A 42-year-old woman suffered an open extensor apparatus injury on the left knee as the result of a motorcycle accident. The injury included a multifragmentary patella fracture (AO/OTA 34C3) and a proximal patellar tendon avulsion (). A 10x16cm soft-tissue defect was diagnosed after debridement. A single-step orthoplastic approach was carried out, consisting of fixation of the patella fracture with cannulated screws, transosseous reattachment of the tendon using a Krakow-type suture, and coverage with a contralateral ALT free flap (). The flap was vascularized by end-to-end venous and end-to-side arterial anastomosis between perforating branches and the distal superficial femoral vessels. It needed anastomotic revision during the first 24 h due to pedicle thrombosis. After two weeks of rest and limb elevation, weight-bearing was initiated. Hospital discharge was achieved after 20 days without complications. Low-molecular-weight heparins were used for deep venous thrombosis prophylaxis for 6 weeks.
The limb was immobilized in extension for 6 weeks. Then, intensive physical therapy began. Despite complete adherence, the patient developed a stiffness of the knee (flexion 70°) five months after surgery. Radiographs showed a consolidated fracture and correct patellar height, and the flap was in perfect condition. The case was discussed with plastic surgeons. The decision was to perform an arthroscopic arthrolysis with portals through the flap itself after pedicle localization with vascular Doppler.
Once in the theater, two standard medial and lateral infrapatellar arthroscopic portals were made. The medial portal passed through the flap in an area away from the pedicle (). Inside the joint, significant fibrosis was found. A wide synovectomy was performed and both retinacula were sectioned under direct vision. Complete release was noticeable due to the great improvement in patellar translation and in range of motion to 90°. The flap showed correct signs of vitality after tourniquet release. Knee flexion was forced, achieving a full range of motion effortlessly. A drainage was used for the first two postoperative days. The rehabilitation began at 24 h, including intensive physiotherapy, manipulation, and the use of a continuous passive movement (CPM) device. The patient remained hospitalized for 15 days, not experiencing complications. The endpoint active joint balance was 0 to 100°, reaching 120° of forced flexion (). The patient returned to her previous activities and was fully satisfied with the result.


A newborn male infant was born at our institution at 41 weeks of gestation via normal spontaneous vaginal delivery to a 20-year-old G1P0 mother with negative prenatal serologies and normal prenatal ultrasounds. There was no known family history of endocrine conditions or midline defects or history of consanguinity between the parents. Birth weight was 3.71 kg. The patient was vigorous after birth, with Apgar scores of 9 at 1 minute and 9 at 5 minutes. However, due to maternal fever, the infant was admitted to the neonatal intensive care unit for suspected sepsis.
On physical exam, the infant was noted to have stretched penile length of 1.5 cm. Neither testis was palpable in the scrotum or inguinal canal. The remainder of the exam was unremarkable, with no cleft lip, cleft palate, or other dysmorphic features.
Initial laboratory evaluation showed normal electrolytes (sodium 137 mmol/L, potassium 3.5 mmol/L, and glucose 4.5 mmol/L). Scrotal ultrasound confirmed that both testes were present in the inguinal canal. No uterus or ovaries were seen. Pediatric endocrinology was consulted, and multiple laboratory tests were ordered to evaluate pituitary, adrenal, and gonadal functions. Pertinent results are presented in .
The patient's cortisol level resulted first as undetectably low, which prompted an ACTH stimulation test. A high-dose stimulation test was performed as it was unclear at that time whether cortisol deficiency was primary or secondary. Cortisol levels drawn at 30 and 60 minutes were both 24.8 nmol/L, consistent with suboptimal response and adrenal insufficiency. Within this context, the low insulin-like growth factor 1 and insulin-like growth factor-binding protein levels were suggestive of growth hormone deficiency. Growth hormone stimulation testing was not performed due to patient's young age. Thyroid function tests revealed central hypothyroidism, with inappropriately normal thyroid-stimulating hormone (TSH) level in the setting of borderline low free thyroxine (T4) level. There was no evidence of diabetes insipidus. The patient's sodium levels ranged 137–143 mmol/L, and mean urine output was 1.3 mL/kg/hour.
Given these findings, the patient was started on growth hormone, levothyroxine, and hydrocortisone therapy. Subsequent MRI revealed a small pituitary gland, absent septum pellucidum, and pointing of the frontal horns, consistent with a diagnosis of septo-optic dysplasia (). Laboratory evaluation at three months of age, during minipuberty of infancy, again showed low total testosterone level (0.73 nmol/L).
Starting at six months of age, the patient underwent a short course of intramuscular testosterone therapy for micropenis, receiving 25 mg testosterone once monthly for a total of three doses. Stretched penile length after treatment completion was 3 cm, within 2.5 standard deviations for age. Our patient also underwent orchiopexy at 8 and 11 months of age, receiving perioperative hydrocortisone stress dosing for both surgeries.
Our patient has been evaluated by a pediatric ophthalmologist, who confirmed the presence of optic nerve hypoplasia. As of 18 months of age, he is tracking well with full extraocular muscle movements and has not, thus far, required eyeglasses. He has been receiving occupational and physical therapy since 9 months of age. The patient has been referred for genetic analysis but has not yet undergone evaluation.


A 62-year-old female with RA, Hashimoto’s thyroiditis, lymphedema, fibromyalgia, and BMI 56 had a large chronic right lower extremity (RLE) wound for the past three years. She was diagnosed with pyoderma gangrenosum on biopsy which showed dense neutrophilic inflammation. Two years prior, she had stopped etanercept for her RA, and for the past year, she had not been to the lymphedema clinic (citing insurance difficulties for both). Skin grafts, including an Apligraft, were attempted three times at an outside facility and all of them failed. Over the next year, she was hospitalized multiple times for poor wound healing and superimposed infection, and treated with gentle debridement, standard vac therapy, and dressing changes with mupirocin and betamethasone. Rheumatology recommended prednisone during her hospitalizations of flare-ups, followed by maintenance methotrexate immunosuppression as an outpatient. Humira was attempted but discontinued due to diarrhea. After initial difficulty with adherence, a stable regimen of methotrexate 20 mg weekly with folic acid supplementation was established for the treatment of her RA. Due to the large size of the RLE wound and recurrent superimposed infections, her PG did not heal with methotrexate and wound care regimen. The PRS service decided to switch to NPWTi-d (Vac Veraflo) with 10 min dwell time, 3.5 hours between soaks, and negative pressure of 125 mmHg. Normal saline and dilute sodium hypochlorite (Dakin’s) solution were used for instillation. Wound care team noted significant improvement with Mepitel dressing as the contact layer on the wound bed, compared to Adaptic. Additionally, the patient preferred Mepitel reporting that it caused less pain during dressing changes. ROCF-CC was placed on top of the Mepitel. This set-up was used for the patient’s last two hospitalizations (Figure ) from day 0 (Figure ) to day 25, and readmission from day 59 to day 115 (Figure ). On day 115, the patient was discharged with traditional NPWT. At her six-month outpatient follow-up visit, her wound was 4 cm x 2 cm. At nine months, the wound had completely healed (Figure ).


A 59-year-old male with a history of heart failure with a New York Heart Association (NYHA) class III status and an improved ejection fraction of 60% status-post automatic implantable cardioverter-defibrillator (on isosorbide mononitrate 60 mg daily), hypertension [on amlodipine 10 mg and ramipril 10 mg daily, and hydralazine 100 mg every eight hours (for 10 years)], diabetes mellitus (on pioglitazone 30 mg and canagliflozin 300 mg daily, and metformin 1 gm every 12 hrs), and dyslipidemia (on atorvastatin 80 mg and aspirin 81 mg daily) presented with hematuria, intermittent periumbilical abdominal pain, and 40-lb weight loss over four months. The patient had initially visited his local hospital in the Philippines; after receiving three packed red blood cells units, he had signed out against medical advice to travel to the US for further diagnostic workup. The patient presented to the hospital complaining of persistent hematuria and symptomatic anemia. Urine analysis showed large blood cells and proteinuria, which prompted additional studies and suspicion for renal involvement, which was confirmed by imaging (Figure ). During his clinical course, the patient developed a new diffuse purpuric rash. Systemic involvement was also evidenced by imaging with ground-glass opacities, significant for diffuse alveolar hemorrhage and peripancreatic inflammatory changes, consistent with small-vessel vasculitis (Figures , ). Immunological tests confirmed ANCA-associated vasculitis, and kidney biopsy showed ANCA-mediated pauci-immune glomerulonephritis supported by the salvage technique used by pronase immunofluorescence, which provides evidence against the glomerular disease of the complex immune type in the setting of MPO-ANCA seropositivity (Figures , , ). The clinical picture was consistent with HAAV affecting small vessels. In addition to withdrawal of hydralazine, the patient was started on immunosuppressive therapy with methylprednisolone, cyclophosphamide, and rituximab with alternating sessions of plasmapheresis. However, he succumbed to acute massive pulmonary and retroperitoneal hemorrhage and ultimately passed away (Figures , ).


An 85-year-old woman presented to the emergency room with acute onset lightheadedness, palpitations, and near syncope. She did not report nausea, vomiting, chest pain, abdominal pain, fevers, chills, polyuria, constipation, or diarrhea. The patient had a medical history of recurrent bladder carcinoma in situ which was originally diagnosed in 2013 and treated with intravesicular bacillus Calmette-Guerin (BCG). She had recurrence of cancer in 2018 and 2019 and was subsequently started on pembrolizumab nine months prior to her current presentation. She had no prior diagnosis of diabetes or history of gestational diabetes. Her home medication list is notable for simvastatin, pembrolizumab, omeprazole, and solifenacin. She did not report taking glucocorticoids. Social history did not reveal alcohol, tobacco, or drug use. Family history was unremarkable for endocrinopathies. Physical examination findings were notable for fatigued appearance (BMI 20.25 kg/m2) and a benign abdominal examination. Initial lab values showed an elevated blood glucose level five times the upper limit of normal, mild hyponatremia, elevated anion gap, elevated beta-hydroxybutyrate, and low serum bicarbonate, all of which indicated an anion gap metabolic acidosis consistent with DKA. Urinalysis was also notable for elevated glucose and ketones further supporting the diagnosis (lab values are reported in Table ). Imaging studies of the pancreas were not performed. The patient was admitted to the intensive care unit for management of DKA.
The patient was volume resuscitated, started on an insulin drip, and appropriately transitioned to subcutaneous insulin. A limited autoimmune hypophysitis workup was done in the setting of consistent pembrolizumab use although the patient did not report hypophysitis-related symptoms. Labs were notable for low insulin-like growth factor 1 (IGF-1), low total triiodothyronine (T3), and low luteinizing hormone (LH). Thyroid-stimulating hormone (TSH), free thyroxine (T4), adrenocorticotropic hormone (ACTH), cortisol, follicle-stimulating hormone (FSH), and anti-glutamic acid decarboxylase (anti-GAD) were within normal limits. Other autoantibodies implicated in type I diabetes mellitus (T1DM) such as islet cell antibodies (ICA) and insulin autoantibodies were not tested in the acute setting. The patient was transferred to the general medicine floor after anion gap closure. She was referred to an endocrinologist for outpatient management of ICI-related diabetes and was subsequently started on daily long-acting insulin of 10 units and meal-time insulin of five units. Pembrolizumab was discontinued by her oncologist. The patient remained on insulin for more than one year after discontinuation of pembrolizumab and will likely have a lifelong insulin requirement.


A 14-year-old girl with Glut1DS (c.398_399delGCinsTT:p. Lys133Phe) presented with absence seizures at age 2 years. At initial presentation, she had a developmental and epileptic encephalopathy dominated by continual absence seizures and mild cognitive impairment. She also had dysarthria, hyperreflexia, and wobbly legs as a measure of paroxysmal exertional dyskinesia, often precipitated by athletic activities. Laboratory tests revealed a CSF glucose of 36 mg/dL when blood glucose was 93 mg/dL (CSF/blood glucose ratio 0.39). A classic KD was initiated with a 4:1 ratio and transitioned to a modified Atkins diet with a carbohydrate allowance as high as 50 g/day. Nevertheless, she could not tolerate the KD due to severe nausea, vomiting, abdominal pain, and hypertriglyceridemia. Trials of levetiracetam, zonisamide, valproic acid, carbamazepine, lacosamide, alpha lipoic acid, and triheptanoin also failed to control seizures. At age 14 years, diazoxide was started with target blood glucoses of 120–180 mg/dL. She was on no other anti-seizure medication at that point. Serial EEG seizure counts documented a seizure-free state after 6 months of diazoxide (Table ). Seizures were identified as generalized 3-Hz spike-and-slow wave discharges >5 s; pre-diazoxide studies had indicated such discharges were clinically correlated with impaired responsiveness. CGM was placed at month 2 of diazoxide and showed an average interstitial glucose of 157 mg/dL with glucose variability of 20.8% (goal <36%) while on diazoxide 7.3 mg/kg/day. This diazoxide dose was within the typical range of 5–20 mg/kg/day used for the treatment of hypoglycemia due to congenital hyperinsulinemia. At home, CGM was used to adjust diazoxide doses 2–4 times a week to achieve target interstitial glucoses of 140–180 mg/dL (Fig. ). Repeat laboratory tests at month 8 of diazoxide revealed a CSF glucose of 55 mg/dL when the blood glucose was 118 mg/dL (CSF/blood glucose ratio 0.47). Current diazoxide dose is 7.6 mg/kg/day, targeting interstitial glucoses of 90–110 mg/dL (glucose variability 17.1%). Most recent hemoglobin A1c was 5.7%.
Prior to diazoxide, the patient performed 3 grade levels below chronological age. At month 5 of diazoxide, at the start of grade 9, she performed at a 5.8 grade level in reading comprehension. By month 12 of diazoxide, reading comprehension improved to the 6.9 grade level. She continues to be seizure-free and EEG tracings remain normal. She routinely reports her day is a 10 on a scale of 1 to 10. She is now more physically active and participates in Special Olympics basketball, softball, swimming, golf, and track (Fig. ).
The patient’s clinical course has been complicated by fluid retention, a known side effect of diazoxide. She developed this complication soon after diazoxide initiation. Diazoxide causes fluid retention by increasing sodium reabsorption at the distal tubule of the kidney. This mechanism was addressed using thiazide diuretics, which inhibit sodium reabsorption at the distal tubule. The patient began daily hydrochlorothiazide 1 month after diazoxide initiation.
At month 8 of diazoxide, the patient developed headache, malaise, and a stiff neck. She did not have papilledema. Lumbar puncture showed opening pressure of 22 cm H2O with benign cell counts. Because there was immediate relief of headache after the lumbar puncture, she was started on acetazolamide empirically for suspected low-pressure intracranial hypertension. At month 9 of diazoxide, she developed hypokalemia (lowest potassium 2.8 mmol/L) and renal insufficiency (peak creatinine 1.11 mg/dL) necessitating transient discontinuation of hydrochlorothiazide. Hydrochlorothiazide was restarted later at a low dose with amiloride (potassium-sparing diuretic). Daily sodium intake was decreased to <2400 mg/day. Serum electrolytes and renal function were followed closely. Acetazolamide was discontinued after normalization of serum sodium and renal function.
To achieve hyperglycemia in the range of 140–180 mg/dL, cornstarch was supplemented at 7 tbsp/day. Simple carbohydrates were given, when necessary, to raise blood glucose levels. Weight gain (13.7 kg) resulted from this regimen, complicating the fluid retention. Nutrition assessment revealed an average intake of 3193 kcal/day composed of carbohydrates (426 g/day), protein (121 g/day), and fat (108 g/day), which exceeded daily requirements of ˜2000 kcal/day. Her nutrition plan was restructured. The family was counseled regarding daily dietary intake to meet the patient’s energy, sodium, and carbohydrate goals. Daily cornstarch dose was decreased and eventually discontinued. To prevent relative “hypoglycemia”, the patient and family were educated about pairing complex carbohydrates with protein at meals and snacks to help sustain blood glucose levels. If relative “hypoglycemia” did occur, defined as blood glucose <90 mg/dL for more than 3–4 h, the patient and family were instructed to correct with 15 g of simple carbohydrates. Three weeks later, average daily caloric intake had decreased over 400 kcal/day. The patient’s nutritional status continues to be monitored closely as her neurological state continues to improve.


Patient 3 (P3), female, 3 years old, the younger of two siblings from non-consanguineous parents. The mother had 4 pregnancies, with one miscarriage at 10 weeks. P3 had uneventful perinatal history, she was born at term, and had no clinical symptoms. Neurodevelopment milestones were normal up to 9 months old when she developed progressive hypotonia and somnolence, followed by a gradual loss of motor skills in the following month. Cerebrospinal fluid was negative for markers of viral infection. Her sister was healthy, however, her father presented epilepsy in infancy and frequent headaches in adulthood.
The first diagnostic hypothesis for P3 was acute disseminated encephalitis, showing normal electroencephalogram, diffuse white matter lesions by MRI and a lactate peak on spectroscopy (). Symptoms improved after treatment with methylprednisolone for three days, with an improvement of the symptoms. However, after a week, a gradual clinical decline was observed with lethargy, dysphagia and general hypotonia. After 13 months, a new MRI (not shown) showed increased white matter lesions, suggesting a mitochondrial disorder. An acylcarnitine profile in blood showed increased concentrations of 3-hydroxy-butyrylcarnitine and acetylcarnitine, amino acid chromatography showed increased alanine (656.1, normal 146 - 494 mcmol/L). Lactate levels in plasma ranged from 2.7 to 7.6 (normal <2.2mmol/L) over one year. Lactic acid levels in cerebrospinal fluid were often increased, ranging from 3.5 to 5.3 (normal <0.8mmol/L). Levels of urinary organic acids were normal. Supplementation with CoQ and carnitine was started but with no significative improvement. At 3 years old, P3 lost neurodevelopmental milestones and developed hypotonia, strabismus and severe inappetence. She was submitted to an endoscopic gastrostomy and current treatment was based on supplementation with CoQ, creatine, sodium bicarbonate, acetyl L-carnitine, riboflavin, and biotin.


A 12-week-old infant male presented to the clinic with dyspnea and grunting. He was born full-term and small for gestational age (SGA), with a weight of 2381 g. Maternal history was noncontributory. The infant was generally well for the first few months of life, although parents reported a history of intermittent constipation. Interestingly, the father was a beekeeper and the family used honey at home instead of sugar.
The infant was sent from the clinic to the emergency department, where he was found to be severely malnourished, hypoxemic, and hypotonic. Additionally, he had a weak cry and areflexia of the lower limbs. He was consequently put on a high-flow nasal cannula (HFNC). An anterior-posterior (AP) view chest x-ray showed an elevated right hemidiaphragm (Figure ). A head ultrasound and a limited swallow study were normal. Other tests included upper respiratory viral polymerase chain reaction (PCR) panel, severe acute respiratory syndrome coronavirus (SARS-CoV-2) PCR, and blood culture - all of which were negative. The newborn screen was normal.
The infant was admitted to the pediatric intensive care unit (PICU) and was placed on bilevel positive airway pressure (BIPAP). The Infant Botulism Treatment and Prevention Program was contacted due to the significant history of honey exposure. Recommendations were to administer the Botulism Immunoglobulin Intravenous (BIGIV) and to send a stool sample to the Center for Disease Control and Prevention. During this time, Neurology and Genetics were also consulted. Neurology recommended magnetic resonance imaging (MRI) of the brain and spine which was normal, with the exception of levocurvature and dextrocurvature of the thoracic and lumbar areas, respectively (Figure ). Genetics recommended an extensive metabolic and genetic workup, which included plasma amino acids, urine organic acids, lactate, pyruvate, acylcarnitine profile, carnitine profile, serum creatinine kinase (CK) level, Prader Willi methylation studies and SMA testing (Table ).
After receiving BIGIV, the infant’s lower limbs were felt to be more reactive to stimuli. Deep tendon reflexes (DTRs) were improved. The infant was switched from BIPAP to HFNC and was transferred to the pediatric floor. However, this clinical improvement was short-lived. On his fourth day on the pediatric floor, the infant became hypotensive and dyspneic. He was transferred back to the PICU where he was placed on BIPAP. He became bradycardic, requiring cardiopulmonary resuscitation (CPR). The infant was subsequently intubated and received an epinephrine dose before recovering.
He remained intubated for the following three weeks. During this time, all the initial metabolic and genetic workups resulted negative. Stool botulism testing resulted in negative. Genetics recommended whole exome sequencing testing, which revealed biallelic mutations in the immunoglobulin mu deoxyribonucleic acid-binding protein 2 (IGHMBP2) gene - the gene responsible for SMARD 1.
The parents were counseled about the diagnosis, natural history and expected poor outcomes. A tracheostomy and a gastrostomy tube were placed. Palliative care was consulted, and the infant was eventually discharged home with palliative care closely followed.


A 28-year-old male presented to the emergency department (ED) with progressively worsening odynophagia and dysphagia. He had been diagnosed with human immunodeficiency virus five months prior after initially presenting to an outside hospital with odynophagia and weight loss. Given difficulty affording his antiretrovirals, he reported only intermittently taking emtricitabine-tenofovir and was lost to follow-up. He was unaware of his oral lesions and overall grim clinical status. Seven days prior to presentation he developed mild dyspnea as well as worsening dysphagia. Physical examination of the oral cavity revealed a 3 × 3 centimeter (cm) violaceous, pedunculated, midline posterior mass partially occluding the airway, as well as a 2 × 2 cm anterior hard palate, violaceous mass ().
The exam was also notable for extensive cervical and inguinal lymphadenopathy, global wasting, and a muffled voice. He was able to speak in full sentences, was tolerating his secretions, and did not have evidence of respiratory distress. Point-of-care ultrasound (POCUS) revealed reactive cervical lymphadenopathy ().
Computed tomography soft tissue neck () and chest revealed nodular thickening of upper airway structures, cervical lymphadenopathy, diffuse ground-glass opacities, and large bilateral pleural effusions.
He was started on broad spectrum antibiotics including trimethoprim/sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. Otolaryngology was consulted in the ED and performed a bedside laryngoscopy.. He was admitted for tracheostomy the following day. Excisional biopsy confirmed the diagnosis of disseminated Kaposi sarcoma. Given his extensive disease burden, he was started on systemic chemotherapy.


A 79-year-old male presented to the ED with a chief complaint of syncope. He had a past medical/surgical history of bladder cancer with prior neoadjuvant chemotherapy and subsequent consolidative cystoprostatectomy with ileal conduit and left nephrectomy. Prior to the syncopal episode, the patient had been complaining of abdominal pain associated with nausea and vomiting for two days. He was afebrile (98.6ºF) with a heart rate of 135 beats per minute, blood pressure of 85/60 millimeters mercury (mm Hg), respiratory rate of 36 breaths per minute, and oxygen saturation of 94% on nasal cannula. On examination, the patient had an ileal conduit without active signs of infection; however, there was severe diffuse abdominal tenderness to palpation, which raised concern for peritonitis.
Point-of-care ultrasound showed a positive FAST exam (focused assessment with sonography for trauma) with free fluid in the abdomen (). It also showed a thick peritoneal stripe with posterior reverberation artifacts consistent with pneumoperitoneum and perforated viscus. Computed tomography of the abdomen/ pelvis was expedited, which confirmed the diagnosis of pneumoperitoneum with viscus perforation. Meanwhile, the patient was given intravenous (IV) fluids, broad spectrum antibiotics, and pain control, and was started on vasopressors. Urology and general surgery were consulted immediately, and the patient was taken to the operating room (OR) emergently for exploratory laparotomy.


An 80-year-old male was brought into the ED from a nursing home for apparent abdominal pain and two weeks without having a bowel movement. The patient had a medical history of diabetes, hypertension, and dementia. He was unable to provide history due to his dementia. On exam, he was afebrile (97.3ºF) with a blood pressure of 110/70 mm Hg, heart rate of 112 beats per minute and respiratory rate of 24 breaths per minute. His abdomen was nondistended, but it was diffusely tender with voluntary guarding.
Point-of-care ultrasound showed a positive FAST with free fluid in the abdomen. It also showed an EPSS suspicious for a perforation (). He was given IV fluids, analgesia, and broad-spectrum antibiotics. Computed tomography of the abdomen/pelvis confirmed free air and free fluid in the abdomen associated with ischemic jejunum with pneumatosis intestinalis (). Surgery was consulted, and the patient was taken to the OR for emergent exploratory laparotomy.


An 88-year-old female was brought into the ED after she was found to be unresponsive at home. She had a medical history of hypertension and diabetes. Family reported that the patient had been lethargic for two days associated with poor oral intake. She also had an episode of nausea and bloody vomiting earlier that day. Upon arrival, she was hypoxic to 82% with respiratory rate of 30 breaths per minute even with non-rebreather mask. Heart rate was 88 beats per minute. She was also hypotensive (74/39 mm Hg) with a mean arterial pressure of 50 mm Hg (reference range: 70–100 mm Hg). She was emergently intubated and was started on IV fluids, antibiotics, and vasopressors. Initial abdominal exam was limited due to her mental status, but her abdomen was noted to be distended.
Ultrasound showed EPSS with free air. The patient was started on broad spectrum antibiotics, and the expedited abdominal CT showed large volume pneumoperitoneum with perforation at the distal stomach. Surgery was consulted emergently; after further discussion her family decided against any surgical intervention and requested comfort care in the ED. The patient was subsequently admitted to the hospital for end-of-life care.


A 24-year-old man was brought to our center with chief complaints of shortness of breath and cough for 6 days. He had shortness of breath even on walking on the level ground. The cough was copious and productive while sputum was yellowish. He had chest pain on right side that aggravated with coughing. He had no history of palpitation, loss of consciousness, lower limb swelling, and fever. He had COVID-19 one month back that was resolved after 25 days of treatment. He had no known comorbidities. He neither smoked nor consumed alcohol.
On examination, patient was ill looking, conscious, and was well oriented to time, place, and person. He had pulse rate 110 beats/minute, respiratory rate 25/min, blood pressure 124/80 mm of Hg, and temperature was 98°F. He had no pallor, icterus, lymphadenopathy, cyanosis, or clubbing. There was bilateral decrease in air entry on chest auscultation over 4th and 5th intercostal spaces which was more on the left side. He had bronchial breath sounds bilaterally.
His laboratory investigations revealed hemoglobin 11.8 gm %, total leucocyte count 23,000/mm3, neutrophils 82%, lymphocytes 11%, and platelet count 508,000/mm3. Prothrombin time (PT) and international normalized ratio (INR) were 16 s and 1.22, respectively. His random blood sugar level was 3.7 mmol/L. The level of urea (10.7 mmol/L) and creatinine (215 µmol/L) was raised in the blood. He had elevated level of AST (86 U/L), ALT (221 U/L), and LDH (960 U/L) but decreased level of albumin (23 gm/L) and total protein (44 gm/L) in the blood.
Chest X-ray showed bilateral consolidation of lungs in the middle zone (Figure ). High-resolution computed tomography (HRCT) of chest revealed bilateral multiple cavitary lesions with diffuse patchy ground-glass opacification, thickened interlobular septa, bilateral lower lobe consolidation, traction bronchiectatic changes, and bilateral pleural effusion with passive atelectasis and mediastinal lymphadenopathy. There was cystic bulla communicating with pleura in the left side. Pleural fluid tapping was done under aseptic conditions with ultrasonography (USG) guidance, and 18 ml of serosanguinous fluid was aspirated. However, there was no growth of bacteria in it.
Based on the radiological findings, diagnosis of left-sided hydropneumothorax, right-sided pneumothorax, and bronchopleural fistula (BPF) on left side was made. Following this, bilateral chest tube was inserted to treat left side hydropneumothorax and right side pneumothorax. He developed fever after 5 days of hospital stay for which culture of the pleural fluid was done that revealed the growth of Acinetobacter lwoffi. He was treated with (piperacillin +tazobactum [4.5 g IV QID], linezolid [600 mg BD], montelukast [10 mg OD], and hydrocortisone [100 mg IV BD]) for 14 days. Repeat chest X-ray was normal following which, chest tube was removed. He improved clinically and was discharged on oral medications (amoxicillin and clavulanic acid [625 mg TDS] for 7 days, azithromycin [500 mg OD] for 5 days, and montelukast [10 mg OD] for 7 days). His follow-up was not eventful.


A 70-year-old Caucasian male, a proper diction teacher with a medical history of hypertension and stable heart disease, was admitted to our neurological department in November 2020 with acute symmetric progressive ascending paresis of the limbs, impaired sensation and bilateral facial nerve palsy. One month earlier (on 20 October 2020) he was treated at home for suspected SARS-CoV-2 infection without serious complications. The infection manifested itself through fever, gastrointestinal symptoms, headaches and severe pain in the thoracic spine. Three weeks later, the patient had an antibody blood test for SARS-CoV-2 with immunoglobulin M (IgM) rate at 4.18 (negative result < 1.00) and immunoglobulin G (IgG) rate at 5.69 (negative result < 1.4). Seven days after the disease laboratory confirmation, he came to the GP because of paraesthesia of the distal parts of the limbs and burning of the tongue. A diagnosis of ulcers (aphthae) in the mouth and sensory disturbances due to changes in the cervical and lumbar spine were made. Then, two days later, bilateral paresis of the facial nerve appeared, and he was thus transported from the private neurological praxis by ambulance to our neurology department.
The systemic examination was normal. In the neurological examination the patient presented the following: complete lower motor neuron facial weakness bilaterally, swallowing difficulties, jaw dropping and dysarthria, symmetrical flaccid quadriparesis, absent deep tendon reflexes and sensory disturbances from the thoracic spinal nerve 6 (T6) downwards. The patient complained of a lack of facial expressions and diplopia. Then, due to diaphragm and intercostal muscles paralysis, respiratory disorders of the “compression of the iron rim” type appeared. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed without any acute pathological finding. In a thoracic MRI (scope of the study T6–L2) examination, due to striped, subtle contrast enhancement at T12–L1 level on the anterior and dorsal surface of the conus medullaris and the roots of the cauda equina, suspicion arose of Guillain-Barré Syndrome. A lumbar puncture was performed, and the CSF picture revealed normal glucose and cell count with 98 mg/dL protein level, albumin level at 56.8 mg/dL and positive oligoclonal bands type IV indicative of damage to the blood–brain barrier. Other laboratory tests were within normal range. A nerve conduction study showed sensorimotor polyneuropathy of a demyelinating-axonal character. The patient received intravenous treatment with immunoglobulins at a dose of 2 g per kilogram body weight; the course of treatment was uneventful and there was gradual improvement. For further recovery, the patient was transferred to the rehabilitation department.


A 66-year-old man with a long history of smoking (20 cigarettes a day for more than 30 years) was admitted to the respiratory department of our hospital on April 16, 2020, with a history of right chest pain over the past 10 days. Chest computed tomography revealed a space-occupying lesion in the right upper lobe and multiple mediastinal lymph node enlargement (Fig. a–f). The patient underwent bronchoscopy, and a bronchial neoplasm with discoloration under fluorescence was observed in the upper lobe of the right lung (Fig. a, b). The histopathological diagnosis was moderately differentiated adenocarcinoma. Genetic testing revealed no mutant genes, including epidermal growth factor receptor-21 (EGFR-21) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EMLA4-ALK) fusion.
The patient was diagnosed with lung adenocarcinoma (T4N2M1), according to the Union for International Cancer Control 7th edition TNM classification of lung cancer. Other detailed laboratory data were as follows: carcinoembryonic antigen = 172 ng/ml (normal range: 0-5 ng/ml), cytokeratin 21–1 fragment = 37.7 ng/ml (normal range: 0–3.3 ng/ml), neuron-specific enolase = 21.00 ng/ml (normal range: 0–16.3 ng/ml). His Eastern Cooperative Oncology Group Performance Status score was 0. The patient was treated with six cycles of systemic chemotherapy combined with bevacizumab, specifically; pemetrexed 800 mg/d + cisplatin 40 mg/d1 − 3 + bevacizumab 300 mg/d, followed by 3 cycles of bevacizumab monotherapy for every 21 days (300 mg/d).Imaging every two months revealed that the tumor decreased in size (Fig. c), and serum lung cancer biomarkers were significantly reduced.
On November 24, 2020, the patient was admitted to our department again with chest tightness and shortness of breath for five days. He complained of severe shortness of breath when eating, as well as right chest pain. His temperature was 36.8 °C, respiratory rate was 25 breaths/min, and the respiratory sound of the right lower lung disappeared. Laboratory data included a white blood cell count of 16.35*109 /L, neutrophil percentage 89.1%, C-reactive protein 310.7 mg/l, procalcitonin 2.548 ng/ml, and D-dimer 4.60ug/ml. All lung cancer biomarkers were normal. Bed-side chest radiography revealed a severe right hydrothorax (Fig. a). Ultrasound detected an unclear fluid sonolucent area in the right thorax, with a floating hyperechoic mass (Fig. b). We performed thoracocentesis, which resulted in the extraction of 50 ml melicera, gray pleural effusion, with food (egg yolk) inside. The patient was subsequently treated with carbapenem antibiotic. EPF was confirmed by upper gastrointestinal radiography after oral administration of iohexol (Fig. c). After pleural effusion drainage, the patient underwent gastroscopy, revealing a 15 mm diameter fistulaon the esophagus 30 mm away from the incisor; however, the proximal esophagus of the fistula could not be exposed and the distal esophagus could not be found (Fig. a–c). Therefore, we contacted the department of general surgery for consultation and performed jejunostomy for internal nutrition. Unfortunately, the patient died of septic shock on January 16, 2021.


A 54-year-old Caucasian male presented with new onset of severe headache 12 days after first vaccination with ChAdOx1 nCoV-19. His prior medical history was completely unremarkable without evidence for an increased thrombotic risk. The patient did not receive any regular medication. On admission, he had thrombocytopenia and signs of disseminated intravascular coagulation (platelet count 37 × 109/L; fibrinogen 0.94 g/L; D-dimer > 30 mg/L; ). SARS-CoV-2 infection was ruled out by PCR from nasopharyngeal swab. Serological antibody testing revealed a normal SARS-CoV-2-spike IgG titer without a signal to nucleocapsid in chemiluminescent immunoassay (CLIA) and immunoblot testing compatible with a vaccine-induced, but not SARS-CoV-2-infection related immunological response (at day 18 after vaccination). Cranial magnetic resonance imaging showed extensive superior sagittal sinus vein thrombosis with frontal hemorrhagic infarction (). Thoracic, abdominal, and pelvic computed tomography (CT) revealed bilateral adrenal hemorrhages (not shown). Follow-up cranial CT revealed CVST with intracranial hemorrhage (ICH) progression to both frontal lobes, requiring hemicraniectomy within 24 h after admission. IVIG (1 g/kg body weight on two consecutive days each) and anticoagulation with argatroban were started immediately. Platelet count increased to 282 × 109/L until day 5. However, three additional courses of IVIG were required to resolve recurrent, almost weekly occurring episodes of thrombocytopenia. Anticoagulation was changed from argatroban to tinzaparine, to argatroban, to danaparoid, and finally to fondaparinux. Anticoagulation was switched four times because of pharmacologic considerations (liver toxicity, half-life, possibility of antagonization) without affecting the platelet count course (B). After ruling out cross-reactivity of VITT antibodies with PF4/heparin complexes, heparin was started, which was well tolerated. Due to recurrent episodes of thrombocytopenia, immunosuppression with prednisolone (70 mg orally) was initiated. From thereon, platelets remained >150 × 109/L, but still dropped from 581 to 182 × 109/L after three months, which could not be explained by changes in medication or other new co-morbidities. During intensive care unit (ICU) treatment, the patient suffered recurrent epileptic seizures requiring antiepileptic treatment, pneumonia with the need for antibiotic treatment but remained otherwise clinically stable. The patient was transferred to a neurological rehabilitation center 40 days after admission and returned to our hospital after 6 weeks for diagnostic and therapeutic re-evaluation. The minor recurrent ICH (V) was diagnosed in a routine imaging control without a clinical correlate at this time point. He was sent to another rehabilitation center at day 90 for further neurological rehabilitation. On day 103 he developed new clinical signs for increased intracranial pressure with vomiting, decreased level of consciousness, pupillary abnormalities, and clinical swelling at the site of hemicraniectomy as a sign of herniation. Four months after VITT onset, the patient developed a new space-occupying intracerebral hemorrhage as a secondary complication to previous CVST/ICH and anticoagulation (V,VI). According to the patient’s and family’s wish, ICU treatment goal was changed to a comfort care approach, and the patient deceased four days later.


During the summer of 2015, a dead 5-week-old female Welsh Corgi with severe diarrhea and vomit was submitted for laboratory investigation. Necropsy of the dog showed hemorrhagic enteritis and lung on their surfaces. At post-mortem examination, samples were from intestine, brain, lungs, spleen, liver, kidneys, heart and mesenteric lymph nodes for real-time RT-PCR investigation of CCoV RNA [].


A 39-year-old man was referred to our clinic with persistent leukocytosis. He complained of feeling feverish with myalgia for one month. He also had diarrhea, up to ten times per day, for five days prior to his presentation to the clinic. There was no abdominal pain or vomiting, and he was able to tolerate orally well. He did not have other constitutional symptoms, such as weight loss or night sweats. He did not have any rashes, cough, shortness of breath, or chest pain. All other systems review was unremarkable. There was no similar episode among other family members.
He worked as an operations manager in a factory and was primarily responsible for overseeing food preparation in the factory dining room. Thus, he was required to touch the raw materials, such as vegetables as part of the quality control measures. He lived in an urban residential area equipped with adequate sanitation and sewerage systems. There was no history of recent travel or recreational activities in the preceding six months. He was an active smoker of 24-pack-years. His past medical history was unremarkable. Specifically, he did not have any history of allergies or atopic medical conditions. He had not been on any medications for the past three months.
Physical examination did not show pallor, rashes, or finger clubbing. He was afebrile with temperature of 36 °C. His heart rate and blood pressure were all within the normal range. Abdominal examination was normal with no hepatosplenomegaly. He did not have any lymphadenopathy. His complete blood count (CBC) showed a white blood cell (WBC) count of 20.69 × 109/L with an absolute eosinophil count (AEC) of 12.44 × 109/L, hemoglobin of 17.1 g/dL, and platelet counts of 365 × 109/L. Hepatic and renal function tests were within the normal range. A peripheral blood film (PBF) showed leukocytosis and eosinophilia with no blast or immature granulocytes seen. There was also polycythemia, and the red bloods cells appeared normocytic and normochromic, with no nucleated red blood cells. The serum erythropoietin (EPO) level was normal (6.4 IU/L).
The fecal microscopic examination showed T. trichiura’s egg, characterized by a barrel-shaped, thick-shelled egg with a pair of polar “plugs” at each end (). He was treated with albendazole 400 mg tablets twice a day for three days. The resolution of clinical symptoms and normalization of leukocyte counts following treatment supported the diagnosis of hypereosinophilia secondary to trichuriasis. Based on the findings of peripheral blood film (absence of immature granulocytes, no blast cells), normal platelet count, and normal serum EPO level, myeloproliferative neoplasms were unlikely []. The elevated hemoglobin was probably due to relative polycythemia (pseudopolycythemia), contributed by his smoking habit, thus an appropriate smoking cessation counselling was offered to the patient. The cytogenetic and molecular testing, such as identification of platelet-derived growth factor receptor alpha gene (PDGFRA) and platelet-derived growth factor receptor beta gene (PDGFRB) rearrangements, was not carried out due to initial findings of T. trichiura’s egg in fecal microscopy and the normalization of eosinophil counts following treatment. His CBC results pre and post treatment with albendazole is shown in .
Other possible diagnosis such as DRESS colitis was highly unlikely as this patient had not been on any new medications which may trigger DRESS syndrome. Furthermore, apart from hypereosinophilia, he did not have any symptoms and signs suggesting this condition, such as rashes and enlarged lymph nodes. Other laboratory findings including liver and renal function tests were also normal.


We report the case of a 13-year-old girl who was medically and surgically free with an eight months history of vague recurrent attacks of abdominal pain, nausea, vomiting, and migratory joint pain. During her several visits to medical centers, the physical examination was unremarkable, but at her last presentation to a higher medical center her laboratory investigation revealed elevated amylase and lipase indicating pancreatitis. At this stage, the patient was transferred to our center for further investigations. Further laboratory investigation showed high PTH (339.4 pg/mL; normal range: 22-88 pg/mL), total calcium (3.02 mmol/L; normal range: 2.2-2.7 mmol/L), adjusted calcium (2.83 mmol/L; normal range: 2.10-2.55 mmol/L), and total 25-OH vitamin D (35.2 nmol/L; optimal: >75 nmol/L). With this high PTH and calcium level, diagnosis of primary hyperparathyroidism (PHPT) was established. CT scan was performed, which showed a lesion in the anterior mediastinum, as seen in Figure . To localize the hyperfunctioning gland, sestamibi scan was performed, as seen in Figure . Genetic testing ruled out MEN1 and MEN2. The patient then underwent laparoscopic thymectomy in a different center, and the family reported that the symptoms had resolved.


An 8-year-old male child presented to the paediatrics out-patient department (OPD) with the complaints of sudden jerky body movements and episodes of fall, progressive over six months. There were no similar complaints in the family. The child was not immunised. Physical examination revealed myoclonic jerks, increased tone with normal power in all four limbs and brisk deep tendon reflexes. EEG showed intermittent bursts of generalised discharges (spike, polyspike and wave) lasting for one to three seconds (Figure ).
CSF sample enzyme-linked immunosorbent assay (ELISA) tested positive for IgG antibodies for measles virus.
Brain MRI examination revealed confluent T2/fluid-attenuated inversion recovery sequence hyperintensities in bilateral (B/L) parietal and frontal white matter (Figure ).
The lesions showed no diffusion restriction/blooming on diffusion-weighted/gradient images. No post-contrast enhancement was noted. On magnetic resonance spectroscopy (MRS), reduced N-acetylaspartate (NAA) levels were seen (Figure ).
An incidental neurocysticercosis lesion was also seen in left frontal lobe (Figure ).


A 15-year-old female child presented to the paediatrics OPD with the complaints of progressive abnormal jerky body movements, inability to walk, episodes of fall and abnormal behaviour over the past 18 months. There was no similar family history. The child was immunised adequately for age. Physical examination revealed myoclonic jerks, increased tone in all four limbs, diminished deep tendon reflexes, power of 5/5 and a normal sensory system evaluation. EEG showed intermittent bursts of generalised discharges (spike, polyspike and wave) lasting for one to three seconds. CSF ELISA test came positive for IgG antibodies to measles virus.
MRI brain showed discrete as well as confluent T2/FLAIR hyperintense lesions seen in the subcortical and deep white matter of bilateral frontal, temporal and parietal lobes (Figure , ).
These lesions showed no diffusion restriction on diffusion-weighted imaging (DWI)/apparent diffusion coefficient (ADC) images and no post-contrast enhancement. No blooming was seen on gradient images. On magnetic resonance spectroscopy, mildly reduced choline and NAA levels were seen in these lesions (Figure ).


A 37-year-old Iraqi man was admitted to the hospital with progressive dyspnea on exertion occurring since 2 years and associated with dry cough. Patient was afebrile. The patient reported two episodes of severe dyspnea and low oxygen saturation occurring 1 month and 2 years ago. In both exacerbations, patient’s chest X-ray revealed left pneumothorax, and a tube thoracostomy was performed subsequently (). The patient served in the military service and was also a carpenter. Patient’s body mass index was 21 and his basal oxygen saturation was 97%. Physical exam showed flattened thorax and hypophonesis accentuated on the leftside during auscultation. At the admission, patient’s laboratory results were: pH = 7.43, PCO2 = 40, PO2 = 84, white blood cells count = 5350, neutrophils = 60, lymphocytes = 30, monocytes = 5.8, eosinophile = 2.1, hemoglobin = 14.1, hematocrit = 40, creatinine = 0.4, TSH = 0.51, free T4 = 11.53. A trans-thoracic echocardiography was made and did not show any significant finding. The purified protein derivative test results, the antinuclear antibody panel test and the rheumatoid factor detection test were negative. A video-assisted thoracoscopic surgery was performed to decorticate a restrictive layer of fibrous tissue overlying the lung, additionally to a wedge biopsy taken from the right apex. Histo-pathologic results reported a prominent interstitial fibrosis involving the subpleural and deep lung parenchyma with limited area of normal tissue intercepted between them (). No gronulomatous tissue was detected. The scarring tissue had a dense fibroelastotic appearance without active fibroblastic foci. Occasional dilated airspaces and ectatic lymphatic spaces were noted in the subpleural fibrotic parenchyma. Therefore, the diagnosis of IPPFE was made, and the other possible differential diagnoses are discussed below.


A 60-year-old female patient, with a prior history of breast cancer, presented with abnormal vaginal bleeding, and biopsy-confirmed grade II endometrial adenocarcinoma with squamous metaplasia. Following her diagnosis, she initially underwent total laparoscopic hysterectomy with pelvic/aortic lymph node dissection, and pathology confirmed IB grade II endometrial adenocarcinoma with squamous metaplasia, and lymphovascular space invasion. Following this, the patient received adjuvant cisplatin and radiotherapy, with pelvic external beam radiotherapy and vaginal brachytherapy (Fig. ).
One year later, she developed persistent back pain, and imaging revealed a single T12 lesion with epidural impingement, and subsequent tumor biopsy confirmed metastatic adenocarcinoma consistent with endometrial cancer. Systemic restaging studies revealed a small but suspicious left-sided para-aortic lymph node at the levels of L2-L3. The patient underwent stereotactic radiosurgery and thermal ablation for cord compression, and she received carboplatin and liposomal doxorubicin for three cycles, followed by focal radiotherapy to persistent para-aortic lymphadenopathy.
Computed tomography (CT) restaging imaging 7 months later revealed disease progression in the lungs, and the patient commenced cisplatin and gemcitabine chemotherapy. However, post cycle 3, imaging revealed T12 metastasis showing a new region of FDG-avidity, compatible with progression and stable pulmonary nodules. MRI spine showed suspected progression of epidural soft tissue metastasis at T12 resulting in mild-to-moderate spinal canal stenosis but no definite cord signal abnormality. She received definitive treatment for her cancer in the spine, with thermal ablation of the T12 region, followed by vertebrectomy and reconstruction with cement stabilization T9-L3, and zolendronic acid therapy was commenced.
Following the further progression of cancer on positron emission tomography (PET) CT, with the increase in size and number of pulmonary metastases and new mesenteric disease, the patient was referred to for consideration of a phase I trial Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. Next-generation sequencing (NGS)– analysis for the detection of somatic mutations in the coding sequence of 50 genes (Ion Ampliseq 50-Gene Assay; Thermo Fisher) of retroperitoneal lymph node revealed an AKT1 E17K activating mutation and no other co-occurring alterations of functional significance (Supplementary Table ). The patient was enrolled on a phase I study of an allosteric pan-AKT inhibitor ARQ751 (NCT02761694). The patient received 25 mg daily orally initially and tolerated treatment without significant toxicity. As the protocol allowed intra-patient dose-escalation, the dose was escalated to 50 mg daily and subsequently increased to 75 mg daily. Treatment was relatively well-tolerated, requiring no dose reductions or interruptions of treatment. She experienced stability of disease (4% reduction by RECIST criteria version 1.1) lasting 27 months.
Following 27 months of AKT inhibition, RECISTv1.1 progressive disease was confirmed on restaging PET-CT imaging, showing an increase in the size of multifocal pulmonary metastases and increase in left axillary nodal metastatic disease. The patient underwent a CT-guided lung biopsy which confirmed adenocarcinoma consistent with the endometrial primary. NGS analysis (Oncomine®, Thermo Fisher) for the detection of somatic mutations in the coding sequence of 143 cancer-related genes was conducted, on this occasion on the DNA extracted from the patients’ metastatic pulmonary lesion, which confirmed the persistence of AKT1 E17K mutation, and an mTOR mutation, mTOR A1459D, annotated to be an activating mTOR mutation. Sequencing on the lung metastasis demonstrated a CTNNB1 G34R mutation which was also noted on the 50 gene panel of the initial sample. There were no other co-occurring alterations identified. Although the original 50 gene hotspot panel did not sequence mTOR, it was hypothesized that the mTOR mutation may be an acquired resistance mutation, thus, the original pre-treatment sample was re-sequenced on the Oncomine platform, confirming that the AKT1 E17K mutation, and but not the mTOR A1459D mutation was detected (Supplementary Table ).
The patient was subsequently enrolled on a phase I study of the mTORC1/2 inhibitor sapanisertib (TAK-228) given 4 mg daily with metformin 500 mg twice daily (NCT03017833). The patient achieved a confirmed partial response (PR) by RECIST criteria version 1.1 post-6 cycles of therapy (maximum reduction 30% from baseline) (Fig. ). The patient remains on trial at 14 months with good tolerability.


A 4-day-old female, born at 35 weeks’ 6 days’ gestation, presented with a skin eruption hours after birth. Pregnancy course included Group B Streptococcus positivity and preterm labor. Family history was negative for autoimmune and autoinflammatory diseases.
Physical exam revealed a comfortable and afebrile neonate with well-defined, annular and polycyclic, blanchable erythematous macules coalescing into patches on the trunk, upper extremities, and lower extremities. On the face, neck, trunk, and upper extremities were confluent, erythematous, blanchable macules and polycyclic patches (). On the lower extremities were erythematous, blanchable macules and patches. The patches were migratory with no single lesion persisting more than 24 hours. The eruption waxed and waned with no identifiable trigger. Labs were significant for an elevated C-reactive protein (CRP) of 158 mg/L (reference: 0.3-6.1 mg/L) and erythrocyte sedimentation rate (ESR) of 50 mm/hr (reference: 2-37 mm/hr). Antinuclear antibody, anti-Ro/SSA, and anti-La/SSB were negative. Infection was considered and infectious studies were negative. Vision and hearing exams were normal.
After several days, arthritis developed in the right 4th and left 2nd proximal interphalangeal joints (). The eruption improved spontaneously, and CRP improved but did not return to normal. A genetic test for autoinflammatory disease was sent and the infant discharged home.
Genetic testing identified a heterozygous VUS in NLRP3. No challenges to genetic testing were encountered. During outpatient follow-up, the infant had recurrent urticaria and irritability and was admitted to the hospital. The infant had aseptic meningitis, transaminitis, and systemic inflammation. Anti-cytokine therapy with anakinra, an IL-1 receptor antagonist, was initiated. Within 24 hours the skin eruption and symptoms improved. The infant continued daily anakinra with good response.


In February 2018, a 73-year-old Chinese man presented with a rough mass in his esophageal mucosa and surface hyperemia under gastroscopy. A biopsy sample of pathological diagnosis showed ESCC (). A computed tomography (CT) scan revealed obvious contrast-enhanced imaging of the upper esophagus with a thickening wall and narrowing lumen but without visible enlargement of the mediastinal lymph nodes (), and he was diagnosed with a T2N0M0, upper esophageal carcinoma. His biopsy tumor specimens were sent for next-generation sequencing (NGS) targeting 543 cancer-related genes as well as a PD-L1 (programmed death-ligand 1) assay at a CAP (College of American Pathologists)-certified laboratory (Genecast Biotechnology Co., Ltd.). Unfortunately, no actionable alterations with strong evidence for targeted therapy were identified in his primary lesion, where the expression level of PD-L1 (SP142 staining) was 5% (CPS close to 6) and microsatellite stability (MSS) was present (, ). Owing to the upper location of his tumor, this patient was unable to receive surgery. Given the fact that he had radioactive esophagitis and tracheitis (grade 3) during radiotherapy, we adjusted the originally planned therapeutic regimen, and sequential chemotherapy plus radiotherapy rather than concomitant definitive chemoradiation was used for him. Specifically, he received 3 cycles of paclitaxel liposome plus nedaplatin for 2 months followed by radical intensity-modulated radiotherapy (IMRT) (66 Gy at 2.2 Gy/session to the esophageal tumor) for 1 month until early July 2018 (). Nevertheless, the CT scan showed multiple enlarged lymph nodes of the right-side neck with suspected metastasis on June 25, 2018 (), which was verified by pathological diagnosis of a puncture biopsy of the right cervical mass (). Next, his punctured samples of the metastatic tumor were sent to the same laboratory as before for another NGS test and PD-L1 assay. Surprisingly, MSI-H along with dMMR () was observed in his metastatic tumor with the soaring percentage (TPS 70%, CPS 75) of PD-L1 (). According to these results, the patient was given adjusted treatments with pembrolizumab (100 mg, recommended dose 2 mg/kg at that time in China) combined with chemotherapy (docetaxel plus tegafur) or local IMRT (66 Gy at 2.2 Gy/session to the metastatic tumor) or single pembrolizumab treatment from July 2018 to March 2019 and exhibited sustained clinical response, regardless of primary or metastatic lesions (). Given the good response after adding pembrolizumab, this patient did not continue to undergo chemotherapy or radiotherapy but just maintained pembrolizumab (100 mg) monotherapy until June 2019 and achieved a complete response (CR) of both primary and metastatic tumors (). Subsequently, he stopped the above therapies in June 2019 and remained CR until the recent radiological evaluation in April 2021 ().


The proband was a 1-year and 11-month old boy at the time of admission. He is the third child with two healthy elder brothers of a non-consanguineous marriage, born after full-term by normal delivery, with a birth weight of 3000 g and allergy history of cephalosporin. No other members in the family have seizures. Nothing abnormal was observed in the perinatal period. Motor development and language development were mildly delayed before the onset of seizures, with an unbalanced gait and dual tone. The first two seizure episodes occurred within half a day when the temperature reached 39 °C at 1-year and 10-month old, which presented with generalized tonic-clonic, lasting for about 2 min per episode. Subsequently, the convulsion occurred twice during the following week without fever or other inducements. Twenty days later, the convulsion occurred again and presented as tonic of four limbs. Then the convulsion occurred more frequently (10–20/day) with varied epileptic seizure types such as myoclonic, atypical absence, atonic seizures a week before admission into our clinical center.
His height, body weight, and head circumference were 85.0 cm, 11.8 kg, and 48.0 cm respectively at the admission. He had no obvious craniofacial dysmorphisms with fontanel closure. No other positive signs were found upon physical examination except slight gait instability. Results from routine examination including urine/blood/cerebrospinal fluid, blood/cerebrospinal fluid biochemistry, blood electrolytes examination, blood glucose, cerebrospinal fluid pathogens, metabolic screening and brain magnetic resonance imagery were normal. Video-EEG monitoring was performed for 3 h which showed slow background activity accompanied by a 2 ~ 3 Hz slow activity major in anterior area (Fig. A), interictal EEG showed a large number of generalized high amplitude 2 ~ 2.5 Hz slow spike-and–wave complexes (Fig. B). Two atypical absence seizures with generalized high amplitude 2.5 ~ 3 Hz spike-and–wave complexes lasting 7 s (Fig. C); two atonic seizures with 1-2 Hz polyspikes-and-wave complexes and electromyography flat (Fig. D); and several myoclonic seizures with 1-2 Hz polyspikes-and-wave complexes and electromyography burst were recorded (Fig. E). The myoclonic seizures disappeared and atypical absence and atonic seizures improved with combined treatment of sodium valproate and nitrazepam. Then focal and general tonic-clonic seizures were seen during sleep occasionally. Follow-up EEG showed a large number of generalized high amplitude 1.5 ~ 2.5 Hz slow spike-and–wave complexes in the slow background (Fig. F). Lamotrigine then was added as the third drug for combination therapy, and after which the focal and general tonic-clonic seizures were well controlled and atypical absence, atonic seizures reduced. However, subsequently epileptic spasms emerged more than 10 times a day especially when he was quiet or shortly after waking up. During the two-month follow-up, the child exhibited gait instability and cognition regression, the Gesell scale scored 55, including gross motor 54, fine motor 47, language 70, cognition 50, social development 54. Based on the aforementioned clinical manifestations, the patient was diagnosed with Lennox-Gastaut syndrome (LGS). He was seizure-free with ketogenic diet combined with antiepileptic drugs forementioned finally. The blood Ketogen level was maintained at about 3 mmol/L.
To identify the potential pathogenic mutations, the proband and the parents’ genomic DNA was extracted from peripheral blood lymphocytes using the QIAamp® Blood Mini Kit (Qiagen, Hilden, Germany) and subjected to whole-exome sequencing (WES) on Illumina NovaSeq6000 (Illumina, San Diego, CA, USA). The read mapping, variant calling, genome annotation, and variant prioritization were performed as described previously [], the variant was classified according to standards and guidelines of the American College of Medical Genetics and Genomics (ACMG) []. The results were also confirmed by Sanger sequencing. WES showed only one de novo heterozygous mutation c.4321C > T (p.Gln1441Ter) in TANC2 gene (NM_025185.4) in the proband (Fig. ). No other rare variants in any other genes associated with LGS reported previously were found in the patient. This nonsense mutation would lead to premature translation termination and has no allele frequency in several commonly used databases (i.e., dbSNP, gnomAD, ClinVar, HGMD). The in silico prediction score of GERP (Genomic Evolutionary Rate Profiling), LRT (Likelihood ratio test) and Mutation Taster is 5.29, 0 and 1 respectively which indicate pathogenicity. According to the ACMG clinical variant interpretation guidelines, the pathogenic evaluation of this variant was “PVS1 + PS2 + PM2”, which classified as “Pathogenic”. The genetic characteristics and pathogenetic analysis of the variant in TANC2 were displayed in Table .


A 52-year-old male presented to the emergency room complaining of intermittent fever, chills, weight loss, and night sweats for the past six months. His medical history was significant for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (CD4 count of 54 cells/mL but adherent to antiretroviral therapy), remote history of intravenous drug use (last use one year ago), and treated hepatitis C infection. He was homeless but currently living in a group home. At presentation, there was no leukocytosis, but he was febrile at 102.1°F. Physical examination revealed decreased breath sounds with low oxygen saturation in the mid 80% requiring nasal cannula; however, no murmurs, Osler nodes, or Janeway lesions were noted. His labs were significant for an elevated C-reactive protein of 113.2 mg/L (0.00-5.00 mg/L) and N-terminal pro b-type natriuretic peptide level of 3,973 pg/mL (0-450 pg/mL). Chest computed tomography with contrast showed enlarged mediastinal lymph nodes and diffuse airspace disease within the right lung. Blood cultures collected before antibiotic administration remained negative at five days. His transthoracic echocardiography (TTE) and transesophageal echocardiogram (TEE) revealed a large, freely prolapsing vegetation on the right coronary cusp of the aortic valve, measuring 2.1 × 0.6 cm with associated severe aortic regurgitation (Figure ). Infectious Disease was consulted seven days after admission due to negative blood cultures and echocardiogram findings. Serologic testing for Bartonella was obtained given the epidemiological history of homelessness, HIV/AIDS, and exposure to cats. Testing revealed a positive immunoglobulin G (IgG) titer of 1:2,560 for B. henselae and IgG titer of 1:640 for B. quintana. The patient completed an inpatient course of gentamicin for the first two weeks and doxycycline and rifabutin for six weeks. Cardiothoracic Surgery was consulted, but the patient was deemed high risk for surgical intervention. Repeat TTE at the end of the antibiotic therapy showed improved aortic regurgitation with a marked reduction in the size of the vegetation to 0.7 × 0.3 cm (Figure ). The modified DUKE criteria were met given the echocardiogram, history of intravenous drug use, fever, and serology. Tuberculosis was ruled out with subsequent negative results on QuantiFERON, bronchoalveolar lavage acid-fast smear, Mycobacterium tuberculosis nucleic acid amplification, and culture. Due to the high risk of septic embolization, lack of early surgical intervention, and immunocompromised state, a decision was made to extend his antibiotic therapy for six more weeks.


A 7-year-old female child was admitted to our hospital (Government General Hospital, Ernakulam) with complaints of dyspnoea on exertion and palpitations. She was apparently normal and even active in sports, a month prior to the development of her symptoms. She was born by full-term normal vaginal delivery and had normal birth weight with no relevant past medical history.
Initial physical examination at the pediatric outpatient department revealed no dysmorphic features apart from soft skin that was not striking, and a high-volume collapsing pulse. A blood pressure of 120/50 mmHg was recorded in bilateral arms. Significant findings from a cardiovascular examination included a precordial bulge, multiple visible pulsations over the precordium, gross cardiomegaly with hyperdynamic apex palpable over the left 5th intercostal space, early diastolic murmur over the second intercostal space/aortic area, and pansystolic murmur over the apex upon auscultation. The electrocardiogram showed sinus rhythm with a rate of 75 per minute and p mitrale (). Upon a cardiology consultation, her echocardiography revealed situs solitus, levocardia, normal AV-VA concordance, intact inter-atrial septum and ventricular septum, good biventricular function, aneurysmal dilatation of the ascending aorta and the arch, severe AI, mild mitral regurgitation with no patent ductus arteriosus, a trileaflet AV without vegetations, no coarctation, and normal left ventricular (LV) ejection fraction.
A computerized tomography (CT) aortogram revealed two fusiform aortic aneurysms involving the ascending aorta and arch, and another involving the distal arch and the proximal descending thoracic aorta with cardiomegaly (). A “sausage link” appearance of the aneurysmal aorta together with the observed arterial tortuosity raised a strong suspicion for hereditary aortopathy (). Parents of the child were not known to be consanguineous. A CT angiogram of the head detected no aneurysms or any other abnormal findings. The laboratory investigations (blood and urine) including troponin levels were within normal limits. Blood cultures taken prior to the initiation of any treatment were sterile after 5 days of incubation. Gene sequencing analysis showed negative findings for mutations in FBN1, FBN2, TGFBR2, TGFBR1, ACTA2, and SLC2A10 but a positive finding for a mutation in EFEMP2. A homozygous missense variation in exon 7 of the EFEMP2 gene (c. 608A>C) resulted in an amino acid substitution of alanine for aspartic acid at codon 203 (p. Asp203Ala), indicative of an autosomal recessive pathogenic variant of cutis laxa type 1B.
The patient was admitted for cardio-thoracic surgical intervention. She underwent a valve-sparing (David V procedure) operation along with an aortic arch replacement (). Histopathological assessments of the resected tissue samples demonstrated disorganization and fragmentation of elastin and collagen fibers (). Intra-operative and postoperative periods were uneventful. Anterior mediastinoscopy and drainage of mediastinal collections were performed after 2 weeks. Post-operative blood, urine and mediastinal cultures were negative. In view of low-grade fever and mediastinal collections, empirical antibiotics (intravenous meropenem and amikacin) were given for a period of 36 days post-operatively. Her post-operative echocardiogram revealed moderate AI, mild mitral regurgitation, mild to moderate LV dysfunction and aortic valve area (1.7 cm2, p = 11 mmHg), negligible tricuspid regurgitation and no pulmonary arterial hypertension. The patient improved symptomatically after the surgery but was retained in the hospital for over 2 months in view of the prevailing COVID-19 pandemic. She was prescribed aspirin (325 mg), furosemide (5 mg), and spironolactone (12.5 mg) and was eventually discharged under good medical conditions, with heeded caution to have systematic, life-long follow-ups.


A 71-year-old male ventilated patient in the intensive care unit (ICU), following a cardiac arrest that required an emergency percutaneous coronary intervention (PCI), had a fine bore (10 French) NGT inserted for enteral feeding. The procedure was uneventful and followed by routine safety checks. Post-procedure x-rays confirmed apparently correct placement and feeding was subsequently started (Figure ). It was noted that he had four different tubes inserted in his first week of ICU stay. Five days following the last NGT insertion, the patient developed abdominal distention and worsening respiratory parameters. A contrast computed tomography (CT) scan of the chest confirmed a gastric perforation with the tip of the NGT lying behind the spleen, as well as a perisplenic collection with localised locules of gas (Figures , ).
As the patient’s condition remained stable with no peritonism on clinical examination, in addition to being a high-risk candidate for surgery due to the ongoing medical issues, conservative management was adopted. The management included proton pump inhibitor (PPI) infusion, total parenteral nutrition (TPN), regular gastric aspiration through a wide bore Ryle tube, and consideration of imaging-guided drainage. Eventually, the stability of his physiological parameters and clinical status suggested a sealed or contained perforation. The patient died a week later due to a massive intra-cardiac thrombus.


A 67-year-old man was referred to our office by his primary care physician for evaluation of hyperglycemia and elevated hemoglobin A1c (HbA1c) level. In previous yearly physical examination, his laboratory data were as follows: plasma glucose, 107 mg/dl; HbA1c, 5.6% at the age of 66. In addition, 3 months before his plasma glucose was 129 mg/dl and HbA1c was 6.8%. There was no significant past medical and family history. His height, body weight, and body mass index (BMI) were 155.0 cm, 55.0 kg, and 22.9 kg/m2, respectively. His vital signs were as follows: temperature, 36.7°C; blood pressure, 118/62 mmHg; heart rate, 76 beats/min; and oxygen saturation, 98%. shows laboratory data on admission. Diabetes-associated data were as follows: plasma glucose, 391 mg/dl; HbA1c, 13.5%; glycoalbumin, 55.3%; total ketone body, 1,195.7 μmol/L; acetoacetate, 265.5 μmol/L; and β-hydroxybuterate 930; 1 μmol/L. In addition, autoimmune markers of diabetes mellitus were as follows: anti-GAD antibody, 61,841.1 U/ml; anti-IA-2 antibody, 18 U/ml; anti-ICA, negative; and anti-ZnT8 antibody, negative.
On admission, we thought that he had acute onset T1DM and started insulin therapy (4 units of aspart before each meal and 4 units of degludec at once). After, his glycemic control was dramatically improved, and he was discharged about 2 weeks later. It is difficult to decide whether we should continue or stop insulin in patients with SPIDDM. In this subject, we chose DPP-4 inhibitor instead of insulin or other medicine for the following reasons. First, a recent consensus statement on latent autoimmune diabetes in adults (LADA), which may be slightly different from SPIDDM in pathology, recommends repeated measurement of serum C-peptide levels and selection of treatments, such as insulin or antidiabetic drug, depending on each C-peptide level (). This report suggests that DPP-4 inhibitors represent a potential therapeutic alternative for effective management of LADA. Second, while metformin is recommended to be used as a first choice in Europe and the USs, DPP-4 inhibitor is often used as a first choice in Japan. In addition, since our patient was not obese, we selected DPP-4 inhibitor, but not another antidiabetic drug such as metformin. Based on the abovementioned reasons, we tapered insulin dose in outpatient clinic. About 3 months later, we discussed the necessity of insulin therapy with our medical staffs and the patient himself, and finally we took the courage to stop insulin therapy and change to 50 mg of sitagliptin. Nonetheless, interestingly, his glycemic control was continuously very good and HbA1c levels were about 6% for over 4 years with sitagliptin therapy alone (). In addition, his homeostatic model of assessment (HOMA)-β, a marker for pancreatic β-cell function (criteria for decreased insulin secretion range: <30), showed that his β-cell function was preserved for such a long period, although it was lower compared to its reference range.
Since β-cell function in this subject was preserved for a long period (about 4 years) with dipeptidyl peptidase-4 inhibitor alone, we examined his glucose-stimulated insulin secretion (GSIS) with 75 g oral glucose tolerance test. As shown in , his GSIS was preserved, although it was decreased. HOMA-β was correlated with insulinogenic index, fasting serum C-peptide immunoreactivity index (CPI) and secretory units of islets in transplantation (SUIT) index. His insulinogenic index, CPI and SUIT index were 0.15 (criteria for decreased insulin secretion: < 0.4), 0.78 (≤0.8) and 25.33 (<30), respectively. The abovementioned all β-cell markers indicated that his β-cell function was not exhausted, although it was deteriorated to some extent.


On February 11, 2020, a 73-year-old woman came to the Fever Clinic of the First Hospital of Changsha, China. Ten minutes later, she was taken to the examination room and evaluated by a clinic doctor. The chief complaint of the patient was a fever—her body temperature peaked at 39°C—with cough, expectoration, shortness of breath, and general weakness that started prior 5 days. She developed mild diarrhea (3–4 stools/day) 2 days prior to coming to the hospital. Her daughter was diagnosed with COVID-19. Given her symptoms and recent close contact with a COVID-19-positive patient, she decided to go to a healthcare provider. The patient had a history of cirrhosis and type 2 diabetes, but no history of smoking or drinking. Physical examination indicated a body temperature of 38.8°C, a pulse of 100 beats/min, a respiratory rate of 22 breaths/min, an oxygen saturation of 85%, and bowel sounds at four times/min. She presented with a characteristic feature of chronic liver disease, hepatic facies, and liver palms, but no spider nevus. In addition, she had thick breathing sounds on both sides of the lungs and audible wet murmurs in both the lungs. The abdomen of the patient was soft and had no lumps. No pain was found in the liver without mobile dullness.
Considering the possibility of SARS-COV-2 infection, we performed a chest CT examination and found bilateral pneumonia (). The results of a nucleic acid amplification test (NAAT) for influenza A and B were negative. Her blood tests demonstrated simultaneous reduction of the ternary systems (red blood cells: 2.83 × 1012 cells/l; peripheral blood hemoglobin: 83 g/l; white blood cells: 0.78 × 109 cells/l; lymphocytes: 0.11 × 109 cells/l; lym%: 14.5%; platelets: 41 × 109 cells/l) and an elevated percentage of neutrophils (0.65 × 109/L; n%: 82.8%), C-reactive protein (62.5 mg/l), and erythrocyte sedimentation rate (129 mm/h) (). In view of the close contact history and clinical examination results of the patient, we carried out COVID-19 test for the patient. Specimens were collected following the Chinese Center for Disease Control and Prevention (CCDC) guidance. The results showed that she tested positive for SARS-COV-2. Therefore, she was admitted to the isolation ward for further treatment.
On day 1 of the hospital stay (illness day 5), the patient was administered lopinavir and ritonavir tablets (2 pills BID peros), which were recommended by the Diagnosis and Treatment of Pneumonitis with COVID-19 Infection (DTPI) published by the National Health Commission of the People's Republic of China (PRC) and interferon alpha-2b injection (5 million IU added into 2 ml of sterile water, inhalation BID). To inhibit inflammation in the lungs, she was treated with methylprednisolone sodium succinate (40 mg QD, intravenously). Yellow-green expectoration predicted the presence of a bacterial infection and, as such, moxifloxacin hydrochloride and sodium chloride injection (0.4 g QD) were given intravenously to the patient as treatment. Moreover, other supportive treatments included human immunoglobulin (10 g QD, intravenously) for improving immunity, Bifidobacterium lactobacillus trifecta orally for regulating the intestinal flora, recombinant human granulocyte colony-stimulating factor for promoting cell proliferation, and ampeptide elemente tablets for promoting the formation of platelets.
On day 2 of the hospital stay (illness day 6), she was asymptomatic apart from a cough, expectoration, chest tightness, and shortness of breath. Additionally, her temperature dropped to 36.9°C, but she reported that diarrhea still existed, approximately four times/day (). CT scans showed that the patchy infiltration was scattered as a small range of ground-glass opacity effusion and strip lesions in the bilateral lungs, which was similar to day 1 in the hospital (). Otherwise, the laboratory results reflected that there was still a reduction in the tertiary system and hypoproteinemia due to liver dysfunction. Human serum albumin (50 ml BID) was then given intravenously. To prevent of episodes of hepatic encephalopathy, which is a chronically debilitating complication of hepatic cirrhosis, lactulose was added to the therapeutic regimen of the patient and nutritious meals were supplied to improve her anemia. The CCDC repeatedly confirmed that the oropharyngeal swabs of this patient tested positive for SARS-CoV-2 by real-time reverse transcription PCR (rRT-PCR) assay.
On day 3 of the hospital stay (illness day 7), the patient reported she felt better. Her pulse oxygen saturation increased significantly, up to 100%, at an oxygen flow rate of 2 l/min. Since that she still had diarrhea symptoms and lactulose was stopped to avoid the occurrence of imbalance of water and electrolytes. On day 4 of her hospital stay (illness day 8), a gastroenterologist was contacted to evaluate the persistent diarrhea of the patient. According to the suggestion of the gastroenterologist, the patient was treated with pantoprazole enteric-coated tablets (40 mg QD orally) for acid suppression. In addition, reduced glutathione (0.6 g QD) was given intravenously to protect her liver from subsequent damage.
On days 5–10 of the hospital day (illness days 9–14), the patient reported that her diarrhea improved to a degree and her clinical condition improved with supportive care. On hospital day 6 of the hospital stay, CT scans showed that the partial patchy lesions in the bilateral lungs were absorbed compared with the CT images obtained previously (). Given the clinical presentation of the patient, treatment with human serum albumin was stopped on day 6 of the hospital stay. Lopinavir and ritonavir tablets, methylprednisolone sodium succinate, moxifloxacin, ampeptide elemente tablets, pantoprazole enteric-coated tablets, and human immunoglobulin were stopped on day 8 of the hospital stay of the patient (). However, the clinical course of the patient continued to deteriorate in terms of her respiratory symptoms, who typically presented with a cough and shortness of breath. Thymosin (0.1 g QD) and plasma (200 ml) from recovered COVID-19 patients plasma were then given intravenously to boost the immunity of the patient. On day 9 of the hospital stay (illness day 13), the C-reactive protein of this patient dropped to 3.4 mg/l. Nevertheless, CT scans of the chest indicated that the symptoms of the bilateral lungs of the patient did not improve on day 10 of the hospital stay (). Moreover, the oropharyngeal swabs of this patient retested positive. Therefore, chloroquine phosphate (0.5 g BID) was administered orally instead. Additionally, the treatments did not improve the level of blood cells because of liver dysfunction and hypersplenism caused by cirrhosis.
On days 11–18 of the hospital stay (illness days 15–22), she was in good clinical condition, except for a persistent cough and intermittent diarrhea. In order to further alleviate the diarrhea of the patient, montmorillonite powder (3 g QD) and loperamide hydrochloride (2 mg QD) were administrated orally. Moreover, interferon alpha-2b injections were stopped due to its limited effect on the clearance of the virus and the plasma from recovered COVID-19 patients was infused again on day 15 of the hospital stay (illness day 19). As the diarrhea of the patient improved, antidiarrheal drugs were discontinued on day 18 of the hospital stay (illness day 22).
On days 19–29 of the hospital stay (illness days 23–33), the vital signs of the patient were largely stable. The patient reported that her cough and diarrhea had abated and her clinical condition improved. Given these good clinical conditions, a reduction in glutathione injections was initiated on day 19 of her hospital stay. However, since the oropharyngeal swabs of this patient tested positive again, she was treated with plasma from a recovered COVID-19 patient for the third time. On day 29 of the hospital stay (illness day 33), CT scans showed that the patchy lesions in the bilateral lungs of the patient had absorbed compared with the CT images obtained previously (). On the same day, the patient tested negative for COVID-19 infection (). On day 30 of the hospital stay (illness day 34), the patient was once again treated with the plasma from a recovered COVID-19 patient in order to ensure that the virus was completely cleared. On days 30–31 of the hospital stay, the patient tested negative for COVID-19 by an rRT-PCR assay for two times. She was discharged on March 13, 2020 (day 32 of the hospital stay, illness day 36).


A 27-year-old female visited the hospital with a complaint of retention of urine for one day. The patient also had a history of low back pain radiating to the right leg, which developed gradually over eight years. She also noted this pain at rest and developed lower limb weakness during the same period. The pain significantly reduced the walking distance. Her past medical history was unremarkable. Neurologic examination revealed decreased strength in the right leg (MRC grade - 3/5). The tone of the anal sphincter was normal. No significant finding was noted in the blood tests. Magnetic resonance imagining (MRI) of the whole spine revealed a large, space-occupying, intradural spinal lesion extending from the D11 to S1 segments (Figure ).
The patient was catheterized and underwent laminectomy from D10 to S1. This allowed intradural exploration and removal of the mass. The tumor was attached to the conus medullaris. It was carefully removed and was duly confirmed by the postoperative MRI (Figure ).
Histopathological examination revealed pseudo-rosettes characteristic of World Health Organization Grade II ependymoma but lacked features unique to the myxopapillary subtype such as mucin (Figure ) [].
The patient tolerated the procedure well and was discharged from the hospital in a stable condition.


A 44-year-old Hispanic man presented in 2014 with a history of hypertension and had a urine protein (pr): creatinine (cr) ratio of 1.34 with 5-10 red blood cells per high power field on urine microscopy. His BUN was 14 and serum creatinine 0.7 mg/dL. Serological workup was negative. Kidney biopsy revealed IgAN with mesangial proliferative and sclerosing changes with mild to moderate activity and mild chronicity. By the updated 2017 Oxford classification of IgAN, he had M1, E0, S1, T0, C2 where M is Mesangial hypercellularity, E is endocapillary proliferation, S is segmental sclerosis, T is tubular atrophy and interstitial fibrosis and C is crescents. In addition, he had mild arteriolosclerosis.
After a four-month trial of an ARB, losartan, titrated to the highest dose, he still had urine pr:cr ratio of 1.16. He then received the Pozzi protocol consisting of six months of corticosteroids with three-day boluses of intravenous solumedrol on months 1, 3, and 5 and prednisone 0.5 mg per kg body weight on alternate days throughout the six month period. He went into remission with a decrease of urine pr:cr ratio to 0.19 within four months by March 2015.
He remained in remission on losartan 100 mg while tested with semiannual urine pr:cr ratios through October 2019. In March 2020, he acquired a COVID-19 infection but was not hospitalized. At an outside laboratory, his urine alb:cr ratio increased to 555 mg/g in August 2020. As noted in Table , in November 2020, his urine alb:cr ratio was 428 mg/g with a urine pr:cr ratio of 0.8. His then ARB (valsartan) dose was increased. One month later, we prescribed dapagliflozin 10 mg as a treatment for IgAN given his rising proteinuria, but he took canagliflozin due to cost considerations. Three months after starting the canagliflozin, his urine pr:cr ratio decreased to 0.3, a 62% reduction in proteinuria.


A 52-year-old woman presented at the emergency department with pyrexia (38,3°C), lower abdominal pain and tenderness in the right iliac fossa. The pain lasted since the night before. She complained of vomiting.
The blood tests showed elevated inflammatory parameters: leucocytes: 19.4 × 109/l (91% of Neutrophils) and C-reactive protein: 312 mg/l.
Abdominal CT showed signs of non-complicated appendicitis: intra-appendicular liquid, microstercoliths and peri-appendicular inflammation ().
The patient underwent appendectomy for acute appendicitis progressing in <24 hours.
The main operative finding was a purulent peritonitis of the right abdomen. There was a lot of inflammation into the ileocecal mesentery. We performed a laparoscopic appendectomy and meticulous peritoneal lavage. We left in place two abdominal drains (Jackson Pratt).
Because of purulent peritonitis and presence of Escherichia Coli in blood cultures, intravenous antibiotherapy (amoxicillin and clavulanic acid) was prolonged after surgery for 5 days.
On the sixth post-operative day, the patient suddenly felt weak. She presents with pallor, hypotension and tachycardia. We noticed some blood in the left drain. We immediately started a fluid resuscitation and performed an urgent CT which showed a fresh 6-cm wide splenic sub capsular hematoma associated with a major hemoperitoneum ().
First, we embolized the splenic artery with coils (). The patient was getting well at intensive unit care, but few hours after embolization, she was shocked again.
We decided then to perform an emergency laparotomy that revealed a massive splenic hematoma and a totally burst spleen. We carried out the splenectomy and controlled the splenic vessels.
A paralytic ileus and a secondary pleural effusion marked the second post-operative period. The patient has recovered in 2 weeks and was finally discharged 1 month after initial admission for acute appendicitis.


A healthy 35-year-old man presented to his local A&E with a short history of left arm weakness and facial droop. He also complained of a right-sided headache and neck stiffness. On examination, his vitals were normal and glasgow coma scale (GCS) was 15/15. Neurological examination revealed mild left facial droop and a power of 4/5 in his left upper limb with sensory loss. Computed tomography brain did not show any infarction or bleeding. A lumbar puncture ruled out meningitis and subarachnoid haemorrhage. He later collapsed with left hemiplegia and was urgently transferred to a tertiary centre where magnetic resonance imaging confirmed multiple embolic infarcts in the right middle cerebral artery (MCA) territory. He was started on dual antiplatelet therapy as standard stroke management. Despite this, he developed two further episodes of hemiplegia with expressive aphasia. Repeat imaging confirmed new infarctions in the right MCA territory, a new infarction in the right anterior cerebral artery territory and a right M1 thrombus. In light of this, he underwent a thrombectomy that did not resolve his symptoms. Numerous blood tests such as anti-ENA, ANCA, HIV and antiphospholipid antibodies were negative. Echocardiography ruled out mural thrombi and a 7-day Holter monitor ruled out arrhythmias. Additional imaging revealed an elongated right styloid in close proximity to a 15-mm internal carotid artery (ICA) dissection, leading to a diagnosis of stylocarotid Eagle’s syndrome.
Treatment modalities vary according to the type of Eagle’s syndrome encountered but are conservative or surgical []. Conservative treatment for the classical type entails the use of non-steroidal anti-inflammatory medication, corticosteroids, anticonvulsants and antidepressants, similar to the treatment of trigeminal neuralgia and neuropathic pain [], in addition to patient education on avoiding over-flexion and over-extension of the neck []. The latter is generally managed surgically, either intraorally or extraorally to resect the elongated styloid, both with high success rates of 93.4% [, ]. Considering the higher morbidity and complication risk with the intraoral approach such as deep neck space infection, neurovascular injury, airway oedema and the need for an ipsilateral tonsillectomy, most surgeons favour a pharyngeal approach through a transcervical incision []. The extraoral approach provides better visualisation of the operative field albeit comes with a price of longer operating time and a visible surgical scar. The risk of iatrogenic neurovascular injury cannot be eliminated either [].


A 54-year-old male sustained an AO 31B2.3 fracture of the left hip (Pauwels type 3 fracture; ). Mechanism of injury was a fall with a moped. Within 6 h we operated the patient in the supine position under general anesthesia. After a Smith-Peterson approach and capsulotomy, a pointed reduction clamp kept the fracture reduced and compressed. Blood supply to the femoral head was confirmed by drilling a small hole in the head that showed bleeding. The fracture was fixated with three fully threaded cannulated screws (7.3 mm) with washers in an inverted triangle configuration. Next, we inserted a 6-hole 3.5 mm titanium reconstruction LCP plate (DePuy Synthes, Amersfoort, the Netherlands).
The plate was contoured and positioned on the anteromedial side of the femoral neck; between the 5 and 6 o'clock position. When testing the hip prior to closure an audible clicking was noted on flexion and rotation of the hip. We thought the posterior cannulated screw was malpositioned with its middle section posteriorly outside of the neck. However, after removing this screw, the click persisted. We noticed that the proximal end of the anteromedial buttress plate was impinging on the acetabulum. The plate was removed, and replaced by a shorter plate (4-hole), more distal and medial (). The posterior cannulated screw was not replaced because we were not sure if it had been malpositioned. Replacing it in a more anterior position was tried but the guidewire kept slipping into the prior entry point. We felt the fixation with 2 screws and a plate was strong enough. He started toe-touch weightbearing for 6 weeks. At 6 weeks, he started partial weightbearing but reported pain after 2 months. Discussing the options of waiting versus early intervention (Pauwels' osteotomy) versus a total hip arthroplasty, the patient elected a Pauwels' osteotomy. We were comfortable offering a Pauwels' osteotomy given our large experience with this technique. This second surgery was 60 days after injury. A lateral closing wedge of 35 degrees was removed. A 5-hole 120-degree angular blade plate (85 mm) was inserted. At 6 weeks the radiographs showed early consolidation of both the femoral neck non-union and the Pauwels' osteotomy. He started partial weight bearing at 6 weeks, and full weight bearing at 3 months. At 4.5 months he was pain-free with full range of motion of his hip and a normal gait. He did not return for follow up until 29 months. Radiographs showed a healed osteotomy and a healed nonunion (). The patient reported 1 on the NRS pain scale (10 being worst pain possible) and 95 points (maximum 100) on the Harris Hip score (HHS).


A 43-year-old male sustained an AO 31B2.3 hip fracture (Pauwels type 3 fracture; ) in a bicycle accident. Within 6 h, we operated the patient in the supine position under general anesthesia. After anatomic reduction via a Smith-Peterson approach, we placed a 5-hole LCP reconstruction plate on the anteromedial side of the femoral neck. Blood supply to the femoral head was confirmed by drilling a small hole in the head that showed bleeding. Three partially threaded cannulated screws (7.3 mm) with washers were inserted. He was toe-touch weightbearing for 6 weeks. Radiographs at 6 weeks suggested bony bridging. He advanced to partial weightbearing at 6 weeks. At 7 months, a CT-scan showed a nonunion (). An MRI at that same time did not show evidence of avascular necrosis. A Pauwels' osteotomy was offered. A lateral closing wedge of 20 degrees was removed. A 110-degree angular blade plate (85 mm) was inserted. At 6 weeks post-operatively, he was partial weight bearing. At 3 months follow up he was fully weight bearing. At 21 months he returned for a follow-up visit. He was pain-free with full range of motion with excellent outcome scores (NRS 1, HHS 94). Radiographs showed consolidation (), Brooker grade 1 heterotopic ossification without avascular necrosis or arthrosis.