics provided only partial relief and the situation continued to escalate to the point where the patient started being verbally abusive to the medical personnel, was refusing medications, radiation therapy, and physical exams. Her respiratory status continued to worsen and she was often heard to voice her wish to die. Therefore, on day 34 a family meeting was held, during which the patient’s poor prognosis was discussed. Although at that time the patient did not wish to pursue comfort care, the prolonged drop in oxygen saturation later that evening was causing her so much discomfort that she decided to make the transition. The patient was pronounced at midnight, from cardiopulmonary failure. Up to the point of death, the patient maintained her belief that the primary cause of her symptoms was a parasitic infestation and that her diagnosis of carcinoma of the lung was “fake”.
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pmc-6313770-1
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A 19-month-old male infant was admitted to our Paediatric Clinic for dehydration due to rotavirus-associated enteritis based on the results of a stool test. Personal anamnesis showed birth at term, perinatal well-being, and normal psycho-motor development. On day 2 of hospitalization, an intermittent fever appeared associated with a cough and rhinitis. The nasal swab tested positive for adenovirus. We sustained the baby with intravenous fluid and antipyretic therapy. At that point, laboratory tests showed pancytopaenia (white blood cells 4330/mm3, 14% neutrophils, haemoglobin 9.3 g/dL, and platelets 70,000/mm3) and an increase in the transaminase values. The peripheral blood smear indicated activated lymphocytes and an absence of signs of haemolysis (Coombs test negative, haptoglobin within the normal range). At the resolution of dehydration, enteritis, and fever, we discharged the infant in excellent clinical condition with a diagnosis of pancytopaenia and liver cytolysis during adenovirus and rotavirus co-infection and suggested clinical and biochemical monitoring 7 days later. The baby lived in a small waterfront town by Trasimeno Lake, where his dog was waiting for him.
Three days after returning home, the fever reoccurred without coenaesthesis impairment. A second hospitalization was established at the follow-up visit; the physical examination showed mucocutaneous pallor and hepatosplenomegaly confirmed by ultrasonography in the absence of generalized lymphadenopathies that was associated with an irregular fever for 6 days. The laboratory tests () confirmed the presence of pancytopaenia (white blood cell counts 3370/mm3, haemoglobin 7.5 g/dL, and platelets 101,000/mm3) and the elevation of inflammatory markers (C reactive protein 6 mg/dL and erythrocyte sedimentation rate 30 mm/1 h). Fibrinogen and the coagulation profile were in range, and the anti-nuclear antibody test was negative. Furthermore, serum immunoglobulin IgA and IgM were normal, but hypergammaglobulinaemia (1855 mg/dL) and high serum ferritin levels (429 ng/mL) were identified. No evidence of echocardiographic abnormalities was found. There was no evidence of malignancy. The peripheral blood immunophenotype, LDH, and uric acid tests were normal, and a chest X-ray was negative for a mediastinal enlargement. An acute EBV infection was found based on positivity for VCA-IgG and VCA-IgM (VCA IgG 409 U/mL, pos >20; VCA IgM 57 U/mL, pos >20; EBNA IgG 3.9 U/mL, pos >5). Epstein–Barr virus DNAemia was not obtained. The remaining serological tests for parvovirus B19, cytomegalovirus, Bartonella henselae, HIV, and Widal–Wright were negative, as were the multiple blood cultures and the Mantoux test. At this point, the working diagnosis was mononucleosis complicated by secondary HLH that might be associated with an EBV infection. In fact, the infant presented 4 of 8 diagnostic criteria suggesting HLH: prolonged fever, persistence of hepatosplenomegaly, pancytopaenia (white blood cells 4300/mm3, haemoglobin 7.3 g/dL, and platelets 90,000/mm3), and elevated triglycerides (546 mg/dL). To obtain a clear diagnosis, bone marrow aspiration was performed. The test revealed the presence of one red blood cell phagocytized by a macrophage but also intracellular and extracellular microorganisms consistent with Leishmania amastigotes (), which were confirmed by positive serology (indirect immunofluorescence IgG titre of 640, with a cutoff of 1:80). In addition, the blood cell lines were normal except for mild lymphocytic hyperplasia with no evidence of malignancy.
Based on the definitive diagnosis of HLH associated with VL and EBV infection, on day 22 of the fever the child started treatment with L-AmB 3 mg/kg/day for 5 days, followed by two other drug infusions of 3 mg/kg at days 14 and 21 after the beginning of therapy []. He showed resolution of fever within 48 h after initiation of treatment, and his clinical condition rapidly improved. The laboratory tests (blood count, triglycerides, and inflammatory indices) gradually normalized. At the follow-up visits, there was no evidence of relapse ().
Management of the case was approved by the Ethics Committee of Santa Maria della Misericordia Hospital, Perugia, Italy (2018-PED-01). The patient’s parents provided their written informed consent for the management of their child and the publication of the case report.
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pmc-6313962-1
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A 57-year-old man presented to the cardiologist's office as a part of the preoperative evaluation before undergoing an ophthalmological surgery. He complained of shortness of breath and fatigue. The patient had a prior history of coronary stents and heart failure. Physical examination was unremarkable. Echocardiogram reported moderate dilation of the left ventricle and hypokinesis of the apical lateral wall and apical septal wall. Ejection fraction was reported to be 35-40% (). The patient was evaluated by a nuclear stress test which came out to be abnormal. The patient then underwent an invasive coronary angiography that showed a 70% eccentric obstruction of the proximal left anterior descending (LAD) artery and a 70% obstruction of the left circumflex artery as well with diffuse calcification. The right coronary artery (RCA) was believed to be anomalous (Figures and ). Cardiothoracic surgery evaluated the patient and coronary artery bypass graft was performed that identified intraoperatively an anomalous origin of RCA from the pulmonary artery which was then successfully reimplanted into the ascending aorta.
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pmc-6313968-1
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We report a case of a 50-year-old woman, normal weight and length (49 kg, 164 cm), known to have HIV for the previous 6 years and who was recently started on ART (2 weeks ago). No report was found of the patient taking any HIV therapy in the past. The ART started was abacavir-lamivudine, respectively, 600mg and 300 mg once daily in combination with darunavir 400mg twice daily. Further medical history consists of depression and anxiety, migraines, gastroesophageal reflux disease, and no known use of illicit drugs. She was admitted in the Intensive Care Unit (ICU) after being apathetic, lethargic, and having a painful cold cyanotic right hand for 4 days. The day of hospitalization she was found very drowsy on the floor by her partner who called the health emergency services immediately. Earlier that week a general practitioner was consulted concerning the painful hand. He suggested this was due to lateral epicondylitis and treated her with NSAID's.
In hospital on admission physical examination revealed a woman with a Glasgow Coma Scale of 13/15, conscious but sleepy, oriented, slow speech, and grossly intact cranial nerves. On examination she had cyanotic cold toes on the right foot and a cyanotic right hand extending to the wrist and no pulsations were felt on all 4 limbs (no sign of edema). The patient had a blood pressure of 140/70 mmHg on the left arm and heart rate of 80 beats/min. On auscultation no irregularities were found and the SpO2 indicated 99%. Examination revealed no abdominal abnormalities, but auscultation showed hyperactive bowel sounds. There were no signs of a fever and the urine output was normal. On admission the SAPS score was 40, APACHE-II score 12, MODScore 6, and SOFA score 4; thus the mortality prediction by the SAPS-II score was 24.7%.
A central venous catheter was inserted at the Emergency Department due to failed attempts of placing a peripheral canula. Complete blood cell count showed a white blood count of 11.5 x 109/L and no further abnormalities (see supplementary information ). The serum biochemistry showed a CRP of 24 mg/dl, CK 2285U/L, normal renal function with a of sodium of 121 mEq/L and chloride 87 mEq/L. Lactate was 0.7 mmol/L and troponins were negative with two consecutive blood samples. Toxicology screening, including ethanol, were also negative. Coagulation showed normal PT and APTT but D-dimers were raised to 2.2 mg/L (reference normally < 0.5). HIV viral load showed 42 copies/mL and CD4 count was 380 cells per cubic millimeter of blood.
Because of the altered consciousness and lethargy a CT scan of the head was done. This showed no acute intracranial abnormality. During the following days the patient deteriorated and showed increasing unconsciousness and ischemic limbs. Platelet and coagulation disorders were excluded and the lumbar puncture showed no abnormalities. On the 3th day of admission, due to quickly lowering Glasgow coma scale, the patient needed intubation. At the same day a CT angiography of the aorta and lower limbs was done to find a cause for the increasingly cyanotic limbs. Findings included (i) multiple renal infarctions, (ii) narrowing of the external iliac arteries, and (iii) bilateral narrowed femoral-popliteal arteries with multitudinous stenosis or occlusions. The radiologists had difficulties to differentiate between thrombogenic pathology, medically induced arterial spasms, hypovolemia, or congenital hypotrophic arteries.
Two days after intubation, when sedation was stopped, clinical examination showed no improvement of consciousness and fixed pupils were noticed. A CT angiography of the head () showed important supratentorial hydrocephalus with narrowing of cortical sulci and cerebral edema. A normal intracranial perfusion, caliber, and patency of the vertebral arteries and the carotid arteries were seen.
On the 6th day, a head MRI () showed extensive recent ischemia in the cerebellum and hemispheres, more pronounced on the right side than the left side. An obstructive dilatation of the third and fourth ventricle with clear signs of edema in the posterior fossa and pontocerebellar cisterna could be noticed. In addition, beginning herniation of the cerebral tonsils in the foramen magnum was visible. The MRI showed flow void in the basilar arteria and internal carotid arteria. Blood results had shown a slow decline in red blood cell count to 2.74 x 1012/L with a hemoglobin of 8.2 g/dl and a rise in white blood cell count up to 17.8 x 109/L with CRP of 27 mg/dl on the day she passed away. Liver function tests and renal function were slightly elevated.
After seeing the evolving ischemia with several CT's that could not clearly differentiate between nonocclusive vasospasms or multitudinous stenosis and no sign of underlying peripheral artery disease, the medical history of the patient was re-examined. This revealed a document 10 years prior to the current hospitalisation suggesting former use of ergotamine containing medication (Cafergot®). Current use of ergotamine prior to hospitalization for a severe migraine attack was also confirmed by the partner. All this information in combination with the clinical presentation led to the diagnosis of ET.
Treatment was promptly started (3 days after admission), with IV nimodipine, intra-arterial sodium nitroprusside, and nitroglycerin transdermal patches on affected limbs (both legs and right arm). In addition, an epidural catheter was placed for infusion of bupivacaine. The HIV medication was discontinued and to prevent secondary thrombosis anticoagulation with low-molecular-weight heparin was started. However, no improvement was noticeable.
Two days after stopping sedation, the patient did not wake up and pupils were fixed. MRI of the head () showed beginning herniation of the cerebral tonsils in the foramen magnum. Neurosurgeons believed that the brain damage due to hydrocephalus was irreversible and that there would be no improvement with external ventricular drainage. Due to the evolving symptomatology and poor prognosis, in agreement with family futile life sustaining therapies were limited and supportive therapy for comfort was started. Patient died 7 days after being admitted at the ICU.
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pmc-6313984-1
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A 28-year-old primigravida, without personal thyroid and autoimmune pathology or relevant family history (no consanguinity and unknown endocrine diseases in relatives), underwent prenatal ultrasonography (US) at 29 weeks' gestation, which revealed a high vascularized, bilobed, and symmetric mass in the anterior region of fetal neck (35 mm of largest diameter), suggesting fetal goiter (see Figures and ). No signs of polyhydramnios, cervical hyperextension, and no other fetal anomalies were detected. The mother denied any medication known to interfere with thyroid function and had an adequate diet. Maternal thyroid evaluation showed an euthyroid status without signs of thyroid autoimmunity. To better evaluate the airway patency, a Magnetic Resonance (MRI) was performed at 31 weeks, and it suggested goiter with 39,5x26,7mm, involving and causing airway deviation, with no signs of polyhydramnios (see Figures and ). At 32 weeks, a new US presented a goiter with 35x18x23mm, and first L-T4 amnioinfusion (300 μg-180 μg/kg estimated fetal weight) was performed with concomitant amniotic fluid withdrawal showing increased levels of thyroid-stimulating hormone (TSH) (3,53 μIU/mL, Normal Range (NR): 0,04-0,51 μIU/mL) and normal levels of free thyroxine (fT4) (0.3 ng/dL, NR: 0,10-0,77 ng/dL). A second amniotic L-T4 infusion (400 μg-180 μg/kg estimated fetal weight) was performed ten days later; at that time goiter showed 36x24x24mm and amniotic hormonal levels were TSH 1,69 μUI/ml (NR: 0,04-0,51 μUI/mL) and fT4 0.6 ng/dL (NR: 0,10-0,77 ng/dL). Serial imaging control did not show goiter size reduction, including last US at 37 weeks with 35x32x27mm, but also did not reveal the development of complications such as polyhydramnios.
Elective cesarean section was performed at 38 weeks of gestational age, and a male neonate was delivered with Apgar scores of 7/9 at first and fifth minutes, weighting 3480 g, showing a palpable goiter and exhibiting some breathing difficulties. He was promptly admitted to the neonatal intensive care unit due to respiratory distress and increasing oxygen requirements with cardiorespiratory insufficiency, moderate pulmonary hypertension, and decreased ventricular function requiring mechanical ventilation and aminergic support. Hormone assays of umbilical cord blood confirmed primary CH with reduced fT4 (0.2 ng/dL NR: 2,00-5,00 ng/dL), elevated TSH (715 μIU/mL NR: 2,3-13,2 μIU/mL), TG (4376 ng/mL NR: 14,7-101,1 ng/mL), and absence of thyroid autoantibodies. Thyroid replacement therapy with L-T4 was promptly started in the first hours of life, at a dose of 10 μg/kg/day. Biochemical control at fourth day of postpartum showed an increasing of fT4 to 0,9 ng/dL and a reduction of TSH to 103,8 μIU/mL.
Postnatal cervical US revealed an enlarged, slightly hypoechoic, and heterogeneous thyroid gland (right lobe: 18x32x18mm; left lobe 18x38x17mm) corroborating prenatal goiter diagnosis. Mechanical ventilation was maintained until the fifth day of life, and aminergic support was discontinued by the sixth day. Clinical evolution was favorable with discharge home at D12 with outpatient pediatric endocrinology follow-up.
He failed the newborn hearing screening by otoacoustic emissions; however hearing loss was not confirmed in the evoked auditory potentials. Genetic study found two pathogenic variants, both heterozygous, in TPO gene [c.1472G>A(;)1993C>T].
Currently, he is six years old with adequate growth without cognitive deficits (the Development Quotient score according to the revised Griffiths' scale was 100 at 44 months, which corresponds to the average level expected for age). He presents goiter with heterogeneous structure without focal lesions and is still under L-T4 treatment, adjusted according to serial hormonal monitoring.
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pmc-6313991-1
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A 59-year-old man was admitted to the neurology department in September 2014 with a four-month history of confusion, dysarthria, and progressive deterioration in deambulation capability.
He had no medical history and was unaware of any familial medical problems.
On admission, his hemoglobin level was 13.5 g/dl, leucocytes count was 9 × 109/L with normal leukocyte differential count, and platelet count was 120 × 109/L. Coagulation tests showed normal values with a fibrinogen level of 237 mg/dl and D-dimer test 698 μg/ml. Common liver and renal function tests (albumin, bilirubin, alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and creatinine) were in a normal range. Antibodies directed against human T-cell lymphotropic virus type 1 and human immunodeficiency virus I/II were negative. The cytomegalovirus and Epstein–Barr virus serology showed a pattern compatible with a past infection. Physical examination revealed hyposthenia of the right side of the body. For this reason, a computed tomography (CT) scan was performed, and it highlighted a focal lesion with enhanced border, measuring 15 mm, in the white matter of the left cerebral hemisphere (). Magnetic resonance imaging (MRI) of the brain confirmed the presence of a lesion with surrounding cerebral edema that involved posterior central cerebral convolution, posterior limb of internal capsule, corpus callosum of the left hemisphere, and right central cerebral convolution (). A positron emission tomogram (PET) scan also showed fludeoxyglucose (FDG) uptake in the left lateral paraventricular region (SUVmax 11.2) (). A lumbar puncture was performed, but no additional information was provided.
During the hospital stay, blood examination showed appearance of leukocytosis (white blood cells, WBC 20 × 103/μL) and thrombocytopenia (platelets 24 × 103/μL); coagulation tests demonstrated normal activated partial thromboplastin time ratio, prothrombin time ratio, and fibrinogen level; D-dimer was 2426 μg/ml.
The morphological examination of peripheral blood showed promyelocytes with Auer bodies; flow cytometric analysis demonstrated CD11b + CD11c + CD15 + CD33 + CD38 + CD64 + CD13 + CD2 + CD117 + blast cells, while HLA-DR, CD34, or CD56 were not expressed. Diagnosis of high-risk classic APL was confirmed by cytogenetic [46, XY, t(15; 17) (q24; q21) [4]/46, XY, t(15; 17) (q24; q21), del(9) (q21q23) [11]/46, XY [2]] and molecular biology tests (PML-RARA/bcr3 fusion transcript). The patient was then transferred to our Hematology Department for the treatment of APL.
In October 2014, in consideration of the APL diagnosis with a suspected CNS involvement, all-trans retinoic acid (ATRA) 45 mg/m2 and intravenous arsenic trioxide (ATO) 0.15 mg/kg daily were administered through an off-label use. The therapy was conducted for four weeks plus prednisone (40 mg daily) to prevent ATRA-ATO-mediated differentiation syndrome, obtaining normalization of blood counts. A neurological improvement was also reported. A bone marrow aspirate performed after a month of ATRA-ATO treatment confirmed molecular remission of APL.
Nevertheless, at the time of interruption of steroid therapy, hyposthenia of the right side of the body and dysarthria reappeared and worsened. We repeated a CT scan and an MRI with gadolinium contrast medium that revealed a new hyperdense circular lesion in the white matter of the left frontal lobe.
The PET scan of the brain confirmed hypermetabolism in the left paraventricular region of the frontal lobe that was presumed to be more likely a glial tumor than a lymphoproliferative lesion.
A magnetic resonance spectroscopy (MRS) was performed with the aim of improving the differentiation of locally infiltrative brain tumor from other types of well-circumscribed intracranial lesions by analyzing the chemical composition in a selected area. The MRS revealed an increase of spectroscopic signals of lactate and a reduction in N-acetylaspartate and choline. These data supported the hypothesis of cerebral localization of APL, but the presence of contrast enhancement and the increase of lactate signal might also support the possibility of an immune reconstitution inflammatory syndrome (IRIS). The lumbar puncture showed normal pressure of cerebrospinal fluid, normal values of glucose and proteins, and only 2 white cells/μL; the viral research on cerebrospinal fluid was negative.
In agreement with neurologists, neuroradiologists, and neurosurgeons, we decided to perform a stereotactic biopsy of the cerebral lesion.
The histological sample was diagnostic for primary central nervous system large B-cell lymphoma. Immunohistochemistry identified large cells that were CD20 + BCL-6 ± PAX5 + CD10-MUM1 + CD5-CD3-TdT-MPO- with a Ki-67 index of 80–90%, confirming the presence of B-cell lymphoma. Therefore, on 21 November 2014, we started the first cycle of chemotherapy with high-dose methotrexate and cytarabine (methotrexate 3.5 g/m2 on day 1 and cytarabine 2 g/m2 every 12 hours on days 2-3) and continued high-dose steroidal therapy (dexamethasone 8 mg b.i.d.).
The chemotherapy was well tolerated, and the hospitalization was complicated by fever of unknown origin treated with empirical antimicrobial therapy. A detailed summary of the main laboratory values is presented in .
The patient experienced a gradual improvement of neurological status and was discharged after two months of hospitalization. Subsequently, for family reasons, the patient was transferred to another hospital where he completed the ATRA-ATO program, but no further treatment for PCNSL was performed due to the progressive worsening of clinical conditions. Detailed dates of APL and PCNSL treatments are summarized in . The patient died on June 2015 for PCNSL progression in APL complete remission.
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pmc-6313995-1
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A 47-year-old male patient noticed a change in his voice (hoarseness) 4 months previously. During the anamnesis, he did not report any addictions or habits, but systemic hypertension had been diagnosed and controlled. During intraoral physical examination, a pediculated exophytic lesion with a rough surface and coloration similar to adjacent mucosa was observed in the right tonsil. Examination by laryngoscopy revealed an exophytic lesion in the right paralyzed vocal fold, occupying its anterior two-thirds, in which the mucosa was covered by fibrinopurulent exudate. An incisional biopsy was performed on the vocal cord and excisional on the palatine tonsil. Microscopically, the vocal cord biopsy revealed a squamous epithelium exhibiting architectural disorganization, covered by a fibrinopurulent membrane. This epithelium exhibited projections towards the connective tissue and was infiltrated into the connective tissue, forming islands and strands of malignant epithelial cells ().
The squamous layer showed clear epithelial cells with a vacuolized nuclei, and some cells similar to koilocytes were present in the upper layers of the epithelium. The epithelium was found with digitiform projections and fibrovascular connective tissue centers containing mononuclear inflammatory infiltrate (). A transitional zone was found in this biopsy, where the atypical epithelium protrudes exophytically with a digitiform aspect (). The malignant component showed atypical cells, with nuclear pleomorphism, sometimes binucleated cells, with a hyperchromatic nucleus and individual keratinization. Atypical mitoses and areas of necrosis were also found (). The result of the incisional biopsy was of a well-differentiated squamous cell carcinoma (SCC) present in the right vocal cord. Histological examination suggested that the SCC originated from a papillomatous lesion, and chromogenic in situ hybridization (CISH) was performed. Both lesions showed a positive result in CISH for high-risk HPV types 16 and 18 (Figures and ) and negative for low-risk HPV types 6 and 11.
On the other hand, the histological sections of the right palatine tonsil region revealed a squamous papilloma demonstrated by proliferation of the stratified squamous epithelium, predominantly nonkeratinized, presenting exocytosis and basal layer hyperplasia with typical mitoses.
The following procedures were carried out from the biopsy block: dewaxing, peroxidase blockade, and enzymatic digestion, followed by a pretreatment with a 95% EDTA bath for 15 min, followed by several rinses with distilled water and dehydration. After drying, the probe was added onto the material, the slices were covered by a coverslip, and sealing was performed. The material was denatured for 5 min at 75°C, and hybridization was performed at 37°C for 60 min for high-risk HPV. The ZytoFast Plus CISH Implementation Kit-HRP-DAB (ZytoVision, Bremerhaven, Germany, and the ZytoFast HPV-type 6/11 Probe and 16/18 Probe) was used. In the next step, the coverslip was removed, and the slides were washed in TBS buffer at 55°C for 5 min, and then, the primary antibody was incubated at 37°C for 30 min in a humid chamber. For tagging, chromogen diaminobenzidine (DakoCytomation, Carpinteria, CA, USA) was used for 10 min, and Mayer's Hematoxylin was used for the counterstaining. Reactions were performed with negative and positive controls.
Surgery was performed, including tracheostomy, with the final diagnosis of SCC originating from LP, staging T3N0M0. One month after the surgical procedure, the patient returned without complaints. In the other nasofibroscopy and bronchoscopy examinations, no changes were observed. Follow-up by a speech therapist was fundamental for significant voice improvement. The patient has been undergoing maintenance for 36 months and has no complaints and no signs of relapse.
Fifteen articles were found, totaling 27 cases of malignant transformation of LP with onset in adult patients. The mean age of the patients was 57.03 years (SD = 13.76). Of these, including the present case, 25 (89.28%) were male patients (), and in 3 (10.71%) cases, there was no history of recurrent LP. The localization of the carcinoma was cited in 10 cases, of which 3 (30%) were malignant lesions in the lung, due to dissemination. In the remaining 7 (70%), the larynx was affected, mainly in the vocal cords. There were 9 (47.36%) smokers, and HPV was identified in 9 of the reports, 2 negative tests, 4 with low-risk HPV and 4 with high-risk HPV.
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pmc-6313996-1
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A 69-year-old male with a remote history of laparoscopic Roux-en-Y gastric bypass 4 years earlier and a known duodenal diverticulum presented to the emergency department for bilateral upper quadrant abdominal pain for several weeks that had progressed rapidly to constant nausea, abdominal distension, and food intolerance. A CT scan of the abdomen revealed a very distended gastric remnant and what appeared to be a bowel obstruction distal to the jejunojejunostomy (). A nasogastric tube was placed for decompression and he was taken emergently to the operating room for an exploratory laparotomy for presumed gallstone ileus. At the time of surgery, a 4.5 cm enterolith was found and removed from the distal jejunum via longitudinal enterotomy, followed by a cholecystectomy in which gallstones were found but no cholecystoenteric fistula was noted. The enterolith was sent to an outside laboratory for stone analysis and was found to contain 100% bile salts (). The remainder of the patient's hospital stay was uneventful, and he was discharged on postoperative day 8. He remained in good health at his postoperative visit 2 weeks after surgery but then was lost to follow-up 1 month after surgery.
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pmc-6313998-1
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A 67-year-old previously healthy Japanese man initially presented with throat discomfort. He underwent an esophagogastroduodenoscopy (EGD) that revealed a type 2 lesion spanning 3/4 of the circumference of the middle thoracic esophagus (Figures and ). Histopathological examination identified it as squamous cell carcinoma. He was diagnosed with stage III EC (T4N1M0) according to the Union for International Cancer Control tumor-node-metastasis (TNM) system and was treated with chemoradiation therapy (CRT) including fluorouracil and cisplatin plus a radiation dose of 59.4 Gy. On the day of administration of the second cycle of chemotherapy, he had hematemesis and anemia. Upon examination, the patient was hypotensive with a blood pressure of 64/39 mmHg and had tachycardia with an irregular heart rate of 70–120/min. He had a high fever (39.4°C) during the previous 1–2 days with general malaise. Laboratory data revealed a hemoglobin level of 3.9 g/dL. A digital rectal examination revealed diarrhea with fresh blood. After resuscitation with 2.5 L of normal saline administered intravenously, and transfusion with 14 units (1820 mL) of packed red blood cells and 4 units (480 mL) of fresh-frozen plasma, AEF was considered and a computed tomography scan (CT) angiogram of the chest and abdomen was obtained (Figures and ). Although we did not detect active bleeding, the CT scan revealed aortic erosion of the intravenous contrast medium within the descending thoracic aorta, as well as extraluminal foci of air between the adjacent esophagus and the aorta. Emergency EGD showed a pale fragile esophageal lesion on the posterior wall (the area previously treated with CRT), as well as massive blood coagulation in the stomach and duodenum. Marking clips were placed on the side opposite the lesion (Figures and ). Soon after endoscopy, as the patient's condition remained life-threatening, and in the absence of an advance directive from the patient, we performed emergency AEF repair using TEVAR (Figures and ). Under a general anesthetic, TAG® stent grafts (26 mm × 10 cm, 28 mm × 15 cm, and 28 mm × 10 cm) were inserted by vascular surgeons via the right common femoral artery using an 8 Fr sheath. Two TAG stent grafts were deployed from the distal arch, referring to the marking clip. After crimping with the trilobe balloon and confirming the absence of bleeding using a contrast medium, the procedure was completed. The operation time was 1.5 hours. He successfully recovered with stable blood pressure and was discharged 10 days after the TEVAR. Approximately 2 months later, he suffered a mycotic aneurysm around the stent in the ascending aorta. He was treated with meropenem, 1.0 g per day, and vancomycin, 1.0 g per day, for 10 days; cefmetazole, 3.0 g per day, for the following 5 days; and then continued on oral cefuroxime, 750 mg per day. His Eastern Cooperative Oncology Group (ECOG) performance status score decreased from 1 at admission to 3, and he refused further surgery. Three months after the TEVAR, he was readmitted with difficulty in swallowing that began a week prior with worsening of back pain. EGD revealed that the aortic stent was exposed and protruded into the ruptured esophagus (Figures and ). Therefore, an esophageal stent was placed adjacent to the aortic stent to push it out and dilate the esophageal lumen (Figures and ). The patient's back pain improved after the stenting, and he was discharged after 11 days. The patient died 16 days later, approximately 4 months after undergoing emergency TEVAR for AEF.
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pmc-6314392-1
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A 69-year-old female presented to our emergency department with chief complaint of neck swelling, sore throat and difficulty swallowing for the past two days. She also complained of fever and voice hoarseness. Flexion and extension of the neck made the pain worse. She denied difficulty breathing, nausea, vomiting, or chest pain. She reported a non-productive cough. She stated that her daughter and grandchildren were sick with a cough and cold. She took diphenhydramine, acetaminophen and some old amoxicillin at home. Her past medical history was significant for salivary gland cancer nine years prior that was treated with chemotherapy and radiation.
Her vital signs were: pulse 103, blood pressure 120/62 mmHg, temperature 37.6°C, respirations 18/min, and room air pulse oximetry 100%. Laboratory analyses revealed an elevated white blood cell count of 33 K/mm3, and an elevated procalcitonin level of 23.67 ng/mL. Radiograph of the soft tissues of the neck revealed an enlarged epiglottis and aryepiglottic folds, consistent with epiglottitis. In addition, subglottic narrowing of the airway is demonstrated (Figure ). The patient received intravenous ampicillin-sulbactam, methylprednisolone and diphenhydramine in the emergency department with some improvement. The patient was initially admitted to the intensive care unit and evaluated by the otolaryngology service using a flexible nasopharyngoscope. The patient was gradually weaned off of intravenous medications and discharged on hospital day three. Blood and throat cultures were negative.
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pmc-6314393-1
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A 60-year-old male with a history of heart failure with reduced ejection fraction (HFrEF) secondary to severe mitral regurgitation (MR), paroxysmal atrial fibrillation and hypertension presented to the emergency department with typical anginal chest discomfort associated with shortness of breath, diaphoresis, nausea, and vomiting. He denied any alcohol or tobacco use. He was not taking any medications. He was adopted, thus family history was unknown. The patent was afebrile and his heart rate was 91 beats per minute (BPM) with a blood pressure of 107/81 mmHg. His oxygen saturation was 91% on 4 L/min via nasal cannula. On physical exam, he was in respiratory distress, had tachypnea with a rate of 30 breath per minute, was noted to use accessory muscles, the jugular vein was distended but had no peripheral edema. On auscultation of the chest, he had diffuse bilateral crackles. The cardiac exam revealed irregular rhythm with MR murmur. Electrocardiogram (EKG) on presentation demonstrated high lateral ST-segment elevation in leads I and aVL with reciprocal ST depression in anterolateral and inferior leads (Figure ). An echocardiogram was obtained and revealed an enlarged left atrium, global hypokinesis with mild mitral regurgitation and an ejection fraction of 25–30%.
He emergently underwent a coronary angiogram. The operator was not able to engage the left coronary system for which an aortic root angiography was performed which failed to reveal any coronary artery take off from the left cusp. Engaging the right coronary system demonstrated an anomalous LAD originating from the right cusp and an absent LCX (Figure ). The LCX territory was supplied by a large RCA (Figure ). The culprit lesion was a 100% first diagonal (D1) occlusion with grade 0 TIMI flow (Figure ). Percutaneous intervention was performed with a drug-eluting stent achieving grade 3 TIMI post-intervention (Figure ). To better visualize his coronary anatomy, cardiac computed tomography (CT) was performed (Figure ). This showed a rudimentary LAD originating from the right coronary cusp that coursed anterior to the pulmonary artery and bifurcated into two branches. The RCA was dominant and with large caliber arising from the right cusp and at the crux of the heart. It had two branches and continued posterolaterally as a large posterior lateral branch.
Post-intervention, the patient reports resolution of dyspnea and chest pain, was able to ambulate with no difficulties and his oxygen saturation improved throughout his hospital stay and was discharged home with no supplemental oxygen needed. The patient was traveling upon presentation and thus returned home to follow with his primary care physician.
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pmc-6314535-1
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A 28-year-old white female without a significant past medical history presented with abdominal pain, nausea, vomiting, and bloody diarrhea without fever, chills, or altered mentation; there was also no dyspnea or chest pain. Her family history was unremarkable. Physical exam revealed pallor, diffuse petechial rash, and generalized abdominal tenderness with an unremarkable neurological exam. Cardiac auscultation revealed normal heart sounds with no murmurs or S3. Her temperature was 37.2 °C, heart rate 90 beats per minute, blood pressure 121/87 mmHg, and an oxygen saturation of 99% on room air. Lab values on admission are shown in Table . A peripheral smear showed schistocytes, and stool studies were remarkable for Shiga toxin-producing E. coli. A diagnosis of HUS secondary to Shiga toxin-producing E. coli was made and she was admitted to the Medical Intensive Care Unit. She underwent supportive care with plasma exchange and transfusion of blood products.
The patient's chest x-ray (CXR) was initially unremarkable (Figure ), as well as her ECG (Figure ). On the following day, the patient developed progressively worsening dyspnea and hypoxemia without chest pain. The physical exam revealed tachycardia at 138 beats per minute, elevated blood pressure at 170/100 mmHg, and diffuse crackles over bilateral lungs. No murmurs were heard and no jugular venous distention was noted. CXR showed diffuse bilateral vascular congestion typical for diffuse pulmonary edema (Figure ); the troponin T level was elevated at 0.43 ng/mL (normal range: 0.00 - 0.01 ng/mL) but subsequently downtrended. The patient was noted to have minimal urine output over the previous few hours. Subsequently, the patient was intubated and hemodialysis initiated due to fluid overload.
An ECG was repeated and revealed new precordial deep T wave inversions with a prolonged QT interval (Figure ). The patient was immediately intubated and urgent hemodialysis was performed. A contrasted computed tomography (CT) of the chest was negative for pulmonary embolism and was suggestive of pulmonary edema (Figure ). A transthoracic echocardiogram (TTE) revealed a normal ejection fraction of 60%, without wall motion or valvular abnormalities (Video ). Her electrolytes were within normal limits during the period of respiratory distress. The patient was extubated the next day after the improvement of her respiratory status and resolution of pulmonary edema on follow-up CXR (Figure ). A repeat TTE was obtained which did not show any abnormality and was virtually the same as the first one. ECG the following day showed improved T wave inversions and shortening of the QT interval (Figure ). She continued to improve clinically and was discharged home. Three months later, the patient was evaluated in the clinic with complete resolution of symptoms and normalization of T-wave inversions (Figure ). In addition to that, a cardiac magnetic resonance imaging (MRI) study was done and ruled out any current or previous ischemic insult.
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pmc-6314689-1
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A 39-year-old Hispanic male, 69 kg, 170 cm (body mass index: 23,), American Society of Anesthesiologist physical status (ASA) I, with a history of untreated peptic ulcer disease and appendectomy (10 years ago) was admitted to the hospital and scheduled to undergo median nerve neurorrhaphy with graft from lower left limb (sural nerve) due to sharp injury under general anesthesia. Preoperative vital signs, physical examination and laboratory assessments were unremarkable. Patient's verbal consent was obtained in order to publish the case report with de-identified data as per institutional standard procedures.
Conventional intraoperative monitoring (electrocardiogram, noninvasive blood pressure, and peripheral oxygen saturation) and intravenous access for fluid/drug administration were performed per institutional routine. During anesthesia induction, the patient in supine position received intravenous propofol (140 mg), cisatracurium (6 mg), and remifentanil 0.5 mcg/kg/min. After loss of consciousness confirmation, a single endotracheal intubation attempt with an 8.0 tube was performed.
Anesthesia maintenance was achieved with isoflurane 0.6 mean alveolar concentration (MAC) and intravenous remifentanil at 0.3 mcg/kg/min. Ventilator mode consisted on continuous mandatory ventilation (CMV) 500 mL, positive end expiratory pressure (PEEP) at 5 cmH2O, respiratory rate (RR) was 10/min, and ratio 1:2. The length of surgery was 150 minutes; the patient remained thermodynamically stable in supine position with 105-minutes tourniquet application on left arm. Intravenous dexamethasone (8 mg) and metoclopramide (10 mg) was administered as antiemetic prophylaxis. Analgesia was managed with intravenous morphine (6 mg). A total of 1500 mL of lactate ringer was infused during surgery.
At the end of surgery, anesthetic agents were ceased and after patient responded to commands, maintained eye contact, and a TOF (Train-Of-Four) of 94% was documented, the endotracheal extubation was performed. However, immediately after extubation, anesthesia care providers observed marked respiratory distress, inspiratory effort, wheezing, cyanosis and rapid development of hypoxia with oxygen saturation level (SpO2) below 90% for approximately 30 seconds. Therefore, immediate positive pressure mask ventilation with 100% fraction of inspired oxygen (FiO2) was started and improved patient clinical status one minute after. Consequently, he was transferred to the postanesthesia care unit (PACU) with normal vital signs and no signs of respiratory distress. Nevertheless, 15 minutes after PACU admission, patient presented multiple episodes of hemoptysis, tachypnea (25 per minute), SpO2 of 82% and abundant bilateral pulmonary rales. Arterial blood gas revealed acute metabolic acidosis and included pH 7.33, partial pressure of oxygen (PaO2) 44.4 mm Hg, partial pressure of carbon dioxide (PaCO2) 40.0 mm Hg, bicarbonate (HCO3) 20.5 mmol/L, base excess −5.5 mmoL and oxygen saturation of 79.3%, lactate 2.4 mmol/L. A baseline chest x-ray revealed symmetric parenchymal opacities with ground-glass attenuation and bilateral multilobar consolidations patterns (Fig. ).
Based on the aforementioned information, a diagnosis of NPPE was established and supportive treatment was immediately initiated with noninvasive mechanical ventilation with a PEEP at 10cmH2O, intravenous furosemide (20 mg) every 12 hours, and fluids restriction. Patient remained in PACU for continuing monitoring and laboratory/imaging follow-up testing until next morning.
On postoperative day 1, patient responded satisfactory to supportive treatment; his arterial blood gas revealed a pH 7.43, PaO2 58.6 mm Hg, PaCO2 39.0 mm Hg, HCO3 25.3 mmol/L, base excess 1.0 mmoL and oxygen saturation of 92.8%; therefore, patient was transferred to the general care floor requiring no oxygen supplementation 12 hours after extubation time.
Subsequently, on postoperative day 3, patient was discharged to home in stable conditions after the evaluation of a chest x-ray that revealed right basal parenchymal opacity related to atelectasis with non-clinical significance (Fig. ).
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pmc-6314694-1
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A 37-year-old male patient was transferred from an outside emergency department with concern of self-described “trench foot” that he reported having for 8 months. The patient worked as a “scrapper” in the local area, wading into swamps and ditches to retrieve junk metal. The patient reported that his feet were often wet, due to his job. When he noticed chronic, progressive, painful, necrotizing infection of his lower left extremity, he sought medical attention. On various occasions during the 8-month time period, he had been prescribed antibiotics, but he did not follow through with them due to financial limitations. The patient's lower left extremity first developed myiasis and ulceration of the toes and lateral calf.
Upon admission, the patient described fevers and chills for several weeks prior. His vitals showed a body temperature of 37.2°C, heart rate of 122 beats per minute, blood pressure of 114/71 mm Hg, respiratory rate of 16 breaths per minute, and 95% oxygen saturation on room air. The patient's lower left extremity presented myiasis between the toes and on the lateral left calf with multiple cavitary lesions and diffused areas of callus, significant erythema, and edema (Fig. ). The myiasis was believed to be caused by Lucilia sericata, more commonly known as the green bottle fly. Lucilia sericata was suspected due to the appearance of the larvae, the vast presence of the species in the United States, including temperate regions, and their association to similar cases of myiasis in literature.[ The patient's medical history revealed spina bifida, tobacco use, poor dentition, and a previous burn with “molten steel” requiring a skin graft on the right leg. The patient was resuscitated, blood cultures were drawn, and he received vancomycin (1.75 g, every 12 h), clindamycin (600 mg, every 6 h), and a combination of piperacillin and tazobactam (4.5 g, every 8 h).
The patient's maggot infestation was removed mechanically in the operating room on hospital day zero (HD#0). Operative goals included the need to reduce contamination and salvage as much viable skin as possible on the patient's leg. Cutaneous maggots were removed by manually scrubbing with chlorhexidine-soaked brushes along with removal of maggots with forceps when necessary. Pulse lavage, using a closed-system to prevent unnecessary contamination, was used to extract cavitary maggots and irrigate the cavitary lesions.[ Chlorhexidine-soaked brushes were also used for cavitary maggots when applicable. A surgical file was used to break up calluses along the wounds (Fig. ).
Given the high likelihood of multiple pathogens in the large wound area, the wound was packed with buffer-neutral bleach which had broad spectrum antibacterial and fungal activity. The patient tolerated the initial therapy well, with no notable remaining maggots at the first dressing change (12 h post-operation) and continued on his antibiotic regimen.
A post-operative MRI (POD#1) of the patient's leg revealed no evidence of osteomyelitis in the tibia, fibula, or ankle. Wounds were cared for with daily pulse lavage, sharp selective debridement, and dressed with Acticoat (Smith & Nephew, London, UK). The leg edema was treated with compression and elevation. Initial blood cultures grew W chitiniclastica, I indica, and Providencia stuartii. The patient responded well to the 3-day course of antibiotics and was de-escalated to cefepime (2 g, every 8 h) on HD#2. Subsequent blood cultures were negative for any growth. On HD#2, a transthoracic echocardiogram was performed to assess for endocarditis and was unremarkable. On HD#4, there was increased granulation tissue with decreasing erythema and edema; therefore, the wound was dressed with Hydrofera Blue (Advanced Tissue, Little Rock, AR) and a light Coban self-adherent wrap (3M, St. Paul, MN) for compression (Fig. ). Upon discharge on HD#10, cefepime was discontinued and current dressing changes were continued with follow-up in outpatient wound care clinic. The patient was recommended to discontinue prolonged exposure to water to decrease the likelihood of recurrence. At 6 months, the patient's wounds were healed, no residual pain or edema was present, and his left leg was fully ambulatory and functional.
The institutional review board of Indiana University Health Methodist Hospital waved the need for approval since the patient was treated by physicians who are reporting this case and personal health information was de-identified, per Indiana University Standard Operating Procedures for Research Involving Human Subjects: Section 3.2.10.3. The patient gave informed consent, allowing this case report.
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pmc-6314700-1
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A 42-year-old man was admitted to The First Affiliated Hospital of China Medical University in February 2017 with abnormal hemogram for 4 months, intermittent fever for 2 months and cough for 1 week. The patient is an HBV carrier without family history of genetic or hematological disease. The peripheral blood examination showed a white blood cell count (WBC) of 25.99∗10^9/L, hemoglobin level (Hb) of 82 g/L and blood platelet count (PLT) of 103∗10^9/L. The liver and renal functions were normal. Routine ultrasound examination showed the patient with multiple lymphadenopathy involving cervical, supraclavicular, subclavian, axillary, inguinal, and posterior abdominal lymph nodes, in addition, multiple low-density foci was found on liver, the large one located on the inferior segment of the right posterior lobe about the size of 2.83∗2.84 cm. Further, the enhanced MRI showed multiple small round foci with long T1 and T2 signal intensity and annular post-contrast enhancement (Fig. ).
The patient underwent BM aspiration which revealed 62.8% of nucleated cells were blasted. The blasts exhibited round, round-like or irregularly shape in different sizes, granular nuclear chromatin, 1 to 4 nucleoli and different amounts of cytoplasm, the large blasts with medullary morphology and the small ones showed lymphatic morphology. Typical Auer bodies also could be seen the some blasts. The features of cytochemical staining were 5% positive and 6% weakly positive for POX, positive for NAE and negative for NAF which can be seen in myeloid primitive cells and lymphatic primitive cells. PAS+ exhibited with diffuse tiny granules which are the feature of myeloid primitive cells rather than scattered thick granules in lymphocytes. In summary, the blasts presented both medullary features and lymphatic features (Fig. ). Flow cytometry of the BM aspirate indicated that the blasts were presenting the stem cell markers CD34+, HLA-DR+, the T-cell markers cCD3dim+, CD2+, CD7+, CD5-, the B-cell markers CD19-,CD10-,and the myeloid cell markers CD13+, CD117+, CD14-, CD64-, CD33-, MPO-, suggesting a diagnosis of ETP-ALL. The chromosomal analysis of the BM cells was 46,XY,?t(5;12)(q33;p13)[10]/46,XY.[ The fusion genes listed in Table were all negative. For gene mutation analysis, DNMT3A mutation and EZH2 mutation were detected in this case (Table ).
The patient received induction chemotherapy with vindesine, cytarabine, idarubicin, prednisone and pegaspargase (VADLP: 4 mg vindesine on days 1, 8, 15, 22; 180 mg cytarabine on days 4, 5, 6; 20 mg idarubicin on day 1 and 10 mg on days 2, 3, 15, 16; prednisone 100 mg on week 1, 80 mg on week 2, 60 mg on week 3 to 4; 5 mL pegaspargase on days 9 and 23). One month later, the routine blood examination was WBC 1.94∗10^9/L, neutrophils 0.59∗10^9/L, lymphocytes 1.29∗10^9/L, Hb 55 g/L and PLT 192∗10^9/l. BM aspiration revealed <5% lympho-blasts and no aberrant phenotypes were detected by flow cytometric immune-phenotyping which indicated that the patient had achieved a complete hematological remission with incomplete blood count recovery. Then the patient received a consolidation chemotherapy (VADLP: Consistent with the previous course of treatment). After 2 months, the routine blood examination of the patient was WBC 2.69∗10^9/L, neutrophils 1.09∗10^9/L, lymphocytes 1.28∗10^9/L, Hb 59 g/L and PLT21∗10^9/L, the BM aspiration and flow cytometric immune-phenotyping indicated the patient still with complete hematological remission. However the lesion in liver always existed without any change, considering the good condition of the patient, we arranged a needle biopsy for the liver-occupying lesions. The pathology exhibited fibrous tissue proliferation and heterotypic lymphocyte infiltration in which T-cells were predominant. And immunohistochemistry was presenting CK-, CD3+, CD20+, Pax-5(±), Bcl-2(+), CyclinD1(+), CD15(+), Ki-67(3%+), CD68(+), TdT(±), CD34(+), and CD117(+) (Fig. ). The final date of follow-up was July 3, 2017, at which point the patient was alive and healthy.
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pmc-6314700-2
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A 27-year-old woman in December 2016 took a visit to hospital who had a fever and headache for 1-week. The patient's peripheral blood was WBC 41.09∗10^9/L, Hb 72 g/L and PLT 83∗10^9/L. The proportion of blasts in peripheral blood was 32%. The liver and renal functions were normal and no abnormality was detected by abdominal ultrasound.
The patient underwent BM aspiration which revealed that the blasts proliferated actively accounted for 86% and exhibited round or round-like shape in different sizes (big cells in the majority), round or round-like nucleus, loose and granular nuclear chromatin, blurry nucleoli and different amounts of cytoplasm (Fig. ). Cytochemical staining was weakly positive for POX, positive for NAE, positive for NAF, and 78% positive for PAS. Flow cytometry of the blasts were mainly CD33+, CD117+, CD7bri, partial CD34+, cCd3+, CD56+, CD38+, CD123+, but CD19-, CD10-, MPO-, CD5-, CD2-, CD13-, CD15-, HLA-DR-, CD1a-, CD64-, CD14-, CD3-, CD4-, CD8-, CD11c-, TdT-, suggesting a diagnosis of ETP-ALL. The fusion genes listed in Table were all negative, for gene mutation analysis, NOTCH1 mutation and JAK3 mutation were detected in this case (Table ). The chromosomal analysis was not performed.
The patient received induction chemotherapy with vindesine, daunorubicin, dexamethasone, cyclophosphamide, pegaspargase, (VCDLP: 4 mg vindesine on days 1, 8, 15, 22; 78 mg daunorubicin on days 1 to 3, 15 to 16; 1.2 g cyclophosphamide on day 1 and 15; 15 mg dexamethasone on days 1 to 12; 5 mL pegaspargase on day 8). One month later, routine blood examination were WBC 5.96∗10^9/L, neutrophils 5∗10^9/L, lymphocytes 0.56∗10^9/L, Hb 92 g/L, and PLT 413∗10^9/L. BM aspiration revealed 4% lympho-blasts and 3.01% aberrant phenotypes were detected by flow cytometric immune-phenotyping. Then the patient received the second course of chemotherapy (3000 mg cytarabine Q12 h on days 1–3; 10 mg dexamethasone on days 1–3; 5 mL pegaspargase on day 3; 4 mg vindesine on day 10; 4 g methotrexate on day 10). After 2 months, the routine blood examination of the patient was WBC 4.26∗10^9/L, neutrophils 2.5∗10^9/L, lymphocytes 1.02∗10^9/L, Hb 103 g/L, and PLT 369∗10^9/L. The BM aspiration and flow cytometric immune-phenotyping indicated the patient with complete hematological remission. The final date of follow-up was July 3, 2017, at which point the patient was alive and healthy.
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pmc-6314718-1
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A 31-year-old pregnant woman presented to the department of emergency with painless vaginal bleeding for 4 hours, at the gestational age of 33 weeks. The patient's previous medical history was unremarkable, except that this current pregnancy was complicated with placenta previa. The parturient was scheduled for elective cesarean delivery, after receiving magnesium sulfate for uterine relaxaion and dexamethasone for promoting fetal lung maturation for consecutive 13 days.
Arriving in the operating room, the patient was in great anxiety, with a heart rate of 122 beats/min, noninvasive blood pressure of 110/68 mmHg, and pulse oxygen saturation of 100%. Spinal anesthesia was performed in lateral recumbent position at the L3 to L4 interspace, with 2.5 mL of 0.5% isobaric bupivacaine. The sensory blockade reached the level of T4. When obstetrician made an incision in the lower segment of the uterus to deliver the fetus, a sudden seizure occurred and the parturient lost her consciousness. There were accompanying rhythmic twitching of upper limbs, trunk, and face. The eyes were deviated to the upside and trismus developed with increased oropharyngeal secretions. At the meantime, the blood pressure was 64/33 mmHg and heart rate was 59 beats/min, while the pulse oxygen saturation could not be detected by the SpO2 sensor.
Jaw thrust and mask ventilation with 100% oxygen were immediately applied. Then, 100 mg propofol was given to terminate the seizure, and 6 mg ephedrine was administrated to stabilize the hemodynamics. Meanwhile, the newborn was delivered, and the Apgar scores at 1-, 5-, and 10- minute were 10, 10, and 10, respectively. One minute later, convulsion resolved. Since the patient was still in apnea, an oropharyngeal airway was inserted to keep the airway open and facilitate mask ventilation. At this moment, pulse oxygen saturation was 100%, and blood pressure and heart rate were 98/45 mmHg and 100 beats/min, respectively. The artery blood gas analysis was performed which showed that: pH 7.402, PO2 82 mmHg, PCO2 28.2 mmHg, BE-7, HCO3− 17.5 mmol/L, K+ 3.7 mmol/L, Na+ 135 mmol/L, HCT 7.5 g/L, Glu 6.3 mmol/L. The body temperature was 36.2 °C. Five more minutes, the patient regained full consciousness and normal spontaneous respiration. She had no recall of the seizure attack. The postoperative recovery was uneventful. Furthermore, the cranial computed tomography scan revealed no abnormalities.
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pmc-6314768-1
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A 60-year-old male presented to our emergency department (ED) with complaints of progressive right chest pain for 1 week, that was preceded by back pain. He had a medical history of hypertension without regular control and denied any trauma history. He was alert, conscious with stable vital signs (body temperature, 37.6°C; pulse, 62 beats/min; respiratory rate, 18 breaths/min; and body pressure, 196/111 mmHg). He mentioned carpentry as his profession. Upon physical and neurological examination, no obvious wounds or vesicle formation were noted, and the patient was neurologically intact. Laboratory test results showed abnormally elevated D-dimer levels (2.01 mg/dL). Electrocardiography showed normal sinus rhythm. Chest radiography showed no mediastinal widening or obvious lesion. Chest computed tomography (CT) was performed to rule out acute cardiovascular and pulmonary diseases (e.g., aortic dissection and pulmonary embolism). The formal radiology report indicated a foreign body in the T4-5 spinal cord and upper back (Figs. and ). A neurosurgeon was consulted with suggestion of operation. We performed T4-5 laminectomy and foreign body removal. The foreign body, stuck to the spinal cord with dural rupture, was removed and found to be a 5 cm-long broken nail. The site was irrigated with antibiotic solution. Prophylactic antibiotics were administered for double protection against the possibility of developing meningitis. The pain resolved immediately post operation; no unusual events or neurological sequelae were observed at further follow-up.
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pmc-6314772-1
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An 82 year-old male visited our hospital for an evaluation of a pancreatic enlargement and a bilateral submandibular adenopathy. He had no abdominal symptom complaints. CT image showed diffuse swelling of the pancreas with a capsule-like rim (Fig. A) and intrahepatic bile duct dilatation and gallbladder enlargement (Fig. B). Serum IgG4 level had elevated to 943 mg/dL; (normal range, 4.8–105.0 mg/dL). Tumor markers, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were within normal range.
The patient was diagnosed as IgG4-RD because of high serum IgG4 levels and organ involvement (bilateral lacrimal submandibular adenopathy and diffuse enlargement of pancreas). The patient was started on 30 mg/day of CS therapy.
Bilateral lacrimal submandibular adenopathy and pancreatic enlargement improved after initial CS treatment. Serum IgG4 level decreased to 315 mg/dL at 4 weeks after CS treatment.
During the tapering of CS, at a dose of 8 mg/day, abdominal CT revealed diffuse wall thickening of gallbladder, although this patient did not show any abdominal symptom. Serum IgG4 level was 299 mg/dL. Laboratory data showed that white blood cell counts and C-reactive protein levels were normal.
Abdominal ultrasonography showed symmetric wall thickening with echogenic foci (Fig. A, white arrow). The inner layer of the gallbladder wall was enhanced by intravenous perflubutane (Sonazoid, a second generation ultrasonographic contrast agent) injection. The surface of inner layer was smooth and laminated (Fig. B, red arrow). T2-weighted MR image showed gallbladder wall thickening and its inner signal was homogeneous, and high signal intensity spot indicating Rokitansky–Aschoff sinus was not detected (Fig. ). Inflammatory changes such as xanthogranulomatous cholecystitis were strongly suspected; however, the possibility of malignancy could not be excluded, and we therefore performed cholecystectomy.
Histological examination of surgical specimens showed a transmural infiltration of plasma cells and diffuse fibrosis without malignant cells. Immunohistochemical staining revealed abundant IgG4 positive plasma cells (>30 per high-power field, IgG4/IgG ratio > 90%) (Fig. ).
The patient was finally diagnosed with IgG4-related sclerosing cholecystitis. After operation, the patient has continued 6 mg of PSL for 3 years, and is free of relapse.
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pmc-6314779-1
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A 11-year-old boy presented with cicatricial alopecia in the vertex after cooking oil burn with scar about 153.0 cm2 in size (Fig. A and B). Tissue expansion was performed in stage 1 with one 250 mL rectangular expander in right postauricular area, one 150 mL rectangular expander in the left postauricular area, and one 150 mL reniform expander in the frontal area. Flap advancement and hair transplantation were applied in stage 2. Six months after stage 2, 91.76% of the alopecia area was restored by hair-bearing scalp (Fig. C and D).
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pmc-6314779-2
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A 26-year-old woman presented with cicatricial alopecia in the frontal area after hot water burn with scar about 199.2 cm2 in size (Fig. A and B). In stage 1, one 250 mL rectangular expander in the vertex, one 200 mL reniform expander in the left occipital area, and one 200 mL rectangular expander in the right occipital area were inserted and inflated. Flap advancement and hair transplantation was performed in stage 2. Hairline restoration was performed in stage 3. Nine months after stage 3, 89.91% of the alopecia area and a natural hairline were restored (Fig. C and D).
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pmc-6314791-1
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A 74-year-old man with chronic back pain presented to the emergency department with a three-day history of worsening back pain that was unresponsive to multiple pain management regimens. Medical history was significant for end-stage renal disease (ESRD) requiring hemodialysis (HD) via his left internal jugular tunneled line, congenital alpha-2-antiplasmin deficiency, chronic pancytopenia, prostate cancer, hypertension, and hyperlipidemia. Two weeks prior to presentation, the patient was admitted for a one-month history of similar symptoms and was treated with fluoroscopy-guided corticosteroid injections of the L3, L4, and L5 vertebral facet joints bilaterally. Initially, he found relief; however, the pain returned after two weeks. On re-presentation, he had diarrhea and endorsed numbness of the right thigh but denied subjective fevers, chills, night sweats, or the recent use of antibiotics.
The physical examination was significant for pain on deep palpation of the lower quadrants of the abdomen bilaterally and with light palpation over the lumbar spine and lumbar paraspinal muscles. Positive psoas signs were elicited bilaterally. The strength of the upper and lower extremities was preserved. Laboratory results were remarkable for pancytopenia (white blood cells 3.66 K/cmm, red blood cells 2.64 M/cmm, platelets 127 K/cmm) with neutropenia (1.38 K/cmm), elevated erythrocyte sedimentation rate (46 mm/hr), and C-reactive protein (116 mg/L). Magnetic resonance imaging (MRI) revealed the evidence of discitis at the L2-L3 vertebral joint, vertebral osteomyelitis with phlegmon, and multiple bilateral psoas abscesses (Figures -).
Cultures from the peripheral venous blood, hemodialysis (HD) line, and urine were obtained, and computed tomography (CT)-guided fine-needle aspiration of the abscesses yielded purulent fluid with gram-positive cocci on initial gram stain. The patient was empirically treated with renally dosed vancomycin and piperacillin-tazobactam after HD sessions. Cultures from the abscess fluid grew S. caprae and the treatment was narrowed to renally dosed cefazolin for six weeks. Several days later, the blood culture from the HD line also grew S. caprae, and the peripheral blood cultures yielded no growth. Therefore, his tunneled HD line was removed and after a 48-hour line holiday, a new tunneled dialysis catheter was placed. The urine culture yielded only normal urogenital flora at 48 hours. Transthoracic echocardiogram revealed no valvular vegetations and a normal systolic function. The patient’s back pain improved and he was discharged from the hospital. Follow-up magnetic resonance imaging (MRI) done 15 days later revealed small fluid collections in the psoas muscles and paraspinal soft tissue bilaterally that had regressed in size when compared to the prior imaging (Figures -).
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pmc-6314792-1
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A 36-year-old Caucasian male presented to the emergency room complaining of a one-day history of abdominal pain. His main symptoms were that of nausea and vomiting, but he also reported periods of diarrhea. In the emergency room, his initial evaluation was significant for lab studies demonstrating a mild metabolic acidosis with a bicarb of 16.6 mEq/L, an elevation of his creatinine to 1.93 mg/dL, and a serum lactate level of 5.4 mmol/L. A computed tomography (CT) scan of the abdomen and pelvis was obtained and reviewed. The appendix was thought to be normal. There was no evidence of free intraperitoneal air, abscess, or volvulus. There did appear to be evidence of enterocolitis involving the ilium, cecum, and the proximal ascending colon. There was no evidence of pneumatosis or obstruction. Over the course of 12 hours the patient underwent conservative medical management, which included intravenous hydration, intravenous steroids, Toradol and Dilaudid for pain management, and the occasional dose of Ativan for agitation. Failure of conservative management along with medical decline lead to an exploratory laparotomy with a right hemicolectomy for an ileocolic intestinal infarction. Postoperative repeat CT scan of the abdomen incidentally showed pulmonary nodules in the lower lobe. A CT scan of the chest was then obtained, which revealed air in the left chest wall and axilla (Figure ). On physical exam there was very subtle mottling of the left shoulder. The patient was emergently taken back to the OR for further exploration of the shoulder with excisional debridement. Seropurulent fluid and extensive subcutaneous emphysema along the fascial planes of the left chest wall were consistent with necrotizing fasciitis. Both wounds were packed with a gauze bandage roll soaked in saline and then the patient was transferred back to the intensive care unit.
Over the course of 15 days the patient underwent repeat trips to the OR for re-exploration, incision and drainage of the wounds, and dressing changes (Table ). On postoperative day 17, the wound, ostomy, continence nurse (WOCN) was consulted to evaluate the wound and make treatment recommendations.
On exam, there was still a significant amount of nonviable tissue in the base of the left chest and axilla wound. The left chest wound measured 8 x 19 x 8 cm and the left axilla wound measured 6.5 x 25 x 4 cm. NPWTi-d with ROCF-CC was applied to these wounds to aid in the removal of the nonviable tissue. Figures - show the presentation of the wounds prior to the application of the NPWTi-d with ROCF-CC.
During the application of the NPWTi-d with ROCF-CC, care was taken to ensure that the contact layer of the dressing was in contact with the entire wound base. Barrier rings were applied to the skin creases along with any area that presented as a high risk for inadequate seal of the drape (Figure ). The therapy settings for the left axilla were 85 ml of hypochlorous acid solution (Vashe®, SteadMed, Fort Worth, TX), dwell time of 10 minutes with NPWT every hour at -125 mmHg. Therapy settings for the left chest wound were 50 ml of hypochlorous acid solution, dwell time of 10 minutes with NPWT every hour at -125 mmHg.
During the first dressing change after the application of the NPWTi-d with ROCF-CC, there were notable improvements in the quality of the tissue in the wound bed (Figure ). The left chest wound bed was noted to have 100% red healthy tissue and the left axilla wound bed had a decrease in nonviable tissue. There was, however, seropurulent drainage noted deep within the intramuscular structures of the left axilla wound.
NPWTi-d with ROCF-CC was reapplied to the axilla wound ensuring that the contact layer was placed deep into the wound bed to facilitate the removal of the seropurulent drainage. The left chest wound was transitioned to NPWTi-d to continue to promote granulation tissue (Figure ). The instillation solution was switched to normal saline due to blockage alarms we encountered with the hypochlorous acid solution without resolution.
The current treatment regimen was continued for two days until the next dressing change. At that time both wound bases were 100% red with granulation tissue present (Figure ). The seropurulent drainage deep in the intramuscular structures was no longer present. Since there was adequate removal of nonviable tissue and the quality of the tissue had significantly improved, the WOCN made the decision to transition both wounds to NPWTi-d instilling normal saline solution with a dwell time of 10 minutes and NPWT every two hours at -125 mmHg.
For the next two weeks the treatment regimen utilizing NPWTi-d to the wounds continued. The dressings were changed three times a week at the bedside by the WOCN. During initial assessment, the axilla wound measured in total volume 650 cm³ and the chest wound measured 1,216 cm³. After 17 days utilizing the combination of NPWTi-d with and without ROCF-CC, the axilla wound measured in total volume 342.25 cm³ and the chest wound measured 554.4 cm³. This presents a significant decrease in overall measurements. At this time, NPWTi-d was discontinued and standard NPWT with black granufoam was utilized to both wounds at -125 mmHg (Figures -).
NPWT was utilized for approximately a month to promote granulation tissue and assist with wound contraction (Figures -). Once the wound had made vast improvements, NPWT was discontinued and a non-adherent antimicrobial alginate dressing (Silvercel™ Non-adherent, Acelity, San Antonio, TX) was lightly packed into the wound bed and covered with a dry sterile dressing. This dressing was then changed three times a week by a visiting nurse association. The wound measurements prior to discharge showed significant improvement in comparison to the wound measurement at presentation, with the left axilla wound measuring 1.5 x 10.5 x 0.3 cm and the left chest wound measuring 3.5 x 9 x 5 cm.
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pmc-6314793-1
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A 68-year-old male presented with a three-day-old, 46% total body surface area (TBSA), third-degree burn to the flank, bilateral upper extremities, and back (Figure ).
Past medical history consisted of hypertension and severe anorexia, with a body mass index (BMI) of 14. The patient suffered a flame burn when his clothes caught fire in a home furnace/heating apparatus. He stayed at home for two days post-injury, refusing treatment, however, on day three, he was found to be in excruciating pain with altered mental status. His partner called emergency services, and he was admitted through our hospital burn emergency department. Upon initial presentation, he was resuscitated, stabilized, and taken for emergent excision debridement and grafting of the burn eschar and affected tissue, according to institution policy (Figure ).
He was taken to the operating room on admission day 2 for excision, debridement, and grafting of all burn and affected tissue. Autograft was harvested from the scalp and bilateral lower extremities, meshed in a 4:1 and 2:1 cadaveric homograft overlay, the so-called sandwich technique [], and applied over burned areas. The depth of the patient's wound extended to the rib periosteum, with exposed necrotic muscle on the trunk and bilateral upper extremities (Figure ).
The standard wound care regimen, with broad-spectrum intravenous antibiotics, topical antibiotics, and soaks, was implemented.
On his second trip to the operating room, one-week post-op, grafts showed an almost 95% graft failure (Figure ) with quantitative tissue cultures growing Escherichia coli, Enterobacter, Acinetobacter, and Klebsiella.
The patients' critical status, impaired nutritional state, and infection burden warranted alternative therapy options, thus, the team elected to try negative pressure wound therapy with dwell time (NPWTi-d) using the KCI Veraflo (KCI Medical, San Antonio, Texas, US) system.
Procedure detail: Black foam sponge was shaped to fit the bilateral upper extremities and torso. Two Veraflo devices were employed: one for the bilateral upper extremities connected utilizing a “y” connector and the second for the torso. The team created two independent and separate suction entities: the bilateral upper extremities and the anterior/posterior torso (Figure ).
Therapy settings were as follows: 18 min dwell time, every 2.5 hours, with a constant pressure of 125 mmHg, utilizing VASHE hypochlorous solution (SteadMed Medical, Fort Worth, Texas, US). Therapy settings were calculated with the assistance of KCI representatives and a review by McKanna et al. which provided information on therapy settings that were adapted to our particular patient. The large wound bed, highly exudative nature of the burn injury, and difficulty in maintaining seal integrity all contributed to the indicated therapy settings []. The solution utilized was due to a hospital safety protocol implemented to prevent the inadvertent administration of similar appearing solutions and medications. The indicated VASHE hypochlorous solution was provided by the hospital pharmacy in blue bottles with readymade caps for introduction into the Veraflo device for seamless therapy.
In between operating room cases, standard burn intensive care was employed with an emphasis on patient rotation every two hours per institution policy to avoid pressure sore formation and the vacuum assisted closure (VAC) devices were checked every hour for signs of copious bleeding or malfunction (loss of suction, machine malfunction, or therapy issues). He was taken to the operating room for VAC exchange, assessment of wounds with cultures, and further debridement every 72-96 hours (Figure -).
Intravenous antibiotics were continued throughout the therapy trial, but topical antimicrobial coverage was stopped, which included Sulfamylon and silver nitrate soaks during the two-week period. In the following images, we see the patient at six weeks post-burn (Figure ). Subsequently, we are able to graft and heal the posterior trunk and initiate physical therapy. The final image in this presentation is Figure , which was taken at six months post-burn.
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pmc-6314794-1
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A 19-year-old male presented in the emergency department with one episode of melena per day, for one week. It was associated with vomiting, shortness of breath and palpitations. His hemoglobin level on initial complete blood count was 5.80 g/dL, signifying severe anemia according to WHO guidelines []. His lab parameters on admission are presented in Table .
Immediately packed red blood cells (RBCs) were requested from the blood bank. On forward typing his blood group was labeled as O positive and his serum showed strongly positive indirect Coomb’s test with a negative direct Coomb’s. On extended 11 cell panel antibody testing, his serum demonstrated pan-agglutination which matched with monoclonal panel cells having anti-Kell, anti-Lub, and anti-Kpb antibodies. On cross match with four O negative and four O positive packed RBCs, +4 incompatibility was seen with all. Meanwhile a detailed history of the patient revealed two distinct episodes of epistaxis in childhood and a family history of his paternal grandmother having an increased bleeding tendency. In view of his past history of fresh frozen plasma infusions, it was interpreted that the patient may have multiple alloantibodies in blood leading to gross incompatibility. Considering the urgency of the situation, one unit of the least incompatible (O negative) packed RBCs was issued after washing with normal saline thrice, to the emergency department. Transfusion was started under strict monitoring by the emergency department physicians. After slow transfusion of around 10 ml blood, the patient started shivering and his temperature spiked to 101°F with tachycardia and hypotension. The transfusion was stopped immediately and the patient was given intravenous antihistamine and hydrocortisone. Meanwhile, he was transferred to the intensive care unit (ICU) where he received intranasal desmopressin and intravenous factor VIII.
Transfusion reaction workup revealed a grade 4+ pan agglutination in his serum. During repeat blood grouping, forward typing did not demonstrate any reaction to anti-A and anti-B antisera, like a normal O blood group. However, on reverse typing, his serum showed strong agglutination with group O pooled control cells. His post saline wash incompatibility with O negative red cell concentrate showed minor difference from grade +4 agglutination (pre-wash) to grade +3 clumping (post-wash). A fresh RBCs sample from the patient showed negative direct Coomb’s test, while fresh serum sample remained positive for indirect Coomb’s test. This workup strongly raised the suspicion of Bombay phenotype and his red cells were tested with anti-H lectin, which showed no agglutination. This confirmed his blood group as Bombay phenotype. The reactions observed with Bombay phenotype compared to other blood groups, on forward and reverse typing, are illustrated in Table .
Immediately, voluntary donor pools were contacted in blood banks throughout the country. Overnight, a donor with Bombay negative blood group was arranged from Karachi. The packed RBCs were airlifted to Islamabad maintaining the cold chain. After crossmatching with recipient’s blood showed no reaction, the donor blood was transfused to the patient. Meanwhile, a distant relative of the patient from a nearby city, with Bombay positive blood group, consented to donate blood at our blood bank. Two days later, another unit of packed RBCs was transfused to the patient. His hemoglobin after two transfusions rose up to 7.40 g/dL. As his melena settled down on supportive therapy, an endoscopy was performed that suggested an underlying hiatal hernia. After surgical consultation, the patient was advised to reduce weight and discharged from the hospital, with a scheduled follow-up visit.
In view of the patient’s past medical history and family history, during the follow-up visit, a von Willebrand factor antigen, von Willebrand factor functional activity and factor VIII levels were ordered. His von Willebrand factor antigen level was <2.0%, von Willebrand factor functional activity was <4.0% and factor VIII level was 18.5%, consistent with type 3 von Willebrand disease. The patient and his family were counselled accordingly and referred to the hematology clinic.
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pmc-6314795-1
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A 62-year-old female presented to the emergency department with complaints of abdominal pain and a decrease in urinary output. She has a past medical history of remote colon and endometrial cancers, chronic obstructions, colocutaneous fistulas, diabetes, hypertension, and atrial fibrillation (a-fib). Her surgical history consists of colostomy, right hemicolectomy, hysterectomy, and wound exploration related to the colocutaneous fistula.
Upon assessment, she had ventral hernias with a leakage of foul-smelling fluid around her colostomy site. She presented with cellulitis of the entire pannus with some superficial epidermal blistering and necrosis, but the subcutaneous tissue appeared viable, as seen in Figure . The computed tomography (CT) scan revealed skin thickening and subcutaneous soft tissue stranding consistent with panniculitis/cellulitis with no drainable abscess. She was started on intravenous vancomycin and cefepime for the treatment of the cellulitis.
Within 24 hours, her abdominal cellulitis had worsened despite receiving broad-spectrum antibiotics. The patient had increased tenderness with palpation to this area. Her white blood cell count (WBC) count increased from 10.2 on admission to 13.4. There was concern for a necrotizing soft tissue infection. She was taken to the operating room that day for emergent debridement. During the debridement, the skin around her hernias was left intact. The surrounding necrotic skin and fat were debrided to the fascia. Her peritoneum was not opened. Tissue samples were obtained, revealing Klebsiella pneumoniae, few Enterococcus faecalis, and Staphylococcus. After debridement, the wound was dressed with betadine-soaked gauze and sterile dressings.
On post-op day (POD) one, the dressings were removed by the wound, ostomy, continence, nurse (WOCN) team. Upon removal of the dressings, an exposed bowel was noted (Figure ). There was necrosis noted to the lateral aspects of the wound. The wound was packed with saline-moistened Kerlix and covered in abdominal pads (ABDs). An ostomy appliance was placed over the fistula. The patient was scheduled for further debridement the next day.
On POD two, general surgery performed a wide debridement of the abdominal wall. The enterocutaneous fistula was taken down.
On POD three, she returned to the operating room for another washout and an open abdomen negative pressure therapy (ABThera) was placed. General surgery placed an ABThera with each washout from POD three until POD seven.
On POD seven, a washout was performed and vicryl mesh was placed over the exposed bowel. General surgery applied negative pressure wound therapy (NPWT) using white foam over the mesh followed by black foam.
On POD nine, the patient was taken to the operating room for wound debridement of the skin and subcutaneous fat (Figure ). After the procedure was completed, an NPWTi-d device was placed in the operating room, as seen in Figure . Four barrier rings were placed at the inferior and lateral wound edges to facilitate a good seal and prevent maceration. Four white foam pieces were placed to protect the area with mesh. A total of four kits consisting of both NPWTi-d and ROCF-CC were utilized. The instillation ports were Y connected to the trac pads and applied to four areas in the wound to improve instillation coverage and prevent leakage in the lateral aspects. The NPWTi-d settings were 130 milliliters (ml) of normal saline solution (NSS) to soak for 10 minutes every three and a half hours. Normal saline solution was chosen because it has been shown that despite its direct antimicrobial activity, it can be as effective as other solutions when used with NPWTi-d []. The settings for the device were based on the parameters set forth by the review of evidence and recommendations for a cycle frequency of two-four hours at -125 mmHg and a dwell time of 10-20 minutes [].
On POD 11, the patient returned to the operating room for a washout and dressing change. The NPWTi-d with ROCF-CC was removed. General surgery placed NPWT utilizing white foam over the mesh and covered then with black foam.
On POD 15, the first NPWTi-d change was performed at the bedside. The wound base had 40% pink tissue, 20% red tissue, and 40% slough, as seen in Figure . White foam was placed over the vicryl mesh. NPWTi-d was placed to the central portion. ROCF-CC was applied to the lateral aspects to assist in the removal of the non-viable tissue, as seen in Figure . The goal of therapy was to improve granulation tissue and prevent repeated trips to the operating room.
The patient underwent four dressing changes at the bedside, utilizing NPWTi-d and ROCF-CC. On POD 22, ROCF-CC was discontinued. There was a decrease in devitalized tissue to the lateral aspects. New granulation tissue was present where the macrocolumns are located as seen in Figure . White foam was placed over the area with mesh followed by NPWTi-d.
On POD 29, the final dressing change was performed utilizing NPWTi-d. The patient was deemed medically stable for discharge. The receiving facility was unable to accept the patient with NPWTi-d in place. She was transitioned to NPWT, utilizing white foam over the bowel and one NPWT machine.
The patient spent a total of 31 days in the hospital. During this time, she had three ABThera applications, five applications utilizing NPWTi-d, and two applications with NPWT. There was a decrease in devitalized tissue and the wound edges were noted to have contracted. The patient’s measurements reduced from 32 x 54 x 5 cm (8,640 cmᵌ) to 19.5 x 53 x5 cm (5,167 cmᵌ).
The patient was readmitted to our facility six days after her discharge for altered mentation and possible wound infection. There was concern for purulent drainage noted in the cannister. The dressing was changed the next day in coordination with the surgery and infectious disease teams. Once the dressing was removed, there were no obvious signs of infection. The wound base had 85% red tissue and 15% tan slough, measuring 16 x 54 x 3.5 cm (3,024 cmᵌ) (Figure ). The patient underwent three dressing changes throughout her readmission. She was discharged to a rehabilitation center where they continued NPWT.
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pmc-6314796-1
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History
A 54-year-old male, with a history of non-insulin dependent diabetes mellitus and polysubstance abuse, presented to the emergency department with an isolated closed left bimalleolar ankle fracture after jumping down from a fence. He was initially diagnosed three days prior at an outside hospital where he was placed in a custom molded fiberglass splint. Upon removal of the splint, multiple hemorrhagic skin blisters were found to the medial and lateral ankle (Figure ). The patient denied any interval trauma. Additionally, although he remained in the splint since its initial application, he noted noncompliance with non-weight bearing precautions.
Physical Exam and Diagnosis
Significant swelling, ecchymosis, and tenderness of the left ankle were noted. There were large intact hemorrhagic blisters both medially and laterally. An overlying blister did prevent assessment of the posterior tibial pulse. However, a strong dorsalis pedis pulse and brisk capillary refill of all digits were noted. No deficits in distal motor or sensation were found. Ankle radiographs demonstrated a displaced medial malleolus and distal fibula fracture with lateral talar subluxation (Figure ). Baseline labs, including a complete blood count, basic metabolic panel, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP), were ordered and found to be within normal ranges.
NPWT-id Technique
An intraarticular hematoma block was provided via the anteromedial ankle. Closed reduction was then performed under mini c-arm fluoroscopic guidance. A circumferential VeraFlo (Acelity, San Antonio, TX, USA) wound vac was then applied prior to splint application (Figure ). During wound vac application, tibiotalar reduction was maintained by holding the ankle in a dorsiflexed and supinated position. Adequate reduction was important to prevent excessive skin tension that would result from fracture displacement. We then decompressed all fracture blisters with the tip of a scalpel blade. The overlying epidermis was left in place. Next, the ankle was lined circumferentially with one-inch adhesive strips at the most proximal and distal fracture blisters margins. VeraFlo sponge was then customized to fit within this lined region. Once fitted, the sponge was sealed using adhesive drapes. Prior to sealing the sponge, adhesive drape sheets were quartered. When sealing the sponge, care was taken to lay the adhesive drapes with as little tension on the skin as possible. Instillation settings were as follows: normal saline at 30 ml soak volume, one-minute soak time, at two-hour intervals. Suction was set at negative one hundred, 25 mmHg. Finally a “U splint” with bulky cast padding was applied.
Hospital Course
The patient was placed on strict non-weight bearing precautions to the left lower extremity. He was instructed to elevate the ankle while in bed. His diabetes was managed by our institutions’ hospitalist service. Additionally, the patient was placed on moderate dose lovenox to minimize the risk of deep venous thrombosis (DVT) formation. Anticoagulation was subsequently discontinued 24 hours prior to surgery. Daily assessment of swelling was started on hospital day three. While the splint was removed during these checks, at no time was the VeraFlo device removed or exchanged.
Operative Course
On hospital day seven, the patient underwent left ankle open reduction internal fixation. Upon removal of the VeraFlo device, the epidermal skin layer of all decompressed fracture blisters had completely necrosed. This tissue was easily removed with moist gauze. Removal of this necrotic layer revealed near complete reepithelialization of the underlying blister bed (Figure ). Additionally, while there was mild maceration of the intact skin surrounding the fracture blisters, the skin appeared relatively uninjured. Given the healthy skin appearance and significant reduction in soft tissue swelling, we decided to proceed with open reduction internal fixation using small incisions at the anteromedial and lateral ankle (Figure ). Post-fixation, all surgical incision sites were closed primarily using 3-0 nylon sutures. A circumferential PREVENA Plus (Acelity, San Antonio, TX, USA) wound vac set at negative one hundred, 25 mmHg continuous suction and U splint were then applied prior to awakening (Figure ).
Results
The patient’s postoperative hospital course was uncomplicated. He did receive 24 hours of intravenous antibiotics and was started on moderate dose lovenox for deep venous thrombosis prophylaxis on postoperative day one. He was subsequently discharged on postoperative day two. First outpatient follow-up occurred one week from the day of surgery. He remained in the circumferential PREVENA Plus wound vac and splint up until this point. Upon removal of the splint and wound vac, complete reepithelialization was observed at all fracture blister beds. While there was mild superficial skin edge necrosis at the anteromedial incision site, both the anteromedial and lateral incision sites were well healing and non-draining (Figure ). Sutures were removed at this visit and the patient was placed in a fracture boot for four additional weeks. At the six-week follow-up all surgical sites demonstrated complete wound healing. No further wound complications were noted.
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pmc-6314796-2
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History and Physical Exam
A 62-year-old male, medical history significant for non-insulin dependent diabetes mellitus, who presented with an isolated closed tibial plateau fracture, Schatzker type 6, suffered from blunt force trauma (Figure ). At the time of presentation significant swelling of the proximal tibia with two large hemorrhagic fracture blisters anteriorly were noted (Figure ). Despite the high degree of swelling there was no clinical evidence of compartment syndrome and the patient remained neurovascularly intact.
NPWT Technique
Similarly, surgery was delayed due to the degree of swelling and skin compromise. A circumferential wound vac consisting of both VeraFlo and PREVENA Plus was placed (Figure ). Fracture blisters were first decompressed without removal of the overlying epidermis. Fracture blister edges were then lined with one-inch strips of adhesive drapes. Veraflo sponge was customized to fill the lined area and subsequently sealed. Normal saline was instilled at a volume of 20 ml with one-minute soak times, at two-hour intervals. Suction was set at negative one hundred, 25 mmHg. Customized strips of PREVENA Plus foam were then applied circumferentially to the remaining tibia and distal femur as pictured in Figure . Attention was made to avoid the popliteal fossa with both the foam and adhesive drapes. Adhesive drapes were placed without tensioning the skin. Continuous suction for the PREVENA Plus wound vac was also set at negative one hundred, 25 mmHg. A knee immobilizer was then applied and the patient was placed on non-weight bearing precautions. Swelling was monitored daily, however, the wound vac was left in place.
Operative Course
On hospital day seven, the patient was scheduled for open reduction internal fixation. Once under general anesthesia the wound vac was removed. There was a significant decrease in the degree of swelling to the proximal tibia. The overlying epidermal layer of the fracture blisters had completely necrosed (Figure ). Upon removal of this layer with moist gauze, we again observed near complete reepithelialization of the blister bed. Additionally, we observed mild maceration to the intact skin that was covered with VeraFlo sponge. Given the healthy appearance of the skin and significant reduction in soft tissue swelling we proceeded with open reduction internal fixation. A single skin incision utilizing a standard anterolateral approach was utilized without alteration (Figure ). Following reduction and fixation with a lateral plate and a combination of locking and nonlocking screws, the wound was closed primarily with deep 2-0 vicryl and superficial 2-0 nylon sutures. A circumferential PREVENA Plus wound vac was applied to the proximal tibia and distal femur as previously described. Continuous suction was set at negative one hundred, 25 mmHg.
Results
The patient completed 24 hours of post-operative intravenous antibiotics and moderate dose lovenox DVT prophylaxis was started on postoperative day one. He was subsequently discharged from the hospital on postoperative day two. Wound checks were performed at one and six weeks following hospital discharge (Figure ). His wounds went on to heal completely without complications.
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pmc-6314797-1
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A 56-year-old homeless male with a history of hypertension and a seizure disorder presented to the emergency department with a one-day history of pain, redness, and swelling of the right lower extremity. In the emergency department, the patient was febrile with a temperature of 102˚F and otherwise had normal vital signs. His physical exam revealed diffuse erythema and swelling to the right lower extremity extending up to the medial aspect of the right thigh. The patient was admitted to the hospital and was started on intravenous cefazolin, intravenous vancomycin, and oral clindamycin.
Despite antibiotic therapy and bedside debridement, the patient’s erythema continued to spread (see Figure ). On hospital Day 4, it was determined that the patient required irrigation and debridement of his right lower extremity wound. Extensive soft tissue debridement was required as a large portion of the right lower extremity was found to be necrotic (see Figure ). Devitalized tissue was removed from the dorsum of the foot, circumferentially around the lower leg and laterally to the level of the knee (see Figures -). An NPWTi-d device was applied over the wound in the operating room (see Figure ). A special three-layer reticulated open cell foam dressing was applied over the dorsum of the foot where the most necrotic tissue was found prior to debridement. This reticulated open cell foam is designed to promote additional debridement. The more proximal wounds were covered with a standard reticulated open cell foam that is designed primarily to promote granulation tissue formation. The wound was irrigated with Prontosan for the first three days after placement of the NPWTi-d device to assist with wound debridement via its surfactant properties. Initial NPWTi-d settings were -125 mmHg with a 2.5 hr negative pressure cycle, 50 mL of instillation, and a 10-minute dwell time. After three days of Prontosan instillation, normal saline was used as an instillation solution to simulate a more physiologic environment that we believe is more conducive to wound healing. The NPWTi-d device was replaced in the operating room every seven days until the wound was sufficiently granulated (see Figures -). Although the manufacturer recommendations are to replace the NPWTi-d device every two to three days, we have seen similar results with replacing these devices once weekly, and our patients prefer the less frequent device changes. After each NPWTi-d replacement, Prontosan was once again used for three days and was then replaced with normal saline.
On hospital Day 29, a skin graft from the right and left thighs were used to cover the wound and a negative pressure wound therapy device was placed over the skin graft (see Figures -). On hospital Day 30, his intravenous antibiotics were discontinued. The patient was discharged on hospital Day 34 to a transitional home for homeless patients requiring additional wound care and social services. Throughout the patient's hospital admission, he was on a regular diet and maintained a body mass index (BMI) of approximately 30 throughout his stay. He did not require any oral antibiotics on discharge. The patient was followed closely with outpatient appointments thereafter. Approximately three months after the initial presentation to the emergency department, the patient was seen in the clinic for a wound check. His right lower extremity wounds were epithelialized and healing well (see Figures -).
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pmc-6314798-1
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A 60-year-old female patient was admitted to the hospital with complaints of shortness of breath. She was noted to meet the septic shock criteria as demonstrated by hypoxia, tachycardia, hypotension, and not responding to fluids. She has a past medical history of hypertension, hypothyroidism, gastroesophageal reflux disease (GERD), VLUs, and ambulatory dysfunction. She has a past surgical history of a back surgery, fracture surgery, hysterectomy, and partial thyroidectomy. She required intubation in the emergency room for her respiratory distress and was transferred to the medical intensive care for the ongoing medical care. Upon skin assessment, she was found to have a large ulcer on the distal aspect of her right lower extremity (RLE). The majority of the wound base was covered in a fibrotic slough. Her leg was shaped like an upside-down champagne bottle with pitting and woody edema. The primary team consulted both the wound, ostomy, and continence nurses (WOCN) team and plastic surgery for evaluation and treatment of the wound. While the surgical team was consulted, the primary team also noted that she was not medically stable for discharge as she was hemodynamically unstable.
Upon primary assessment of the WOCN team, the patient was noted to have two ulcerations on the RLE with the larger distal ulceration measuring 10 x 16 x 1.5 cm (240 cm³) with 20 percent brown tissue, 40 percent pink tissue, and 40 percent tan tissue in the base (Figures , ). There was a malodor noted as well. She was being treated with intravenous cefepime, clindamycin, and vancomycin, pending wound culture results as per the primary medical team.
Within 24 hours of admission, the WOCN team applied a novel ROCT-CC on to the wound base with NPWTi-d (Figure ). The instillation solution chosen was hypochlorite solution (Dakin’s) 0.125% for the first 24 hours. The team utilized ostomy barrier rings surrounding the wound edge to facilitate a good seal and prevent periwound maceration. The settings for NPWTi-d were as follows: 34 mL of solution, dwell 10 minutes, and -125 mmHg every one hour. The arterial brachial index (ABI) revealed a normal arterial blood flow to the foot. X-ray and erythrocyte sedimentation rate (ESR) were ordered to evaluate for a deeper infection, given the close proximity to the tibia. The X-ray and ESR were normal. The following day, the solution was changed to a normal saline solution, and the machine was checked for any alarms. No alarms were noted, and the solution volume remained at 34 mL.
On the day of treatment (DOT) #2, the plastic surgeon met the WOCN team at the bedside to evaluate the wound for a surgical debridement. While the patient remained in the Medical Intensive Care Unit (MICU), she was off vasopressors and her respiratory status was improved. She was deemed medically stable for the OR. Her culture results showed Streptococcus agalactiae (Group B Strep) and Proteus vulgaris. Cefepime was stopped due to a rash, and levofloxacin was started. Upon removal of the first ROCF-CC dressing, the wound base demonstrated a rapid improvement in the granulation tissues (Figures , ). The plastic surgeon evaluated the wound and deemed no surgical intervention was required at this time and that NPWTi-d should continue with ROCF-CC. The patient would be evaluated in one week for wound closure with grafting.
The patient continued with routine dressing changes every 48-72 hours. On the eighth day of therapy, the patient was transitioned to NPWTi-d with ROCF (not ROCF-CC) for an additional two days (Figure ). The decision to transition to the different dressing was due to the lack of a thick exudate or non-viable tissue in the wound base.
At the next dressing change on DOT#10, the patient was transitioned from NPWTi-d to local wound care with a collagen dressing with oxidized regenerated cellulose (ORC), a silver alginate with non-adherent contact layer, and multiplayer compression therapy for management of lymphedema (Figures , ).
This dressing was changed every 48-72 hours over the next 11 days until the plastic surgeon applied an allograft to the wound base (Figures -). An absorptive secondary dressing was applied over the graft, and multi-layer compression was reapplied.
The patient was then discharged from the acute care hospital to a skilled nursing facility (SNF) for rehabilitation services and the ongoing wound and lymphedema care.
The patient spent 23 days in the acute care hospital before being discharged to the SNF. She underwent no operative debridement, three applications of NPWTi-d with ROCF-CC, one application of NPWTi-d with ROCF, five applications of local wound care (utilizing a collagen matrix dressing with ORC and silver alginate and multiplayer compression), and then closure with the use of an allograft.
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pmc-6314822-1
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A 75-year-old Caucasian woman with a past medical history significant for hypertension, dyslipidemia, and depression was admitted to our hospital for evaluation of an incidentally discovered left ventricular mass. The patient denied having a history of stroke, peripheral embolization, or myocardial infarction. The patient reported compliance with her medications and had been taking furosemide 20 mg, amlodipine/benazeprilat 5/20 mg, rosuvastatin 40 mg, aspirin 81 mg, sertraline 100 mg, zolpidem 5 mg, and omega-3 fatty acids/fish oil. The patient reported food allergies to bananas, pecans, and walnuts. The patient denied any significant surgical history. Her social history was significant for tobacco abuse in the past but denies current use of tobacco products, alcohol, and recreational drugs. Transthoracic echocardiography (TTE) was performed for shortness of air and revealed the left ventricular mass. The patient then underwent a transesophageal echocardiogram (TEE) for further evaluation, which localized the mass to the subchordal apparatus of the anterior mitral valve leaflet (Figures -).
The mass was globular and non-pedunculated and measured 1.9 cm within the chordae tendinae. The echo dense core differentiated the globular mass from vegetation or thrombus. The rest of the echocardiography findings showed normal left ventricular systolic function with a normal ejection fraction of 55% to 60%. The patient was then referred to cardiothoracic surgery, who wanted cardiac magnetic resonance imaging (CMR) for better identification and visualization of the mass. CMR revealed a 1.8 x 1.0 x 0.3-cm lesion on the anterior leaflet of the mitral valve (Figure ).
Consent was obtained, and the patient agreed to resection to decrease the risk of stroke, myocardial infarction, peripheral embolization, and sudden death. Prior to the surgical resection, the patient underwent coronary angiography to look for patency of the coronary vessels, which demonstrated a left dominant arterial supply system with no significant obstructive coronary artery disease and TIMI-3 flow in all the coronary vessels. Left ventricular end-diastolic pressure (LVEDP) was mildly elevated at 19 mm Hg, indicative of mild diastolic dysfunction. Preoperative electrocardiogram (EKG) was normal and showed that the patient was in normal sinus rhythm. During the surgery, gentle retraction of the aortic valve leaflets allowed visualization of the mass.
The mass was located within the left ventricle attached to the papillary muscle and chordae tendinae of the anterior leaflet of the mitral valve. The mass was shaved off without difficulty. The tumor was flushed in appearance, rubbery to spongy in texture, and 1.7 x 1.1 x 0.4 cm in size. No residual tumor was left behind. The tumor was thought to be a myxoma upon macroscopic inspection. No complications were encountered during the surgery. Histological examination of the mass from the pathology revealed narrow, elongated, and branching papillary fronds composed of central avascular collagen and variable elastic tissues surrounded by acid mucopolysaccharide and lined by hyperplastic endothelial cells (Figure ).
The surface lining cells were highlighted with CD-34, and the intermediate cells stained with vimentin and S-100 (Figure ). These findings confirmed the diagnosis of CPF.
Immediately post-op, the patient was confused, light-headed, and complained of dyspnea on exertion. These problems resolved by post-op day two. Following this, the patient’s post-operative course was uneventful. She was discharged to home on post-op day six with home health care.
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pmc-6314998-1
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A male in his early 60s had been living in his car. He was found dead in the car approximately 1 month after he had last been seen alive. A police officer stated that he frequently consumed potatoes in the car. On external examination, the man was 178 cm in height and 69.2 kg in weight. Toxicological evaluation of postmortem cardiac blood was performed by using the LC/MS/MS rapid toxicology screening system ver. 2 (Shimadzu); drugs that could have directly caused his death were not detected. For the qualitative and quantitative analyses of α-solanine and α-chaconine, the validated method described in the present report was used.
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pmc-6315145-1
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We describe a 2.5-year-old female proband, born from non-consanguineous and healthy parents of Caucasian ancestry (Figure ). The child was the product of a 35-week gestation pregnancy that was complicated by fetal bradycardia and intrauterine growth retardation that prompted an emergency C-section. The family history was negative for developmental delay, sick sinus syndrome, and epilepsy, with the exception of a maternal uncle and a paternal first-cousin, both suspected to have autism spectrum disorder.
At birth she required positive-pressure ventilation for 3 min. Apgar scores at 1 and 5 min were 1 and 7, respectively. Birth weight was 1698 g (<1st percentile). She was hospitalized for 3 weeks in the neonatal intensive care unit for prematurity and intrauterine growth restriction being less than 2000 grams. Due to her feeding difficulties, she was fed by nasogastric tube. After 20 days she was discharged home on full oral feeds. At 8 months of age she was noted to have plagiocephaly associated with torticollis, solved with molding helmet therapy. The typical developmental milestones were not met at 1 year of age. When she was 13 months old her gross motor skills were noted to be at the 10-month level, her fine motor skills and receptive language skills were at the 9-month level, and her expressive language skills were at the 5-month level, indicating delays of 3 to 8 months. At 15 months, her developmental quotient, calculated by Capute scores () was between 50 and 55; therefore, her psychomotor delay was assessed as ranging between mild to moderate.
She had strabismus, which was surgically corrected at 16 months. At the same age, she also had implantation of bilateral tympanostomy tubes. Following intensive therapies, her developmental skills have improved. She began walking independently at 18 months. Additionally, she has hypotonia, a wide-based gait, and poor balance. She was described as falling more frequently than expected. However, her communication, particularly expressive language skills, represents the biggest challenge. Currently, her spoken vocabulary consists of about 12 words, and she can also use some sign language. She is social, curious, and interactive and has a high activity level and short attention span compared to peers.
Following identification of her GNB5 variants and the reported clinical spectrum of IDDCA which includes early-onset sick sinus syndrome and epileptic encephalopathy among other cardinal manifestations, the patient was referred to cardiology and neurology.
An electrocardiogram (ECG) showed sinus bradycardia with heart rate of ∼50 at the age of 18 months. A 24-h Holter monitor showed evidence of sinus node dysfunction, with over 3,000 sudden rate drops and pauses that exceeded 3 s. A pacemaker was placed at 2 years of age. Her frequent falls and poor balance improved after pacemaker placement, raising the possibility that those falls were related to sinus pauses. The neurologic evaluation was normal; no evidence of epileptic encephalopathy was detected. Due to lack of relevant clinical findings, an EEG was not performed.
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pmc-6315157-1
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An 18 year old woman was referred to our outpatient clinic of Endocrinology, University-Hospital of Naples Federico II because of hypothyroidism due to Hashimoto's thyroiditis. Blood samples showed high levels of thyroperoxidase and thyroglobulin antibodies and normal calcitonin serum levels. The patient was euthyroid with normal serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) during replacement therapy with L-T4. At physical examination, a palpable nodule of ~2 cm in size was detected in the isthmus of the thyroid. There were no palpable cervical lymph-nodes. An US evaluation confirmed an isolated lesion located in the isthmus, showing an isoechoic solid nodule with smooth margins; its size was 18 × 13 × 6 mm with intra and perilesional vascularity (Figure ). Therefore, a FNA was performed and cytological results revealed a TIR3A lesion. The cytological specimen showed an increased cellularity with some microfollicular structures in the background of scant colloid (Figure ). Thus, we assessed the risk factors associated with the isolated TIR 3A nodule of our patient. According to the ATA guidelines we repeated the FNA which confirmed the same result (TIR3A). The second US (after 6 months) showed that there were no clear signs suggesting malignancy such as microcalcifications or taller than wide-shaped nodules. However, we found a small hypoechoic cranial component in the nodule with blurred margins and elastography revealed an increased stiffness in this cranial component. No nodules were detected in the contralateral lobes by US; cervical lymph nodes were normal. Among the possible risk factors, our patient referred a familial history of thyroid cancer. Her mother was submitted to total thyroidectomy for a follicular variant of PTC twenty years ago; our subsequent evaluation showed that she was disease free at the moment.
On this basis, we decided that a surgical treatment was indicated for our patient and assessed the risk/benefit of total thyroidectomy vs. isthmusectomy.
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pmc-6315203-1
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A 70-year-old woman with a severe headache, vertigo, fever, and arrhythmia, suspected with Parkinson's disease was admitted to Mazandaran Heart Center, Sari, north of Iran, in 2017. She had a history of symptomatic sever mitral stenosis probably due to rheumatic heart disease in her childhood for which she underwent mitral commissurotomy when she was 25 years old. After her first surgery, she administered penicillin G benzathine 1.2 million units IM once a month up to her last admission. She was also subjected to echocardiography every 6 months.
In 2010, the patient suffered from persistent fever, which was unresponsive to antibiotics for 2 weeks. Echocardiography revealed infective endocarditis; however, no microbial strain was isolated from blood culture. After treatment, symptoms reduced; nonetheless, a few days after discharging from the hospital, her blood cell profile was deteriorated gradually. The diagnosis of MDS was eventually confirmed after performing bone marrow aspiration for three times. Thereafter, the patient was subjected to androgen therapy with danazol (10 mg/kg b.w./day), and Prednisolone (1 mg/kg b.w./day). When the white blood cell count became normal, danazol was discontinued; however, the consumption of prednisolone (5 mg/day) was continued. During the long-term use of prednisolone, she was afflicted with steroid-induced diabetes and oral lichen planus due to the impairment of immune system.
On October 2015, due to the deterioration of patient's general condition, she was transferred to Tehran Heart Center for further evaluation. Transesophageal echocardiography (TEE) revealed severe mitral valve (MV) stenoses; as a result, she was subjected to percutaneous transvenous mitral commissurotomy.
On May 2016, the patient was admitted to hospital due to persistent fever and general weakness, and was detected with MV regurgitation. She was prescribed vancomycin (20 mg/kg), gentamicin (1 mg/kg), and ciprofloxacin (10 mg/kg). She had a fever of up to 40°C that was unresponsive to antibiotics and persisted after a week. Imipenem was replaced with ciprofloxacin and continued for 6 weeks. The TEE showed mobile MV vegetation that involved more than 3/4 of the valves. Therefore, the patient underwent MV replacement with a biological (porcine) prosthetic valve.
Following the use of broad-spectrum antibiotics, she was diagnosed with Candida onychomycosis and recurrent Candida vulvovaginitis, and therefore prescribed fluconazole (150 mg) for 3 weeks and caspofungin (intravenous [IV]; 50 mg three times a day) for 6 weeks, coupled with vancomycin and gentamicin.
On February 2017, she presented flu-like symptoms, such as fever and chills, dizziness, severe headache, and heart arrhythmias for 5 days prior to hospital admission. She was admitted to the Cardiac Care Unit of Mazandaran Heart Center in Sari and prescribed ceftizoxime (IV, 500 mg). Echocardiography revealed a large vegetation on the MV annulus.
Two consecutive blood samples were obtained from the patient and inoculated into biphasic brain heart infusion medium. After one week of incubation at 37°C, the blood cultures were positive. The yeast isolate was presumptively identified as C. albicans using conventional methods including chlamydospore production test, germ tube test, and appearance on CHROMagar Candida.
On March 2017, the patient’s condition deteriorated. The blood cultures were negative. She underwent the second prosthetic valve replacement. The surgery revealed the formation of huge fungal white and creamy vegetation and abscess overall the prosthetic valve. The explanted valve and vegetation were sent to laboratory for further evaluations. Direct examination (KOH 20%) and calcofluor white staining of the sample showed lots of budding yeast cells.
To identify the species, the yeast colonies were yielded on Sabouraud dextrose agar medium after a 24-hour incubation at 27ºC. The isolated yeast was identified as Candida albicans using the conventional methods. The diagnosis was confirmed by polymerase chain reaction (PCR) assay using the two universal primers, namely ITS1 and ITS4 []. The amplicons were sequenced and compared with the GenBank database; then, they were submitted to GenBank and received accession number MG763751.
Amphotericin B, deoxycolate (1 mg/kg/day), caspofungin (70 mg/kg on the first day and 50 mg/kg in the next days), and voriconazole (6 mg/kg bid on the first day and 4 mg/kg bid in the next days) together with broad-spectrum antibiotics, including vancomycin (20 mg/kg bid) and gentamicin (1 mg/kg bid) were administered. However, 48 h later, the patient presented with dyspnea, decreased consciousness, and decreased blood cells, resulting in a coma. The patient passed away due to sepsis probably related to the candidemia and Candida PVE with antifungal-resistant Candida
albicans.
In vitro antifungal susceptibility testing of Candida
albicans isolate was carried out based on the clinical and laboratory standards institute (CLSI) M27-A3 [] and M27-S4 guidelines [8]. Based on the breakpoint, the isolate was resistant to voriconazole (16 μg/ml), itraconazole (16 μg/ml), fluconazole (64 μg/ml), posaconazole (16 μg/ml), and amphotericin B (4 μg/ml). Furthermore, it was susceptible to anidulafungin (0.008 μg/ml) and micafungin (0.008 μg/ml), and intermediate to caspofungin (0.5 μg/ml).
The study protocol was approved by the Ethics Committee of Mazandaran University of Medical Sciences, Sari, Iran.
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pmc-6315272-1
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Patient 14 (Group 1) is a 64-year-old male diagnosed with type 2 diabetes at 53 years of age. He has no history of foot ulceration or amputation and has experienced neuropathic pain for the past 8 years. His feet showed no visible signs of injury (see ). Patient 14 wore the socks for 6 hours, during which minor variations in temperature between the contralateral locations were observed with differences of less than 2.2°C or 4°F (see ). The continuous monitoring of the temperature by the socks show minor variations over the 6-hour period. Consistent with the initial observations and medical history, no temperature elevations were found.
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pmc-6315272-2
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Patient 30 (Group 2) is a 63-year-old male diagnosed with type 2 diabetes at 45 years of age. He has a history of ulcers and was diagnosed with Charcot arthropathy of the right foot at 57 years of age. Intake photographs (see ) and examination showed Charcot of the right foot with a collapsed midfoot. Patient 30 wore the sensor-embedded socks for 8 hours, during which period the right foot was consistently warmer than the left foot. The temperatures on the right hallux, MTP 1, MTP 3, MTP 5, and midfoot (arch) were elevated more than 2.2°C or 4°F, up to 8°C (see ).
Thus, the findings from continuous temperature monitoring are consistent with the patient’s medical history and intake evaluation of Charcot of the right foot. This suggests that the clinical assessment of Charcot arthropathy may benefit from this monitoring system, as it provides a temperature map of the entire foot over a long period of time, rather than static and local temperature changes.
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pmc-6315272-3
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Patient 16 (Group 3) is a 73-year-old male diagnosed with type 2 diabetes at 65 years of age. He has a history of preulcerative lesions. Intake photographs (see ) and exam indicated a current preulcerative lesion at the right plantar region between the second and third metatarsal. Patient 16 wore the socks for 9 hours, during which higher temperatures were recorded by two of the six sensors, at the positions of the right metatarsals 3 and 5 (see ). This observation is consistent with the patient’s medical records indicating a preulcerative lesion in the MTP 2-3 area. These data suggest that in high-risk patients, continuous monitoring may be able to pick up an injury or preulcerative lesion.
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pmc-6316510-1
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A woman over 70 years old presented to a local emergency room in the summer of 2017 with a 2-day history of chills, nausea, vomiting, reduced oral intake, and generalized weakness. She was unable to get out of bed over the past 24 h. Upon review of systems, she had no urinary symptoms, abdominal pain, diarrhea, or other complaints. Past medical history was remarkable for metastatic breast cancer, hypertension, and depression. Her home medications included oral letrozole, sertraline, amlodipine, and carvedilol. The patient was briefly hospitalized three months prior for new brain metastases. However, she did not receive antimicrobials or chemotherapy during that hospitalization or elsewhere over the past 6 months. She had no other known healthcare exposures or invasive procedures over the same period. The patient had no documentation of prior infections or colonization with multidrug-resistant bacteria.
The patient had signs of sepsis on initial presentation with hypotension (blood pressure: 61/39 mmHg) and tachypnea (respiratory rate: 27 breaths/minute). Her tympanic temperature was 99.2 degrees Fahrenheit, and her heart rate was 76 beats per minute. She was alert and awake during the physical examination with dry skin and mucus membranes. A tunneled central venous port in the anterior chest had no erythema, drainage, or tenderness to touch. Significant laboratory findings included a peripheral white blood cell (WBC) count of 12,400/mm3 with bandemia (21%), elevated serum creatinine from baseline (2.9 mg/dL), and high serum procalcitonin (187 ng/mL). Urinalysis with microscopy demonstrated large leukocyte esterase, 95 WBCs with few WBC clumps, and 6 red blood cells. Rare bacteria were observed by urine microscopic examination. No new pulmonary infiltrates were noted on a chest X-ray.
The patient was admitted to the intensive care unit for management of suspected sepsis. Intravenous fluid resuscitation and empirical broad-spectrum antimicrobials (intravenous vancomycin and piperacillin/tazobactam) were started following collection of blood and urine cultures. An antimicrobial stewardship alert was triggered by the growth of Gram-negative bacilli on blood cultures after 12 h of collection. A BioFire FilmArray® multiplex PCR Blood Culture Identification (BCID) panel detected Enterobacteriaceae and Escherichia coli. The Klebsiella pneumoniae carbapenemase (KPC) gene was not detected. A urine culture also grew Escherichia coli as identified by MALDI-TOF. At this point, the local antimicrobial stewardship team recommended discontinuation of vancomycin. Recommendations also included de-escalation of antimicrobial therapy from piperacillin/tazobactam to ceftriaxone given growth of E. coli in the bloodstream and the patient’s low risk of extended-spectrum beta-lactamases (ESBLs) given the absence of recent antimicrobial use or prior infections or colonization with ESBL-producing bacteria [,]. The primary team discontinued vancomycin; however, they preferred to continue intravenous piperacillin/tazobactam at 2.25 g every 6 h (dose adjusted for calculated creatinine clearance of 15 mL/min) until the availability of in vitro antimicrobial susceptibility testing results of the E. coli isolate.
Following an initial relative improvement in hemodynamics with fluid resuscitation, the patient’s clinical response plateaued during the first three days of antimicrobial therapy. She continued to manifest signs of sepsis with a systolic blood pressure of <100 mmHg and a respiratory rate of >22 breaths/minute. On the fourth day of hospitalization, she developed a fever (102 degrees Fahrenheit) and new-onset diarrhea (5 watery bowel movements within 24 h), and her respiratory rate increased from 24–26 to 30 breaths/minute. Clostridioides difficile PCR was positive in a stool sample. Retroperitoneal ultrasound did not demonstrate ureteric obstruction or hydro-nephrosis. The in vitro antimicrobial susceptibility results of the E. coli bloodstream and urinary isolate are demonstrated in . Non-susceptibility to piperacillin/tazobactam via the automated VITEK® 2 system was confirmed using the Kirby–Bauer method. In addition, ESBL screening by disk diffusion using cefotaxime/clavulanate combination disks was negative. The primary team requested a consultation with a specialist in Infectious Diseases for antimicrobial management.
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pmc-6317081-1
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A 68-year-old male with history of end stage renal disease presented with abdominal pain and cloudy effluent for one-day duration. Patient has been on automated peritoneal dialysis for 2 years and never had an episode of peritonitis. Patient admitted working in his garden one day prior to the presentation. Other medical problems include hypertension, diabetes, and anemia of chronic disease. Patient was afebrile and vital signs were stable. Physical examination revealed diffuse abdominal tenderness and no drainage from exit site. No tenderness was elicited along the tunnel of peritoneal dialysis catheter. Peritoneal dialysis effluent showed elevated WBC with cell count 1991 cells/ul (with 94% neutrophils). Gram stain revealed few WBC and no organisms were seen. Effluent grew gram-negative rods both in aerobic and anaerobic cultures. Confirmation of M. osloensis was made by 16S PCR phenotypic and sequencing technique. Susceptibilities were not performed on this organism by the reference laboratory, as no Clinical & Laboratory Standards Institute (CLSI) guidelines are available. Patient was empirically treated with intraperitoneal ceftazidime 1 gram daily for 3 weeks. Post treatment peritoneal dialysis effluent was clear with WBC count <20 cells/ul and repeat fluid culture was negative.
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pmc-6317083-1
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A 42-year-old woman was admitted to our hospital with change in mental status, slurred speech, and fever 9 days following the administration of one cycle of the intravenous infusion of ipilimumab 1 mg/kg and nivolumab 3 mg/kg for the treatment of metastatic renal cell carcinoma (RCC). Her history is significant for a right radical nephrectomy with lymphadenectomy for a kidney mass identified on CT abdomen and pelvis during the work up of hematuria (January 2018). Pathology confirmed papillary RCC with extensive sarcomatoid features. Eight of the 11 lymph nodes were involved with cancer. She received Sutent (50 mg orally daily, 4 weeks on and 2 weeks off) for 4 months and then stopped due to progression of disease. Spine MRI revealed a C3 compression deformity with tumor extension as well as osteolytic metastatic disease at C4 and the right C5 pedicle. She underwent C2 to C5 posterolateral arthrodesis and instrumentation. Ipilimumab and nivolumab were initiated on 06/04/2018. Four days later, she presented to clinic with significant fatigue. Laboratory results revealed hemoglobin (Hb) 4.9 g/dL; hematocrit (HCT) 16.4%; and platelets (PLT) 36,000 per microliter. She was given prednisone 1 mg/kg orally daily for presumed immunotherapy-induced immune thrombocytopenia (ITP) and received 2 units of packed RBCs. Her overall health deteriorated so she got admitted on 06/13/2018. Laboratory studies on admission are available in .
MRI brain revealed calvarial metastasis but no evidence of intracranial disease. Electroencephalogram (EEG) revealed moderate generalized disturbance in the cerebral slowing activity. A diagnosis of TTP was made on the basis of laboratory and clinical findings. Methylprednisolone 125 mg IV every 6 hours, therapeutic plasma exchange (TPE: 1 to 1.5 plasma volumes per treatment; a total of 8 treatments; exchange fluid of 5% human albumin and FFP), and rituximab (weekly 4 doses) were initiated. ADAMTS13 activity less than 3% and inhibitory titer 9.9 Bethesda Units/mL confirmed acquired TTP. Ten days after initiating the appropriate therapy, the mental status improved, the platelet count increased to 116,000 per microliter, and the LDH level decreased to 406 U/L.
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pmc-6317086-1
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This case report was reviewed by the local IRB at Eastern Virginia Medical School (18-09-NH-0217) and deemed “not human subjects research.”
A 14-year-old male with a past medical history of mild intermittent asthma presented in December 2017 with a subdural empyema resulting from direct extension from frontal sinusitis. His intracranial abscess was surgically drained as part of a hemicraniectomy procedure. Cultures of his intracranial abscess grew Streptococcus intermedius, and he was treated with antibiotics for 2 months. His craniectomy plate was reimplanted in June 2018. Two and a half weeks later, he presented with pain and mild wound dehiscence. Several patches of alopecia along the edges of the wound were noted. A culture of purulent material expressed from the wound grew rare Pseudomonas aeruginosa. Despite appropriate antibiotics, there was no clinical improvement in drainage or pain, leading to surgical removal of the reimplanted bone in July 2018. One week postoperatively, he reported increasing pain along the incision while being treated with ceftazidime. There were fluctuance and profound tenderness to palpation along the incision site (), and a new thick purulent discharge was expressible from the wound. There were a few patchy areas of alopecia along the wound edges, which at the time were attributed to preoperative shaving, frequent wound cleaning, and removal of dressings and tape. The skin in the areas of alopecia was not scaly. Expressed purulent drainage was cultured, and his antibiotics were switched to vancomycin and meropenem. The new wound culture grew hyphal fungus on a blood agar plate after 4 days. In total, six wound cultures of the expressed purulent material from the wound were performed over two weeks, and all grew colonies with branched hyphae morphologically consistent with Trichophyton (). Once identification of Trichophyton was made, he was started on oral terbinafine and his antibiotics were discontinued. His wound infection improved rapidly thereafter with decreasing amounts of purulent drainage, fluctuance, pain, and tenderness. After three weeks of terbinafine treatment, all discharge and tenderness had resolved. Follow-up after 6.5 weeks of terbinafine treatment demonstrated an optimal response, including patchy regrowth of hair, and terbinafine was discontinued.
University of Texas Health San Antonio (UTHSA) identified the fungal species as T. tonsurans. Fungal susceptibility testing was also performed by UTHSA. Identification included phenotypic characterization and DNA sequencing of the following targets: ITS, D1/D2, and TUB. This isolate was susceptible to terbinafine (MIC = 0.008 mcg/ml) and griseofulvin (MIC = 1 mcg/ml).
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pmc-6317091-1
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A 56-year-old male with a history of hypothyroidism and hyperlipidemia was admitted to the hospital after a motor vehicle accident where he sustained a closed right subtrochanteric femur fracture with 4 cm of foreshortening []. On admission his hemoglobin was 14 g/dL, white blood cell count 7.7 x 103/μL, platelet count 220 x 103/μL, and metabolic panel normal with the exception of plasma venous glucose of 120 mg/dL. His urine drug screen was negative and he was alert with no mental status disturbance. He was taken to the operative room within the first few hours of admission and underwent central medullary nailing without any intraoperative complications. Immediately post-op he was drowsy from the anesthesia but following commands properly. On postoperative day 1, he was found to be very lethargic and confused with altered mental status. He was normotensive, with temperature of 37.7 C, heart rate of 109 beats per minute, respiratory rate of 24 breaths per minute, and pulse oximetry showing 92% oxygen saturation on room air. On examination he was very drowsy but following basic commands. His right leg was immobilized with ecchymosis of the same leg noticed and distal extremity pulses were normal bilaterally. On neurologic examination, a right sided weakness of the upper extremity was appreciated, but muscle tone was normal, and reflexes were preserved. The Glasgow score was 10/15. His skin was warm and dry with no evidence of petechial rash at that time. His pupils were reacting to light, and his fundoscopy was within normal limits. His routine investigations revealed no significant derangements in the complete blood count and renal or liver functions. There was no evidence of thrombocytopenia. The differential diagnosis included narcotic overdose since he was getting pain medications, fat embolism, postoperative delirium, acute cerebrovascular accident (CVA), and sepsis.
One dose of naloxone, 0.4 mg intravenously, was given without improvement. He was placed under stroke alert. No acute intracranial hemorrhage was seen on noncontrast computerized tomographic (CT) scan of the head and his electrocardiogram (EKG) was normal. A right lower extremity artery duplex Doppler examination was normal and chest CT angiogram was negative for pulmonary embolism. As the day progressed he became more obtunded requiring an intensive care unit (ICU) admission and endotracheal intubation for airway protection. Magnetic resonance imaging (MRI) of the brain revealed multiple bilateral acute cerebral infarcts with restricted diffusion areas in a “starfield” pattern favoring the diagnosis of cerebral fat embolism []. He remained unresponsive and continued neuromonitoring revealed multifocal epileptiform discharges and continual ictal discharges from the right anterior quadrant with contralateral spread consistent with nonconvulsive status epilepticus. He was immediately started on midazolam drip at 5 mg/hour, loaded with 20mg/kg of fosphenytoin maintenance dose of 100 mg every 8 hrs. Due to failure on ictal discharge suppression after initial intervention, midazolam drip was titrated up and a second antiepileptic drug was started, levetiracetam 1000 mg every 8 hrs. Nonconvulsive status epilepticus resolved after 72 hours of the diagnosis. Lumbar puncture was not considered necessary for his management. Within the first 48 hours of ICU admission he developed a bilateral patchy opacity in a “snowstorm” pattern on chest X-Ray [] and his BNP (brain natriuretic peptide) was 24 (normal 0-100 pg/mL). There was a petechial rash noted on his anterior chest []. Further workup demonstrated a patent foramen ovale (PFO) with a significant right to left shunt [] by transesophageal echocardiogram (TEE). There was also a positive bubble study []. A diagnosis of fat embolism syndrome was made. He improved with antiepileptics and supportive care. He was extubated on postoperative day 6 with significant mental status improvements; however, he had dense right-sided weakness, which improved significantly after 3 more days. He was discharged to inpatient rehabilitation on postoperative day 15.
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pmc-6317098-1
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A 73-year-old African American male presented to an outside hospital with a three-week history of shortness of breath on exertion, 3 pillow orthopnea, and bilateral lower extremity swelling. The patient had been diagnosed with heart failure with reduced ejection fraction (HFrEF) 4 months prior, but he stopped his cardiac medications when he developed worsening symptoms. Other medical history included hypertension, diabetes mellitus, hyperlipidemia, and ongoing high alcohol consumption. Physical examination revealed bilateral lower extremity edema, elevated jugular venous pressure, and bibasilar pulmonary rales. One day after admission, his troponin I peaked at 18 ng/ml (reference range < 0.04 ng/ml). Electrocardiography revealed nonspecific T wave changes in the anterolateral leads. He was treated for acute coronary syndrome (ACS) with aspirin, clopidogrel, low molecular weight heparin, and intravenous furosemide. A transthoracic echocardiogram (TTE) showed an ejection fraction (EF) of 30-35%, moderate biatrial enlargement, and moderate right ventricular (RV) systolic dysfunction. In addition, a 2.0 cm spherical mobile echodensity was noted to be attached to the left side of the interatrial septum, concerning for myxoma vs. thrombus. Given the TTE findings and the need for coronary angiography, transfer was requested to our hospital.
Coronary angiography was performed and showed thrombotic subtotal occlusion of the ramus intermedius coronary artery branch, thought likely to be the culprit lesion. He also had 80-90% occlusion of the second obtuse marginal (OM2) and 50% occlusion of the distal left anterior descending (LAD) artery. Due to the need for further evaluation of the left atrial (LA) mass, no intervention was performed. TTE subsequently showed severe global hypokinesis of the left ventricle (LV) (EF 10-15%) and mild LV hypertrophy. The previously noted LA mass measured 2.1 cm by 1.4 cm, appeared pedunculated and was attached to the left side of the interatrial septum with echogenic characteristics concerning for atrial myxoma (). Within the right atrium (RA) was a large (3.2 × 2.0 cm) semimobile mural thrombus (), and spontaneous echo contrast was also evident in the LV cavity. He remained anticoagulated with unfractionated heparin. Despite this, subsequent TTE imaging demonstrated the development of biventricular thrombi over the course of several days (). On hospital day 7, he went to the operating room. Intraoperative transesophageal echocardiogram (TEE) showed a new subcentimeter mass on the RV free wall. The previously noted masses in the RA and LA were resected (). Two-vessel coronary artery bypass grafting was performed with the left internal mammary artery to LAD and saphenous vein graft to OM2. Given that the etiology of his cardiomyopathy was also yet to be determined, an intraoperative LV biopsy was performed. Pathology of both the RA and pedunculated LA masses showed organized thrombus. The LV biopsy was negative for histopathologic evidence of inflammatory infiltrate, granulomas, or eosinophils but was strikingly positive for amyloid deposition by Congo red staining. Liquid chromatography tandem mass spectrometry demonstrated ATTRwt amyloidosis and did not detect an amino acid sequence abnormality in the TTR protein. The patient's postoperative recovery was complicated by a left frontal cerebrovascular accident, thought likely to be cardioembolic in nature. He was discharged for rehabilitation on postoperative day 15 on chronic anticoagulation with warfarin.
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pmc-6317102-1
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In March 2018, a 68-year-old male patient was admitted to our department because of multiple renal tumors bilaterally, incidentally discovered during abdominal ultrasonography for screening purpose. His medical history included allergic reaction to iodinated contrast agent.
Preoperative Magnetic Resonance Imaging (MRI) demonstrated the followings: (1) a 6.2x6.3 cm in size, solid mass at the lower pole of the right kidney, (2) a 2.4 cm solid mass at the upper pole of the right kidney, and (3) a 5.4x4.5 cm in size, solid mass at the lower pole of the left kidney (). The lesions were exophytic and they demonstrated hyperintense signal on T2-weighted sequences and hypointense signal on T1-weighted sequences. All of them presented heterogeneous enhancement after intravenous administration of paramagnetic contrast agent. Blood chemistry levels were in the normal range. Preoperative serum creatinine value was 1 mg/dl (with normal values 0.6-1.2 mg/dl) and preoperative estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) formula was 78.98 ml/min/1.73m2.
The patient underwent transperitoneal laparoscopic left partial nephrectomy (PN), which is the standard operative technique for cT1 renal tumors in our department, under general anesthesia. We decided to perform firstly PN on the left side to obtain histological information and to evaluate renal function before treating the right side. Standard operative technique in our department involves the application of warm ischemia (WI), by using a 2 mm, 30 cm vessel loop, a 2 cm cylinder sheath prepared from a 16 Fr Levin tube, and a large Hem-o-Lok clip (Rummel Tourniquet technique) in order to occlude renal artery (). WI time was 24 minutes and the duration of the operation was 184 minutes. Postoperative course was complicated by fever and by an episode of atrial fibrillation (classified as Clavien grades 1 and 2, respectively, according to the modified Clavien scale). The patient was discharged on 5th postoperative day, the serum creatinine value was 1.8 mg/dl, and eGFR was 40.08 ml/min/1.73m2. Histology revealed clear-cell RCC, 5 cm in size, Fuhrman nuclear grade 3, and negative surgical margins (pT1b) ().
Forty days postoperatively, the patient was readmitted in order to be operated for the tumors of the right kidney. Serum creatinine value was 1.7 mg/dl and eGFR was 42.81 ml/min/1.73m2. The patient underwent open right PN under general anesthesia. We removed both of the polar tumors simultaneously. We did not apply any kind of ischemia in order to preserve renal function, but we just applied manual compression at the resection edges periodically in order to facilitate tumors' removal and completion of renorrhaphy (). The patient had an uneventful postoperative course, his eGFR remained stable, and he was discharged on 5th postoperative day. Histology revealed clear-cell RCC, 2.2 cm in size, and Fuhrman nuclear grade 3 for the tumor of the upper pole (pT1a), with negative surgical margins and clear-cell RCC, 5.5 cm in size, and Fuhrman nuclear grade 2 for the tumor of the lower pole (pT1b). Focal microscopic invasion of the pseudocapsule was evident at the base of the low-grade tumor of the lower pole.
Six month postoperatively, the serum creatinine value was 1.44 mg/dl, eGFR was 51.85 ml/min/1.73m2, and there was no recurrence on MRI. The patient is scheduled for follow-up 12 months postoperatively.
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pmc-6317112-1
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In March of 2018, a 62-year-old male with a history significant for hypertension and dyslipidemia, and a body-mass index of 30.4, presented with symptoms of acute myocardial infarction. After counseling and informed consent, the patient was treated with a staged treatment approach, beginning with PCI and stent placement in the codominant right coronary artery (RCA). He was asked to return three weeks later for angiography and robotic-assisted PCI to the left anterior descending (LAD) coronary artery.
Angiography confirmed the presence of a patent stent in the RCA, a class IIB severe, long, diffuse, and calcified lesion of the proximal to mid LAD segments (90% stenosis; TIMI grade 1 flow). A severe lesion of the first obtuse marginal artery was also identified.
Prior to the procedure, the patient was sedated and an appropriate local anesthetic was applied at the radial access site. Clopidogrel, acetylsalicylic acid, and heparin were administered. Preparation for the robotic PCI procedure involved manual introduction of a radial access guide catheter (6F, EBU 3.5; Medtronic, Minneapolis, MN) and cannulation of the LAD according to standard practice. The guide catheter was then connected to the Y-connector, which was loaded into the appropriate drive of the robot's single-use cassette. A coronary guidewire (Balance Middleweight, 0.014 × 190 cm; Abbott Vascular, Abbott Park, Illinois, USA) was then introduced through the Y-connector into the guide catheter, and the distal end was also loaded into the cassette's guidewire track.
With set up of the robotic system complete, the operator was seated at the radiation-shielded workstation and began advancing the guidewire to the LAD under fluoroscopic guidance, employing the joystick controls on the robotic console, with the Rotate-on-Retract feature enabled. On initial advancement of the guidewire toward the LAD, the wire went into a diagonal branch. It was retracted and readvanced, and it went into another new branch. Following the second retraction, the guidewire moved forward to enter the target lesion (refer to the Supplemental Video ()). Total time for guidewire placement was a few seconds. Once the guidewire was in position at the target lesion, a rapid-exchange coronary angiography balloon was loaded and advanced for predilation using the robotic system.
A rapid-exchange system for the delivery of two everolimus-eluting stents (XIENCE, Abbott Vascular) was subsequently loaded, delivered, and deployed using the robotic system. One 3.00 mm × 23 mm stent and one 3.50 mm × 28 mm stent were delivered to the mid and proximal LAD segments, respectively. Total procedure time was 1 h 55 min with 19.9 minutes of total fluoroscopy time. The entire PCI procedure was performed using the robotic system, and there were no intraprocedural dissections, perforations, device malfunctions, or other complications. At the conclusion of the case, vessel patency was confirmed by angiography with no evidence of residual stenosis and angiographic flow of TIMI grade 3 ().
The patient returned later for scheduled PCI to the first obtuse marginal artery. He experienced a complete recovery.
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pmc-6317118-1
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A 24-year-old male presented with a history of nonresolving pneumonias. Nine months prior to presentation, the patient was severely obese (body mass index = 41 kg/m2) for which he underwent gastric sleeve surgery. Thereafter, his weight decreased from 108 kg to 54 kg.
Four months prior to presentation, the patient was having a whitish, productive cough and was diagnosed with pneumonia which was treated with oral antibiotics. The patient then presented to the emergency department with severe shortness of breath for four days, left-sided noncardiac chest pain, and weight loss.
Physical examination revealed a decreased air entry in the left lung, scattered rhonchi, generalized body pain, and fever. The first impression was that of pneumonia.
The patient was initially admitted under pulmonology with a picture of left lung pneumonia with pulmonary effusion. The patient had a pigtail insertion in the left side, for which pleural fluid was sent for cultures. The patient was assessed and examined by thoracic surgery, and the decision was made for a left chest decortication.
Preop imaging showed a large gastric leak with perisplenic collection (). The collection was communicating with the upper pole of the spleen. There was a questionable pleural fistula at the collection. Therefore, the surgery was aborted, and an upper GI endoscopy was requested.
The chest CT revealed a partly loculated, large left pleural effusion with complete atelectasis of the left lower lobe and partial atelectasis of the left upper lobe. Few alveolar and tree-in-bud opacities were noted in the right upper lobe and apical segment of the right lower lobe, representing pulmonary infections ().
An 8-French pigtail drainage catheter was inserted into the left pleural cavity, and the infected empyema was aspirated. Then, the abdominal and pelvis CT showed a large leak, with perisplenic collection measuring 2.5 × 5.5 × 5.7 cm. This collection was communicating with the other collection seen at the upper pole of the spleen that measured 4 × 4.2 cm. The pleural collection measured 1.8 × 2 × 4.2 cm. The abdominal collection was connected to the pleural collection through a fistula ().
The upper GI endoscopy showed a large fistula coming out of the stomach and the upper boarder of the gastric cardia. The upper GI series showed a frank extravasation of the oral contrast at the site of the proximal suture ().
A covered esophageal stent and nasojejunal tube were inserted to control the gastric leak. Through a transoral approach, a wire and a 5F catheter were used to canalize the remaining part of the stomach. Contrast was given which showed a leak at the left lateral aspect. Then, the catheter over the wire was passed into the bowel reaching to the jejunal loop, followed by an exchange to a stiffer wire. Subsequently, an esophageal stent, measuring 24 mm × 23 cm, was successfully placed.
Eight days later, another upper GI series was performed which showed no gastric leak upon comparison with the previous upper GI study (). The guidewire and catheter passed down the esophageal stent, which was completely retrieved using crocodile forceps under fluoroscopy. An Esophogram demonstrated an initial hold-up of contrast at the distal esophagus. Contrast eventually passed through the stomach into the small bowel.
Prior to discharge, repeated imaging showed an improvement of the left-sided pleural effusion and splenic collection. Therefore, the patient was discharged in a stable condition with antibiotics and pain killers. Follow-up in the clinic after 3, 6, and 15 months of the diagnosis confirmed that the patient was medically free with no active issues.
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pmc-6317122-1
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A 20-year-old female with a body mass index (BMI) of 42 kg/m2, who met the National Institutes of Health criteria for bariatric surgery, underwent sleeve gastrectomy surgery in July 2016. She was discharged home without any complications. The initial 3-month postoperative period was uneventful without any nausea or vomiting. Net postoperative weight loss was 30 kg in 4 months. In early November 2016, she reported feeling flu-like symptoms (cough, sore throat, and runny nose) with a low-grade fever. Her upper respiratory symptoms improved, but 2 weeks later, symptoms rapidly progressed to bilateral ascending lower limb (LL) numbness reaching her waist. The numbness became progressively worse and she started to develop bilateral lower extremity weakness with recurrent falling attacks and severe leg pain. In addition, she developed choking attacks, hoarseness with on and off dysphagia, dyspnea, and constipation without urinary retention.
The neurologist's evaluation showed reduced distal and proximal muscle power, diminished LL reflexes, and decreased pinprick sensation up to L1 bilaterally. In addition, big toe proprioception was impaired and the patient had a decreased sense of vibration up to the knee bilaterally. There was no involvement of the upper limbs (ULs), and the cerebellum and cranial nerves were intact.
Initial laboratory test results were unremarkable, including a thyroid function test and vitamin B12 levels (1186 pmol/L). A lumber puncture was performed and cerebrospinal fluid (CSF) revealed the following: white blood cell count (WBC) 1 cell/cubic mm, red blood cell count (RBC) 11 cell/cubic mm, protein level 0.31 g/L, glucose level 3.4 mol/L. CSF bacterial and fungal culture results were negative. Serologic tests showed normal complement and high immunoglobulin G (16.7 g\L) levels, as well as negative antinuclear antibody (ANA) results. Because of her progression in symptoms, the patient underwent further neurological workup. Magnetic resonance imaging (MRI) scan results for the spinal cord were normal except for a high-signal density on the L1 vertebral body. The results of nerve conduction study (NCS) was normal apart from the absence of F waves, and electromyography (EMG) testing showed axonal involvement. These findings were consistent with the axonal form of GBS.
The patient required intubation and was admitted to the intensive care unit (ICU), where she received intravenous immunoglobulin (IVIG) for 5 days. Nutritional supplements, including IV thiamine, vitamin B6, and vitamin B12, were given in addition to selenium. She continued rehabilitation and physical therapy. Her symptoms gradually improved, but she required the assistance of walkers before her symptoms completely resolved.
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pmc-6317122-2
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A 36-year-old female with diabetes mellitus, hypertension, and hypothyroidism underwent a cesarean section a few weeks prior to admission and a gastric sleeve procedure 1 year before that.
Two days before admission to hospital, the patient developed ascending numbness followed by weakness, which progressed over 2 days. It interfered with her movement, making her bed bound. She reported a 1-day history of subjective fever and diarrhea a week before the onset of symptoms, which subsided spontaneously. Weakness was not associated with double vision, shortness of breath, slurred speech, abnormal movement, or confusion. She did not have fever, diarrhea, or abdominal pain and did not have similar attacks previously.
She lost approximately 40 kg in 2 months; she did not receive any vitamin supplementation after surgery. The patient reported vomiting three to four times daily postoperatively until a month before her presentation.
Examination showed that the cranial nerves were intact with no motor or sensory abnormalities. Her UL and LL tone was normal. There was a symmetrical decrease in power in her ULs both proximally and distally. LL power was also decreased. Her reflexes were diminished but elicitable, but her plantar response was mute with various maneuvers. The sensory examination was unremarkable and her coordination was intact.
The patient was admitted to hospital as a case of postbariatric surgery myeloneuropathy or GBS. IVIG was given for a complete course of five continuous days. Thiamine loading and maintenance were given parentally. Vitamin B12 and D levels were within normal limits. She was discharged with persistent weakness to undergo rehabilitation. No MRI or NCS was done at admission.
She presented again with the same concern and was admitted to neurology inpatient services. An MRI scan of the entire spine was performed, which showed early dorsal spine spondylitic changes with small anterior osteophytes at the lower dorsal spine. An EMG/NCS was also done, showing pure motor neuropathy and myopathic changes at proximal muscle and a normal sensory picture, suggestive of acute motor axonal neuropathy for early Guillain-Barré syndrome.
She continued to receive vitamin supplementation and physiotherapy. Plasma exchange was discussed but declined by the family. She will require ongoing extensive neurorehabilitation at a dedicated center at King Faisal Specialist Hospital and Research Centre or King Fahad Medical City in Riyadh.
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pmc-6317122-3
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A 22-year-old Saudi female with a case of morbid obesity (initial BMI of 43 kg/m2 and final postoperative BMI of 34.6 kg/m2), who met the National Institute of Health criteria for bariatric surgery, underwent an elective laparoscopic gastric sleeve procedure on January 22, 2017. She was discharged home 1-day postoperatively without any complications.
A month after surgery, she developed gradual bilateral LL numbness described as a tingling sensation, followed by LL weakness that progressed to pain. In addition, she reported short-term memory impairment. Initially, she was unable to walk without support, which gradually progressed to a complete inability to walk. There was no UL involvement. The patient reported falling down numerous times because of dizziness; however, she did not lose consciousness or have any convulsions. She also reported hoarseness of speech but no other bulbar symptoms. The patient did not have urinary or bowel changes, nor did she have visual changes. Her family history was unremarkable.
The physical examination showed that she was pale, in pain, dehydrated but conscious, oriented and alert, hemodynamically stable, and afebrile. The motor examination revealed normal LL tone, a slight decrease in power with absent reflexes, and decreased sensation up to the knees. UL reflexes were decreased. Initial laboratory test results (complete blood count, erythrocyte sedimentation rate, and C-reactive protein) were normal. Nutritional assessment showed the following results: normal vitamin B12 (456 μmol/L), normal selenium (1.16 μmol/L), low vitamin D, low vitamin B1 (0.28 μmol/L), and normal copper (16 μmol/L) levels. Her electrolyte levels were normal except for decreased potassium (K: 2.9 mmol/L). Serum protein electrophoresis demonstrated hypoalbuminemia (31 g/L).
A lumber puncture revealed clear colorless CSF with a volume of 0.5 mL and the following results: WBC 3 cells/mm3, RBC 107 cells/mm3, glucose level 4 mmol/L, and protein level 0.80 g/L. CSF viral bacterial and fungal culture results were negative. Because of the progression of her symptoms, she underwent further neurological workup. An MRI study of the dorsal spine was unremarkable, except for EMG axonal involvement. These findings were consistent with GBS.
She did not require admission to ICU but received a course of IVIG (30 g daily), nutritional replacement, vitamin B complex, and vitamin D. She started physiotherapy and was discharged from hospital in good condition.
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pmc-6317207-1
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A 3-year-old female alpaca was submitted to the Clinic for Ruminants and Swine, Leipzig University with a clinical history of markedly reduced food and water intake. At admission the animal presented dehydrated and showed salivation as well as inappetence. Initially, feces were dry with mucous and traces of blood; after 1–2 days defecation was watery and bloody and then nearly completely ceased. Since its admission to the clinic, the alpaca had received intravenous infusions of glucose and electrolyte solutions as well as antiphlogistic and antibiotic treatments. First the general condition of the alpaca was stable, and it showed intake of solely a little bit grass and some water. One day prior to its death, its general condition markedly deteriorated; the alpaca was recumbent with colicky abdominal pain. The animal deceased spontaneously 4 days after its admission to the clinic and was submitted for a complete post mortem examination.
At necropsy, the carcass was found in a good nutritional condition. The subcutis, the parietal and pulmonary pleura as well as the heart showed multiple endo- and epicardial petechial to ecchymotic hemorrhages. The myocardium, pulmonary artery, aorta, liver and kidneys showed no gross lesions. The abdominal cavity contained 40 mL of serosanguinous effusion. There was a moderate fibrinous to fibroblastic peritonitis with adhesions between the intestinal loops as well as well as the stomach. Multifocal moderate acute serosal hemorrhages were observed as well. The mucosa of the 2nd and 3rd stomach compartment (C2 and C3) was diffusely dark red indicative of acute gastritis. Jejunum, ileum and colon displayed a marked acute to subacute diphtheroid-necrotizing enteritis. Mesenteric lymph nodes were moderately enlarged. Lungs were incompletely collapsed with acute alveolar edema. The right frontal lobe contained a 1.5 × 1.0 × 1.7 cm lesion with loss of normal cortical and medullary architecture that extended within the meninges. In the center of the lesion, the brain tissue was beige and soft with multifocal mild cavitation and contained a few small foci of brownish discoloration. The peripheral parts of the lesion were composed of firm whitish-beige tissue interpreted as fibrous connective tissue (Fig. a).
Samples of multiple organs including the stomach compartments C2 and C3, small and large intestines, mesenteric lymph nodes, lungs and brain (cerebrum with the lesion, additional parts of the ipsi- and contralateral cerebrum, hippocampus, cerebellum, midbrain and medulla oblongata) were fixed in 10% neutral buffered formalin, processed routinely and embedded in paraffin for microscopic examination. Two µm-thick sections were cut with a HM 400R Manual Sliding Microtome (Microm, Heidelberg, Germany). The microscopic evaluation was performed on hematoxylin–eosin stained tissue sections. For a better characterization of the brain lesions, a picrosirius red staining [] for the detection of fibrous connective tissue and a Prussian blue staining [] to identify hemosiderin pigment were used.
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pmc-6317215-1
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She was a 74-year-old woman (Table ), whose family history revealed that her mother complained of dementia and visual hallucinations with onset at 83 years and died at the age of 84 years. The disease duration was 8 months. The proband’s sister suffered of a dementing illness whose phenotype is described as Case 2 in this paper. A 46-year-old son of the proband was affected by mental retardation and movement abnormalities probably caused by a congenital malformation mainly involving cerebellum (Fig. a).
The proband’s disease began two months before her admission to hospital with visual hallucinations, delusions, overvalued ideas and confabulation, rapidly evolving towards confusion, psychomotor slowness, abnormal behavior, loss of autonomy in daily life activities and incontinence. Serial CT brain scans during this period showed only a mild atrophy in frontal lobes.
During the last week before hospitalization, the clinical picture was characterized by fast psychomotor deterioration. The patient became unable to walk and showed clear speech difficulties, tonic grasping, asymmetric hypertonia involving mainly left arms, reduced alertness.
Electroencephalogram (EEG) showed a slow background activity (delta rhythm) and the presence of recurrent theta sharp waves especially in the anterior brain regions. No periodic wave complexes were observed in two different EEG recordings performed 3 months after the onset of the disease, during the hospitalization. Brain DWI MR images (Fig. , panels a,d) showed high signal in caudate heads and diffuse hyperintensity in the cortex with predominance of frontal and parietal lobes; cortical atrophy of frontal lobes; mild leukoaraiosis.
CSF analysis showed the presence of 14–3-3 protein. Total tau and phosphorylated tau levels in CSF were 3433 pg/ml (n.v. < 500 pg/ml) and 44 pg/ml (n.v. < 61 pg/ml), respectively.
She died five months after the onset of the disease and underwent autopsy. Her neuropathological picture is detailed below (see Neuropathology paragraph).
The CSF study was completed after death by amplification PrPSc assay with RT-QuIC. The test was positive, confirming the presence of pathological prion protein in CSF sample of the patient (Fig. a).
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pmc-6317215-2
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This patient was a 71-year-old man with a 2-month history of short-term memory deficits and fluctuating confusion (Table ). The family history was unremarkable except for two cases of late-onset depression (> 60 years) in two sisters of his father. The patient underwent neurologic evaluation that resulted to be normal: a presumptive diagnosis of reactive depression was made and a treatment with sertraline was suggested. Since the lack of response and the worsening of cognitive symptoms, the patient was subjected to a brain MRI study that showed marked signal abnormalities in frontal and parietal right cortex and in right cingulum in DWI sequences (Fig. , panels c,f). A further neurologic examination disclosed a mild temporal disorientation with bilateral cerebellar dysmetria with dysdiadochokinesia and gait unbalance. Moreover, rare myoclonic jerks were evident.
The EEG pattern was possibly suggestive of a prion disease since the inconstant occurrence of bilateral periodic sharp wave complexes. CSF analysis showed the presence of 14–3-3 protein. Total tau in CSF was 9250 pg/ml (n.v. < 500 pg/ml) and phosphorylated tau 42 pg/ml (n.v. < 61 pg/ml). RT-QuIC analysis of CSF sample was positive.
Overall these tests were performed 2,5 months after disease onset.
A diagnosis of probable CJD was made.
The clinical picture rapidly deteriorated and the patient became tetraparetic, and unable to speak and swallow in two weeks. Therefore, he was transferred to his community hospital in the North-East of Piemonte where he died 2 months from the first hospital admission due to a multi-organ failure. Autopsy was performed to confirm CJD diagnosis.
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pmc-6317215-3
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This patient was a 69-year-old man with no family history of dementia or neurodegenerative diseases (Fig. ), who was admitted to his community hospital because of progressive gait unbalance, writing difficulties and behavior changes started in the previous two months (Table ). On neurologic examination, cerebellar ataxia with dysmetria and dysdiadochokinesia were evident as well as spatiotemporal disorientation. MMSE score was 12/30.
On brain MRI, there was an hyperintensity in DWI sequences at level of bilateral frontoparietal and left insular cortices and, mildly, at level of the right posterior thalamic region with no Gadolinium enhancement. All the EEG recordings were not typical for a prion disease, being characterized by a bilateral theta-delta activity in frontotemporal regions without evidence of PSWs. CSF analysis showed a weak 14–3-3 positivity with total tau levels of 1780 pg/ml and phosphorylated tau of 73.4 pg/ml, respectively. MRI, EEG, and CSF analysis were performed 2 months after the onset of the symptoms.
A diagnosis of probable CJD was made.
Clinical picture rapidly evolved towards a persistent vegetative status with diffuse spontaneous myoclonus. The patient died two months after the hospital admission because of a multi-organ failure and underwent autopsy to confirm CJD diagnosis.
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pmc-6317256-1
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A 32 year old woman, gravida three para one with a history of cervical incompetence, polycystic ovarian syndrome, antiphospholipid antibody syndrome (APLS), and tubal factor infertility, conceived with frozen embryo transfer of a single blastocyst resulting from standard insemination technique; intracellular sperm injection was not performed. They did not opt for preimplantation genetic screening. The embryo was originally frozen in 2013, 2 years before the first identification of a Zika case in Haiti. Embryo transfer occurred in April of 2016. Her husband was actively traveling back and forth to Haiti for work before and during the pregnancy.
Her history of two mid-trimester losses was managed with an abdominal cerclage placed pre-pregnancy. She was treated with prophylactic low molecular weight heparin for APLS and insulin for her type two diabetes mellitus. She received betamethasone in the early third trimester for an episode of threated preterm labor. At delivery she was euglycemic.
Endemic Zika was identified in Haiti per the CDC early in the epidemic []. When recommendations were issued regarding the possibility of sexual transmission of Zika virus in August 2016, her maternal fetal medicine provider counseled her to use condoms or refrain from intercourse with her husband, whose business travel continued through the pregnancy []. She herself never left the greater Boston area prior to or during the pregnancy. She had not been to her native Haiti in over 10 years. There has never been any local transmission of Zika virus in the state of Massachusetts. Additionally, interview with the couple after delivery confirmed that neither of them ever experienced any symptoms of Zika infection. In the absence of symptoms in either partner, it was not our practice to recommend Zika serology during the pregnancy to screen for sexual exposure.
The patient underwent extensive fetal surveillance because of her multiple morbidities. She had a level II fetal survey at 18 weeks that revealed normal intracranial anatomy and head circumference (HC), and occipitofrontal diameter (OFD) measuring only 2 days smaller than her best dates. Biometry performed at 29 and 33 weeks was normal, and neither the HC nor the OFD measured less than 5%ile for gestational age. There was never any evidence of intracranial calcifications, ventriculomegaly, or abnormal posturing on antenatal ultrasound. She delivered in the 37th week via scheduled cesarean section. Her baby boy had APGARs of 8 (− 2 for color) and 9 (− 1 for color) at 1 and 5 min. He weighed 2775 g (30%ile by Fenton curve), was 49.5 cm long (65%ile) and had a head circumference of 29.2 cm (0%ile). The placenta was sent for conventional pathologic analysis given the maternal comorbidities. In addition, in light of the small measured neonatal HC and possible Zika virus sexual exposure, samples were sent to the CDC for evaluation. The timing of the IVF cycle relative to the Zika epidemic in Haiti was discussed with the Massachusetts Department of Public Health and CDC at length and the frozen embryo was determined not to be the source of infection.
The baby had a normal hearing screen and was discharged on day of life (DOL) 6. His workup for microcephaly included serum and urine Zika RT-PCR and IgM, both of which were ultimately negative; CMV, head ultrasound and MRI were also negative. Head ultrasound performed in the first week of life was notable for bilateral mineralizing vasculopathy but no intraparenchymal calcifications and otherwise normal anatomy. A subsequent head MRI was normal. The mother was rubella immune and had negative testing for other relevant TORCH infections. Approximately 3 months after delivery, confirmation was received from the CDC that all placental samples were positive for Zika RNA, thus supporting the diagnosis of congenital Zika syndrome. By the time the placental results from the CDC had been received, both parents were too far removed from the time of suspected infection to be able to do serology. HC at a pediatric visit shortly after receipt of the CDC report revealed an interval increase in HC, although it was still less than third percentile for his age. The child continues to meet normal pediatric milestones and receives early intervention services as well as assessment by pediatric neurodevelopment specialists. A genetics evaluation will be pursued if there is any lag in his neurodevelopment.
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pmc-6317397-1
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Case 1: A 50-year-old woman was complaining of postmenopausal uterine bleeding. Her medical history revealed that she was diagnosed with breast carcinoma 2 years ago. At that time she enderwent a radical mastectomy associated with axillary lymph node dissection pathological examination of the tumor revealed invasive lobular breast carcinoma (); stage IIb (T2 N1 M0). Immunohistochemical staining showed strongly positive for estrogen receptors (ER) and progesterone receptors (PR), negative for cerbB2. After surgery, she received adjuvant chemotherapy and left breast radiation. Since the tumor showed strongly positive estrogen receptors expression,we decided to put her under endocrine therapy treatment for 5 years. However, during the 23th month of tamoxifen, she presented with postmenopausal uterine bleeding. Gynecologic examination was normal, pelvic ultrasound revealed that the endometrial thickeness was 13mm (). Endometrial biopsy confirmed metastasis to the endometrium, from lobular breast carcinoma. Magnetic resonance imaging (MRI) revealed tumor infiltration of the myometrium less than 50% (stage IA as classified by FIGO 2009) (). She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically.
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pmc-6317397-2
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Case 2: A 67-year-old woman was complaining of postmenopausal uterine bleeding. She has a medical history of hypertension and she is undergoing an hematologic exploration of bicytopenia. She was also diagnosed with bilateral breast carcinoma 3 years ago. She underwent a routine scintigraphy which revealed a single bony metastases on the spine treated with radiotherapy. At that time she underwent a left radical mastectomy and a right concervative breast cancer treatement (tumerectomy) associated with bilateral axillary lymph node dissection.Pathology was consistent with a multifocal infiltrating ductal carcinoma with 15 metastatic lymphnodes out of 16 at the left breast and an infiltrating ductal carcinoma measuring 1.5cm with no positif lymphnodes out of 15 at the left breast, ER/PR + and Her-2 Neu+. After surgery, she received adjuvant chemotherapy and bilateral breast radiation. Since the tumor showed strongly positive hormone receptors expression,we decided to put her under endocrine therapy treatment for 5 years. However, after 3 years, she presented with postmenopausal uterine bleeding. Gynecologic examination was normal, pelvic ultrasound revealed that the endometrial thickeness was 21mm. Endometrial biopsy confirmed metastasis to the endometrium, from lobular breast carcinoma. Magnetic resonance imaging (MRI) revealed stage Ib cancer as classified by FIGO 2009. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically.
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pmc-6317617-1
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A fourteen-year-old otherwise healthy boy with no family history of disease presented
with severe chest pain while he had been jogging for 5 minutes. The pain lasted for
2 hours and was followed by generalized weakness, dyspnea and confusional state. He
was initially treated on a secondary care local clinic in which a baseline
electrocardiogram reported ST segment depression in all precordial leads and serum
Troponin I taken within 24 hours of symptom onset reached > 30 ng/mL (reference
level of fluorescence immunoassay 0-0.4 ng/mL). The patient developed pulmonary
edema and spent 7 days in the intensive care unit. After stabilization, he was
referred to our tertiary care hospital. On hospital admission, he was
hemodynamically stable, cardiac and pulmonary examination were normal. Plain chest
x-ray was normal and the electrocardiogram showed sinus rhythm with ST segment
depression and repolarization abnormalities in precordial leads V1 to V3. Complete
blood count reported leukocytosis with neutrophilia; lipid profile and the
toxicologic screening, including cocaine, came back normal. A transthoracic
echocardiogram was performed which revealed a hypokinetic anteroseptal wall with
normal systolic and diastolic function; no report of coronary anomalies was
documented in the first place. Polymerase chain reaction tests for various viruses
(Coxsackie type A and B, Parvovirus, Ebstein Barr, Cytomegalovirus, Poliovirus,
Echovirus and Herpes Simplex 1,2,6,7 and 8) on peripheral blood samples were
negative. He was pharmacologically managed with aspirin, atenolol and ivabradine. A
rest perfusion magnetic resonance imaging detected an anterior, anteroseptal and
lateral nontransmural myocardial infarction with systolic left ventricular
dysfunction (ejection fraction of 45%) alongside an anomalous origin of the left
coronary artery arising at the right sinus of Valsalva with an interarterial
stenotic tract. A CT angiography demonstrated a left coronary artery arising at the
right sinus of Valsalva from a separate ostium with an acute take-off angle and
proximal oval-like narrowing with an extension of 11 mm running throughout the
interarterial segment ( and ). Coronary translocation was discarded because
the proximal interarterial segment was very stenotic and hypoplastic. Translocation
was technically difficult and would not have restored normal coronary flow. Instead,
through median sternotomy, cardiovascular surgeons performed revascularization of
the anterior descending coronary artery with an internal mammary artery graft. Seven
days after surgery he was discharged. The patient underwent treadmill stress testing
according to the Bruce protocol and accomplished 9 sessions achieving a work level
of 10.2 METS with adequate tolerance. He has been followed up in the cardiology
outpatient clinic. Up to 18 months after surgery he is reported asymptomatic with
normal electrocardiograms and echocardiographic evidence of normal systo-diastolic
function. The cardiology team decided to restrict any strenuous physical
activity.
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pmc-6318081-1
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The patient was a 65-year-old Caucasian woman with a history of 25-pack-year cigarette use. She was diagnosed with double primary NSCLC, a centrally necrotizing tumor with invasion of the mediastinum in the left upper lobe (stage T4NxM0) and a peripheral tumor located dorsally in the right upper lobe (stage T1N0M0) (Figure ). Initial treatment consisted of four cycles of carboplatin and pemetrexed, followed by sequential radiotherapy to the left upper lobe (60 Gy in 20 fractions) and stereotactic body radiotherapy (SBRT) of the right upper lobe (51 Gy in three fractions, fiducial tracking).
Initially, she did well but developed a pathology-proven recurrence in the left upper lobe after 2.5 years. This local recurrence was an in-field recurrence and she was reirradiated with SBRT (50 Gy in five fractions, fiducial tracking). During that period, she also developed some first complaints of pain at her left thorax radiating to her left arm, for which she got a cervical epidural with corticosteroids followed by fentanyl, 12 mcg, with rescue medication consisting of paracetamol and diclofenac. This pain persisted over the years with some flares over time. The presence of a metastatic tumor as the cause of the complaints had been excluded by thoracic computed tomography (CT) scans and positron emission tomography (PET) imaging. Additionally, there were also some persistent complaints of pain on the right side of the thorax, which were most likely caused by a radiation-induced fracture of the ribs (Figure ).
At this moment, 6.5 years after her initial radiotherapy and without any additional therapy after reirradiation, the patient is still alive without the presence of disease. Unfortunately, she keeps having lingering complaints related to her left thorax. These complaints started five years after the first treatments when she was hospitalized with severe pain and restricted movements of her left arm. This was caused by a parasternal abscess due to osteonecrosis of the sternoclavicular joint, and she was treated with surgical drainage and antibiotics. During the following months, it was difficult to control the pain. Four months later, she was hospitalized again because of the persistent inflammation of the skin, located laterally of the sternum at the left thorax with infiltration to underlying structures. Treatment consisted of antibiotics and cleaning of the wound three times a day. The existence of an abscess was excluded with a CT scan, but echography of the thorax showed the presence of a tract. A biopsy showed a combination of an active and chronic inflammation.
Due to the persistent complaints, a plastic surgeon was consulted to discuss possible surgical interventions for the persistent ulcus based on osteonecrosis (Figure ). The affected area was resected, followed by reconstruction with a mini deep inferior epigastric artery perforator (DIEP) flap.
To determine whether the radiotherapy contributed to the osteonecrosis of the sternoclavicular joint (Figure ), an analysis of the radiation schedules was performed. In order to analyze the total dose delivered to the affected structures, we accumulated the doses of the three radiotherapy treatments. Since the fractionation schemes were different between treatments, doses were converted to an equivalent dose of 2 Gy (EQD2) before accumulation. An α/β-ratio of 3 Gy was used for all structures because our main point of concern was the late effects in the organs at risk. Dose accumulation was performed by registering the CT scans and subsequently warping the dose according to the calculated spatial transformation. For this, the scans were initially aligned using a rigid registration followed by a deformable registration. The accumulated dose showed a maximum dose between 100 - 140 Gy EQD2 in the sternoclavicular joint (Figure ). Since the rib fracture was diagnosed before reirradiation, the planning CT scan could be used for dose analysis. The maximum point dose (Dmax) in the fifth right rib was 306 Gy EQD2, based on the dose volume histogram (Figure ).
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pmc-6318082-1
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A 44-year-old African American lady with a past medical history of schizophrenia and hypertension presented to the emergency department with a rapidly progressing severe throbbing frontal headache of 10 over 10 intensity. The headache started a few hours before presentation and was associated with generalized weakness, blurry vision, and dizziness. She denied nausea, vomiting, head trauma, any focal neurologic deficit (including loss of sensation or motor power, gait disturbance, dysarthria, and dysphagia), loss of consciousness, chest pain, back pain, shortness of breath, palpitations, or any personal or family history of intracranial bleeding. She is a 30 pack/year smoker with no other history of substance use. Her blood pressure was 107/51 mmHg, her heart rate was 60 beats/min, her respiratory rate was 16 breaths/min, her temperature was 36.6°C, and her oxygen saturation was 95% on room air. On neurologic examination, her cranial nerves examination was insignificant, and there were no other focal neurologic deficits. Signs of meningeal irritation were absent, and papilledema was not seen on fundoscopy. The remainder of the examination was unremarkable. Her laboratory workup showed normal hemoglobin, platelets, white blood cells, renal function, hypokalemia of 2.7 mmol/L (normal: 3.5-5.0 mmol/L), and hypoalbuminemia of 2.9 g/dL (normal: 3.4-5 g/dL) (Table ).
A brain computed tomography (CT) scan was negative for intracranial bleeding. She was then admitted to the regular nursing floor with opioids as needed for her headache. The following day, her blood pressure became uncontrolled with values up to 200/95 mmHg, and she reported a worsening frontal headache. A magnetic resonance imaging (MRI) of the brain and its vessels was done that showed possible punctate lacunar infarcts without evidence of a vascular aneurysm, venous thrombosis, or a space-occupying lesion (Figure ).
The patient was treated as per the standard ischemic stroke protocol: aspirin and statin were initiated as well as nicardipine infusion as needed. The next day, she developed transient chest pain and sudden onset of left leg numbness. On physical examination, a new parasternal early diastolic murmur was found with no significant change in the neurologic examination. A repeat MRI of the brain showed scattered foci of restricted diffusion within the right frontal, parietal, and superior right occipital lobes compatible with an acute or early subacute infarction (Figure ).
As a part of the routine stroke/transient ischemic attack workup, transthoracic echocardiography was done, which showed the diameter of the aortic root to be 4.0 cm (normal: less than 2.1 cm) and moderate-to-severe aortic regurgitation. A CT angiography of the chest showed an ascending thoracic aortic dissection with extension into the origin of the left common carotid, right innominate, and right common carotid arteries with significant (90%) luminal narrowing of the proximal right common carotid artery (Figure ).
Vascular surgery was emergently consulted, and the patient had a successful surgical repair with no significant complications.
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