A 55-year-old, 68 kg male with no significant past medical history and surgical history presented to the emergency room for the emergent repair of obstructed umbilical hernia. Clinical examination and laboratory evaluation were in normal range except for a mild increase in blood urea nitrogen (BUN). The patient was classified as American Society of Anesthesiologists (ASA) class 2. Initially, he was managed conservatively and later shifted to the operating room after a fast of 6 hours. He denied a history of previous exposure to anesthetic agents and preoperative evaluation did not reveal any features suggestive of difficult intubation. Ringer lactate infusion was done via 18G IV cannula and premedicated with nalbuphine. Monitoring included electrocardiography (EKG/ECG), noninvasive blood pressure (NIBP), and pulse oximetry (SpO2). Baseline SpO2 was 98% on room air with a blood pressure of 135/92 and a heart rate of 108 beats per minute, respectively. General anesthesia (GA) was planned. The patient was pre-oxygenated with 100% oxygen for 5 minutes, and induction was performed using propofol 10 mg in incremental doses and succinylcholine (100 mg). After a minute of observing no fasciculations, laryngoscopy was attempted but failed due to the inability to open the mouth. His jaw was fixed, absolutely immobile (Jaws of steel) that made laryngoscopy impossible. Considering the risk of masseter muscle spasm, intubation was aborted and mask ventilation was started. Mask ventilation maintained oxygen saturation at 100%. The patient regained spontaneous respiration after 10 minutes abandoning external ventilation. Meanwhile, the temperature was checked and found to be 98°F. His musculoskeletal examination did not reveal any rigidity or stiffness anywhere else in the body. Urine output was also adequate and non-bloody.
Keeping in view high susceptibility of malignant hyperthermia (MH) and unavailability of life-saving drug dantrolene at our center, all halogen-containing anesthetics were withheld and the decision was changed from GA in favor of total intravenous anesthesia (TIVA). He was assessed again for mouth opening; jaw was a bit lax but still unable to perform laryngoscopy. Laryngeal mask airway (LMA) was possible and placed. Propofol was used for anesthesia maintenance for its demonstrated benefits and atracurium for muscle relaxation. Intraoperative vital monitoring remained unremarkable during the entire procedure. Neostigmine 2.5 mg and atropine 1 mg were used as reversal agents. The patient regained spontaneous respiration with adequate breathing effort and tidal volume. LMA was removed and SpO2 maintained at 98% on room air. His muscle power was normal with a head lift for more than 5 seconds. His mouth opening was now possible without any difficulty, returning to the baseline.
Post-operatively, the patient was upgraded to the intensive care unit (ICU) for closed observation of MH. Continuous vital signs monitoring was done for 24 hours and the patient remained afebrile, throughout. Laboratory evaluations were significant for creatine phosphokinase (CPK) levels of 889 U/L (normal range: 22-198 U/L) and serum potassium (K+) levels of 5.7 mmol/L (normal range: 3.5-5.2 mmol/L) with normal serum chemistry, hematology, and urinalysis. Absence of rigidity/stiffness anywhere else, normal body temperature, and elevated CPK; a diagnosis of isolated masseter muscle rigidity induced by succinylcholine was made and the patient was downgraded to floor. The patient's postoperative period was uneventful and was discharged on the third postoperative day with special instructions of not receiving succinylcholine or other halogenated anesthetics in the future. A muscle biopsy with caffeine testing was advised to rule out MH.


An 85-year-old woman from a nursing home who had a past medical history of end-stage renal disease on hemodialysis, type 2 diabetes, hypertension, coronary artery disease, Alzheimer’s dementia, and deep vein thrombosis transferred to our facility from her nursing home due to desaturation. A CT angiography (CTA) was performed, and pulmonary embolism was not found. The patient was then diagnosed with sepsis due to pneumonia and an infected decubitus ulcer.
The patient was nonverbal as a baseline, and because she had difficulty in swallowing, it was necessary to initiate feeding with an NGT. A house staff resident blindly performed the NGT insertion, and the tube entered the patient’s left lung. A portable bedside CX-ray confirmed the incorrect NGT placement in the left main bronchus that resulted in left-sided PTX (Figure ).
CT of the chest revealed a partial collapse of the left lung (Figure ), confirming left-sided PTX secondary to NGT placement.
The patient was placed on oxygen with a nonrebreather mask, on 15 L/minute, and with 80% fraction of inspired oxygen. Immediate insertion of a chest tube (12 Fr catheter) resulted in a subcomplete resolution of the PTX on the left side, with remaining apical PTX. The CX-ray taken after the first chest tube placement revealed remaining apical PTX and suboptimal expansion (Figure ).
The next day, it was necessary to place another chest tube due to the incomplete resolution of the left-sided PTX. The chest tubes were set to intermittent wall suction. The CX-ray after the second chest tube placement shows almost complete resolution of left-sided PTX (Figure ).
After complete resolution of the PTX, the two chest tubes were removed in a stepwise manner over three days, and an additional CX-ray was obtained.
The patient still required an NGT for feeding, and therefore, VAL (GlideScope®, Verathon Inc., Bothell, WA) was used to prevent incorrect insertion of the NGT. After the NGT was placed, a CX-ray was performed (Figure ).
After proper insertion into the stomach, enteral feeding was successful. The patient later finished the treatment course and eventually was discharged back to the nursing home.


A 71-year-old male with a past medical history of dementia and seizures was brought by paramedics due to five episodes of witnessed generalized tonic-clonic seizures. The patient was post-ictal on arrival in the emergency and was slightly agitated later on. There was no reported history of tongue biting or loss of bladder or bowel incontinence. The patient was reportedly compliant with his antiseizure medications, which included oxcarbazepine and lacosamide. On physical examination, vital signs were stable. The patient was disoriented, agitated, and not following commands. The rest of the physical examination was unremarkable. Labs, including complete blood count and basic metabolic panel, were unremarkable except mildly elevated white blood cell count of 12.3 x 103/uL. Creatinine kinase levels were normal. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) for COVID-19 came back positive. Chest X-ray (Figure ) showed cardiomegaly, but no acute infiltrates. Computed tomography (CT) of the head did not show any acute abnormalities. The patient was loaded with intravenous Keppra® and admitted to the hospital. Electroencephalography (EEG) (Figure ) showed generalized sharps with slowing. The patient subsequently improved with his mentation back to the baseline. He did not have any further seizures. The patient was finally discharged with increased doses of oxcarbazepine and lacosamide.


A 78-year-old male resident of a nursing home with a past medical history of hypertension, diabetes type 2, and dementia presented to the hospital with the symptoms of altered mental status. The patient started having generalized tonic-clonic seizures on arrival in the emergency room. The patient did not have any witnessed seizure activity in the nursing home but had fallen with face down on the floor. The patient did receive Versed® by paramedics. The patient was unresponsive in the emergency room after the seizure. On physical examination, vitals were stable with no evidence of hypoxemia. The chest was clear to auscultation. The cardiovascular examination was unremarkable. The abdomen was soft and non-tender, and bowel sounds were positive. Neurological examination was significant for unresponsiveness, with the patient only responding to painful stimuli. Pupils were equal and reactive to light. Initial workup in the emergency room was significant for leukocytosis, metabolic acidosis with lactic acid greater than 18 mmol/L, and acute renal failure. Labs are shown in Table . rRT-PCR for COVID-19 was positive. Chest X-ray (Figure ) showed bibasilar small airspace disease. CT of the head was unremarkable for any acute abnormalities. Magnetic resonance imaging (MRI) of the brain was unremarkable as well. CT of the abdomen also showed no acute abnormalities. The patient was started on intravenous fluids and empiric intravenous antibiotics. Ammonia levels were 354 umol/L on admission, and the patient was started on lactulose through a nasogastric tube for hepatic encephalopathy. Ultrasound liver did not show any evidence of liver disease. EEG (Figure ) performed on admission did show left-sided sharps with background slowing. The patient was also loaded with intravenous Keppra on arrival in the emergency room and later on continued during the hospital course. The patient did not have any further seizures during the hospital course. The patient made a remarkable recovery with no need for ventilation and recovered back to his baseline with the resolution of acidosis and renal failure. Ammonia levels normalized as well. All other laboratory parameters also improved. The patient was finally discharged on oral Keppra back to the extended care facility.


A 70-year-old male resident of the nursing home with a past medical history of ischemic stroke with residual left-sided hemiparesis, seizure disorder, Crohn's disease, hyperlipidemia, and dementia on Aricept presented to the emergency room with generalized tonic-clonic seizures. The seizure was witnessed in the nursing home. The patient was post-ictal on arrival in the emergency room. The patient was also agitated afterward. The patient had no respiratory symptoms. On physical examination, vitals were stable. The neurological examination was significant for dysarthric speech and left-sided hemiparesis, and the patient was disoriented. The rest of the physical examination was unremarkable. Labs, including complete blood count and comprehensive metabolic panel, were unremarkable. Troponin, creatine phosphokinase, and C-reactive protein were within normal limits. rRT-PCR for COVID-19 came back positive. Chest X-ray (Figure ) showed focal consolidation in the medial right lung base. CT brain (Figure ) showed old right encephalomalacia with no acute abnormalities. EEG (Figure ) showed slowing with right-sided sharps. The patient was loaded with intravenous Keppra in the emergency room. The patient did not have any further episodes. The patient gradually improved and was finally discharged back to the nursing home with the same regimen of lacosamide and lamotrigine, with no dose changes.


A 22-year-old woman was referred to her local renal unit for assessment of hypertension and advanced renal impairment, with a serum creatinine of 500 μmol/l. She had a normal birth and childhood development. Her medical history was unremarkable, except for sensorineural deafness, requiring hearing aids. There was no family history of kidney disease. Investigations revealed a negative autoimmune screen, including a negative ANCA. She proceeded to a renal biopsy, which demonstrated diffuse segmental sclerosis in all glomeruli, marked tubular atrophy, interstitial fibrosis and chronic inflammation. Small vessels were constricted with some fibrinoid change in the walls. This was interpreted as being due to a pauci-immune ANCA-negative vasculitis. She received 3 months of cyclophosphamide and prednisolone, followed by azathioprine and prednisolone.
Following a rapid and progressive decline in kidney function, she was established on peritoneal dialysis. Two years later she underwent a living unrelated donor renal transplant, achieving excellent renal function with creatinine between 90 and 100 μmol/l within 2 weeks after transplantation. After 1 year she developed post transplantation diabetes mellitus (PTDM) and was commenced on long acting insulin, with subsequent addition of metformin. She later developed amenorrhea and dizziness.
Fifteen years post renal transplantation she was assessed by an ophthalmologist, following a deterioration in vision, who diagnosed retinal atrophy. She subsequently developed cognitive decline associated with cerebral atrophy on brain MRI. As a result of the neurological symptoms and signs, and in view of the retinal abnormalities, further genetic testing was undertaken. Restriction fragment length polymorphism of mtDNA extracted from blood leukocytes and urinary epithelial cells confirmed the m.3243A > G mutation in MT-TL1 at 21 and 14% mutant loads, respectively. Maternal screening was declined. The patient was commenced on Co-enzyme Q10 supplementation. Renal function has remained stable with creatinine between 75 and 90 μmol/l during the 22 years following post transplantation. She had no vasculitis related illness throughout her prolonged follow up, suggesting the MC was the likely cause of her ESRD. Case 1 is summarised in Fig. .


A 31-year-old woman with a background of Asperger’s syndrome, thyroid goitre, aortic and mitral valve regurgitation, and sensorineural deafness, presented with ESRD. There was no family history of renal disease. At the time of presentation an acute renal immunology screen was negative and ultrasound scan demonstrated bilateral small, smooth kidneys. Renal biopsy was therefore not possible and she was commenced on haemodialysis. Five months later she received a living-related donor renal transplant from her mother. Graft function following transplantation was excellent, with a creatinine that reached a nadir of 88 μmol/l after 4 weeks and stabilised over a 10 year period at 110 μmol/l.
Two years following transplantation the patient developed impaired glucose tolerance, treated with dietary modification. Three years later she developed diabetic ketoacidosis, requiring hospital admission, and was commenced on insulin therapy. Four years post transplantation she was hospitalised with an acute psychotic episode for which she commenced Olanzapine and Mirtazepine. A number of admissions followed with deterioration in mental health. Six years following the transplant there was a gradual reduction in mobility and she was investigated by neurologists who performed a muscle biopsy and genetic testing. Muscle histology revealed mild myopathic changes with no specific features of mitochondrial disease. Next generation sequencing of mtDNA extracted from blood leukocytes, cultured fibroblasts and skeletal muscle tissue confirmed the presence of the pathogenic m.8618dup in MT-ATP6 at 20, 45 and 65% mutant loads, respectively []. The mutation was detected in other maternal relatives, albeit at lower levels (Fig. ). She has since developed cataracts, which required removal, retinal thinning and optic atrophy, but no evidence of diabetic retinopathy. Case 2 is summarised in Fig. , and previously reported in [].


A 56-year-old Hispanic female with a past medical history of hypertension and fibromyalgia presented to the outpatient clinic for the evaluation of fatigue. She reported that she had been following a strict ketogenic diet along with daily regular exercise for approximately 30-40 days prior to this visit. Her diet consisted of low-carbohydrate vegetables, seafood, avocados, eggs, and coconut oil. The patient’s physical examination was unremarkable. At the time of the visit, her BMI was calculated at 28 kg/m2, with a weight loss of approximately six to seven pounds since starting the ketogenic diet. Her fasting lipid profile showed a total cholesterol level of 283 mg/dl, LDL-C of 199 mg/dl, HDL-C of 59 mg/dl, and triglyceride level of 124 mg/dl. Her creatine phosphokinase (CPK) level was 94 U/l. She was instructed to stop the ketogenic diet and to incorporate a balanced diet, which includes a higher amount of carbohydrates and lower fat. She was also started on high-intensity atorvastatin. However, she reported experiencing myalgias soon after initiating atorvastatin; therefore, the medication was switched to rosuvastatin 10 mg at bedtime. During her follow-up appointment, she reported not having consistently taken rosuvastatin due to concerns of worsening myalgias. CPK levels were reordered and found to be unchanged. Furthermore, she denied prominent muscle pain, tenderness, or weakness during this follow-up appointment; hence, statin-induced myopathy was ruled out. Her lipid profile, after four weeks of ketogenic diet discontinuation and inconsistent use of statins, showed a significant improvement resulting in a total cholesterol level of 190 mg/dl and LDL-C of 106 mg/dl. Statin therapy was discontinued, and the patient maintained optimal LDL-C levels on subsequent testing.


A 22-year old female dentist had treated a patient, with deep caries management under rubber dam isolation. During the treatment, the dentist got injured with a spicule from the cavity in the right eye. She rinsed her eyes with the water couple of times. In spite of regularly rinsing, the dentist developed irritation and foreign body sensation in the right eye immediately after the procedure. Three days later, a full-blown infection was noticed. She developed redness, pain, inability to fully open the eye without discomfort, yellowish discharge which often sealed the eye shut during sleeping, and generalized malaise. The right eye had diffuse swelling of the upper lid with a normal anterior segment and mild pain and difficulty in opening (Fig. ). Mild congestion was seen in the left eye (Fig. ) and then she visited the Ophthalmology department. Upon consultation, the ophthalmologist performed slit lamp examination and was diagnosed with Bacterial Blepharitis. There was no blurring of vision, no dilation of pupils, and no abnormality was detected in the adjoining structures. She was prescribed antibiotic ointment (Moxigram, Moxifloxacin Hydrochloride 0.5% w/v three times a day for a week) with topical eye drops (Toba, Tobramycin Ophthamic solution, 0.3% w/v four times a day for 1 week) and normal lubricating eye drops (Zyaqua, Carboxymethyl cellulose sodium eye drops, 0.5% w/v) for one month for symptomatic relief. Along with this, she was advised to apply warm compresses to the eyelids for several minutes, two to four times daily. She was counselled to take complete rest, to avoid any cosmetics and not to treat any patients till the symptoms resolve. After 4 days of the treatment, the eyelid swelling got resolved and there was no pain and redness. After a week, she treated another patient for direct pulp capping procedure and encountered similar infection again, but the severity of the infection was in a milder form. The right eye showed nodular swelling at the medial margin of the upper lid with normal anterior segment (Fig. ). There was no associated redness or pain present. The patient was advised to continue the lubricating eye drops. She was informed to report back to the ophthalmologist if the symptoms persist. After a month of treatment, she had no redness, no eyelid swelling or pain and had complete recovery.


The patient was a 68-year-old woman with insidious onset of balance difficulties in the context of prior 8-year alcohol abuse. She had progressive ataxia in spite of minimal alcohol use 2 years following symptom onset. She was diagnosed with idiopathic cerebellar ataxia 5 years following symptom onset, with neuroimaging showing prominent midline cerebellar atrophy. She was noted to have ataxic dysarthria, an axial tremor, and appendicular dysmetria. She did not report orthostatic symptoms, urinary retention, or dream enactment behavior. At her initial visit she was evaluated with a rheumatologic screen. An ANA dilution of 1:160 and a positive SSA antibody level were detected. SSB antibody was negative. Subsequent CSF studies showed an elevated IgG index as well as 3 oligoclonal bands in her spinal fluid, 2 of which were also present in serum. Given the possibility that this could be a neurologic manifestation of pSS, sicca symptoms were identified and a salivary gland biopsy showed lymphocytic infiltration, consistent with a diagnosis of pSS. She was treated with extended-release propranolol for tremor and high-dose oral prednisone and received 2 doses of intravenous cyclophosphamide for pSS-associated cerebellar ataxia. The was no improvement in ataxia following immunosuppression. She developed symptomatic orthostatic hypotension in the context of a hospitalization for cyclophosphamide infusions. She died 6 weeks following the second infusion of cyclophosphamide.
Grossly, there was severe, diffuse cerebellar and pontine atrophy. The substantia nigra and locus coeruleus were mildly hypopigmented. Cut sections showed diffuse, severe loss of cerebellar white matter not confined to the vermis. The mammillary bodies were unremarkable. Microscopically, there was severe Purkinje cell dropout, cerebellar white matter atrophy, and atrophy of the pontine crossing fibers. Staining for α-synuclein showed moderate-to-frequent glial and neuronal cytoplasmic inclusions and focal intranuclear inclusions in the cerebellum (white matter and granular layer), cerebral peduncle, pontine white matter, medulla, putamen, thalamus, and subthalamic nucleus. There was focal endoneurial and perivascular inflammation within cranial nerve V that consisted of CD4+ and CD8+ T cells (CD3). Tau, β-amyloid, and TDP-43 were negative. No evidence for vasculitis was noted. These neuropathologic findings established a diagnosis of definite MSA.


The patient was a 62-year-old woman with plaque psoriasis. She was evaluated initially at age 59 with a 2-year history of dizziness and balance difficulties. She was noted to have cerebellar dysarthria, limb dysmetria, and gait difficulties. Mild cerebellar atrophy was observed on the brain MRI. The patient was found to have a positive ANA and SSA/anti-Ro antibody. A lip biopsy showed chronic sialadenitis (). This, together with her sicca symptoms, confirmed the diagnosis of pSS. She underwent infusions of cyclophosphamide for pSS-associated cerebellar ataxia. She had an improvement in ataxia with improved gait, alternating movements, and dysmetria at a 6 month follow-up visit. She was maintained on mycophenolate. She subsequently, however, had a progressive decline in gait over the next 6 months and underwent treatment again with cyclophosphamide and rituximab. An MRI in at age 61 showed progression of diffuse volume loss in bilateral cerebellar hemispheres, with new midbrain, pons, and medulla atrophy (). She developed symptomatic orthostatic hypotension and parkinsonism. At age 62, she reported choking often, frequent urinary tract infections, and was wheelchair dependent. She was transitioned to hospice care and passed away 2 months subsequently.
Grossly, there was moderate-to-severe atrophy of the basis pontis and severe, diffuse atrophy of the cerebellar white matter (). The substantia nigra and locus coeruleus were hypopigmented. Microscopically, there was severe thinning and gliosis of white matter and diffuse loss of Purkinje cells in the cerebellum (). There was severe atrophy of the pons and middle cerebellar peduncle, loss of pontine neurons, and increased gliosis. A full neurodegenerative evaluation demonstrated α-synuclein+ moderate-to-severe glial cell inclusions and synuclein positive threads in the cerebellum, midbrain, pons, basal ganglia, and inferior olivary nucleus (). No evidence for vasculitis was noted. These neuropathologic findings established a diagnosis of definite MSA.


A 69-year-old female patient presented with fever, headache, nausea, and vomiting of several days’ duration. She had a past medical history of aortic valve replacement with a mechanical valve due to aortic regurgitation 4 years prior to admission. When she was admitted to the hospital, she presented with hypotension, with a systolic blood pressure as low as 80 mm Hg. Her blood pressure increased after fluid replacement was initiated due to suspected intravascular dehydration based on the finding of collapsed inferior vena cava. Heart murmurs and abdominal tenderness were denied, and the physical findings revealed no clue as to the cause of her fever. Blood tests denied any increase in total bilirubin (0.4 mg/dL) but confirmed an increased in hepatobiliary enzymes, including AST (153 IU/L), ALT (128 IU/L), and ALP (500 IU/L).
Furthermore, computed tomography (CT) suggested cholecystitis due to gallbladder expansion. Even though her previous aortic valve surgery led us to consider the possibility of IE, transthoracic echocardiography (TTE) denied vegetation. (Figure ) Transesophageal transthoracic echocardiography (TEE) was not performed because the patient was unable to give her consent due to severe nausea.
Based on the elevated hepatobiliary enzymes and CT results, treatment for cholecystitis was started with cefmetazole.
The hepatobiliary enzymes peaked on day 2 of admission. On day 3, gram-positive cocci were detected in a blood culture. The presence of enterococci from cholecystitis was suspected, and vancomycin administration was started. Thereafter, the patient's symptoms gradually improved. On day 5, penicillin-susceptible Streptococcus pneumoniae were detected in a blood culture, and vancomycin was switched to penicillin. At this point, a serial blood culture was again performed, but the results were later confirmed to be negative.
The patient experienced a convulsion on day 6, and endotracheal intubation was done due to her deteriorating consciousness status, reduced respiratory effort, and persistent hypotension. Pulseless electrical activity (PEA) was noted during the intubation, and resuscitation was started immediately. When resuscitation proved unsuccessful, intra-aortic balloon pump (IABP) and percutaneous cardiopulmonary support (PCPS) were implemented to stabilize the patient's condition. Contrast CT revealed no identifiable causes of the cardiac arrest, including pulmonary embolism and acute aortic dissection. Moreover, a coronary angiography showed no lesions. At the time of the aortography, no aortic dissection was observed, and the deviation of the valve was not noticed at this point. (Figure ).
The patient was stabilized in the intensive care unit and closely monitored. The PCPS flow was unable to be maintained, and the patient became bradycardic despite aggressive fluid resuscitation, including a blood transfusion. The arterial blood gas showed severe metabolic acidosis, with pH 6.83 and lactate 10.9 mmol/L. Unfortunately, the patient died despite our strenuous efforts at resuscitation.
An autopsy showed deviation of the artificial aortic valve toward the left ventricle. (Figure ) Although this change was thought to be associated with cardiopulmonary resuscitation, microscopy revealed the formation of micro-abscesses with marked neutrophil infiltration from the epicardium to the myocardium and the presence of fibrous tissue at the valve margins which had altered the shape of the valve. Debris consisting of collections of neutrophils was also attached to the prosthetic valve, but the presence of a bacterial mass was unable to be confirmed even with Gram staining.
These results indicated that the cause of death was aortic valve detachment due to the infiltration of inflammatory cells associated with infective endocarditis.


A 7-year-old boy presented to a tertiary referral academic hospital: Parirenyatwa Group of Teaching Hospitals (PGH) from a provincial hospital (Bindura) to which he had reported with a two day history of bilateral loin pain and gross uniform hematuria with episodic clots for one day. He had fallen off a moving scotch cart in the company of siblings, but in otherwise unclear circumstances. He had no other relevant symptoms; Specifically, he had neither neurological nor gastrointestinal symptoms.
A hemoglobin level of 8.3 g/dL with a low hematocrit of 24.4% and an ultrasound scan all done at the hospital of first presentation, suggested bilateral renal trauma but plain x rays of the chest, abdomen and pelvis were normal.
Initial examination on arrival at the tertiary referral center (PGH) revealed pallor, full consciousness, and no apparent distress. He had a tachycardia of 110 beats per minute, with a normal blood pressure for his age (systolic reading of 107 mm Hg and diastolic of 59 mm Hg). He had bruising in both renal angle areas but clinically no tenderness in the chest, suprapubic area or any perineal/scrotal bruising or tenderness (See Figure ). Urinalysis showed blood ++++, but negative leucocytes or protein.
A repeat hematological profile done at the PGH showed a white cell count of 11.0 × 103/μL, a low hemoglobin level of 7.0 g/dL, and a low hematocrit of 21.0%, with a normal platelet count of 301 × 103/μL. The electrolytes were renal panel was deranged with sodium of 135 mmol/L, a potassium of 4.5 mmol/L, a high urea of 23.4 mmol/L and a raised creatinine of 187 μmol/L.
The patient was resuscitated using intravenous 0.9% normal saline over 6 hours. He remained stable hemodynamically with blood pressure maintained within a range of systolic 107 to 114 mm Hg and a diastolic of between 59 and 77 mm Hg.
An urgent computer tomography scan (CT scan, Figure ) of the abdomen and pelvis showed American Association for the Surgery of Trauma (ASTT) grade 5 injury to the left kidney with no contrast uptake, avulsion of the renal pedicle and associated renal devascularization. The right kidney showed contrast uptake and a grade 4 injury with multiple parenchymal lacerations traversing full thickness of parenchyma. There were no other injuries or fractures noted on the CT scan.
An immediate emergency left nephrectomy was done 8 hours after arrival at PGH with findings of an associated left hemi-peritoneum of approximately 250 mL but no other intra-abdominal associated injuries. There was vasoconstriction with thrombosis of the renal artery stump and multiple deep lacerations to the left renal parenchyma.
The patient was transfused 220 mL of packed cells intra operatively and taken to the pediatric intensive care unit (ICU). The patient's postoperative hemoglobin level was 10.1 g/dL with a hematocrit of 30.3% and electrolytes improved as shown in Table .
The patient had an uneventful postoperative recovery and was moved from the pediatric ICU day 4 postoperatively. He was subsequently discharged home on day 6 postoperatively.
The patient was scheduled to come back for review at the tertiary institution clinic but did not return. Financial constraints and the fact that he came from a remote rural area 200 km from our teaching hospital may have contributed to his inability to come for review.


In this study, we report the case of a 67-year-old female who presented after becoming aware of a sudden decrease of visual acuity (VA) in her right eye. In April 2016, hyperemia was noted in the patient's right eye, and in July 2016, the patient was diagnosed with scleritis. Symptoms were relieved after the patient was treated with predonine 30 mg and steroid eye drops. In mid October 2016, the patient experienced general malaise and fever, and subsequently presented at the Department of Internal Medicine at a nearby hospital. Upon examination, inflammatory responses were observed, as indicated by a C-reactive protein (CRP) level of 33 mg/dL and a white blood cell (WBC) count of 26,000/μL. On October 24, 2016, the patient became aware of a sudden decrease of VA in her right eye and presented at the Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Osaka, Japan for a detailed examination. This case study was approved by the Ethics Committee of Osaka Medical College, and was performed in accordance with the tenets set forth in the Declaration of Helsinki. Informed written consent was obtained from the patient for publication of this case report and the accompanying images.
Upon examination, the patient's corrected VA was hand motion at 50 cm in her right eye and 1.2 in her left eye. Intraocular pressure was 5 mm Hg in her right eye and 9 mm Hg in her left eye. The light reflex was decreased in the right eye, which was positive for relative afferent pupillary defect. Slit-lamp microscopy examination revealed no obvious inflammation in the anterior chamber, yet did reveal thinning of the sclera on the superior temporal aspect (Fig. ). Fundus examination revealed retinal edema with a macular cherry-red spot appearance in her right eye (Fig. ). At her initial visit, an optical coherence tomography (OCT) examination revealed hyperreflectivity and edema in the inner retina, as well as an irregular ellipsoid zone and choroidal folds, in her right eye (Fig. ). No abnormalities were observed in the left eye. Fluorescein angiography (FA) of the fundus showed a delayed arm-to-retinal circulation time of 18 s and scattered areas of no retinal perfusion in the periphery (Fig. ). Although indocyanine green angiography (IA) of the fundus showed no delay in choroidal circulation time, the right eye, overall, appeared slightly more hypofluorescent than the left eye (Fig. ), and pale areas of excessive leakage were observed in the late phase.
Blood test results were as follows: WBC count, 16.4 × 103/μL; erythrocyte sedimentation rate, 61 mm/h; CRP, 18.11 mg/dL; ferritin, 1839.0 ng/mL: MPO-ANCA, 70.3 U/mL (reference value: <3.5 U/mL); PR3-ANCA, <1.0 U/mL, and a D-dimer, 9.5 μg/mL (reference value: <5 ng/mL). There were no particular abnormalities in the skin or neurologic findings. Since a magnetic resonance imaging examination of the patient's head showed a beaded dilatation of the temporal artery, a temporal arterial biopsy was performed. Although infiltration of lymphocytes and plasma cells was observed, no giant cells were detected. Thus, there was no diagnosis of temporal arteritis. Based on these findings, the patient was diagnosed as CRAO due to ANCA-associated vasculitis, and steroid semi-pulse therapy was started.
After steroid semi-pulse therapy was administered, the systemic condition was markedly improved, and predonine was tapered. On November 22, 2016, a combined therapy of predonine (50 mg/day) and azathioprine (50 mg/day) was initiated. On December 8, 2016, an examination revealed that the patient had become negative for MPO-ANCA. Retinal edema with a macular cherry-red spot appearance in her right eye resolved, and VA was improved to 0.08. An OCT examination performed 1 month after the initiation of treatment showed thinning of the inner retina, however, the choroidal folds were found to have completely disappeared.


A 59-year-old male with a past medical history of Crohn’s disease, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, bipolar disorder, and chronic back pain presented to the hospital with lethargy and vomiting. He had cough, nausea, vomiting and chronic back pain, but he denied chills, headaches, sore throat, diarrhea, loss of taste or smell, shortness of breath and muscle aches. Of note, he had a recent hospitalization for COVID-19 pneumonia two months prior where he was treated with ten days of hydroxychloroquine and five days of azithromycin. The patient reported no residual symptoms from his prior SARS-CoV-2 infection.
Upon admission, the patient reported that he had taken seven unspecified muscle relaxants to help alleviate his back pain. His home medications are listed in Table . Home medications were stopped on admission. He was not on any medications for Crohn's disease as he had no symptoms of the disease.
He appeared well-nourished, cooperative, and in no acute distress. He was conscious, alert and oriented to person, place and time, but seemed lethargic. The physical exam was significant for poor dentition but otherwise unremarkable, including a benign abdominal exam and a nonfocal neurological examination. Initial vitals are listed in Table and pertinent lab results on admission are listed in Table . COVID-19 PCR test was positive for antigen and COVID-19 IgG antibody test was positive as well. Urine toxicology was positive for benzodiazepines and cannabinoids.
His initial infectious disease workup on day one was negative. On day two, one blood culture became positive for M.osleonsis and Streptococcus species (salivarius, vestibularis). He was started on 1 gram of intravenous ceftriaxone daily for 14 days, and repeat blood cultures on day four revealed no growth.
The following imaging studies were done. A chest X-ray showed no acute cardiopulmonary disease findings (Figure ). CT of the chest showed mild right apical paraseptal and centrilobular emphysematous change and dependent atelectatic changes at lung bases (Figure ). CT of the brain showed no acute intracranial hemorrhage or mass effect from vasogenic edema (Figure ). Transthoracic echocardiogram showed no vegetations with a left ventricular ejection fraction of 60% (Figure ).
As mentioned, he continued intravenous ceftriaxone throughout his hospital stay. Valproic acid was restarted on day three once the valproic acid level was therapeutic. His encephalopathy improved drastically over time and the patient was discharged on day six. On discharge, he was prescribed an eighth-day course of intravenous ceftriaxone for completion of the antibiotic regimen. Dental evaluation, infectious disease, and psychiatry appointments were scheduled for outpatient follow-ups.


A 22-year-old incarcerated male with no known past medical history presented with a two-month history of hemoptysis, subjective fevers, pleuritic chest pain, and unintentional weight loss of approximately 30 pounds. He had recently emigrated from El Salvador and was incarcerated for approximately seven months prior to symptom onset.
CT-angiography of the chest in the ED revealed a 12 cm mass in the anterior mediastinum, with mass effect on the superior vena cava (SVC), leftward displacement of the mediastinum and heart, and a right pleural effusion (Figure ). Notable labs included normocytic anemia, leukocytosis, and an elevated alpha-fetoprotein (AFP) with a normal β-hCG. Pathology was consistent with a non-seminomatous germ cell tumor of the yolk sac type (Figure ). A follow-up testicular ultrasound showed no focal abnormalities (Figure ).
The patient was treated with one cycle of bleomycin, ifosfamide, cisplatin (BIP) and filgrastim chemotherapy before discharge. No additional outpatient information was available for internal assessment of the patient’s status.


A 55-year-old woman with no known systemic disorder and without any history of ocular disease, trauma, and surgery presented with a nonremitting conjunctival redness on her left eye that was existing since her childhood. Since she has never reported none of the ocular symptoms such as burning and foreign body sensation accompanying to redness in her eye, she had received several topical treatments including artificial tear drops, steroids, antibiotics, and nonsteroidal anti-inflammatory eye drops with poor response. She denied any family history and accompanying dermatological disorder or any systemic diseases such as hypertension, diabetes, and hyperlipidemia.
Static and dynamic assessment of both eyelids were normal without any port-wine stain, hemangioma, or facial abnormality. There was no exophthalmos or globe deviation. On ophthalmological examination, the best-corrected visual acuity was 20/20 in both eyes; intraocular pressure was 16 mmHg in the right and 17 mmHg in the left eye. Slit-lamp anterior segment examination of the right eye was normal; however, left eye revealed conjunctival and episcleral vascular dilation and tortuosity with an accompanying bulbar conjunctival telangiectasia most prominent in the lower conjunctiva near to limbus (Figures –). The dilated examination of the fundus and fluorescein angiography was normal in the right eye; contrary, the retinal vessels were strikingly tortuous and slightly dilated in all four quadrants of the left eye without any other accompanying retinal findings such as exudation or hemorrhage (Figures –). The optic disc and macula were normal bilaterally. There was no mass lesion, retinal capillary haemangioma, choroidal haemangioma, or racemose angioma in the retinal periphery on indirect ophthalmoscopy. Fundus autofluorescence imaging and optical coherence tomography angiography of the left eye revealed a striking retinal vascular tortuosity; optical coherence tomography imaging scans were normal for both eyes (Figures –). Schirmer I and tear break-up time tests were within normal limits bilaterally.
The patient was referred to internal medicine, cardiology, dermatology, and neurology departments in order to exclude some systemic syndromes that can accompany conjunctival telangiectasia such as hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease), ataxia telangiectasia, Fabry's disease, Alport syndrome, and Bloom syndrome and some systemic diseases that can accompany retinal vascular tortuosity such as systemic hypertension, pulmonary arterial hypertension, atherosclerosis, polycythemia vera, and sickle cell anemia. Neuroradiological assessment including brain and orbital magnetic resonance imaging with magnetic resonance angiography was performed in order to exclude any accompanying retroorbital or cranial vascular abnormality and caroticocavernous fistula. After all those aforementioned evaluations, no systemic coexistence was identified.
The patient was monitored for visual acuity, intraocular pressure, slit-lamp anterior segment, and fundus examinations during follow-up visits. The clinical findings were stable without any symptoms, and there was no change in the appearance and shape of the conjunctival, episcleral, and retinal vessels 12 months after initial examination.


This case report describes a 37-year-old female currently undergoing treatment for metastatic breast cancer. The patient presented to the Otolaryngology Clinic with complaints of hemoptysis, odynophonia, and odynophagia. She expressed waking several times in two weeks choking on blood and the feeling of “water in her throat” when she coughed. She also showed recent upper respiratory infection symptoms with rhinorrhea and cough.
She had a pertinent past medical history of metastatic breast cancer with metastasis in the lungs, neck, and bone. Since starting chemotherapy, she had a history of iron deficiency anemia, menorrhagia, hematochezia, and thrombocytopenia. She was previously treated with docetaxel, standard trastuzumab, and pertuzumab every three weeks for six doses. Due to progression of disease, her chemotherapeutic regimen was changed to T-DM1, zolendronic acid, and tamoxifen. Her last infusion of T-DM1 was 26 days prior to the incidence of hemoptysis and had 15 total infusions of T-DM1 prior to presentation.
A complete head and neck examination was performed, including nasopharyngolaryngoscopy, which revealed a friable, excoriated nasal septum, bilateral vocal fold edema with ulceration of vocal folds, and no associated submucosal hemorrhage, with epithelial bleeding noted on the supraglottic and glottic surfaces. There was no surrounding ecchymosis (Figures and ). The patient had no prior history of laryngeal mucosal bleeding. We recommended admission to the hospital to rule out pulmonary hemorrhage, in addition to airway monitoring, humidification, cough suppression, and laryngopharyngeal reflux prevention. She was evaluated with computed tomography scan which was negative for contributing factors. The Pulmonology team determined that this was not related to progression of metastatic lung lesions or lung-related hemoptysis. Laryngoscopy was completed 24 hours after admission. Findings included petechia of the supraglottis, false vocal folds, interarytenoid region, and scabbing of the vocal folds (Figures and ). Hematology and Oncology teams were consulted to evaluate for possible bleeding disorders, and von Willebrand disease was ruled out via laboratory studies. The patient was discharged with vocal hygiene and humidification. Upon discharge from the hospital, she has been followed in the Otolaryngology Clinic at four different occasions. Follow-up examinations revealed no further laryngeal hemorrhage but did reveal new, profuse, and recurrent epistaxis laryngitis, differential diagnosis including staphlococcus. She was treated appropriately with nasal hygiene and antibiotic therapy. Ultimately, the patient's cancer progressed, and the T-DM1 was discontinued. She has had no further episodes of hemoptysis.


A 60-year-old male patient who previously had a traumatic road traffic accident and sustained right sided pneumothorax and ribs fractures suffers from recurrent right pleural effusions. He was referred for imaging options to investigate the cause of the recurrent pleural effusions. The patient had a lymphoscintigraphy (Tc-99m-Antimony sulphide colloid). It showed normal nodal uptake in the abdominal para-aortic nodal chains with activity within the thoracic duct between 1 and 2 h. By the end of the study at 5 h, there was no activity in the moderate right pleural effusion and no evidence of Chyle leak (). However, a subsequent thoracoscopy and samples confirmed chylothorax. A DCE MR lymphangiogram was performed to locate the site of leak for surgical planning. It showed contrast enhancement of the right pleural effusion (). The enhancing fluid could be tracked along the bronchovascular bundles, into the right hilum, and appeared to communicate with the thoracic duct (). The findings were consistent with a lymphatic leak into the right pleural effusion, from the thoracic duct. The patient subsequently had successful right thoracotomy and clipping of thoracic duct.


A 58-year-old male patient had recent oesophagectomy due to oesophageal malignancy. He had bilateral pleural effusions on the post-operative CT (), and went on to have DCE MR lymphangiogram to assess the integrity of the thoracic duct. The coronal T1 weighted images with fat saturation showed progressive enhancement of the abdominal lymphatics, cisterna chyli and inferior thoracic duct up to the level of T11-12 (). This corresponded to the position of the metallic clips seen on the coronal CT and represent the position of thoracic duct ligation. There was no enhancement proximal to this level and no lymphatic leak into the pleural effusion.


This is a 75-year-old male patient who also had recent oesophagectomy due to oesophageal malignancy. He had ongoing high-volume output from a mid-mediastinal drain that was left in-situ post-oesophagectomy. This patient had DCE MR lymphangiogram to investigate the site of chyle leak. The coronal T1 weighted images with fat saturation showed accumulation of gadolinium in the middle mediastinum, and the tip of the surgical drain is positioned in the superior aspect of the collection ().


This was a 57-year-old female patient who presented with dyspnoea and echocardiogram excluded heart failure. The chest CT of the patient showed significant stranding in the mediastinal fat and bilateral smooth interlobular septal thickening (). The chest CT findings could represent lymphatic proliferation, which raised the possibility of pulmonary lymphangiomatosis. Subsequent DCE MR lymphangiogram showed no evidence of abnormal dilated intrathoracic lymphatic vessels ().


A 58-year-old woman with ovarian cancer was electively admitted to our gynecologic oncology division for surgical debulking. CT showed a right ovarian tumor measuring 2.2X2.6 cm, ascites and an omental mass. The uterus and left ovary appeared normal. Her CA-125 level was 233 U/mL. CT-guided-biopsy from the omentum revealed high-grade-serous-carcinoma. Her past medical history included anxiety and fibromyalgia treated with serotonin reuptake inhibitors (SRI’s) and Tramadol. She had no other medical, family and psycho-social history including relevant genetic information.
Upon admission, she had no complaints with normal physical-examination and lab work. Upon entrance to the operating room (OR) and before any procedures were performed, she started to demonstrate convulsions in the face and rigidity accompanied by foam from the mouth and irregular eye movement. This episode lasted 10 min and was accompanied by increased blood pressure (maximal measurement of 190/100) and bradycardia. The blood pressure and bradycardia normalized within several minutes without any treatment.
As soon as the patient resumed consciousness, she complained of blindness, severe headache and appeared confused. A neurological examination performed in the OR demonstrated a positive bilateral Babinski sign as the only pathological finding.
Ophthalmologic and psychiatric evaluations were normal. Brain CT was normal with no signs of active bleeding or mass. During the hours that followed the acute onset, there was further deterioration in her confusion and blindness and the patient reported continuation of the severe headache which did not respond to analgesia. In addition, fever was measured (38.7 °C). The only abnormal laboratory finding was an elevated white blood cell (WBC) count of 12,200 103/μL with 93% polymorphonuclear cells (PMNs(.
Due to the possible diagnosis of meningitis/encephalitis, an empiric Acyclovir treatment was begun and lumbar puncture (LP) was done. The LP fluid was clear, with an opening pressure of 201 mmH2O, increased WBC count (37 cells/mm3, mostly PMN’s) increased protein count (125 mg/dl) with normal glucose level (72 mg/dl) and a decreased chloride level (123 mmol/L). Culture from the CSF was negative. In addition, since there was uncertainty regarding the origin of seizures, Valproic acid was initiated. EEG showed a non-specific sign of left temporal irregularity. No epileptic activity was demonstrated.
Brain MRI including T1, T2, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC) and susceptibility weighted imaging (SWI) sequences were performed before and after Gadolinium administration. Occipital cortical and subcortical T2 hyperintense signals were observed mainly on the left side (Fig. a) and, to a lesser extent, on the right side (Fig. b). There was moderate hyperintensity on DWI in the left occipital cortex (Fig. c). There was no abnormal enhancement after Gadolinium administration (Fig. d). Mild diffusion restriction was demonstrated on the ADC maps (Fig. e).
Polymerase chain reaction (PCR) for Herpes simplex virus, Varicella zoster virus and Enterovirus were negative. Urine and blood cultures were negative. Chemistry including creatinine kinase, liver function tests and electrolytes were normal. Urine toxicology yielded no abnormal findings.
During her hospitalization, the patient demonstrated a continuous improvement. Repeat neurological examination showed complete consciousness, intact visual fields and no neurological deficits. Virology results came back negative excluding viral encephalitis. No other treatments were given, including steroids.
As it is known that seizures can be a manifestation of paraneoplastic syndromes, specifically, paraneoplastic epilepsy, a panel of tests for the detection of paraneoplastic syndromes were obtained from the patient’s blood and CSF fluid according to latest recommendations []. A neuronal autoimmune antibody (Ab) screen was performed including Abs against GABAB, NMDR, CASPR2, AMPAR1, AMPAR2, LGl1, Amphiphysin, CRMP-5 (CV2), PNMA2, Ri, Yo, Hu, Recoverin, SOX1 and Titin (see abbreviations).
All tested antibodies in the CSF and serum came back negative except for CRMP-5 Abs which tested positive in the CSF but was negative in the serum.
CRMP5 protein, also known as Neuronal CV2, is thought to be involved in neural development and antibodies to CRMP5 were found in some patients with paraneoplastic syndromes presenting with neurologic symptoms []. As antibodies against CRMP5 are known to be associated with small cell lung carcinomas and thymomas [], a chest CT was performed in our patient and came back normal. All other tested autoimmune antibodies were negative.
In view of all the clinical presentation, imaging and laboratory results, the woman was diagnosed with PRES.
The patient was discharged with complete resolution of her symptoms. Repeat MRI one month later showed complete disappearance of the previously described radiologic findings. She was started on Paclitaxel and Carboplatin chemotherapy. After 3 chemotherapy cycles she was doing well with no neurological complaints. Abdominal CT showed good response to the chemotherapy and the patient underwent interval debulking including bilateral salpingo-oophorectomy, hysterectomy, omentectomy with transverse colectomy for complete cytoreduction. No neurological symptoms were observed prior or after the operation.


A 17-year-old girl experiencing progressive psychosis, agitation, and oral-facial dyskinesia for 4 days was admitted. The initial EEG results showed typical generalized EDB. Diffuse low-density lesion involving the white matter of the bilateral temporal and occipital lobes was noted by computerized tomography (CT) scan. She was diagnosed as anti-NMDAR encephalitis after NMDAR antibody was detected in her serum and CSF. Glucocorticoid with a dose of 500 mg/day was given but symptoms remained. Over the next 3 weeks, the patient developed hyperpyrexia, severe pneumonia, and pyothorax. On day 23, she began to have rhythmical jerking of bilateral limbs with cessation of choreic movement and oral-facial dyskinesia. Corresponding EEG patterns showed generalized synchronous delta rhythm with fast spike activity riding on it (Figure ). Seizure terminated after intravenous injection of midazolam at a dose of 0.2 mg/kg, but oral-facial dyskinesia reappeared. Midazolam at a dose of 0.2 mg/kg/h was continuously infused and terminated 2 days later. Subsequent immunotherapy (plasma exchange, intravenous immunoglobulin, and cyclophosphamide) was given routinely, and she recovered with a mRS score of 1 after 3 months. No seizure was reported after withdrawing AEDs (Table ).


A 24-year-old man suffering psychosis and recurrent focal tonic seizures of right limbs for 7 days was admitted. Prolonged fever, right hypesthesia, and stiffness of right face were also reported. The initial EEG results presented generalized RDA. Magnetic resonance imaging (MRI) scan showed nothing remarkable. A NMDAR antibody with titer of 1:32 was detected in his CSF. Glucocorticoid with a dose of 1000 mg/day was given, but the patient developed aggravating impaired awareness and began to have oral-facial dyskinesia. On day 6 in the hospital, focal status epilepticus with stiffening of the right arm and leg was recorded. The EEG pattern showed RDA with frontal fast spike activity, most prominent over the left region. Seizure was controlled but oral-facial dyskinesia remained after intravenous injection of midazolam at a dose of 0.2 mg/kg (Figure ). The patient successively received intravenous immunoglobulin and AEDs. After 3 months, the patient had a mRS score of 1. The patient was treated with oxcarbazepine at a dose of 600 mg/day, and no seizure was reported (Table ).


An 87-year-old female underwent a radical cystectomy with an ileal conduit for invasive bladder cancer. Pathological examination demonstrated G3 urothelial carcinoma with a component of squamous cell carcinoma (<5%), pT3b. she underwent two cycles of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin and was in good condition without metastatic disease.
Nineteen years after the cystectomy, she was admitted to our hospital with anemia and Hb of 8 g/dL. Bleeding from the stoma continued and contrast-enhanced CT showed a tumor measuring 35 × 30 × 25 mm on the right-side wall of the conduit (Fig. ). Biopsy examination of the tumor revealed erosive mucosa and granulation tissue without malignancy. The bleeding from the stoma stopped with conservative therapy and she refused invasive treatment at the time; she was therefore discharged after 13 days’ hospitalization. After hospitalization, she underwent outpatient checkups every 3 months, with no recurrence of bleeding thereafter.
Three years later, acute bleeding from the stoma recurred and she was hospitalized again with severe anemia (Hb of 5.9 g/dL). Contrast-enhanced CT revealed an enlarged tumor measuring 50 × 45 × 40 mm in the ileal conduit (Fig. ).
The bleeding did not stop this time with conservative therapy and the size of this tumor had been gradually increasing over 3 years, so she underwent a complete resection of the tumor 16 days after admission.
The tumor was recognized from the surface of her abdominal wall under general anesthesia. Five centimeters incision was made just beside the stoma on the opposite side of mesentery and the tumor was dragged out of the stoma. The mass was not adhered to its surrounding tissue and we performed en bloc resection of the tumor with its stalk from the wall of conduit. It was a solid and multinodular 50*45*40-mm-sized tumor, mostly covered with mucosa of the small intestine (Fig. ). The cut surface of this tumor was light gray in color (Fig. ). Surgical margin was histologically negative, therefore her conduit was preserved. Histopathological examination showed the tumor consisted of irregularly arranged spindle cells as well as rounded cells (Fig. ). The mitotic count was below 5 per 50 HPF.
Immunohistochemical examination revealed reactivity of CD117 (KIT) and SMA antibodies. However, CD34 and S100 were not stained. The tumor was histopathologically diagnosed as a GIST (low-risk type).
The patient was discharged in a good condition 11 days after surgery without any adverse post-operative events. She has had no recurrence or metastasis 4 years since the tumor was resected.


A 50-year-old woman was referred to our department with a superior mediastinal mass detected using imaging. She had been receiving outpatient treatment at a local medical clinic for chronic cough for four months. Plain computed tomography (CT) of the lung was carried out because of the poor improvement of her symptoms, but a superior mediastinal mass was incidentally pointed out. Her medical history included cervical carcinoma in situ, but there were no other notable findings. She had no history of allergies or smoking, and alcohol consumption was intermittent.
Contrast-enhanced CT revealed a well-demarcated mass measuring 40 mm in diameter, extending from the thoracic inlet to the superior mediastinum (Figure , ). Orthotopic thyroid tissue was observed, and the mass lesion was not continuous with the thyroid gland. The lesion was slightly less well absorbed than the thyroid tissue (Figure , ) and was enhanced somewhat heterogeneously. The vasculature entering the mass from the thoracic sides could be observed (Figure , ). Laboratory tests showed normal white blood cell counts and a negative C-reactive protein level. Her serum interleukin-2 receptor level was within the normal range (271.0 U/mL), and serum toxoplasma IgM and IgG antibodies were both negative. Thyroid functions were also within normal limits, and serum-free T4 was 0.99 ng/dL, serum-free T3 was 2.61 pg/mL, and thyroid-stimulating hormone was 1.25 μIU/mL; thereafter, both antithyroid peroxidase antibody and antithyroglobulin antibody levels were normal. Only an elevated serum thyroglobulin level of 87.7 ng/mL could be measured. Ultrasonography also showed clear separation of the mass from the orthotopic normal thyroid, and echo-guided fine needle aspiration cytology specimens showed only large and small lymphocytes.
Based on these results, thymoma, malignant lymphoma, and Castleman’s disease could not be ruled out, and it was decided to perform surgical resection. We consulted with a respiratory surgeon before the operation, and prepared for sternotomy, although unlikely, when the surgical approach was difficult. Transcervical resection of the superior mediastinal mass was performed (Figure ). Because the thyroid gland was clearly separated from the mass, it was preserved, and no combined resection was performed. Multiple inflow vessels from the thorax into the mass were confirmed during surgery. All were carefully ligated, and the mass could be resected through the neck without any issues. The mass seemed to have independent blood supply from those vessels. The recurrent laryngeal nerve could be preserved without needing to be identified. The resected specimen was a mass macroscopically suggestive of thyroid tissue itself (Figure ). Operation time was 70 minutes, and blood count was 10 mL. The postoperative course was uneventful and without any complications.
Histopathological examination revealed ectopic thyroid tissue and a nodular goiter consisting of large and small colloid follicles (Figure ). Postoperative laboratory testing also demonstrated that it was euthyroid.


An 88-year-old woman presented with episodes of hemoptysis for a week. She was referred to our hospital due to abnormal shadows on chest X-ray. She had a history of complete surgical resection for ascending colon cancer at 72-years-old and basal cell carcinoma of the face at 79-years-old, and conservative treatment for early-stage gastric cancer at 88-years-old. She was taking pharmacotherapies for hypertension, angina and dyslipidemia, but had no history of immune-related diseases. She was an ex-smoker with three packs/day for 35 years. Neither of her family had multiple cancers except her.
She was diagnosed with squamous cell lung cancer in the right lower lobe, categorized as cT3N1M1a cStage IVA from computed tomography (CT)-guided biopsy. Tumor proportion score on PD-L1 was 100% as evaluated by 22C3 antibody. First, radiation therapy (60 Gy/30 fr) was performed because she had recognized back pain because of direct invasion of the cancer around the ribs. She was administered pembrolizumab at 200 mg/bodyweight every four weeks. After four cycles, a partial response (PR) was achieved according to RECIST (Response Evaluation Criteria in Solid Tumors version 1.1) criteria (Fig ). The tumor maintained PR for a few months after four cycles of pembrolizumab. Because the field of radiation included the primary cancer in the right lower lobe, radiation pneumonitis developed and the primary tumor shrank (Fig ). After four cycles of pembrolizumab, her pneumonitis was exacerbated but the tumor size shrank further (Fig ). As a result of radiation therapy and four cycles of pembrolizumab, the tumor shrank without any adverse events. After five cycles of pembrolizumab, routine laboratory investigations showed mild pancytopenia, with a white blood cell count (WBC) of 3.13 × 103/μL. Hemoglobin (Hgb) was 10.8 g/dL and platelet count (Plt) was 5.8 × 104/μL. The sixth cycle of pembrolizumab was suspended after pembrolizumab-induced pancytopenia was suspected. Severe pancytopenia developed within six months after starting pembrolizumab. At that time, the nadir WBC was 1.92 × 103/μL (grade 3 according to CTCAE version 5), nadir Hgb was 7.8 g/dL (grade 3) and nadir Plt was 2.5 × 104/μL (grade 3). After consultation with a specialist hematologist, the cause of pancytopenia was suspected to be due to pembrolizumab or myelodysplastic syndrome (MDS). Negative results were obtained for antiplatelet antibody. Bone marrow biopsy was performed to confirm the diagnosis, but pathological findings did not indicate any hematological diseases such as MDS (Fig ). The bone marrow specimen showed normocellular bone marrow. The pancytopenia was considered to have been induced by pembrolizumab. Although oral steroid administration (prednisolone at 1 mg/kg) to manage pancytopenia as a grade 3 irAE was suggested, the patient declined steroids because of the risk of adverse events.
The pancytopenia improved naturally within six months after suspension of pembrolizumab, although a red blood cell transfusion was needed to assist patient recovery. No additional severe adverse events were encountered (Fig ). There was no other agent administered other than pembrolizumab. The antiplatelet antibody and autoimmune antibody related with collagen diseases results were negative. Biopsy of the bone marrow did not show any significant findings. Considering the results and long course of observation, we concluded that pembrolizumab induced pancytopenia by autoimmune reaction. Fortunately, antitumor efficacy continued even after cessation of pembrolizumab and performance status was able to be maintained without any additional treatments for 11 months.


A 53-year-old man with a history of smoking (30 pack-years) presented to the hospital for physical examination in March 2017. Chest computed tomography (CT) scan showed space-occupying lesions of the lower left lung. A CT-guided percutaneous pneumocentesis biopsy was performed and histological adenocarcinoma was diagnosed. There was no opportunity for surgery at that time because he was already at stage IIIB (cT3N2M0) of diagnosis, with mediastinal lymph node metastasis. He subsequently underwent four courses of chemotherapy (pemetrexed 800 mg D1 plus cisplatin 30 mg D1-4) and achieved a partial response (PR) based on the Response Evaluation Criteria In Solid Tumors 1.1 (RECIST), during March 2017 to June 2017. Subsequently, primary lung lesions and mediastinal lymph node metastases received intensity modulated radiation therapy (60 Gy/30 F) and the patient also received oral TS-1 treatment. In October 2017, polymerase chain reaction (PCR) test of the tumor showed EGFR exon 19del, but targeted therapy was refused at the time of genotyping. Unfortunately, he was found to have PD (progressive disease) with enlarged primary lung lesions and left hilar nodes in January 2018 after a PFS of 9.6 months receiving first-line chemotherapy. Based on this, he received gefitinib (250 mg once a day) as the second-line of treatment. In May 2018, the patient was evaluated and confirmed to have PD following the emergence of right adrenal and liver metastasis, despite a shrunken lung lesion and PFS which had lasted 4.1 months. In consideration of the benefits of gefitinib, treatment with gefitinib was continued until July 2018. On 3 July 2018, the patient underwent rebiopsy of the right adrenal through CT-guided percutaneous puncture and the histology still indicated adenocarcinoma, and notably PD-L1 expression 15% + by IHC on Roche Vantana Benchmark IHC (immunohistochemistry) platform with antibody of SP142. Next-generation sequencing (NGS, Burning Rock, Guangzhou, People's Republic of China) test for a large panel containing 520 oncogenic genes was used for molecular testing of the adrenal biopsy sample, which confirmed the presence of MET (MET proto-oncogene, receptor tyrosine kinase) gene amplification (copy number 10.3) (Fig ), in addition to the baseline EGFR exon 19 del with an allele frequency of 47.5%, and tumor mutation burden (TMB) was calculated (7.9 mutations/Mb). The patient was subsequently switched to bevacizumab (375 mg) combined with gefitinib (250 mg once a day) from July to October 2018. Unfortunately, the disease continued to progress with increases in left adrenal lesions and other metastases (Fig ).
Due to the poor response to bevacizumab plus gefitinib therapy and PD-L1 expression 15% + (IHC) on adrenal puncture sample, sintilimab combined with bevacizumab treatment was commenced on 11 November 2018, at a dose of 200 mg and 400 mg, respectively, every three weeks for four times and a PR was obtained after four weeks (Fig ). During the sintilimab plus bevacizumab treatment, the patient developed grade 3 rashes which can reoccur spontaneously. Myelosuppression, hypertension, diarrhea, or other adverse events were not apparent. Symptoms of dry cough and pain were improved during ICI plus angiogenesis inhibitor treatment. A PFS of 6.0 months was achieved.
Unfortunately, thereafter, the patient had progression of bilateral adrenal metastases (Fig ), his general condition worsened, and he had a dry cough, expectoration and pain. Even if we had attempted to use sintilimab combined with anlotinib or docetaxel, it would not have stopped the disease from deteriorating. The patient died in June 2019.


The proband was a 45-years-old-Chinese female who was admitted to Peking Union Medical College hospital for a recurrence of left adrenal PCC. At the age of 31 years, the patient presented with paroxysmal dizziness, sweating, palpitation, and hypertension attacks with a maximal blood pressure of 200/100 mmHg. Abdominal computed tomography (CT) indicated a mass with a size of 10 cm in the left adrenal gland. The patient underwent left adrenalectomy, and the tumor was pathologically diagnosed as PCC. Her symptoms disappeared postoperatively. However, she suffered from paroxysmal palpitation and sweating at age 45. Her blood pressure was 170/100 mmHg at hypertension attacks. Then she was referred to our hospital for further examination and treatment.
Laboratory examinations were as follows: 24-h urinary norepinephrine, 325.44 μg/24 h (normal, 16.69–40.65); epinephrine, 4.07 μg/24 h (normal, 1.74–6.42); and dopamine, 235 μg/24 h (normal, 121–331). Contrast-enhanced CT showed multiple masses in the left adrenal, the largest of which was 2.1 × 1.3 cm, wrapping the left renal artery. It also showed multiple enlarged lymph nodes in retroperitoneum and mesenterium. Metaiodobenzylguanidine (MIBG) scintigraphy revealed the abnormally increased uptake in the left adrenal gland mass. These findings indicated recurrent PCC in the left adrenal, but the patient and her family refused surgery. The mass enlarged gradually. Three years later, contrast-enhanced CT showed an irregular left adrenal mass (4.1 × 2.7 × 3.3 cm), which was markedly enhanced and wrapping the left renal artery (). Plasma free normetanephrine was 9.35 nmol/L (normal, <0.9), and plasma free metanephrine was 0.46 nmol/L (normal, <0.5). The mass was surgically removed and pathologically diagnosed as PCC with lymph node metastasis (). Her symptoms disappeared again, and biochemical indexes decreased to normal range postoperatively. The patient had undergone partial thyroidectomy for papillary carcinoma of thyroid at the age of 46 years.


Our first patient was a 58-year-old male with primary biliary cirrhosis and nonalcoholic steatohepatitis. Portal flow was not visualized on preoperative Doppler ultrasound. Contrast enhanced CT demonstrated complete PVT with cavernous transformation () and clot extending into the distal SMV. A large splenorenal shunt and large upper abdominal varices were noted (). Intraoperatively, a large left upper quadrant varix was identified as the target portal inflow vessel prior to the hepatectomy. As predicted, the portal vein was completely atretic and without flow, and there were numerous collaterals in the porta hepatis. Once anhepatic, a Satinsky clamp was placed on the target varix and a segment of donor ileac vein was sewn end-to-side to the varix using 6-0 Prolene. No attempt was made to encircle or otherwise dissect the varix. When the anastomosis was complete, the vein graft was occluded distally and the Satinsky was removed. Flow in the conduit was satisfactory, but to further augment portal flow, the left renal vein was ligated. Implantation was then completed with end-to-end anastomosis of the ileac vein jump graft to the donor portal vein. Allograft function was excellent.


Our second case was a 61-year-old male with cryptogenic cirrhosis and hepatocellular carcinoma. Preoperative imaging revealed cavernous transformation with numerous portal venous collaterals most prominent in the paraesophageal () and perigastric regions (). The left renal vein was nondilated, and a splenorenal shunt was not present. Variant portal inflow was created by joining an ileac vein graft to a large perigastric varix (Figures –). Portal flow and hepatic function were excellent.


A 4-year-old boy from the city of Huaraz (3,052 m) presented with a 2-day sudden onset of the disease, with a progressive course characterized by respiratory difficulty, hemoptoic productive cough, and precordial pain after arrival to the city of Huaraz from the city of Lima. His time of stay in Lima was approximately 13 days and he had a history of being treated for respiratory infection. His vital functions on admission to the emergency unit were as follows:
The following were noted: heart rate = 151 bpm, respiratory rate = 22 breaths/min, blood pressure = 100/60 mmHg, temperature = 36.5°C, and arterial oxygen saturation = 79%. Upon physical examination, subcostal pulses and respiratory effort were evident. Similarly, upon auscultation, there was decreased vesicular murmur in both sides of the hemithorax, and diffuse crackles in both the lung fields. Likewise, a congestive, erythematous oropharynx was evident without plaques or tonsils. Neurologically, the patient was sleepy and scored 15/15 on the Glasgow coma scale. All other laboratory tests were within normal range. Upon admission, he was diagnosed with pneumonia, whereas high-altitude pulmonary edema was ruled out by a score of 7 on the Lake Louise scale. The patient was placed on 4 liters of oxygen through nasal cannula and treatment started with 4 mg of dexamethasone every 6 hours intravenously, 1.4 g of ceftriaxone every 24 hours intravenously, and intensive care unit (ICU) management. On the first day of admission to the ICU, the patient showed ventilatory improvement; therefore, the oxygen volume was reduced to 2 L/min through nasal cannula, and antibiotic treatment was continued upon admission. A cardiology consultation was held, and the patient underwent an echocardiogram that showed moderate pulmonary hypertension with a preserved ejection fraction. On the second day of admission, the patient presented 97% oxygen saturation; consequently, the supplementary oxygen was removed. On the third day of admission to the ICU, the dose of intravenous dexamethasone was reduced to 2 mg every 8 hours, and the patient was discharged from the ICU and moved to the hospitalization floor (). The patient presented a radiographic film with favorable evolution and clinical improvement on the fifth day of admission Figures and and was subsequently discharged.


A 69-year-old man came for consultation due to an unexplained weight loss of 3 kg in 2 months. He denied other symptoms such as anorexia, nausea, vomiting, fatigue, or melena. The laboratory tests were normal. Computed tomography (CT) showed a heterogeneously enhanced tumor mass (Fig. A) located between the pancreas and the stomach, and no evidence of metastasis was found in other parts of the body. Endoscopy revealed a submucosal mass without any ulcer on its surface located on the body of the stomach (Fig. B). The first gastroscopic mucosal biopsy showed chronic inflammation, so we performed the second biopsy and the result were consistent with the first. The third mucosal biopsy was refused by the patient. The clinical diagnosis by CT and gastroscopy was GIST. Therefore, laparoscopic exploration was performed, which revealed a large and exophytic mass originating from the posterior wall of the stomach and invading the pancreas and splenic vessels (Fig. ). The tumor was completely dissected using total gastrectomy, distal pancreatectomy, and splenectomy. The intraoperative rapid frozen pathology found SCC. The postoperative pathological examination found moderately differentiated SCC in the resected specimen (Fig. A-C). No metastasis was observed in the 19 dissected lymph nodes. Immunohistochemistry markers were positive for P63 and cytokeratin (CK) 5/6 and negative for the cluster of differentiation (CD) 117 (Fig. D-F). No evidence of SCC in other organs was reported. Therefore, the postoperative diagnosis was primary GSCC. According to the Eighth Edition AJCC Cancer Staging Manual, it was diagnosed as T4bN0M0, pStage IIIA. The patient was discharged 7 days after surgery without any complications and referred to the medical oncology to receive adjuvant chemotherapy, but he refused. The follow-up CT scan showed no evidence of metastatic disease 6 months after the surgery.


A 40-year-old right-handed female who works at a meat shop visited our clinic due to pain and active limitation of the range of motion (ROM) of the PIP joint of her left long finger (Fig. A and B). She had previously experienced a cut on the dorsal aspect of the third PIP joint while cutting meat about a year earlier but did not receive any specific treatment for the injury. A physical examination revealed a wound scar and thinning of the skin. Passive ROM in the PIP and distal interphalangeal (DIP) joints was normal, and extension could be maintained when the PIP joint was passively extended. With the patient under regional anesthesia, the extensor tendon was explored through a dorsal zig–zag incision. Surgical findings showed complete rupture of the central slip and lateral bands in the PIP joint area, with ∼1 cm of the distal stump of the central slip remaining (Fig. ). Debridement was performed on the stump, followed by tenolysis after fixing the extended PIP joint using a 1.0-mm Kirschner (K)-wire, advancing the distal stump, and repairing the area with 4-0 prolene sutures (PROLENE 4-0 Suture, ETHICON, Cincinnati, OH) using a modified Kessler technique and epitendinous cross-over repair (Fig. ). At postoperative 4 weeks, the K-wire was removed and a dynamic splint was applied to initiate active joint motion. At the 12-month follow-up, the patient was completely asymptomatic and had excellent PIP joint ROM (0°–90°) in her left long finger (Fig. A and B).


Patient 1 is a 51-year-old male who received tocilizumab prior to transfer to our hospital. His D-dimer was over 6 times the upper limit of normal (ULN) and started on intensified prophylaxis with unfractionated heparin infusion (UFH) 7500 units TID per our COVID anticoagulation protocol []. His C-reactive protein (CRP) and fibrinogen were within normal limits, while ferritin and IL-6 were both elevated. On day 3 of admission, ischemia of the first 3 toes was noted with no capillary refill, and no pulse on bedside ultrasound (US). Patient anticoagulation plan was changed to heparin DVT/PE protocol (aPTT 60–85 s). CT angiogram showed partially detaching/floating thrombi noted 4 cm infrarenal abdominal aorta, compromising the lumen and leading to acute limb ischemia with extensive abdominal and bilateral lower extremity thrombus. D-dimer was still over 6 times ULN while all other markers were lower than at admission. Patient was screened for lupus anticoagulant (LAC), and returned negative. Patient developed secondary ischemia of bilateral lower extremity developing left foot dry gangrene requiring below-knee amputation. Patient eventually improved and was discharged on day 75 of admission on oral anticoagulation.


Patient 2, a 79-year-old male, showed no acute or chronic pulmonary embolism (PE) on CT chest with PE protocol at admission. CRP was elevated and D-dimer was over 6 times the upper limit of normal. He received DVT prophylaxis with Enoxaparin 40 mg subcutaneously (SC) daily. On Day 3 of admission, tocilizumab 400 mg intravenously was administered. Patient remained critically ill and on mechanical ventilation, having failed weaning trials. Two weeks into admission, he had a sudden increase in O2 requirement, which was contributed to by secondary bacterial infection. However, given prolonged ICU course and known COVID-19 status, DVT US of lower extremities was performed. DVT in bilateral calf veins was evident, and patient was started on full anticoagulation using unfractionated heparin infusion. His D-dimer was > 4 ULN at that time while CRP and ferritin were elevated, but much lower than admission. Almost 30 days post ICU admission, he suddenly went into Pulseless Electrical Activity rhythm. Bedside focused ICU ECHO showed very subtle cardiac motion, no pericardial effusion, no carotid or femoral arteries pulsation, and with evidence of large clot in the right atrium, likely representing massive PE. As patient was already on comfort care measures, tissue plasminogen activator was not given and patient was pronounced dead. Patient was not screened for lupus anticoagulant.


Patient 3 is a 31-year-old male, with thalassemia trait and mild intermittent asthma, admitted with flulike symptoms. Patient was hypoxemic on presentation, and was transferred to the ICU with SPO2 in the 80s requiring nonrebreather oxygen mask. CXR showed pulmonary infiltrates. COVID-19 RT-PCR test was positive from day 1, and patient received tocilizumab on same day. Biomarkers on admission showed a D-dimer elevation of 3 times ULN. Patient was placed on standard dose DVT prophylaxis with low molecular weight heparin. A point of care US performed on day 7 in response to bilateral lower limb pain and D-dimer elevation to over 6 times ULN revealed occlusive deep vein thrombosis of the right distal femoral, popliteal, posterior tibial, and peroneal veins, as well as the left popliteal, gastrocnemius, and peroneal veins. Patient thromboprophylaxis was escalated to therapeutic dose anticoagulation and was then transferred to a medical floor 2 days later. On day 10 of admission, a CTPA performed in response to worsening pleuritic chest pain revealed subsegmental pulmonary embolus within the right lower lobe basilar pulmonary artery. Treatment strategy was thus switched to heparin therapeutic intravenous drip. Patient continued to improve and was subsequently discharged on oral anticoagulation with apixaban on day 17 of admission. Patient was screened for LAC and returned positive.


Patient 4 is a 36-year-old male with unremarkable past medical history, presented with fever and chills ongoing for 8 days. COVID-19 RT-PCR test was positive from day 1 of admission. CXR showed left mid-lung mild airspace opacities, with patient initially treated on a medical floor. Admission D-dimer was only slightly elevated, and patient was placed on standard DVT prophylaxis. On day 3 of admission patient was transferred to the ICU for worsening hypoxia and received tocilizumab. D-dimer continued to progressively increase and reached 6 times ULN on day 7; patient was thus placed on high intensity prophylaxis with enoxaparin 40 mg BID. On day 11 of admission a CTPA obtained due to progressive hypoxia revealed large saddle embolus. Extension of embolus into the upper and lower lobar pulmonary arteries was evident, with resulting right heart strain. Patient received systemic alteplase followed by heparin drip for therapeutic anticoagulation. Patient improved and was transferred to a medical ward on day 14 of admission and eventually discharged home on oral anticoagulation on day 21 of admission. Patient was screened for LAC and returned positive.


Patient 5, a 51-year-old male, with history of hypertension transferred from outside hospital to the ICU at our institution on mechanical ventilation following severe COVID-19 ARDS. D-dimer was over 6 times ULN on transfer: Patient was directly placed on high intensity thromboprophylaxis with heparin 7500 SC TID and received tocilizumab on second day of admission. Patient’s overall condition continued to worsen, developing acute kidney injury requiring continuous renal replacement therapy. CT chest with IV contrast obtained on day 11 to rule out collection as source of infection revealed bilateral PE, and patient was thus commenced on therapeutic IV heparin. D-dimer continued to be 6 times ULN throughout admission and up until day of event. Patient was screened for LAC and returned positive. His condition continued to deteriorate, developing bacteremia and cavitary lung disease with confirmed aspergillosis. Patient was treated with anti-fungal but progressed to invasive form with hemoptysis. Patient had a cardiac arrest and expired on day 76 of admission. All data related to the five patients is outlined in Table .


A 45-year-old HIV-infected African-American woman was seen for initial evaluation for multinodular goiter in December 2015. The patient presented with a cushingoid appearance and classic findings of wide purple striae, central obesity, round facies, and proximal muscle weakness. She was a poor historian on the initial visit and was unable to provide an adequate account of the progression of her cushingoid symptoms. Other notable medical history included HIV infection, asthma, hypertension, and obstructive sleep apnea. Relevant medications were ritonavir 10 mg PO twice daily, raltegravir 400 mg PO twice daily, darunavir 800 mg PO once daily, fluticasone propionate HFA (110 mcg/ACT Inhalation Aerosol) one puff twice daily, and fluticasone propionate (50 mcg/ACT Nasal Suspension) two sprays in each nostril once daily.
Physical examination at the initial evaluation showed an obese female with a body mass index (BMI) of 37.6 (Figure ); she had “moon-like facies”, significant dorsocervical and supraclavicular fat pads, and wide purple striae on the abdomen. The patient’s clinical picture was consistent with Cushing’s syndrome. However, a 1 mg dexamethasone suppression test (DST) was normal and 24-hour urine cortisol was undetectable, raising suspicion for adrenal insufficiency. A follow-up ACTH stimulation test was also abnormal with baseline cortisol of 0 pmol/L and 60 minutes stimulated cortisol level of 9 pmol/L and low normal ACTH of 9.1 pg/ml (7.2-63.3) confirming the diagnosis of adrenal insufficiency (Table ). The patient was then initiated on hydrocortisone 10 mg PO twice daily.
It was discovered that the patient had been taking HAART since 1996 in addition to fluticasone nasal spray for several years. A diagnosis of iatrogenic Cushing’s syndrome due to inhibition of fluticasone metabolism from PI therapy with secondary adrenal suppression was made. Fluticasone nasal spray and HFA were discontinued, and hydrocortisone dose was increased to the maintenance dose.
Cushing’s related symptoms improved over several months after stopping fluticasone with the resolution of cushingoid facies. Weight loss of 80 lbs was achieved by September 2016. An ACTH stimulation test was normal in September 2016, indicating recovery of adrenal function (Table ). Patient self-discontinued hydrocortisone at that time. Interestingly, the patient developed non-PTH-mediated hypercalcemia. Adrenal insufficiency was excluded by normal ACTH stimulation testing. A detailed lab evaluation looking for etiology for hypercalcemia was unremarkable except for elevated urine N-telopeptide/creatinine ratio of 139 nM bone collagen equivalents (BCE)/nM Cr (0-89). In November 2016, an ACTH stimulation test was again normal and the patient’s weight had begun to stabilize (Figure ). X-rays of the chest and hip did not show any pathology related to hypercalcemia. However, a dual-energy x-ray absorptiometry (DEXA) scan demonstrated osteopenia. While the etiology of hypercalcemia remained unclear, new symptoms of hip pain developed. A nuclear medicine three-phase bone scan demonstrated non-specific focally increased uptake within the right proximal femur (Figure ).
MRIs of both hips showed bilateral AVN of the right hip with acute, subacute, and chronic findings, and subacute changes of the left hip (Figure ). Sickle cell screen was negative and a right hip replacement was completed in May 2017. Since the patient developed non-PTH mediated hypercalcemia after adrenal functions returned to normal, hypercalcemia was deemed secondary to AVN. Serum calcium normalized over the next few months (Table ). At follow-up in August 2017, serum calcium levels remained normal and both Cushing's syndrome and adrenal insufficiency had resolved.


The patient, a 36-year-old Caucasian man, initially presented with altered mental status and a 5-day history of progressively slurred speech. The patient progressively became non-verbal and then developed fecal and urinary incontinence with watery diarrhea. This patient had no history of prior cerebral nervous system events or head trauma. In addition, there is no history of recent illnesses or any prior medical conditions. Pertinent social history includes an occupation focusing on outdoor pest and termite control for 13 years as well as an 8-year history of IV oxycodone use. There is no pertinent family history and the patient denies any outdoor hobbies. On physical exam, the patient remained afebrile, had delayed speech and communicated mainly through hand gestures. Comprehension was limited to single-step commands but strength was 5/5 bilaterally in both the upper and lower extremities. The remainder of the physical exam was unremarkable. The only laboratory abnormality discovered was a mild leukocytosis at 12 800 ul−1. His urine drug screen was negative, and both the patient and family denied any drug use. In addition, the urinalysis, chest x-ray and electrocardiogram were all unremarkable. The patient’s head computed tomography without contrast demonstrated the presence of possible bilateral infarcts or masses involving the basal ganglia and periventricular white matter greater on the right.
The next day neurology examined the patient and aside from new onset right facial diplegia, the physical exam findings remained unchanged from above. At that time, a magnetic resonance imaging (MRI) scan with and without contrast, a magnetic resonance angiography (MRA) scan of the head, a carotid ultrasound and an electroencephalogram (EEG) were all ordered. The EEG returned a finding of frontal intermittent rhythmic delta activity, a non-specific finding, often found in the setting of toxic or metabolic encephalopathies. The MRI results remained uncertain of whether the patient was presenting with bilateral masses or infarcts. Of note, paranasal sinuses and mastoid air cells were reportedly clear. The patient’s condition and prognosis at this time remained unclear and after several days his condition seemed to improve clinically according to family members. The patient’s improvement, perceived low suspicion for infection, and the current prevailing diagnosis of neurosarcoidosis prompted the initiation of a 5-day course of intravenous methylprednisolone 1 g/day. On day 3 of hospitalization, the patient continued to have diarrhea and reported a headache of unknown duration. Steroid administration led to a mild improvement in the patient’s condition, but the patient continued to remain mostly non-verbal.
On day 6 of hospitalization, the patient developed a new onset left hemiparesis, which prompted neurology to conduct a lumbar puncture showing a red blood cell (RBC) count of 35 µl−1, white blood cell (WBC) count of 590 µl−1 with 82 % lymphocytes, a glucose of 41 mg dl−1, and protein of 140 mg dl−1. The lumbar puncture was suggestive of an inflammatory process consistent with autoimmune, paraneoplastic or viral process. This was consistent with the initial course of treatment, however due to the lack of improvement, the etiology of this neurocognitive dysfunction was reassessed. On day 7 of hospitalization, the patient had a repeat MRI that demonstrated increased cerebral edema on the right side with the center of the mass demonstrating necrosis (see ). On day 8, the patient’s mental condition declined, his left hemiparesis worsened and the patient was no longer able to follow simple commands. Because of the prevailing thought of an autoimmune etiology, the patient was begun on dexamethasone 4 mg every 6 h. On hospitalization day 11, with recommendation from neurosurgery, the patient received a right basal ganglia and deep white matter stereotactic brain biopsy, which demonstrated non-caseating granulomatous inflammation with giant cells (see ). With this biopsy result, the infectious disease specialist recommended the addition of liposomal amphotericin B to cover the possibility of a fungal etiology. On day 14, the full pathology report returned with Gomori methenamine-silver stain revealing the presence of fungal hyphae favoring non-septate/pauciseptate hyphae (see ), which was consistent with an isolated cerebral mucormycosis infection. More specifically, PCR demonstrated Rhizopus oryzae fungus. Otolaryngology was consulted to identify a source of the mucormycosis infection; however, no point of entry could be ascertained as the paranasal sinuses were clear and no cutaneous manifestations were present. Due to the extent of the neurologic involvement, posaconazole was incorporated into treatment at the suggestion of the otolaryngologist. Of note, the otolaryngologist identified an otitis media but denied it as the source of the mucormycosis infection. After about 4 months of consistent antifungal therapy, the patient has improved significantly. He has regained much of his neurological functioning, including the ability to speak intelligibly and purposefully move his extremities. While the patient is still in recovery, he is slowly approaching a level commensurate with his pre-infection state.


A 17-year-old Hispanic male with no prior medical, cardiac, or known substance abuse history and no familial cardiac history presented to an outside hospital approximately 12 hours after feeling a sensation of “heart pounding”, chest pain, and dizziness that began a few hours after work as a furniture mover. The chest pain was localized to his left-central chest and radiated with pain and numbness to his jaw and lower face. The patient was hemodynamically stable with no notable vital sign changes. He was noted to have an elevated qualitative iStat troponin and electrocardiogram (ECG) showing ST-segment elevations in V2 and V3, but no other lab abnormalities including a normal erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell (WBC) count. The patient reported that he had used marijuana via a vaporizer three-to-four hours before the incident. He had no recent illnesses and reported no sick contacts, recent travel, or use of any other substances including cocaine. He was placed on telemetry for the duration of his admission.
On admission to our institution, approximately 24 hours after the initiation of symptoms, his troponin I level was elevated to 4.54 ng/mL (normal range 0.00-0.04 ng/mL), his ECG was notable for persistent ST-segment elevation in V2 and V3, CRP and ESR were both within normal limits (0.5 mg/dL and 4 mm, respectively), and his creatine kinase, creatinine, and serum lipids were within normal limits (Figure ). His urine drug screen was positive for cannabinoids and negative for cocaine and opiates. Screening for synthetic cannabinoids was also negative. An echocardiogram on admission showed no abnormal findings, and a respiratory panel was done with no viruses detected. He had no murmurs or extra sounds on cardiac exam and his physical exam was otherwise unremarkable. The patient at this time reported continued chest pain, but his palpitations and dizziness had resolved.
One day into hospitalization (two days after initiation of symptoms), his troponin I had downtrended to 3.09 ng/mL and no acute events were noted on telemetry. The patient reported improvement in his clinical condition, with a decrease in chest pain and no recurrences of palpitations. Vital signs remained stable throughout admission. A cardiac MRI was performed to rule-out inflammatory or structural heart disease and showed no evidence of inflammation, fibrosis, myocarditis, infarction, or altered perfusion as well as no anomalous origins of coronary arteries.
By hospital day two, his troponin I had decreased to 2.62 ng/mL, he had no recurrence of chest pain or palpitations, and he was discharged home after a discussion on the importance of avoiding marijuana and with the plan to follow-up as an outpatient (Figure ).
At one-month outpatient follow-up, the patient reported no recurrence of symptoms and at this time had a normal troponin I level. Additionally, the importance of avoiding marijuana in the future was re-iterated and drug abuse counseling was recommended.


Case 1 involved a 72-year-old female with underlying diabetes mellitus, hypertension, and prior cerebral vascular accident (CVA). The patient had been previously treated for T12/L1 and L1/L2 pyogenic discitis with concurrent L1 vertebral osteomyelitis with antibiotics 1 year prior. She was referred to our clinic due to progressive back pain. She had completed her course of antibiotics four months prior, and C-reactive protein (CRP) had been below 5 mg/L for 2 months. Radiographs and CT showed a collapsed nonhealing L1 vertebra with destruction of both upper and lower endplates (Figures –). Due to the patient's age and underlying comorbidities, we wanted to avoid an anterior approach, so a posterior one-stage approach was used. T12/L1 and L1/L2 transforaminal debridement and impaction of mixed autologous bone and allograft (Figures and ) were performed for T12-L1-L2 interbody fusion (Figures and ), followed by posterior instrumentation using cement-augmented pedicle screws from T11-L3 (Figures and ). Postoperatively, back pain improved significantly. Because the patient had osteoporosis (BMD T-score: -2.8), the patient was given teriparatide 20 μg daily for 12 months after surgery to promote growth of new bone. After 12 months of teriparatide treatment, the patient was switched to 60 mg denosumab every 6 months, which they are still currently taking. At three years follow-up, the fusion mass between T12/L1 and L1/L2 was solid, and the patient had minimal pain (Figures and ). Instrumentation has remained intact without loosening until the latest follow-up, and no further surgery to remove instrumentation is planned.


Case 2 involved a 62-year-old woman who had received conservative treatment for an L1 burst fracture six months prior. At that time, the patient developed progressive back pain and kyphotic deformity, for which she was referred to our clinic. Radiographs showed a collapsed nonhealed L1 fracture and 39 degrees of local kyphosis (). CT and MRI showed L1 vertebral body destruction similar to Kummell's disease, with destruction of the inferior endplate (Figures and ). A retropulsed bone fragment was observed in the canal (). The patient also complained of left inguinal pain. Left hemilaminectomy was performed at T12/L1, followed by transforaminal interbody impaction of allograft into the T12/L1 disc space (). The postoperative kyphotic angle improved from 39 degrees to 12 degrees (). At three months follow-up, her VAS back pain had improved from 8 to 1, and she was able to bend forward without pain (). Due to osteoporosis (BMD: T-score: -2.6), teriparatide 20 μg daily was given for 3 months, followed by denosumab 60 mg every 6 months, which the patient continues to take. The kyphotic angle was 20 degrees at three years follow-up (), at which time X-ray showed solid union and instrumentation remained intact. The patient has no back pain and has kept regular radiographic and clinical follow-up to 3 years.