A 53-year-old African-American female with a past medical history of morbid obesity, hypertension, bipolar disorder, anxiety, and asthma, presented to the hospital with right lower extremity weakness, numbness, and right foot drop. She had multiple falls in the past few weeks before the initial presentation and was complaining of right leg numbness and urinary incontinence for the past six months. Cervical magnetic resonance imaging (MRI) revealed compressive cervical myelopathy due to disc protrusions. She subsequently underwent a corpectomy of C6 and an anterior cervical discectomy and fusion (ACDF) of C4-C7 and was transferred to a rehabilitation facility. Two months later, she was readmitted after developing complete loss of strength in her right lower extremity (LE) that had progressed to involve her left lower extremity. Physical exam at presentation revealed complete loss of strength and sensations in her right lower extremity, Left lower extremity’s strength exam revealed: hip flexion 0/5, hip abduction and adduction 2/5, quadriceps 4/5, hamstring 3/5, tibialis anterior 4/5, gastrocnemius 4/5. Deep tendon reflexes were diminished in both lower extremities, and no rash was observed at the time.
To diagnose the etiology of her weakness, we performed a series of tests. Laboratory investigations (Table ) showed a mildly elevated creatinine kinase (CK), aldolase, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR). Various autoantibodies tested were not detected. Rheumatoid factor and antinuclear-antibodies titers were also not elevated. She had normal protein electrophoresis. Viral serological tests for hepatitis B and C were negative, and a lumbar puncture (LP) showed normal cerebrospinal fluid (CSF) analysis. A lumbosacral MRI showed no nerve root compression. However, it revealed symmetric areas of edema within the paraspinal and pelvic musculature that was consistent with myositis. Other imaging studies that included computed tomography (CT) of chest, abdomen, and pelvis did not reveal any abnormalities suggestive of a malignancy.
Initial nerve conduction studies (NCS) of LE (Table ) showed profoundly diminished tibial nerve compound muscle action potential (CMAP) amplitude and no peroneal responses distally or proximally with absent sural and superficial peroneal sensory responses. Electromyography (EMG) of LE musculature (Table ) revealed signs of extensive axonal denervation. In light of these findings, a biopsy of the superficial peroneal nerve and long peroneal muscle was done. Pathology findings showed mixed myopathic and neuropathic features, myocyte hypertrophy with a dominance of type I fibers, CD20 B-cell and CD4 T-cell predominant chronic inflammatory infiltrate involving the perimysial connective tissue, and presence of nuclear bag fibers and atrophic angular fibers without fiber type grouping which is consistent with acute denervation (Figure ).
Three months after admission, the weakness had spread to involve both left and right upper extremities (UE). Physical exam of muscle strength in upper extremities revealed: shoulder abduction 4/5, arms extension 4/5, digit extension 5-/5. Her left hand was mildly numb to touch. By then, there was a complete loss of strength in bilateral LEs. The patient was started on a course of corticosteroids but with little to no improvement. A subsequent biopsy from the deltoid muscle done eight months after admission showed CD20 B-cell and CD4 T-cell predominant inflammatory infiltrate involving the perimysial connective tissue, scattered regenerating and degenerating fibers, increased perimysial and endomysial fibrosis, type I fiber predominance, and myophagocytosis. No rimmed vacuoles were seen with the Gomori trichrome stain. These pathological findings were consistent with a predominantly myopathic process. EMG of right UE muscles (Table ) showed signs of irritable advanced myopathy with proximal predominance. She was later started on azathioprine but had no improvement.
Seven months after admission, the patient developed a weak cough, dysphagia, and her phonation was decreased. Weakness eventually spread to involve her respiratory muscles, which caused her to become ventilator-dependent. She received two courses of intravenous immunoglobulin (IVIG) and was finally maintained on methotrexate. This medication regimen failed to alter the course of her progressive weakness. The patient ultimately had a cardiopulmonary arrest and passed away.


A 78-year-old man presented with a six-month history of progressive hoarseness denying dysphagia, odynophagia, hemoptysis, otalgia, or dyspnea. He was initially treated for a marginal zone lymphoma of the right orbit 2 years prior. Given his concern for vision loss, a low-dose radiation strategy of 4 Gy over 2 fractions was used, and he had a complete clinical response. He had been doing well until his new onset of hoarseness.
A CT with contrast was obtained showing a tumor involving the left larynx at the level of the anterior false vocal fold extending into the laryngeal ventricle, true cords, and with a mild subglottic component ().
Further evaluation was conducted with in-office flexible nasolaryngoscopy that confirmed a submucosal mass visible on the left false vocal cord. He then underwent microdirect laryngoscopy and biopsy of the mass ().
Analysis revealed small monocytoid B-cells positive for CD20 with aberrant CD43 expression and negative for CD3, CD5, CD10, and BCL-6, confirming a diagnosis of extranodal marginal zone B-cell lymphoma of MALT type.
A staging FDG-PET scan did not show any sign of FDG avid malignancy, including at the primary site. Following multidisciplinary tumor board review, since he responded well to low-dose radiation to his orbit, he was again recommended to undergo low-dose radiation 4 Gy/2fx to his larynx. After completion of radiation treatment, he reported a resolution of his hoarseness and normalization of his voice. At four-month follow-up, repeat in-office flexible nasolaryngoscopy revealed a normal exam with fully mobile vocal folds bilaterally and no evidence of recurrence or persistence. He also had a PET-CT scan which confirmed he had no evidence of disease. Unfortunately, at 7 months following treatment, the patient died unexpectedly of unknown causes.


A 60-year-old woman presented with one year of worsening throat discomfort, intermittent cough, and dyspnea with exertion. She denied any hemoptysis, otalgia, or odynophagia. She had no other significant past medical or social history including no history of tobacco use.
A CT neck with contrast demonstrated a mass involving the anterolateral right subglottic larynx with extension along the upper cervical trachea ().
In-office flexible nasolaryngoscopy identified a fleshy pink-colored mass in the immediate right subglottis obstructing approximately 50% of the airway. She then underwent microdirect laryngoscopy and bronchoscopy for debulking and biopsy ().
Operative findings were notable for extension of the mass approximately 1 cm below the true vocal fold.
Pathologic analysis noted small B-cells positive for CD19, CD20, and PAX5 and negative for CD5, CD10, and cyclin D21. FISH was negative for the 18q21 MALT1 gene. The combination of these findings confirmed the diagnosis of extranodal marginal zone B-cell lymphoma of MALT type was made.
A staging CT neck/chest/abdomen/pelvis scan was negative for metastatic disease. Following multidisciplinary tumor board review, she was recommended low-dose radiation at 24–30 Gy in 2 Gy daily fractions for approximately 3 weeks contingent upon review of a bone marrow biopsy. Bone marrow biopsy was negative, and radiation treatment was finalized as 30 Gy in 15 fractions over the course of 1 month. Treatment was completed by May 2018. Following radiation treatment, she reported mild dysphagia and dysgeusia which has improved. Her breathing has improved, and she has returned to her normal exercise tolerance. At 21-month follow-up, there was no evidence of disease on exam or imaging; however, she continues to report a mild cough intermittently with no issues with eating, drinking, or breathing.


A 62-year-old female presented to the office complaining of bilateral groin pain that developed 8 months prior to presentation. The patient sought medical consultation at another facility and a radiographic evaluation was conducted revealing negative findings. Symptomatic treatment was prescribed with no improvement. Her past medical history included a homozygote pseudocholinesterase deficiency, a gastric banding 15 years ago, followed by an MGB-OAGB 5 years back. The patient discontinued her prescribed multivitamins 5 years ago. Her body mass index (BMI) at presentation was 25.43 kg/m2.
The pain was described as being sharp, intermittent, and radiating to the anterior thigh with no accompanying paresthesia or muscle weakness. It increased in severity with time and activity, especially upon weight bearing and was rated 7/10 using the Visual Analog Scale (VAS).
Physical examination revealed bilateral groin pain on ambulation and tenderness on palpation. Patient had a normal active and passive hip range of motion bilaterally with normal lower extremity neurovascular examination.
Pelvic X-rays revealed a bilateral medial unicortical transverse fracture in the subtrochanteric area involving <50% of the femoral canal diameter. A mild periosteal reaction was observed, mainly on the left side, with medial sclerosis surrounding the fracture line (). Computed tomography (CT) scan and magnetic resonance imaging (MRI) were done that confirmed the radiological findings of a bilateral subtrochanteric insufficiency fracture involving the medial cortices ().
Following clinical and radiological findings, a serum blood test was ordered to rule out bone metabolism abnormalities. Patient was noted to have a vitamin D level of 6 [30–60 ng/mL] and Parathyroid Hormone (PTH) of 395 [15–65 pg/mL]. Sedimentation rate, C-reactive protein, thyroid stimulating hormone (TSH), Calcium, and Phosphorus levels were within the normal range. A parathyroid scintigraphy ordered to rule out a parathyroid adenoma was negative. Findings were consistent with secondary hyperparathyroidism caused by vitamin D deficiency.
The patient was treated with bilateral prophylactic surgical fixation using short cephalomedullary nails. A full weight bearing postoperative protocol was implemented (). Patient was followed-up at 3 weeks, 6 weeks, and 3 months with complete resolution of symptoms.


Figure depicts the sequence of events over 7 years.
A 37-year-old Qatari female presented to our outpatient bariatric clinic (Hamad General Hospital, largest tertiary care institution in Qatar) with a 4-month complaint of generalized fatigability and progressive bilateral lower limbs swelling with occasional numbness of the distal aspects of the lower limbs but no weakness. Her complaints had worsened over time, and were affecting her quality of life and ability to work. She also had frequent episodes of palpitations, exertional shortness of breath, but no chest pain. There was no nausea or vomiting, but she indicated that there was an increase in her bowel motions which had become more greasy. She denied bloody stools abdominal pain, change in appetite, fever, joint pain, or skin changes. She also complained of occasional headaches but no visual changes. Past medical history was remarkable for T2DM controlled with oral hypoglycemic agents (sitagliptin 50 mg and metformin 1000) and basal insulin, hypertension controlled by antihypertensives (valsartan 160 mg and hydrochlorothiazide 12.5 mg), bronchial asthma with recurrent exacerbations, primary infertility, and severe obesity.
The patient had undertaken laparoscopic sleeve gastrectomy (LSG) on April 2013 (Fig. ) as her weight then was 162 kg (BMI 57 kg/m2). After the LSG, her minimum post-operative weight was 90 kg, the T2DM and hypertension resolved within the first year post-operatively and she was off medications for both conditions. Moreover, her asthma exacerbations became minimal. Weight regain started on the second year post-LSG until she reached 118 kg (BMI 42 kg/m2). Hence, 3 years after her initial LSG, in December 2016, she underwent revisional laparoscopic SADI-S. Eleven months after the SADI-S (November 2017), she presented to our bariatric surgery clinic with the abovementioned complaints, claimed to be adherent to the multivitamin with minerals daily tablets and iron supplements, and denied smoking or alcohol consumption.
Upon examination, she appeared vitally stable, weighed 93.6 kg (BMI 35.6 kg/m2), with normal cardiovascular, chest, and abdominal examinations, and no neurological deficits. She appeared pale and had significant bilateral lower limb edema (Grade 3), and was admitted for inpatient assessment and further management.
Laboratory results upon admission showed microcytic hypochromic anemia, leucopenia, thrombocytopenia, hypoalbuminemia, and high level of vitamin B12 (Fig. ). She was started on IV multivitamins and trace elements, thiamine IV, and high-protein diet, and eventually required total parental nutrition until laboratory results became available. Peripheral blood smear confirmed pancytopenia with cellular atypia (Fig. ). Further investigations revealed low ceruloplasmin, and severe deficiencies of copper, zinc, selenium, vitamin D, and folate but normal cholesterol and lipid profile (Fig. ). Hemoglobin electrophoresis showed normal hemoglobin pattern.
For the severe microcytic hypochromic anemia, she received a transfusion of two units of packed red blood cells (Fig. ) that resulted in a transient rise in hematocrit count and hemoglobin level (Fig. ), followed by a gradual drop of both levels over the following days (Fig. ). The pancytopenia progressively improved following the initiation of an additional 0.5 mg of copper chloride IV daily dose after diagnosis of copper deficiency.
Screening for celiac disease was negative and esophagogastroduodenoscopy was normal. She was hospitalized for 2 weeks. At discharge, her blood picture was improving (Fig. ). She was prescribed multivitamin and minerals daily tablet, copper gluconate 2 mg daily, selenium 200 mcg bid, vitamin D, calcium and iron supplements, cyanocobalamin 1 mg daily, pancreatic enzymes for suspected pancreatic insufficiency, and high-protein supplement. At follow-up, 2 weeks after discharge, her laboratory results showed a normal level of serum copper, resolution of the leukopenia, neutropenia, and thrombocytopenia, and improvement of microcytic hypochromic anemia (Fig. ). She reported significant improvements in her symptoms and better quality of life.


A 21-year-old female patient presented to the neurology clinic with recurrent episodes of left-sided mouth deviation, unilateral ptosis, ipsilateral blurred vision, dysphagia, jaw claudication, and upper lip swelling. This happened four times over the year prior to presentation, with alternation in the sides affected. She reported having her first episode at the age of eight years. Physical examination revealed loss of facial wrinkling on the right side, drooping of the right corner of the mouth, facial edema mainly in the upper lip, and tongue fissuring (Figure ). The patient could not close her right eye on resistance, and could not reveal her teeth properly, demonstrating a lower motor neuron lesion in the right facial nerve. Her hearing was intact in the previous and current episodes. Laboratory tests were unremarkable for blood count, electrolytes, liver, and kidney tests. Serum IgM and IgG for Borrelia burgdorferi were negative, ruling out Lyme disease. Testing for herpes simplex virus, herpes zoster virus, and brucellosis was not done due to a low suspicion given lack of associated clinical signs.
Chest X-ray (Figure ) did not show any lung lesions. Sarcoidosis was not suspected, especially without a rash, cough, lymphadenopathy, fever, or weight loss. Therefore, angiotensin-converting enzyme (ACE) level was not checked.
Brain MRI with and without contrast (Figure ) was unremarkable. Lumbar puncture was contemplated but eventually not done due to lack of meningeal signs, unilateral presentation, and recurrence of these episodes. The diagnosis of MRS was made after excluding the relevant differential diagnoses of recurrent Bell's palsy. There is not a proven treatment for MRS. Our patient did not recall the treatment modalities of her prior episodes. She was started on azathioprine and prednisone. The patient responded completely to within a few weeks and continues to be symptom free.


The patient was a 47-year-old man, who initially presented to a cardiologist with exertional dyspnoea and dry cough for several months. There was no fever, no neck or chest pain, no haemoptysis, no joint pain or skin eruption, and no visual, nasal, or auditory complaints. He did not have abdominal discomfort, chronic diarrhoea, or haematochezia. His childhood growth and past medical history were unremarkable. He was an ex-smoker and worked as an operator of forklift at a warehouse. Initial workups including the electrocardiogram, the echocardiography, a treadmill stress test, and a thallium-201 myocardial scan were normal. He was treated with aspirin and beta-blocker, but the symptoms persisted. Upon the combined examination by a pulmonologist and a rheumatologist six months later, neither stridor nor wheeze was auscultated. Ophthalmologic, auricular, and nasopharyngeal examinations were unremarkable; his hearing test was normal. However, the initial chest radiograph showed evident narrowing of both the extra- and intra-thoracic trachea (Fig. ). The pulmonary spirometry also detected an obstructive ventilatory deficit (Table ), wherein a “flattening curve” was observed in both the inspiratory and expiratory phases (Fig. ), suggesting a fixed central airway obstruction. Computed tomography (CT) of the chest revealed diffuse thickening of the cartilaginous portion of his trachea that spared the posterior membranous portion (Fig. ); there was not enlarged lymph node in the cervical, clavicular, or mediastinal regions. Although an elevated erythrocyte sedimentation rate (ESR: 50, normal range: 0–15, mm/h) was found, other pertinent blood workups (including the haemogram, renal and hepatic parameters, the albumin-to-globulin ratio, and levels of C-reactive protein, creatinine kinase, rheumatoid factor, immunoglobulins, and selected autoantibodies; Table ) reported normal values. A gallium-67 inflammation scan also revealed no definite inflammatory focus. Under fibreoptic bronchoscopy, significant narrowing of the mid-to-lower portion of the trachea was readily observed, but without excessive invagination or outpouching of the posterior wall. The narrowed lumen was neither crescent-shaped nor sabre-sheath-like in the transverse view, and the mucosal surface was smooth without nodularity (Fig. , Video , Supporting Information). A subsequent magnetic resonance imaging (MRI) showed hyperintensity and post-gadolinium enhancement typically involving the periphery of the cartilaginous portions of the trachea (Fig. ). The diagnosis of RP was established following multidisciplinary evaluation and discussion, and treatment with high-dose oral prednisolone (1 mg/kg/day) plus methotrexate (15 mg/week) was initiated. Just three weeks into treatment, the patient had an episode of severe Pneumocystis jirovecii pneumonia (PJP), which was diagnosed based on the typical radiographic findings of bilateral ground-glass opacity and the detection of P. jirovecii in the deep tracheal aspirate (using an automated quantitative real-time polymerase chain reaction (PCR) platform from Becton Dickinson in the central laboratory). The disease led to acute respiratory distress syndrome (ARDS) within three days. Methotrexate was discontinued immediately, but systemic steroid was maintained (and adjusted) as part of the treatment for PJP. After 13 days of invasive mechanical ventilation, the patient was successfully extubated and recovered well afterwards. No other pathogen (including mycobacteria) was isolated from his lower airway specimens. Over the next five months, corticosteroid therapy was carefully tapered to 2.5–5 mg daily of oral prednisolone, with a prophylaxis against PJP. His exertional dyspnoea and cough gradually improved, and he was able to return to work. CT of the chest five months later revealed decreased thickness of the tracheal cartilages, which remained stable at 10 months (Fig. ). The follow-up pulmonary function test showed a significant improvement in his obstructive deficit (Table ), and serial ESR levels were within normal ranges (Table ). Two years had passed since the first onset of his symptoms, and the patient still receives active surveillance and has not developed new symptoms.


The patient was a 14-year-old healthy female referred to us after an intrathoracic mass was incidentally discovered in the left hemithorax on a CT scan (Fig. ) obtained in the setting of a roll-over all-terrain vehicle (ATV) accident. She had no history of previous injuries or hospitalizations. She denied any previous history of symptoms that could be related to the mass, including no shortness of breath or chest pain. Her family history was noncontributory, and physical exam was unremarkable. Contrast enhancement on CT demonstrated an approximately 9.7 × 6.3 cm mass. Blood supply appeared to originate from the left internal mammary artery and the inferior phrenic artery. The left inferior phrenic vein appeared enlarged. Lungs, pleura, esophagus, and chest wall were without abnormalities. No lymphadenopathy was noted. Due to the large size of the mass, and diagnostic uncertainty we recommended resection. Differential included sequestration, malignancy and accessory spleen.
She underwent a left sided video assisted thoracoscopy surgery (VATS). A total of four ports were required -5 mm port in the left 5th intercostal space along the anterior axillary line, 12 mm port in the eighth intercostal space in the mid axillary line on the left (subsequently extended into a 5 cm mini-thoracotomy by dividing the intercostal muscles and latissimus dorsi for retrieval of the specimen), 5 mm port in the third intercostal space in the anterior axillary line, and 5 mm port in the fourth intercostal space in the posterior axillary line. The mass was extra-pleural and in the medial inferior portion of the left thoracic cavity. A LigaSure™ device was used to release the pleural attachments and adhesions along the borders of the mass. Small arterial and venous tributaries were encountered on the anteromedial surface heading towards the internal mammary vessels along the anterior border of the pericardium, as well as, inferomedial arterial vessels headed towards the diaphragm. All vessels were ligated using 5 mm hemoclips and the LigaSure™. Following this, the specimen was dissected fully from the extra-pleural space, the specimen was placed in a specimen bag, partially morcellated and removed through the 12 mm port incision that was extended into a 5 cm mini-thoracotomy by dividing the intercostal muscles and latissimus dorsi. A portion of the sample was sent for frozen section analyses and pathology returned as “Lymphoid and spindle cell lesion, no overt features of malignancy”.
A 20-French chest tube was placed intraoperatively, all port sites were closed, and she was extubated to room air in stable condition. Her hospital course was uneventful. Briefly, chest tube was discontinued on postoperative day (POD) 1, and she was discharged later that day. She was seen again in clinic 2 weeks following discharge and was doing well. Chest X-ray was unremarkable and we arranged for follow up as needed. She continued to do well without concerns 5 months following discharge.


An 18-year-old girl presented to the emergency department in our hospital with syncopal attack for 30 s. The patient had experienced palpitation, external dyspnea and chest discomfort for a week before admission. She did not have recent history of trauma, immobilization and infectious disease. She did not have any known underlying disease and was not pregnant. She has never smoked, drunken alcohol, or taken oral contraceptive. She was alert but complained mild dizziness. Her neurologic examination showed normal findings. Her vital signs were as follows: blood pressure, 70/50 mmHg; pulse rate, 110 beats/minute; temperature, 36.5oC; respiratory rate, 34/min; and oxygen saturation, 94.3% in ambient conditions. Blood studies revealed the following: white blood cell count, 11,440/μL; hemoglobin, 14.4 g/dL; non-fasting glucose, 104 mg/dL; blood urea nitrogen, 13.1 mg/dL; creatinine, 0.7 mg/dL; aspartate transaminase, 118 IU/L; and alanine transaminase, 88 IU/L. A thyroid function test indicated a state of thyrotoxicosis [T3 236.5 ng/dL (normal range, 80–200), free T4 28 pg/mL (8.9–17.9), thyroid-stimulating hormone, 0.08 mIU/L (0.17–4.05), thyrotropin binding inhibiting immunoglobulins (TBII), less than 0.3 (0 – 1 IU/L)]. Several coagulation factors were abnormal [D-dimer, 6.77 mg/L (0–0.55); protein S activity, 18% (55–123); protein S antigen, 19.2% (50–150); protein C Ag, 76% (72–160); and protein C activity, 81% (70–130)]. Other immunological workup did not reveal any evidence of connective tissue disease or antiphospholipid syndrome. An electrocardiogram showed T wave inversions in the inferior and precordial leads (Fig. ). Chest computed tomography (CT) showed massive PTE in both central pulmonary arteries and diffuse goiter (Fig. a, b). However, there were no DVT in lower extremities, upper extremities and jugular veins. An echocardiogram showed severe pulmonary hypertension (right ventricular systolic pressure (RVSP) = 64 mmHg), and a dilated RV, right atrium and main pulmonary artery (Fig. a-c). Therefore, the patient was diagnosed with massive PTE, thyrotoxicosis, and partial protein S deficiency. To manage the PTE, we administered low molecular weight heparin for 5 days and added warfarin while adjusting the prothrombin time such that the internal normalized ratio was between 2.0 and 3.0. On the 7th day after admission, she was discharged with oral warfarin and methimazole. A follow-up echocardiogram obtained 3 months after anticoagulation therapy demonstrated normal dimensions and systolic function of the RV and disappearance of the D-shaped left ventricle (LV) (Fig. d-f). After thyrotoxicosis was treated with methimazole for a month, a euthyroid state was achieved and the goiter decreased to a normal size (Fig. ). The methimazole was gradually tapered off and stopped at 4 months. At a 6-month follow up visit, PTE and pulmonary hypertension had disappeared (Fig. c, d) but the patient still had a partial protein S deficiency. We decided to stop all medication with careful monitoring. During a 4-year follow-up period after the episode, she was asymptomatic without any evidence of recurrent systemic thromboembolism or hyperthyroidism and had still a partial protein S deficiency.


A 36-year-old multiparous woman, with a history of idiopathic bronchiectasis and gestational diabetes, was admitted to the delivery emergencies unit for active labor at 33 weeks of gestation. On admission, her body temperature was 37.4 °C, and her respiratory and hemodynamic parameters were within the normal ranges. Maternal antibiotic therapy and intramuscular corticosteroids for fetal pulmonary maturation were not administrated due to a rapid labor that lead to the vaginal birth, with meconium-stained amniotic fluid, of a preterm male infant. During the vaginal delivery, the mother developed a persistent cough and dyspnea, so she was suspected of being infected with COVID-19, and droplet and contact precautions were immediately initiated. RT-PCR of a nasopharyngeal swab from the mother was performed just after delivery and was positive for SARS-COV2 (130,000 copies/uL) and her thoracic CT scan showed peripheral ground glass opacities associated with unilateral bronchiectasis. The neonate was born weighing 1830 g with an Apgar score of five at 1 min, seven at 5 min, and nine at 10 min. Skin-to-skin contact with his mother was not performed; he was transferred to the neonatal intensive care unit (NICU) on non-invasive intermittent positive pressure ventilation. He was in a closed incubator throughout his admission, and the mother’s access was not permitted in the NICU as she was symptomatic.
On admission, he was clinically stable on non-invasive intermittent positive pressure ventilation with a mild transient respiratory distress that resolved within 24 h; his fractional concentrations of oxygen in inspired air (FiO2) remained at 21%. Furthermore, he was exclusively formula fed and was given prophylactic intravenous antibiotic therapy (Cefotaxim and Gentallin) that was stopped at 48 h as the blood culture was negative and the C-reactive protein (CRP) was normal. A nasopharyngeal swab RT-PCR was performed at 24 h of life and showed a positive result for SARS-COV2 with a viral load of 918,000 copies/uL. The RNA extraction was done with the QIAsymphony DSP Virus/pathogen Midi Kit (QIAGEN®).
The chest X-ray showed normal lung aeration without pneumonia (a).
The infant remained stable and was switched to nasal continuous positive airway pressure at 2 days of life, and gradually weaned to low nasal flow cannula for 48 h; he was then completely weaned to room air at around 7 days of life.
By 14 days of life, the infant developed a fever with progressive signs of increased breathing difficulties, such tachypnea and chest retractions, but his hemodynamic status remained normal.
A thoracic CT scan revealed bilateral ground glass opacities and consolidations (b). Echocardiography showed a mild pericardial effusion (3 mm). A new nasopharyngeal swab RT- PCR was performed at 14 days of life and was positive for SARS-COV2. The summarizes the results of the laboratory tests. Nosocomial infection was ruled out, a high nasal flow cannula was initiated, and oral azithromycin was administered at a dose of 20 mg/kg/day for 5 days. A nasopharyngeal swab analyzed via RT-PCR was negative at 21 days of life.
The follow-up showed mild respiratory worsening by day 35; a secondary infection was ruled out and the patient was switched to nasal continuous positive airway pressure. He was weaned to room air after 45 days of life and discharged by day 50. Follow-up visits were planned for one week and one month following the discharge.


A 50-year-old lady presented to the emergency department with a history of right shoulder pain for 4 days. Right shoulder X-ray was done and showed a mediastinal mass at the edge of the film (). The patient had other associated symptoms, including fatigue, dyspnea on exertion, dizziness and weight loss of 10 kg over 1 year. She noticed a growing abdominal mass over the past few months but didn't seek any medical advice. She denied any melena, hematuria, hematemesis or heavy menstruation. For this reason, multiple imaging studies were performed including the following: chest radiograph, chest, abdomen and pelvis CT scan with intravenous contrast and lumber spine MRI with contrast.
Hematological evaluation revealed an elevated erythrocyte sedimentation rate with severe anemia. Chest CT scan with intravenous contrast showed a multilobulated heterogeneously enhancing mediastinal mass with multiple hypoenhancing/necrotic areas (). It caused destruction and infiltration of the adjacent D1 vertebral body and directly extended through the right nerve root exit foramen to the spinal canal at the same level. Multilobulated lung parenchymal soft tissue mass with central necrotic areas involving medial, anterior and basal aspects of the right lower lobe (). It abutted, but did not invade, the adjacent pericardium. Lung window showed multiple nodules likely metastatic in nature (). Abdomen and pelvis CT scan with intravenous contrast showed a retroperitoneal mass () with similar characteristics to the aforementioned right lung mass. The mass located with its epicenter at the left upper aspect of the peritoneum. The adjacent bowel loops, vascular structures and pancreas were displaced with no local invasion noted. A fourth mass was found in the uterus with similar characteristics of other primary tumors ().
Cervical spine MRI with intravenous contrast showed the superior mediastinal mass with T1 sequence heterogeneously isointense signal, short tau inversion recovery sequence heterogeneously mildly hyperintense signal relative to muscle signal and T1 post-contrast sequence heterogeneous hyperenhancement with involvement of D1 vertebral body and extension into the spinal canal through the right neural foramen (). Sagittal T2 sequence showed its cranial extension to the level of cricoid cartilage ().
Lumber spine MRI with intravenous contrast showed a uterine mass with irregular margins and central cystic/hemorrhagic areas (). The diffuse bone marrow signal intensity reduction is due to chronic anemia.
Histopathology of ultrasound-guided biopsy of the retroperitoneal mass confirmed the diagnosis of high grade leiomyosarcoma ().


A 74-year-old man with no significant medical history presented with his left clavicular pain. A chest X-ray showed a neoplastic fracture in the left clavicle. Abdominal and chest CT examination revealed the renal mass with early enhancement in right kidney with 35 mm diameter (Fig. ). In addition, CT scan showed osteolytic mass in the left clavicle, left iliac crest, and small nodule in middle lobe of the right lung (Fig. ). It is the basic policy of our institution to recommend radical nephrectomy for clinical stage T1 and T2, and subsequently he underwent laparoscopic radical nephrectomy. The pathological examination showed clear cell RCC (Fuhrman grade 2) with tumor invasion of perirenal fat, leading to the diagnosis of stage pT3aN0M1. With a diagnosis of left clavicle and iliac bone metastasis, the patient received the treatment with zoledronic acid 4 mg intravenously every 4 weeks.
According to the International Metastatic RCC Database Consortium score, the patient was classified as poor risk (<1 year from time of diagnosis to systemic therapy, Karnofsky Performance Status 70, low hemoglobin value) and began to receive nivolumab plus ipilimumab combination therapy for his multiple metastatic sites.
After one cycle of combination therapy, he felt listlessness of the right forearm and difficulty in speaking clearly. The brain magnetic resonance imaging showed a brain metastasis and cyber knife therapy was performed for brain metastasis (Fig. ). In parallel with radiotherapy, the patient received the second course of the combination therapy. Two weeks later, he complained of grade 3 nausea and anorexia. He also experienced grade 3 diarrhea, grade 2 liver dysfunction, and grade 1 rash, leading to discontinuation of third course of combination therapy (Fig. ). We suspected severe irAEs due to various symptoms, but we were unable to exclude the possibility of bacterial enteritis and started the administration of 40 mg (1 mg/kg per day) PSL for the patient. With the negative test result of fecal culture, the dose of PSL was increased to 80 mg and irAEs gradually improved within next 7 weeks. Finally, the dose of PSL was tapered to 7.5 mg. Metastatic sites maintained partial response for 30 weeks after the discontinuation of ICIs without any additional therapy (Fig. ). However, follow-up CT examination showed the new lung metastatic lesion after 41 weeks after discontinuation (Fig. ) and we decided to start readministration of nivolumab monotherapy (Fig. ). As a result, he experienced only grade 1 diarrhea after three cycles of nivolumab, which can be controlled with the temporary increasing dose of PSL. Importantly, any other irAEs such as nausea, anorexia, liver dysfunction, and rash did not appear after the introduction of nivolumab monotherapy.
Follow-up CT scan at 12 weeks after the introduction of nivolumab showed the increase in lung and iliac bone metastasis, leading to withdrawal of nivolumab and subsequent axitinib therapy.


A 24-year-old native Japanese man presented to our hospital after developing high-grade fever. He had travelled to Vietnam and Cambodia for 14 days. After leaving Japan, he visited the beach in Halong Bay, the forest region near the border of China, and Siem Reap in Cambodia. During his stay, he had participated in forest trekking tourism and had stayed in a youth hostel. For dietary intake, he ate home-cooked food and drank beverages with ice, in a similar manner to local people. Fourteen days after he returned to Japan, he developed a mild headache, chills and malaise, and 2 days later, he developed a high fever with chills and rigors. He did not have any abdominal pain or diarrhoea. His past medical history, family history and social history were unremarkable. On examination, his temperature was 39 ℃, his blood pressure was 128/68 mmHg, his pulse was 101 beats per minute, his respiratory rate was 18 breaths per minute and his oxygen saturation was 98 % with room air. He did not present a rash, lymph node swelling, abdominal tenderness, or hepatosplenomegaly. His laboratory examination demonstrated elevated serum C-reactive protein (5.1 mg dl−1; normal range, 0–0.3 mg dl−1). The blood cell counts and the other biochemical tests were normal (WBC 6900 µl−1, AST 20 U l−1, ALT 19 U l−1). The HIV test result was negative, while contrast-enhanced computed tomography (CT) revealed ileocecal lymphadenopathy. We did not detect enterocolitis, arthritis, or abscesses. We also did not detect an aneurysm or abscess via brain magnetic resonance imaging (MRI).
Based on his travel history and clinical findings, we suspected primary bacteraemia from typhoid fever. He was admitted to our hospital for observation and treated with antibiotics. On the day of admission, ceftriaxone (2 g/day) and minocycline (200 mg/day) were administered. On hospital day two, the initial blood cultures yielded Gram-negative bacilli, which were identified as by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The bacterial subspecies could not be identified by biochemical testing at our hospital. Antibiotic susceptibility testing revealed that the organism was not resistant to the following antibiotics: ampicillin, piperacillin, cefotiam, cefotaxime, ceftizoxime, ceftazidime, cefepime, imipenem, meropenem, azythromycin, levofloxacin, ciprofloxacin and fosfomycin. Only minomycin had an MIC90 value of >8 µg ml−1.
After 1 day of ceftriaxone and minocycline, his fever, malaise and headache remitted. We discontinued minocycline, and ceftriaxone was continued for 14 days. The patient was discharged on day 10 and had an uneventful recovery with no recurrence of fever.
Further testing using commercial O and H antisera (Denka Seiken Co. Ltd, Tokyo, Japan) according to the Antigenic Formulae of the (9th ed.) [] identified the organism as serovar Corvallis (at Hokkaido Institute of Public Health, Sapporo, Japan). Thus, serovar Corvallis was likely to have caused the primary bacteraemia in this patient, as described.


A 31-year-old female who was 26 weeks pregnant presented with intermittent cough and expectoration on December 2017. Two months later, she began to suffer right back pain. On April 2018, she developed pain in her right eye with progressive visual loss and subsequent loss of sight after delivery. Fundoscopy, OCT images and ophthalmic ultrasound identified a solid mass in the right eye, exudative retinal detachment caused by mass compression leading to visual loss, and choroidal metastasis was suspected. Further evaluation with contrast-enhanced CT revealed a mass originating in the upper lobe of the left lung with multiple metastatic loci in the left supraclavicular (1L), mediastinum (2R, 3A, 4R/L, 5, 6, 7) and left hilar lymph nodes; and the contralateral lung, liver, left adrenal gland and bones. A lesion about 1.7 x 0.9 cm was seen in the posterior wall of the right eyeball, with moderate enhancement. Lung and mediastinal lymph node biopsy confirmed the patient had lung adenocarcinoma. Immunohistochemistry results were TTF-1(+), c-met (strong+>75%), ALK-neg (−), ALK-pos (+), ALK-tissue (−), HER-2 (2+), ROS-1 (−), Ki-67 (60%), and PD-L1 (+5%). Whole exon sequencing (WES) of the left lung tumor tissue showed (Fig ): TP53(+), NF1(+), tumor mutation burden (TMB) 5.9 mutations/Mb (cutoff 6.3 mutations/Mb), and MSS. We also performed clonal evolution analyses to determine the subclonal composition, and these were generated based on somatic mutations and copy number data. The fraction of cancer cells carrying variations in driver genes, TP53, MUC6 and CACNA1A, are presented in Fig and Table . Mutations of these three driver genes were clonal variants, and were present in high cancer cell fraction (CCF) regions.
Transpupillary thermotherapy (TTT) of the right eye was performed on 25 April 2018. Systemic chemotherapy of pemetrexed plus carboplatin was administered from 14 May 2018 for six cycles (18 weeks) in total. The patient's visual acuity improved after TTT and the first cycle of chemotherapy, OCT and ultrasonography showed remission of exudative retinal detachment, especially in the macular area. The patient achieved a partial response (PR) after two cycles of chemotherapy. Ranibizumab was injected into the vitreous cavity every month, 1 mg on each occasion, three times in total. After four cycles of treatment the patient was still PR. However, the left lung lesions increased after six cycles, whereas the intraocular lesion remained stable. Second-line chemotherapy consisting of pemetrexed plus bevacizumab was administered from 29 September 2018, and the lesions remained stable after two cycles of treatment. After three cycles, the left pulmonary lesion was found to be slightly larger than before, and radiofrequency ablation was performed. During treatment, the ocular symptoms continued to resolve, but after five cycles of treatment, the patient presented with multiple brain metastasis and pleural metastasis. The patient's condition subsequently deteriorated and she died in April 2019. The changes which occurred in the metastatic lesion in the right eye during treatment are shown in Fig .


A 16-year-old male was referred to our Tertiary/Quaternary Care Hospital, King Abdullah Medical City, in 2015 with a history of allergic fungal rhinosinusitis (AFRS) and functional endoscopic sinus surgery (FESS) one year ago. The operative report included left frontal sinus stenting using a biliary T-tube stent. The patient came to the outpatient department complaining of bilateral nasal obstruction and decreased smell sensation along with left ocular symptoms. Ophthalmic symptoms included left eye pain, discomfort, and redness without eye movement restriction.
On examination, recurrent grade 3 nasal polyps were found bilaterally. The CT report showed a migrating frontal stent that pushes against the left lamina papyracea (). The lamina papyracea was intact in all previous follow-up CT scans. In our institution, the patient underwent extended endoscopic sinus surgery with the Draf III procedure performed by the senior author (I.R.H.). Intraoperatively, granulation tissue was forming around the stent, which was removed, and the specimen was sent for histopathological analysis (Figures and ). The latter was initially interpreted as possible granulomatous invasive fungal sinusitis, but then proved to be foreign body granulation tissue in reaction to the stent ().


A 26-year-old G4P3 woman with a history of methylene tetrahydrofolate reductase (MTHFR) mutation and previous delivery of a microcephalic infant with a chromosomal abnormality presented for fetal ultrasound at a gestational age of 23 weeks, 2 days. An ultrasound indicated absent/reversed end diastolic flow, severe intrauterine growth restriction, and a fetal bradycardia. She was admitted to the Labor and Delivery Unit and given betamethasone for fetal lung maturity.
At the time of admission, she denied tobacco, drug, and alcohol use, and her urine drug screen was negative. Her prenatal serological tests were negative for HSV-1, HSV-2, HIV, chlamydia, syphilis, hepatitis B, and Neisseria gonorrhoeae. She was immune to Rubella. Toxoplasma IgG antibodies and CMV IgM and IgG antibodies were positive.
A cesarean delivery was performed shortly after admission due to non-reassuring fetal status. After delivery of the female infant, it was noted that the infant's skin was sloughing and had numerous large vesicles. At 1 minute of life, she was limp and blue with a heart rate of 20 beats per minute. Intubation attempts were made at 2 and 6 minutes of life, with successful intubation performed at 6.5 minutes of life. She was given surfactant at 8–10 minutes of life. Her heart rate remained <60 beats per minute, and she remained cyanotic despite administration of 100% FiO2. At 12.5 minutes of life, the family requested life-saving measures be discontinued. The infant's time of death was just under two hours after delivery. As per the family's request, an autopsy was performed, and the placenta was evaluated for any abnormalities.
External examination revealed a well-developed, preterm female neonate with extensive skin sloughing and erythematous annular skin lesions with large portions of the body denuded (Figures and ). There were no other significant external findings except those consistent with preterm birth.
Internal examination revealed approximately 2.0 mL of straw-colored fluid in the right thoracic cavity and 0.5 mL of similar fluid in the left thoracic cavity. The heart, spleen, lymph nodes, respiratory system, pancreas, genitourinary system, gastrointestinal system, and endocrine system were unremarkable. The liver capsule was smooth and glistening but had innumerable tan-yellow, round lesions up to 0.2 cm in diameter on the capsular surface; similar lesions were disseminated in the parenchyma (). The brain was friable and lacked gyral/sulcal development but was otherwise unremarkable.
Microscopic evaluation revealed dramatic histological changes affecting the liver, heart, and skin. The liver lesions revealed numerous areas of necrosis with large, multinucleate cells with margination and molding of their nuclei and Cowdry bodies that were immunopositive for HSV (using an HSV1/HSV2 antibody cocktail) (). The skin and myocardium had similar cytopathologic changes and necrosis (Figures and ). The thymus, spleen, stomach, adrenal glands, and lungs also contained foci with weak cytoplasmic immunopositivity for HSV but with minimal cytopathologic changes. There was necrosis of the muscularis propria of the large bowel.
Microscopic examination of the brain did not reveal evidence of HSV infection. The cerebral sections lacked myelin (as seen with Luxol fast blue stains) consistent with an estimated gestational age of less than 22 weeks. The placental sections revealed immature placental architecture, subchorionic laminar decidual necrosis, and chronic villitis.
The infant's mother had no history of HSV infection and was asymptomatic at the time of delivery. A sample of the mother's blood from the time of delivery was negative by a PCR technique for HSV-1 and HSV-2.


A 39-year-old African American female with a medical history of chronic focal epilepsy presented to Stony Brook University Hospital emergency department with three days of fevers (>38°C) and mildly pruritic erythematous maculopapular rash. The rash began two weeks prior in the left arm and gradually spread bilaterally to the trunk, face, oropharynx, periocular space, and legs (). As there was initial suspicion for a drug-related rash, the patient's medication history was reviewed. She had been recently started on an antibiotic course of amoxicillin by her primary doctor for unilateral neck lymphadenopathy and exudative pharyngitis. Additionally, she had been on a long-term carbamazepine therapy for epilepsy. One year ago, the patient's antiepileptic medication regimen was changed as she wanted to become pregnant. She had been slowly tapering off carbamazepine and was started on lamotrigine. At the time of presentation, she was taking both carbamazepine and lamotrigine.
The patient's initial laboratory studies showed an elevated neutrophil count (10.47 K/ul), mild eosinophilia (6–8%), and transaminitis (AST : 48 IU/L; ALT : 42 IU/L). Initial evaluation by the dermatology service suggested a differential diagnosis of AGEP secondary to amoxicillin versus DIHS secondary to lamotrigine or carbamazepine use. A computed tomography (CT) scan revealed no clear etiology of infection, blood cultures were negative, skin cultures from pustules only grew normal skin flora, and skin biopsy revealed nonspecific findings most consistent with AGEP (). CT abdominal scan showed multiple wedge-shaped lesions within the spleen suspicious for focal areas of infarction and ischemia. This discovery in conjunction with the rest of the patient's presentation yielded a diagnosis of DRESS []. Over the next four months, this patient would have multiple hospitalizations with several admissions to the medical intensive care unit (MICU). The patient had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome (ARDS) requiring intubation, diabetic ketoacidosis (DKA), nonalcoholic steatohepatitis, liver failure requiring transfer to a liver transplant center (transplant was ultimately not needed), and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants (e.g., cyclosporine). Of interest to this case report, the patient developed persistently uncontrolled hyperglycemia complicated by DKA in the setting of sepsis.
Approximately, a month following onset of the rash, the patient's serum glucose was found to be over 500 mg/dL with a hemoglobin A1C of 7.1% without a prior history of diabetes mellitus (DM). The patient was started on insulin therapy for probable steroid-induced diabetes mellitus (SIDM), as she was requiring a high-dose steroid regimen for DRESS. The patient's SIDM was complicated by DKA during a sepsis episode precipitated by a bacterial pneumonia. She remained in the MICU for several weeks where she was managed with respiratory support, antibiotics, insulin, and steroids. She was eventually discharged from the hospital following improvement of her respiratory status, sepsis, liver failure, DRESS rash, and serum glucose levels. The steroids were tapered off during outpatient follow-up, and her SIDM briefly improved. However, despite continuing a steroid taper, she had significant fluctuating fasting glucose levels and her insulin regimen was titrated. The patient continued to have persistently elevated serum glucose levels (>300 mg/dL) requiring insulin therapy despite cessation of steroids. She required multiple daily insulin injections and wore a continuous glucose monitoring device (CGM). Glutamic acid decarboxylase (GAD) antibodies and islet cell cytoplasmic autoantibodies (ICAs) were tested for correlation with autoimmune subtype of type 1 DM; however, they were found to be negative. The patient's new onset uncontrolled type 1 DM was originally diagnosed as SIDM, which normally improves following reduction or cessation of steroids. However, given her worsening glycemic control in the context of tapering and short-term cessation of steroids, the patient was diagnosed as having a rare but previously documented type of fulminant type 1 DM as a sequela of DRESS [].


A 48-year-old male with a history of a left kidney mass consistent with renal cancer underwent a left radical nephrectomy with a pathology remarkable for grade IV chromophobe RCC with extensive sarcomatoid and rhabdoid features. Two out of eight lymph nodes were involved with the disease. His cancer was pathologically staged as T3N1 disease. Staging CT scans of the chest, abdomen, and pelvis (CAP) ruled out metastasis. Three months after his surgery, his CT CAP showed extensive retroperitoneal (RTPN) lymphadenopathy; he also had a right middle lobe (RML) lung nodule measuring almost 1 cm, all of which were radiologically consistent with metastatic disease (Figure ).
The patient was started on a modified three-weekly regimen of sunitinib, where he received a daily dose of 25 mg (two weeks on and one week off), with a plan to escalate the dose gradually by 12.5 mg in subsequent cycles until it reached 50 mg daily. A repeat CT CAP was done after four cycles of three-weekly sunitinib course and showed an interval regression in his metastatic RTPN lymphadenopathy and RML lung nodule. However, it showed a small left pneumothorax with the greatest diameter measured at 1 cm. Multiple bilateral cavitary lesions were noted as well (Figure ).
He was asymptomatic on review, and pneumothorax was treated conservatively with follow-up chest X-rays indicating its stability. Therefore, sunitinib was continued as per treatment plan. While approaching the end of the cycle eight, the patient developed sudden-onset shortness of breath that prompted an urgent chest X-ray followed by a repeat CT CAP, which showed persistence of the small left-sided pneumothorax and the appearance of a new right pneumothorax. Further regression in the RTPN lymphadenopathy and lung nodules was noted (cystic and cavitary lesions increased in number). Thoracic surgery service was consulted, and a right chest tube was inserted, which led to an immediate improvement in his symptoms. The left pneumothorax was treated conservatively (Figure ).
The patient had no history of chronic lung diseases or trauma; he had never smoked and was not taking any other medications. We elected to stop his sunitinib and switch him to second-line nivolumab immunotherapy a few weeks after this event. Regular follow-up in the clinic and chest X-rays did not show any further pneumothoraces.


An 11-year-old boy admitted with vomiting, generalized edema, and hyperglycemia, which was preceded by 5 days of coryzal symptoms, lethargy, and oral aft without fever. He was admitted to another hospital with hypotensive syncope and severe vomiting (20 times/day), and intravenous hydration was initiated. His blood glucose was 13.8 mmol/L and urine glucose was +++ at admission. Initially, he was diagnosed with stress hyperglycemia and acute gastroenteritis. After one day, he was referred to our hospital because of his persisting symptoms and hyperglycemia. There was no specific indicative feature in his personal or family history. His weight was 30 kg (−1.02 SDS), height was 147 cm (+0.75 SDS), heart rate was 118/minute, and blood pressure was 90/40 mm/Hg, and generalized nonitching systemic edema was present on his physical examination.
The laboratory tests showed that severe hemoconcentration was present. His biochemical findings were as follows: white blood cell count: 1.8 × 109 L; hemoglobin: 184 g/L; hematocrit: 51.3%; sodium: 130 mmol/L; potassium: 4.8 mmol/L; chloride: 105 mmol/L; urea: 20 mmol/L; creatinine: 45 µmol/L; and blood glucose: 11.1 mmol/L. On arterial blood gas analysis, pH was 7.33 and HCO3 was 13.6 mmol/L (). On sepsis work-up, CRP was 3 mg/L, and urine, stool, and blood culture were negative. Respiratory virus panel PCR was positive for respiratory syncytial virus (RSV) and enterovirus.
Aggressive fluid replacement was initiated at admission due to hypotension. Although urine output was normal during the first two days of hospitalization, his diuresis was inadequate on the third day (0.3 cc/kg/hr), and so 3000 cc/m2 5% dextrose and 0.45% NaCl were administered as maintenance fluid therapy. The patient's serum albumin levels, as well as his globulin levels, were highly reduced because of capillary leak (). There was severe hypogammaglobulinemia at admission. Additional laboratory examinations were performed in order to make the differential diagnoses of generalized edema, hyperglycemia, hyponatremia, prerenal acute renal failure, hypoalbuminemia, and hemoconcentration. The urine analysis showed that the urine density was 1033, and the 24-hour urine protein test, blood lipids, and renal tubular tests were within normal limits excluding renal diseases. To eliminate congestive heart failure, chest radiography, electrocardiography, cardiac enzymes test, and echocardiography were performed and were all proven to be within normal limits. The patient's feces alpha-1 antitrypsin level was negative, and protein-losing enteropathies were excluded. Complement studies and lymphocyte subset analysis by flow cytometry were within normal ranges when compared to his age references.
After initial stabilization with intravenous fluid boluses and insulin infusion the first two days, the patient's generalized edema increased, albumin values dropped to 1.9 g/dL, he had diarrhea, and he gained 3 kg of weight. Subcutaneous insulin treatment started with a dose of 0.3 IU/kg/day at the end of the second day. Intravenous human albumin treatment was given on the 2nd, 4th, and 7th day of admission. On the fourth day, the patient was given the ISCLS diagnosis by ruling out other causes. Following the diagnosis, intravenous immunoglobulin (IVIG) treatment was given on two consecutive days (). His edema decreased on the fifth day, and he was deemed clinically well on the 7th day, weighing 29 kg. As for the systemic effects of ISCLS, there was seldom amount of free fluid in the abdomen, the diameter of the appendix was increased, and minimal pleural effusion was found bilaterally. There was no compartment syndrome, rhabdomyolysis, or pulmonary edema during the recovery period.
For the differential diagnosis of DM, his fasting serum glucose was 13.8 mmol/L, simultaneous C-peptide was 0.44 nmol/L, HbA1c was 64 mmol/mol, and urine ketone was positive. Antiglutamic acid decarboxylase, anti-insulin antibody, and islet cell antibody were negative. The patient harbors type 1 DM predisposing HLA II haplotypes as follows: DRB1∗0301, DRB1∗0302, and DRB1∗0201. Although there was no family history for DM, since his autoantibodies were negative, next-generation gene sequencing for 14 MODY genes including GCK, HNF1A, HNF4A, HNF1B, PDX1, CEL, KLF11, NEUROD1, PAX4, INS, and BLK was analyzed, and they were all negative. Whole exome sequencing of the patient for candidate genes is ongoing. At the 6th and 12th month marks, as well as at the last outpatient visit, his insulin dose was still 0.4 IU/kg/day and HbA1c was 40 mmol/mol.


A 61-year-old female was diagnosed in December 2018 with Philadelphia chromosome-positive acute lymphoblastic leukaemia. Her past medical history was significant for hypertension and type 2 diabetes mellitus for more than 10 years. At the moment of diagnosis, the total white blood cell count was 31 × 109/L (WBC) with peripheral blood smear showing 47% blasts, haemoglobin 7.4 g/dL, and 100 × 109/L platelets count (PLT). The bone marrow smears showed hypercellularity with more than 90% blast cells. The flow cytometry revealed 75% blast cells compatible with common B cell acute lymphoblastic leukaemia. The cytogenetic and fluorescence in situ hybridization analysis have identified the translocation t (9;22)(q34;q11)(Philadelphia chromosome). The molecular analysis was positive for BCR-ABL fusion gene (p210 isoform), and the BCR-ABL/ABL ratio was 31.55%. The patient received treatment according to GRAAPH2005 protocol with Imatinib 600 mg/day. The patient achieved complete morphological remission after the induction, with a molecular response BCR-ABL/ABL ratio of 0.12% IS.
The 6 months follow-up assessment showed a deep molecular response (molecular analysis ratio BCR-ABL/ABL: 0.0086% -MR4.0 log IS). The cytogenetic analysis 46,XX [20] was consistent with a complete cytogenetic response, and the bone marrow aspiration showed trilineage dysplasia. Her treatment was continued with the same regimen.
On day eight after consolidation therapy with cycle 3 (Methotrexate 1 g/m2 at day 1, Cytarabine 500 mg/m2 BID at day 2 and day 3), a severe aplasia developed (0.76 × 109/L WBC, 0 × 109/L absolute neutrophil count (ANC), 7 × 109/L PLT), and she became febrile with a mild cough and a small area of right perihilar infiltration on chest X-rays (Fig. ), despite prophylactic treatment with levofloxacin. Sputum culture and peripheral blood cultures were performed, and the patient was started on empirical broad-spectrum antibiotics (piperacillin-tazobactam, amikacin) and fluconazole.
Over the next 2 days, the respiratory status worsened, and the patient developed severe cough and hemoptysis, dyspnea and an increased in the oxygen demand. Considering the worsening clinical status, the risk of multidrug-resistant (MDR) germs infection, as well as severe bone marrow aplasia with multiple hospitalizations, the antibiotic treatment was escalated to meropenem, linezolid, amikacin, and fluconazole was switched to voriconazole. The patient received platelets and subcutaneous granulocyte colony-stimulating factor treatment.
Four days after the onset of fever (11 days after chemotherapy), the patient was admitted to ICU for type I respiratory failure and pulmonary haemorrhage. On ICU admission, the patient was conscious and oriented, very dyspneic and tachypneic with a respiratory rate of 38/min, and a SpO278% on 12 l per minute (lpm) O2 on facial mask, and bilateral auscultatory pulmonary crackles. The blood pressure was 200/120 mmHg, and the heart rate was 100 beats per minute, sinus rhythm. There were no signs of peripheral hypoperfusion. The temperature was 37.3o Celsius. The arterial blood gases revealed a pH 7.39, PaO264 mmHg, PaCO2 30 mmHg, lactate 1.5 mmol/L. The antibiotic cover was broadened with the addition of colistin. After 2 h on high flow nasal oxygen (FiO2 1, flow 50 lpm) and in the absence of clinical improvement (persistent respiratory effort), mechanical ventilation (6 ml/kg, positive end-expiratory pressure titrated at 12 cm H2O, plateau pressure 28 cm H2O), sedation, and continuous muscle paralysis were initiated. One-hour post intubation, the PaO2/FiO2 ratio was to 52, on 100% O2. The decision to initiate ventilation in prone position for 18 h was made at this point, with poor respiratory responsiveness (PaO2/FiO2 ratio 114). The chest X-rays at this moment is shown in Fig. . The acute respiratory distress syndrome (ARDS) diagnosis was established. Within the next 24 h in the ICU (day 12 after chemotherapy), the patient recovered from aplasia (10.14 × 109/L WBC, 8.36 × 109/L ANC, 103 × 109/L PLT). The neuromuscular blockade was discontinued after 48 h.
The clinical state and blood results prior to ICU admission are summarized in Fig. .
The sputum culture was positive for Stenotrophomonas maltophilia (cultured on day 9 after chemotherapy, 2 days before the ICU admission). Therefore, the antibiotic treatment has been de-escalated to colistin (4.5 MIU, BID, after initial bolus dose of 9 MIU) and trimethoprim/sulfamethoxazole (800 mg/160 mg, QID). After other 2 days, the antibiogram showed a germ susceptible to trimethoprim/sulfamethoxazole (TMP/SMX), intermediary susceptible to levofloxacin, and resistant to all beta-lactams and aminoglycosides (no determined MIC available). The antibiotic treatment has been further de-escalated the next day to TMP/SMX only for a total duration of 7 days. Unfortunately, the laboratory was logistically unable to test the susceptibility to colistin at this point. All blood cultures were reported negative during the hospital stay.
The respiratory improvement allowed for a bronchoscopy with bronchoalveolar lavage, 3 days after ICU admission, which showed a non-haemorrhagic mucosa, and numerous blood clots. The cytologic examination was very rich in red blood cells with some macrophages, rare lymphocytes and neutrophils. Respiratory cultures from the bronchoalveolar lavage were negative.
The clinical course was marked by a failed extubation at day 11 of ICU, explained by ICU-induced neuromyopathy and ventilator-associated pneumonia (VAP) with MDR Pseudomonas aeruginosa susceptible only to colistin (MIC 2), and resistant to carbapenems and other antibiotics. Treatment with IV and nebulized colistin was introduced for a total duration of 2 weeks. The respiratory status progressively improved, allowing the successful extubation on day 20 in ICU. The chest X-rays post extubation is shown in Fig. .
The patient was transferred to the haematology ward after 26 days of ICU stay and 37 days after chemotherapy. The patient was discharged home soon after, on family request, and her clinical condition and respiratory function were excellent at 10 months follow up.


A 25 y/o female complained from a pulsatile mass over her right frontal area. She had no history of trauma. Physical examinations revealed a large pulsatile mass-like lesion measuring about 5x5x2 cm with at least 2 feeder arteries on the scalp and one feeder artery from the right superficial temporal artery. The involved scalp was tender. There was no evidence of any facial nerve compromise or any other neurologic deficits. Brain and neck CT angiography was performed to rule out any intracranial or extracranial vascular lesions.
Spiral CT-angiography of cervical region demonstrated multiple dilated tortuous vessels in subcutaneous fat of right side of the scalp in the right frontal and supplied by branching from right external carotid artery suggestive of scalp arteriovenous malformation in the right frontal area. There were no signs of any intracranial involvement or bone erosion ( and ). Also, spiral CT angiography of the brain was normal with no sign of AVM.
Due to the proximity of one feeder artery to the right orbit, we decided to choose a surgical approach instead of the endovascular approach to prevent any ophthalmic complications. A written consent was provided from the patient. First, via two facial incisions, superficial temporal artery was ligated and then, circumferential sutures were applied on the scalp for transient bleeding control, and all feeding arteries were ligated and AVM was resected completely (). Finally, hemostatic sutures were removed and the patient had an uneventful post-op course.


A 21-year-old G2P1 patient with no past medical history presented to the emergency department at 17 1/7 weeks' gestation complaining of lower abdominal cramping and vaginal bleeding following an MVC earlier the same day. The patient was a restrained driver-side rear passenger involved in a moderate speed MVC in which her vehicle was struck on the rear passenger side at approximately 40 miles per hour. Side curtain airbags were deployed. She was able to extricate herself from the vehicle with no difficulty and was ambulatory. She had complaints of minimal abdominal pain without vaginal bleeding. She was evaluated at the scene of the accident by emergency medical services and advised to seek immediate medical attention. She declined transport against medical advice and was told to seek care if her condition changed.
An hour after the collision, while at home, the patient experienced worsening abdominal pain and developed vaginal bleeding (approximately 20 mL). At this point, she activated Emergency Medical Services (EMS) and was transported to the closest trauma center. On arrival to the trauma center, she was immediately assessed by the trauma and obstetrics teams. Her vital signs included a blood pressure of 133/77 mmHg, heart rate of 105 beats per minute (bpm), respiratory rate of 18 breaths per minute, and oxygen saturation of 98% on room air. Physical examination revealed no evidence of distress, and a gravid abdomen with minimal tenderness to palpation in the lower abdomen.
Bedside focused assessment with sonography was negative for free fluid in the abdomen or pelvis, had no evidence of pericardial effusion, and showed normal lung sliding. The fetal heart rate was calculated to be 158 bpm by ultrasound. Vaginal exam revealed a closed, long cervix with pooling of blood without active bleeding. A formal ultrasound was obtained that demonstrated a posterior placenta with an anterior 12.0 x 5.4 x 9.5 cm heterogeneous and hypoechoic mass suspicious for placental abruption (Figures , ). Bedside cardiotocographic monitoring revealed a category 1 tracing. Initial laboratory workup was significant for a negative Kleihauer-Betke test, maternal blood type O+, and leukocytosis of 19.0 × 103/µL (normal range: 4.3-10.8 × 103/µL).
The patient was subsequently admitted to labor and delivery for observation. Management options discussed with the patient included expectant management, and induction termination due to concern for fetal hemorrhage and compromise from placental abruption. The patient opted to pursue expectant management. She was observed for evidence of progressive bleeding and disseminated intravascular coagulopathy. She developed an elevated international normalized ratio (INR) of 1.7 (normal range: 1.0-1.5) with an elevated d-dimer level, concerning for early disseminated intravascular coagulation (DIC). The initial hemoglobin dropped from 11.4 to 8.5 g/dL and hematocrit decreased from 33.9% to 25.5%. Subsequently, the patient was administered one unit of fresh frozen plasma. On her second hospital day, she developed increasing vaginal bleeding and contractions and subsequently delivered a stillborn fetus. The postnatal examination of the placenta revealed approximately 50% abruption.


A 25-year-old man with no past medical or drug history, presented to the emergency room with an acute pain of the right upper quadrant and flank evolving for three days associated with fever. The patient reported no chronic abdominal pain or transit disorders.
Physical examination showed that the patient had fever 39 °c. The abdominal examination revealed the presence of a 10 cm - regularly shaped, soft, and fixed mass in the right hypochondria and flank. The rest of the abdomen revealed no remarkable abnormalities.
Laboratory tests showed a high c-reactive protein level (173.5mg/l) but a normal white blood cell count (7553/μl). No anemia nor hemostasis disorders were noticed. Furthermore, urine culture was normal.
Firstly, we decided to perform an abdominal ultrasound that showed a cystic formation of the right pericolic gutter with a thick wall and several septa within. The mass had close relationships with the sixth liver segment and the ascending colon. At first, we suspected a hydatid cyst of the liver because Tunisia is an hydatid endemic area. However, a malignant tumor of the colon could not be ruled out.
Therefore, we indicated an abdominal CT scan to characterize the mass and determine its exact location. It revealed a regular 10-cm- intraperitoneal cystic mass independent from the liver but repressing the ascending colon with heterogonous internal density. Moreover, the mass was multilocular edged by thick walls showing low contrast enhancement after intravenous injection. Peritoneal effusion was detected on CT scan in the pericolic gutter and douglas pouch, to boot (, ).
An infected cystic lymphangioma was then suspected besides the diagnosis of intraperitoneal hydatid disease or infected malignant tumor of the colon. We decided then to perform open surgery for diagnostic and therapeutic purpose.
We found a 10-cm-cystic-mass containing a serous bloody fluid in the right pericolic gutter depending from the ascending colon. The colon was not distended. No liver metastasis nor peritoneal carcinosis were noticed. An ileocolic en bloc -resection was performed with an immediate ileocolic anastomosis. ().
Macroscopically, the 10 –cm colonic cystic mass had many septas and contained serous fluid. It was obviously arising from the ascending colon. In addition, histopathological examination revealed dilated lymphatic and vascular components lined with attenuated endothelial cells. These findings were consistent with the diagnosis of a cystic lymphangioma. The patient's post-operative course was uneventful. He was discharged on the 5th post-operative day. A 6-months clinical and radiological follow-up showed no symptoms or recurrence with good tolerance to regular diet.


A 57-year-old man was referred to our hospital for New York Heart Association functional class 4 HF and extremely elevated liver enzymes. He had palpitation from 2 weeks ago which was accompanied with orthopnoea and serious fatigue on admission, despite being healthy without any history of AF. The electrocardiography showed AF tachycardia of approximately 180 beats per minute, and the bedside echocardiography showed low LVEF of 20%. In addition to fatigue, coexisting hypotension and elevated lactate of 13 mmol/L indicated LOS. Electrical cardioversion was conducted, barely terminated AF successfully on day 1, and restored blood pressure and urinalysis response to intravenous furosemide. Intravenous landiolol hydrochloride was administered for AF tachycardia. HF and LOS were treated with intravenous dobutamine, intravenous furosemide and oral tolvaptan, and non-invasive positive pressure ventilation under mild sedation using intravenous dexmedetomidine hydrochloride. On day 2, torsade de pointes suddenly occurred subsequent to a premature atrial beat in a long-short manner of coupling interval with QT prolongation. Cardiopulmonary resuscitation with electric cardioversions, intratracheal intubation, and establishment of mechanical ventilation were carried out, which achieved return of spontaneous circulation. Temporary atrium-atrium inhibited pacing was emergently established to shorten prolonged QT and maintain regular heart rate. However, AF tachycardia recurred repetitively. Repeated electrical cardioversions failed to terminate AF. Hypotension continued along with oliguria. The liver dysfunction was further exacerbated with aspartate aminotransferase of 11,708 U/L. The intravenous amiodarone was started. On day 3, AF tachycardia with hypotension still occurred despite intravenous amiodarone and gradually became resistant to electrical cardioversions. The atrial tachycardia (AT) and common-type atrial flutter (AFL) appeared in addition to AF. On day 4, disseminated intravascular coagulation (DIC) was diagnosed according to the Japanese Society on Thrombosis and Hemostasis criteria, with DIC score of 6 points []. Acute kidney injury was diagnosed according to the Kidney Disease Improving Global Outcomes criteria, fulfilling both serum creatine and urine output criteria []. At this time, because the patient’s general condition was becoming worse and more resistant to treatment, we decided to perform semi-urgent rescue ablation to AF and common-type AFL for acute-phase rhythm control to treat HF and MOF.
The patient’s family agreed with our treatment policy and signed informed consent for the semi-urgent rescue ablation procedure.
On the same day, prior to the procedure, trans-oesophageal echocardiography was performed and found no detectable thrombus in the left atrium (LA). PVI to the AF and cavotricuspid isthmus ablation to common-type AFL were planned. Fortunately, the patient’s haemodynamics did not collapse at the time of ablation, we performed our institutional standard procedure including 3-D mapping. The cryoballoon was chosen as a PVI catheter because cryoballoon ablation was expected to have a shorter procedure time and lesser thrombogenic effect than other catheter types [, ]. A 20-polar catheter (Response™; Abbott, St. Paul, MN, USA) was placed in the coronary sinus. A three-dimensional electroanatomical mapping was constituted by a cardiac mapping system (EnSite velocity™; Abbott). Transseptal access was obtained using the standard Brockenbrough needle technique with intracardiac ultrasound and fluoroscopic guidance, and an 8-Fr SL0 sheath (Swartz™; Abbott) was inserted into the LA. The cardiac geometry including all pulmonary veins (PV) was established using a 20-pole circular mapping catheter (Reflexion Spiral™; Abbott). No left atriography was conducted because of acute kidney injury. Then, we changed the SL0 sheath to a steerable sheath (FlexCath Advance™; Medtronic Inc., Minneapolis, MN, USA) and inserted a 28-mm second-generation cryoballoon catheter (Arctic Front Advance™; Medtronic Inc.). In each PV, the cryoballoon was placed at the ostium of each PV in turns, and cryoballoon ablation was performed after complete occlusion of each PV as confirmed by the minimum amount of contrast agent. During cryoenergy deliveries, the oesophageal temperature and diaphragmatic compound motor action potential were monitored to avoid LA-oesophageal fistula and phrenic nerve injury. Additional touch-up radiofrequency ablation using FlexAbility™ (Abbott) to the residual LA-PV conduction gap at the bottom of the right inferior PV after cryoballoon ablation was conducted, and complete PVI was achieved (detailed PVI procedural data is shown in Table and Fig. ). Subsequently, a 20-polar catheter (Livewire™; Abbott) was placed around the tricuspid annulus, confirming that the AFL was cavotricuspid-isthmus dependent. The cavotricuspid isthmus ablation for common-type AFL was performed by standard procedure using radiofrequency ablation catheter and successfully achieved bidirectional block. The whole procedure was finished uneventfully and restored sinus rhythm and blood pressure of approximately 110 mmHg.
Thereafter, AF and other atrial arrhythmias seldom occurred and was terminated by single electrical cardioversion (Fig. ). Normal blood pressure and urine output were restored (Fig. ). The hepatic and renal functions were improved gradually as well. On day 7, intravenous amiodarone was discontinued. On day 11, the patient was weaned from the ventilator support. The DIC was restored eventually. On day 18, pulmonary abscess that required long-term antimicrobial treatment was cured. On day 22, AF recurred, but oral amiodarone was restarted and suppressed the AF. Although the patient had a pulmonary abscess that required approximately one-month antimicrobial treatment after ventilator withdrawal, he was discharged alive on day 72. The elective coronary angiography and left ventriculography revealed no significant coronary stenosis and LVEF normalisation, diagnosing that the tachycardia-induced cardiomyopathy due to AF tachycardia was the cause of reduced left ventricular function. For 2 years, albeit the discontinuation of HF drugs and amiodarone, the patient has been free from HF symptoms and atrial arrhythmias including AF and AFL.


Patient X is an eight-year-old boy who presented to the Children’s Hospital at HSC-Winnipeg in early April 2020 with foreign body aspiration. He had a week-long history of cough and respiratory symptoms that began after eating sunflower seeds. The patient had no other symptoms of COVID-19 disease at the time (no fever, sore throat, rhinorrhea) but did have paroxysmal coughing and shortness of breath. Patient X’s past medical and surgical history were unremarkable, and the patient had no known travel, contacts, or risk factors for COVID-19. The patient had been transferred from a community hospital, where a lateral neck X-ray and chest X-ray had revealed a large opaque foreign body consistent with a seed located in the upper trachea (Fig. ). The patient was noted to have increased work of breathing, and biphasic stridor was noted throughout the chest. The Pediatric Otolaryngology service was consulted, and plans were made for emergency bronchoscopy and foreign body removal.
The surgical team consisted of two pediatric anesthesiologists, a senior pediatric otolaryngologist, and two operating room nurses. The case was deemed emergent, and therefore not appropriate to wait for pre-operative COVID-19 testing and confirmation of negative status. Point of care testing was not available at our institution. The operation itself was conducted in a negative pressure theatre identified to require 30 min of time for full air exchange. All extraneous equipment was removed from the room. Appropriate signage was displayed on the doors to the theatre that identified this case as a possible COVID-19 case. Doffing locations within and outside the operating theatre were identified. All operating room personnel wore N95 masks, Stryker Flyte Hoods, long sleeve surgical gowns, and extended cuff gloves. Bronchoscopic equipment and appropriate optical forceps were selected prior to the patient entering the theatre. We used a two “camera-telescope-light cord” setup, one for the diagnostic bronchoscopy, and the other loaded into the optical forceps (Fig. ). Several bronchoscopes and laryngoscopes were selected and available. Instrumentation was organized to be passed smoothly to the surgeon’s hands, while light cords were directed towards the back of the table for easy access and plugging into the video tower light sources. A flexible suction and suction trap were available for bronchial secretion collection.
The patient was brought to the operating theatre wearing a standard surgical mask for droplet precautions. Anesthesia was performed with an intravenous technique, maintaining spontaneous ventilation. The vocal cords were sprayed with local anesthetic by the anesthesiologist using a video laryngoscope and a droplet applicator. Once the appropriate plane of anesthesia was achieved, the patient’s surgical mask was removed, laryngoscopy performed. The epiglottis and vocal cords were unremarkable in appearance. A size 5 × 30 cm rigid bronchoscope (Storz) was advanced into the airway, and a large sunflower seed was identified, lodged at the inferior aspect of the cricoid cartilage (Fig. ). The seed was so large it could only transit between the inferior border of the cricoid cartilage and the carina. The optical forceps could only grasp the seed at its’ front aspect as the seed was so large; it could not be withdrawn completely into the bronchoscope. The seed, forceps, and bronchoscope were all removed from the trachea and the larynx together; however, once past the glottis the seed was inadvertently dropped into the oropharynx.
We attempted to expose the oropharynx and foreign body with the Parsons laryngoscope, however its straight design and narrow aperture made it difficult to get adequate exposure. We intubated the patient in order to ensure the foreign body did not return to the airway. The standard anesthetic laryngoscope with Macintosh blade proved to provide sufficient exposure to visualize the foreign body and remove it with the optical forceps. Removing the foreign body from the oropharynx with the 36 cm optical forceps was successful, but cumbersome to perform. The ideal tool to remove the foreign body from the oropharynx would have been a Magill forceps; this was not present in the room for the case. Repeat bronchoscopy assessment revealed no secondary foreign bodies. We aspirated secretions from the right upper lobe bronchus with a size 7 French flexible catheter and sent for viral testing. Suction was clamped before and after aspiration. The patient’s standard surgical mask was once again replaced over the mouth and nose.
After waiting 30 min for air exchange to be completed, the surgical team proceeded with doffing their personal protective equipment. We did this one at a time, beginning with the most experienced nurses in the room. We doffed our gowns and gloves in the operating room, and then removed our Stryker Flyte Hoods and N95 masks outside the theatre in a designated doffing area. An additional nurse was available outside the operating room to assist with the process and to ensure doffing was done correctly. Each person required approximately 5 min to correctly doff their personal protective equipment for a total of 25 min of time from beginning to end of doffing process for the surgical team. Once doffing was complete, the patient was transferred to the recovery room where staff with appropriate personal protective equipment were present to take over care. The patient was subsequently transferred home in stable condition later that same day. The patient’s bronchial aspirate returned a “negative” result 3 days later.


A 44-year-old woman with bipolar disorder was referred to our outpatient clinic 2 months after her first manic episode. She developed bipolar disorder with depressive episodes when she was 42 years old. Her first depressive episode was ameliorated with 3 months’ treatment with sertraline. She had no previous episodes of hypomania or mixed states, and no history of thyroid disease. When she presented at our clinic, she had been treated with quetiapine for 1 month, but still had elevated mood, irritability, and mood-congruent delusions. According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, we diagnosed her as having bipolar I disorder, and added 200 mg of valproate on 100 mg of quetiapine. Valproate was later increased to 400 mg, after which, her manic symptoms ameliorated.
Despite her mood being well controlled, she developed severe fatigue 30 days after starting valproate. She had no depression-related symptoms other than fatigue, and no findings suggesting sedation with valproate such as somnolence or impaired attention. Her blood concentration of valproate was 24.2 μg/mL, which was not at the toxic level (normal range 50–100 μg/mL). She had never had a similar reaction to previously used psychotropics. A physical examination and laboratory test found no abnormalities except for low values of free thyroxine 0.50 ng/dL (F-T4; normal range 0.8–1.5 ng/dL) and free triiodothyronine 1.85 pg/mL (F-T3; normal range 2.0–3.8 pg/mL). Although F-T4 was decreased, thyroid-stimulating hormone 2.97 μU/mL (TSH; normal range 0.34–3.8 μU/mL) was within the normal range, suggesting central hypothyroidism. Since other fatigue-causing medical conditions and medications were ruled out by systematic evaluations, we considered that the severe fatigue was associated with hypothyroidism. Thyroid autoantibodies were negative, and gadolinium-enhanced magnetic resonance imaging of the pituitary gland showed no evidence of a pituitary lesion. Considering that her F-T4 levels progressively decreased with increasing doses of valproate (F-T4 0.70 ng/dL under 200 mg and F-T4 0.50 ng/dL under 400 mg), we suspected that her hypothyroidism was caused by valproate. Therefore, we stopped valproate 33 days after its introduction. Her severe fatigue then improved, completely disappearing in about 20 days. A laboratory test 35 days after stopping valproate confirmed that her thyroid function had normalized (TSH 2.17 μU/mL, F-T3 2.99 pg/mL, F-T4 1.10 ng/dL). For the next 12 months, she had no recurrence of mood episodes, hypothyroidism, or fatigue under maintenance treatment with risperidone and carbamazepine.


We present the case of a 75-year-old woman who underwent a laparoscopic monolateral suspension for vaginal vault prolapse. The patient was a Caucasian woman in good general health with two previous spontaneous deliveries and a vaginal hysterectomy for uterine prolapse in 2001.
She was admitted to our hospital with a diagnosis of a recurrence of stage 4 of vaginal vault prolapse following the Pelvic Organ Prolapse Quantification (POP-Q) System, without stress urinary incontinence. The main symptoms she reported were a sense of weight and vaginal pressure. Considering the anamnesis, pelvic examination, clinical symptoms, and recurrence of pelvic organ prolapse, the surgical procedure chosen was a laparoscopic sacral colpopexy. The patient received adequate information on the surgical technique via laparoscopic access and, in case needed, via laparotomic or vaginal access.
A consent form was provided and signed. During surgery, the parietal peritoneum was opened at the level of the sacral promontory with subsequent incision of the presacral fascia and identification of the longitudinal ligament. After the visualization of the right ureter and homolateral hypogastric inferior right nerve [], we performed a recto-vaginal dissection toward the perineal and anorectal junction together with dissection of the vesicovaginal space until the endopelvic fascia.
In our surgical practice, a 30 × 30 cm polypropylene mesh (Restorelle XL- Coloplast A/S, 3050 Denmark) with a single arm is used. Before its insertion in the abdominal cavity, the mesh is tailored only in the portion that will be anchored to the vaginal and rectal space, while the other end is left intact in its length and subsequently tailored after its attachment to the sacral promontory.
After the mesh was anchored on the vesical-vaginal space with 12 interrupted sutures (Ethibond 3–0 needle), multiple attempts to fix the mesh to the sacral promontory were tried firstly with an Ethibond 0 needle and then with non-absorbable helicoidal clips (5 mm CapSure–Permanent fixation System. Davol Inc. Subsidiary of C.R. Bard, Inc. 100 Crossings Boulevard Warwick, RI 02886 USA) but any attempt to penetrate the site was unsuccessful (Fig. ). Considering that the mesh was already fixed to the anterior and posterior vaginal compartment, we intraoperatively decided to convert the procedure into a modified laparoscopic lateral suspension (LLS) with a monolateral right mesh, on the basis of the original technique described by Dubuisson et al., where a V-shaped mesh is used []. We carried out a retroperitoneal tunnel using laparoscopic forceps through the right lateral access under transperitoneal visualization, putting in tension and fixing the mesh to the Camper fascia with two interrupted sutures, using an Ethibond 2–0 needle.
At the end of the procedure, the vaginal vault was well suspended (Fig. ). This strategy was possible because the sacral portion of the mesh was not shaped before its fixation to the sacral promontory and was long enough to allow its anchorage to the right lateral Camper fascia.
During the post-operative recovery, we performed a 3D reconstruction CT scan to evaluate the sacrum which detected an exuberant osteophytic bridge at the level of the anterior right margin of L5 and S1 that protruded for 17 mm (Figs. and ).
The patient was discharged after 3 postoperative days with no post-surgical complication. At the follow-up visit, scheduled at 6 months after surgery, the vaginal vault was well suspended, with no signs of genital prolapse. The patient reported clinical well-being, without pelvic pressure or sensation of a vaginal bulge.


A 36-year-old male patient with a left calf skin defect for 20 days underwent surgical debridement and negative-pressure VSD. There was a wound with a size of approximately 7.5 cm × 6 cm after VSD was performed. Adjustable external fixators and K-wires were used to stretch and close the skin, and the wounds were sutured. The external fixators and K-wires were dismantled on the third postoperative day. At the 4-month follow-up, the size of the scar was 9 cm × 2.5 cm, and the level of sensation was S3+ (Fig. ).


Our patient is a 44-year-old Caucasian female with a history of essential hypertension, depression, gastroesophageal reflux disease (GERD), and morbid obesity who presented with a 10-day history of fluctuating left upper extremity weakness, numbness, and slurred speech, in mid-2019. She was seen at the emergency department when the symptoms first started, and the CT head was negative for acute abnormalities. She was discharged to home with instructions to follow up with her primary care provider (PCP), as her symptoms spontaneously resolved in the ED. Two days later, she started having recurrent left-hand weakness lasting 10-15 minutes. Mild headache and lightheadedness was associated with weakness. No visual disturbances, facial droop, word-finding difficulties, lower extremity symptoms, or gait abnormalities were noted. She was admitted for further workup.
The magnetic resonance angiogram of the head revealed right hemisphere infarcts, bilateral anterior cerebral artery occlusions, high-grade stenosis versus segmental occlusion of the right middle cerebral artery M1 segment, and tiny collateral vessels adjacent to the right middle cerebral artery and bilateral posterior cerebral arteries raising the question of Moyamoya disease (Figure ).
Computed tomography angiography was performed, and it showed occlusion of the bilateral anterior cerebral arteries. It also demonstrated possible tiny collateral vessels adjacent to the right middle cerebral artery and anterior cerebral arteries, which continued to raise suspicion of Moyamoya. The patient was then advised to undergo diagnostic catheter angiography (Figure ).
Diagnostic cerebral angiogram was completed, that showed a high-grade stenosis involving the right middle cerebral artery. Additionally, there was a ridge network of right-sided collateral vessels consistent with a Moyamoya appearance. She was started on Aspirin, Plavix, and atorvastatin therapy (Figure ).
A hypercoagulation profile was ordered. She was found to be negative for Factor 5 Leiden, negative for prothrombin gene mutation, and negative antinuclear antibody. IgM and IgG for anticardiolipin were negative, and so was IgA, IgM, and IgG for beta glycoprotein.
She was evaluated by a physical therapist, occupational therapist, and speech therapist, and was cleared to return home without further therapy indicated. The National Institutes of Health Stroke Scale (NIHSS), a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit, was found to be Zero.
The patient had an appointment with a neurosurgeon following discharge who discussed the pros and cons of the three different management approaches at length, namely, medical therapy, endovascular revascularization, and open bypass superficial temporal artery to the middle cerebral artery (STA-MCA). After mutual decision making, she chose medical therapy with dual antiplatelets and postponed invasive intervention until another event.
The neurosurgeon decided that clinical surveillance with phone calls every three months will take place and she will schedule in-person visits at six months. Red flags were discussed with the patient and she was advised to seek immediate medical attention if she developed any of them, and she agreed with the treatment and plan. The patient has been compliant with her office visits and is currently asymptomatic and completely functional at baseline. As of early June, when she was last seen in the office, she denied any new neurological symptoms and is presently on dual antiplatelet therapy, including Aspirin and Plavix.


49-year-old male with morbid obesity, (BMI 47.2), coronary artery disease and heart failure, presented with a one-week history of fever, nonproductive cough, anosmia and shortness of breath. The patient never smoked and had no underlying lung disease. He required oxygen via nasal cannula (SF ratio 215). His chest x-ray (CXR) showed infiltrates in peripheral midlung zones and bases bilaterally. A CT scan of the chest showed patchy ground glass opacities and consolidations in a peripheral distribution in both lungs. His nasopharyngeal swab for SARS CoV-2 was positive. His laboratory findings were significant for lymphopenia and elevated inflammatory markers. He was admitted to the hospital and received antibiotics, corticosteroids, convalescent plasma and off label Tocilizumab. A week later, the patient developed worsening hypoxia (PF ratio of 65) and was placed on a high-flow nasal cannula (HFNC). A CT angiogram was done to rule out possible PE and demonstrated a large left sided pneumothorax. A chest tube was placed using an open surgical approach. His pneumothorax resolved within 12 h. His hospital course was complicated by worsening hypoxia due to COVID-19 pneumonia, necessitating initiating invasive mechanical ventilation and placement of venous-venous extracorporeal membrane oxygenation (ECMO). Patient developed multiorgan failure and died despite providing resuscitative measures.


59-year-old male with obesity (BMI 32.77) presented with 10-days symptoms of fatigue, fevers, cough and shortness of breath. He was febrile and hypoxic needing oxygen via HFNC on admission (SF ratio 156). His labs were significant for lymphopenia and elevated inflammatory markers. A CXR showed multifocal bilateral airspace opacities. A CT scan of the chest showed areas of crazy paving, diffuse large areas of mixed consolidative and ground glass opacities. His nasopharyngeal swab for SARS-CoV-2 was positive. He was started on antibiotics and corticosteroids. In addition, the patient later received convalescent plasma and off label Tocilizumab. He was intubated 2 days later given persistent hypoxia and increased work of breathing while on HFNC (PF ratio 61). Ten days after intubation, the decision was made to proceed with percutaneous tracheostomy given prediction of prolonged intubation. Prior to the procedure, the ventilator settings were respiratory rate (RR) 16 bpm, tidal volume (TV) 450 ml, FiO2 60% and positive end-expiratory pressure (PEEP) 10 cm H2O. His peak inspiratory pressure (PIP) was 26 and plateau pressure 22 cm H2O. During the procedure, and soon after placement of the endotracheal tube, the patient had gradual oxygen desaturation and became hemodynamically unstable. High peak pressures were observed on the ventilator. Bedside ultrasound revealed absence of lung sliding bilaterally. Given concern for tension pneumothorax, bilateral chest tubes were placed via surgical approach. The patient’s hemodynamics and oxygenation improved. An endotracheal tube (ETT) was then successfully placed. A postprocedural CXR showed subcutaneous emphysema but no residual pneumothorax. He was weaned off the ventilator a week later. Eventually his chest tubes were removed, and he was discharged to an acute rehabilitation facility.


81-year-old female with prior history of hypertension and a stroke presented with progressive fatigue, loss of appetite and diarrhea. Her labs were significant for lymphopenia and mildly elevated inflammatory markers. She was diagnosed with COVID-19 disease based on PCR nasopharyngeal swab 5 days prior to her presentation. A CT scan of the chest showed diffuse bilateral patchy ground glass opacities and consolidations in the peripheral, posterior lung regions. She initially required 4 l of oxygen via nasal cannula (SF ratio of 218). She was started on corticosteroids, antibiotics, and received Remdesivir (within a clinical trial). Soon after her admission, she became more hypoxemic needing oxygen via HFNC. Her chest imaging revealed increased bilateral consolidations. Four days after, she was found to have a small right basilar pneumothorax that enlarged within 2 days. A decision was made to place a chest tube under CT guidance. Three days after resolution of the pneumothorax, the chest tube was removed. Patient’s oxygen requirements again increased a few days later, and a repeat chest x-ray revealed a new large left sided pneumothorax and a recurrent small right sided pneumothorax. A chest tube was placed on the left with resolution of the pneumothorax. Unfortunately, on the following days the patient’s clinical status continued to worsen and she expired after comfort measures were taken.