The participant is a 21-year-old woman (163 cm, 55 kg) with no previous disease with Th12 vertebra fracture associated with spinal cord compression and spinal cord injury at the level Th11 (ASI A), multiple rib fractures, contused lung, traumatic hiatal hernia, kidney contusion, followed by paraplegia, sensory loss, loss of bladder and bowel control. Urgently, she underwent hepatorrhaphy, and 5 days after injury, the decompression spine surgery at the level Th12, followed by reduction spondylodesis Th11-L1 (). A computed tomography scan (CT) was performed before surgery and magnetic resonance imaging (MRI) was captured post-surgery, although, some distortion was apparent due to spinal fixation hardware (). Additionally, injury site was assessed with ultrasound (). One year after SCI, participant was enrolled into the study and underwent a re-evaluation of neurological functions below the lesion along with electrophysiologic assessment with positional changes and subject-driven reinforcement maneuvers. The neurological assessment was consistent with paraplegia with decreased muscle tone in proximal leg muscles and increased in distal muscles, neurological level of injury Th11. Light touch sensory loss from the level Th12 bilaterally, pinprick sensory loss from the level Th12 from the left side and L1 from the right side, joint position sense loss from the level Th12, loss of bladder control (uses clean intermittent catheterization, residual urine volume: 200–400 ml), loss of bowel control. summarizes tested in this report electrophysiological assessment: (I) examination of spinally evoked motor potentials (SEMP) to transcutaneous stimulation (tSCS) applied at Th9-10, Th10-11, Th11-12, Th12-L1, L1-2 levels; (II) the evaluation of the supraspinal influence and afferent signaling by assessment the effect of reinforcement maneuver (Jendrassik maneuver, JM) and positional changes. First, the effect of the JM was evaluated during testing H-reflex in supine position. Then, we investigated the combination of JM and afferent signaling with tSCS in supine and upright (less than 30% body weight support) positions (). The visual assessment of the leg muscle activation during JM was evaluated in supine and in vertically suspended (100% body weight support) positions; (III) the impact of the motor rehabilitation on facilitation of the mono- and polysynaptic spinal cord circuitry. During the initial electrophysiological assessment, the subject with SCI was evaluated with techniques I and II (). After the initial assessment 65 rehabilitation sessions, approximately 45 min each, consisting of trainer-assisted standing and weight supported stepping were performed over 16 weeks, with the following electrophysiological assessment (; see ).


A 21 years old right-handed woman, from Christian Arab ancestry, who was born in a cesarean section following an uneventful pregnancy. Her early development was normal, and she achieved the developmental milestones in time. One second-degree cousin had epilepsy. There was no history of head trauma. She graduated from high school, and, during her current assessment, was a college student.
Febrile seizures started at the age of 11 months and were treated with valproate until the age of 5 years. Between the ages of 5–16 years, the patient was seizure-free. Focal seizures started at the age of sixteen, characterized by altered consciousness with oral and bimanual automatism lasting up to a minute. A non-specific frontal cephalic aura preceded the seizures. The patient started Lamotrigine treatment with an increase of dose up to 400 mg/day, with no documented seizures at all. This typical seizure semiology was constant until the age of twenty.
At the age of twenty, approximately 6 months following a sexual assault by an unfamiliar man, the patient began suffering from nocturnal seizures with hyper-motor semiology accompanied by screaming, at the frequency of one to two events per week. She presented with right-hand automatism (fondling her genitalia) as well as verbal automatism (saying “take him away from me” and “no, dad”). At times she would hide under her blanket during seizures. She had no recollection of these events afterward (see ). There were no subjective memory problems, yet she reported anxiety symptoms and referred to psychotherapy.
Neurological examination was unremarkable. Overall intellectual functioning was at the average range (25th percentile) both for visuospatial tasks and for verbal tasks. Performance on word list recall and memory for faces was within the normal range for her age. Standard EEG recording demonstrated inter-ictal epileptiform discharges and mild intermittent slowing over the right temporal region. T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI scan revealed hyperintense signal in the mesial aspect of the right temporal lobe (), and PET-CT demonstrated bilateral temporal hypo-metabolism, more prominent on the right side (). Carbamazepine with a dose of up to 500 mg/d was added to her usual Lamotrigine treatment, and she was referred to the EMU for evaluation of the new type of events (Hyper-motor seizures vs. Psychogenic non-epileptic seizures). At EMU, after the gradual withdrawal of Carbamazepine, there were two ictal events; both were with vocalization, automatism, and resembled the newly described semiology. Ictal EEG showed right temporal epileptic activity spreading quickly over the right frontotemporal leads ( and ). Interictal EEG was significant for right temporal epileptiform discharges and mild intermittent slowing. The dual therapy of Lamotrigine and Carbamazepine was not effective in controlling seizures, with up to 2–3 focal seizures with impaired consciousness per month, and the treatment scheme was gradually switched to Lacosamide 500 mg/d and Clobazam 30 mg/d. During 3 years of follow-up in the epilepsy outpatient clinic, the patient and her family members reported the occurrence of up to 2–3 occasional seizures per year, all with the “new” semiology, and no seizures with the “old” semiology.
Psychiatric workup established the diagnosis of PTSD, based upon clinical interview and structured evaluation (). The patient met the following DSM-5 criteria for PTSD: A – Exposure to a traumatic event (A1); B – Intrusion symptoms (B1,3-5); C – Avoidance symptoms (C1-2); D – Cognition and mood change (D1-4); E – Arousal and reactivity (E3-5); The disorder lasted more than a month (F criteria), caused significant distress (G criteria) and was not attributed to other etiology (H criteria) (). Her PTSD Checklist for DSM-5 (PCL-5) score was 12, suggestive of mild PTSD symptomatology (). Aside from the PTSD symptomatology, the patient had minimal anxiety and no apparent depression, with scores of 6 and 3 on the Beck Anxiety Inventory and Beck Depression Inventory-II respectively (, ). She was prescribed with a Selective Serotonin Reuptake Inhibitor, which she declined to take and was referred to psychotherapy.


A 75-year-old Japanese man complained of a swollen right scrotum, which had grown slowly for 1 year. A huge elastic hard mass was palpable in his right scrotum. The surface of the skin showed no redness, rash, ulcers, or other skin abnormalities. He had neither pain nor obstruction of urination. He had worked as a farmer for a long time. He had a smoking history (20 pack-year) but did not consume alcohol. There was no history of disease or surgery. There was no specific family history, including of cancer. Physical and neurological examinations were normal, except for a 26 cm tumor in his right scrotum and right inguinal lymphadenopathy (3 cm). His blood pressure was 146/80, heart rate 86, and temperature 36.8 degrees. Laboratory findings are shown in Table ; there were no abnormal findings. The findings by computed tomography (CT) were shown in Fig. a. In addition, multiple lung nodules were detected on chest CT (Fig. ). Our patient underwent radical orchiectomy and lymph node dissection. Histological analysis revealed the proliferation of spindle and pleomorphic cells containing bizarre hyperchromatic nuclear cells with both poorly and well-differentiated areas. On immunohistochemistry, tumor cells were negative for cytokeratin AE1/AE3, desmin, S-100, STAT6, BCL-2, and MIC2, but positive for smooth muscle actin, CDK4, and MDM2 (Fig. ). These findings led to a pathological diagnosis of dedifferentiated PTL. Histological examination showed no microscopic invasion to the testis. Based on the soft tissue sarcoma classification, the disease was T2bN1M1 (IV) stage. At 2 months after surgery, the lung nodules showed rapid progression (+ 40% for 2 months) (Fig. ). First-line treatment was then started with gemcitabine (1000 mg/m2 day 1) plus docetaxel (30 mg/m2, day 1) chemotherapy every 2 weeks. The metastasis in his left lung was set as a target lesion by chest radiography. The time course of the imaging studies is shown in Fig. . The disease was well controlled by gemcitabine plus docetaxel chemotherapy for 1 year without any adverse events until its progression. We subsequently performed second-line eribulin (1.4 mg/m2, day 1, 8, every 3 weeks) chemotherapy. Despite the progression of the lung metastases, his symptoms remained stable. However, at 4.5 months after second-line chemotherapy, chest radiography showed progression of metastatic nodules and the presence of pleural effusion. In all, he underwent chemotherapy for 18 months and died at 22 months after diagnosis. An autopsy was not performed.


A 36-year-old male patient presented with a chronic MH (with optical coherence tomography [OCT] documentation for 3 years) following blunt trauma with a cricket ball 6 years earlier.
On examination, his best corrected visual acuity (BCVA) was 6/60 in the right eye and 6/6 in the left eye. Intraocular pressure was normal in both eyes. Anterior segment examination results were within normal limits. Fundus examination of the right eye showed a normal optic disc and a large full thickness TMH with no sign of posterior vitreous detachment. Choroidal rupture scar was seen about 3 disc diameters temporal to the fovea and a pigment clump was seen superotemporal to the disc. OCT measured the minimum MH diameter as 769 µ, the basal diameter 1431 µ and height 272 µ. Intraretinal cystic spaces were present on the temporal side of the MH (Figure 1 ).
The patient underwent PPV with inverted temporal ILM flap technique and 14% perfluoropropane (C3F8) tamponade. After 23G PPV, ILM was stained with 0.05% brilliant blue G. A semicircular ILM peeling was carried out about 2 disc diameters above the fovea extending circumferentially via temporal approach to end just below the macula. ILM peel was done just up to the temporal edge of the hole and the flap was inverted and gently coaxed over the MH. Fluid-gas exchange was promptly done and the vitreous cavity filled with non-expansile concentration of 14% C3F8. The patient was advised to remain in the face-down position for one week. The postoperative period was uneventful.
Two weeks after the surgery, the visual acuity improved to 6/36 and OCT showed a gradual decrease in size of the MH. Six months postoperatively, the patient’s BCVA improved to 6/18, closure of TMH was seen clinically (Figure 2 ), and OCT showed type 1 anatomical closure (Figure 3 ).


A 62-year-old Caucasian woman was admitted to the hospital complaining of abdominal pain in the right upper quadrant that started a month ago. The pain was severe, nonradiating, and colic. It was exacerbated by eating fatty meals and was responded to heavy analgesics. She also suffered from nausea, bilious vomiting, constipation, fever reaching 39°C that lasted for 10 days, chills, anorexia, and fatigue. There was no history of weight loss, pallor, jaundice, smoking, or alcohol consumption. Formerly, she was in good health as she did not report any previous illnesses or surgeries and her family history was unremarkable.
On examination, Murphy's sign was positive and there was tenderness over the gallbladder area with a firm palpable mass.
Laboratory workup showed a normal hemogram and liver function tests. On abdominal ultrasonography, the gallbladder measured 8.7 × 4.8 cm and was filled with necrotized mass and all edges of the gallbladder were clear except for the bottom (). Therefore, the presence of a gallbladder adenocarcinoma was suspected. Spleen, pancreas, kidney, and liver were normal. MSCT demonstrated the same findings, and there was no metastasis.
As a result, a provisional diagnosis of gallbladder adenocarcinoma was made and extensive cholecystectomy that involved cholecystectomy, main bile duct resection, and regional lymph node dissection was performed. Intraoperative findings showed no liver metastasis, ascites, peritoneal, or omental deposits. Porta was free, and there was no colonic or duodenal infiltration and no enlarged pericholedochal, paraaortic, or aortocaval lymph nodes.
On microscopy, the tumor consisted of diffuse proliferation of pleomorphic spindle to oval tumor cells with marked variation in size and shape and the presence of many abnormal mitoses and large hyperchromatic nuclei (). Furthermore, the gallbladder epithelium mucosa was congested and ulcerated with a mild degree of lymphocytic infiltration.
Immunohistochemical investigations were strongly positive for smooth muscle actin (SMA) and desmin and negative for CK, CD117, and CD34 (). Therefore, we put the conclusive diagnosis as primary leiomyosarcoma of the gallbladder. However, we could not perform any further immunohistochemical markers.
Although there is no sufficient evidence regarding the effectiveness of adjuvant chemotherapy with or without radiotherapy, our patient received 6 cycles of adjuvant chemotherapy as the following regimen: (doxorubicin (day 1: 60 mg/m2)+ifosfamide (days 1-3: 2000 μg/m2); repeated monthly for 6 cycles). No serious adverse effect or toxicity has occurred. However, radiotherapy is not available in our city. The patient was on follow-up for 2 years; there was no clinical or radiological evidence of recurrence or relapse as observational MSCT scans were clear for any local invasion or distal metastasis, and the patient is doing well till date.


A 54-year-old woman was referred to our hospital for occipital soft tissue swelling and headache. The patient’s history was remarkable for resection and radiation therapy for a hemangiopericytoma (HPC) in the left gluteal musculature 10 years previously. The patient had also undergone multiple pulmonary metastases resections. An ultrasound of the occipital region revealed a heterogeneous soft tissue mass with destruction of the occipital bone of up to 6 cm (Figure ). Computed tomography (CT) of the brain showed an extra-axial mass in the fossa posterior extending through the tentorium and lysis of the overlying occipital bone (Figure ). On MRI the mass was isointense to grey matter on both T1- and T2-weighted images (WI), flow voids were noted (Figure , arrowheads). The lesion demonstrated mildly heterogenous, avid contrast enhancement (Figure ). There was no restricted diffusion. The patient underwent selective intra-arterial embolization before surgical resection to minimize blood loss. Afterwards the patient received adjuvant radiotherapy.


The patient is a 16-year-old female with CF (genotype: F508del/W1282X), CF-related diabetes requiring insulin, and CF-related liver disease after liver transplant, who experienced a precipitous decline in lung function over the prior year, requiring frequent- near monthly -hospital admissions for intravenous antibiotics targeting her primary respiratory pathogen, B. multivorans. The patient acquired this pathogen in her sputum six years before, and over time, it developed increasing antibiotic resistance (). Notably, the patient required long-term immunosuppressive therapy following liver transplant 21 months before. Her frequency of hospital admission for pulmonary exacerbations remained unchanged for the first year after liver transplant but doubled in the succeeding 9 months. Her pulmonary exacerbations would only briefly respond to a single antibiotic, intravenous meropenem-vaborbactam. Furthermore, the patient's weight remained stagnant at the 10th percentile.
Female sex, body mass index ≤18 kg/m2, CF-related diabetes requiring insulin, B. cepacia complex infection, and frequent pulmonary exacerbations have all been identified as risk factors for mortality in individuals with CF and low lung function []. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to increase lung function and decrease rates of pulmonary exacerbation in individuals with CF [, ]; however, the patient's genotype and history of liver transplantation precluded her from qualifying for any CFTR modulators available at the time or therapeutic trials, respectively. Lung transplantation was discussed though the patient's colonizing pathogen and adolescent age are controversially associated with poorer outcomes [, ].
High-dose inhaled NO administration via a mechanical ventilator fitted with scavenging chambers was reviewed and approved under an institutional process called “Innovative Diagnostics and Therapeutics,” by which independent hospital leadership evaluate novel approaches to the care of individual patients. The patient assented, and her parents provided consent for this therapy.
The patient received a total of 46 intermittent inhalations of 160 ppm NO over a 28-day period during two separate hospital admissions: days 1–12 and days 16–28 (). During the first admission, inhaled NO was given over 30-minute intervals up to three times daily (27 total doses). In the second admission, the treatment interval was gradually increased to 60 minutes, two times daily (19 total doses), starting with 30-minute inhalations up to three times daily (9 doses), transitioned to 45-minute inhalations twice daily (2 doses), and ultimately 60-minute inhalations twice daily (8 doses). She concurrently received intravenous meropenem-vaborbactam (dose: 4 grams every 8 hours) on days 4–10 and 16–28.
The NO gas source was commercially available as 850 ppm nitric oxide in nitrogen tanks that meet the Environmental Protection Agency (EPA) traceability protocol requirements (Airgas Inc., Radnor Township, Pennsylvania, USA). Oxygen, medical air, and NO were blended and introduced through a ventilator (Puritan Bennett 980 Series, Medtronic, Minneapolis, Minnesota, USA) (). A target level of 160 ppm inhaled NO and 0.21 FiO2 were delivered via a tight-fitting noninvasive mask using a pressure support mode of 2 cmH2O driving pressure over a positive end-expiratory pressure of 5 cmH2O. Because the NO source of 850 ppm is mixed with nitrogen, the ventilator was set to a range of 0.25-0.26 FiO2, in order to deliver an FiO2 of 0.21 to the patient.
Nitric oxide and nitrogen dioxide (NO2) analyzers were attached to a sampling port proximal to the facemask and provided real-time measurements. Nitrogen dioxide, a potentially harmful gas that develops when oxygen and NO are mixed, was scavenged with calcium hydroxide chambers (Spherasorb™, Intersurgical Ltd, Berkshire, UK), and levels remained less than 1.5 ppm in the circuit. Ambient NO and NO2 levels were intermittently measured in the patient's room and consistently remained below EPA recommendations [] at less than 4 parts-per-billion (ppb) and 12 ppb, respectively.
There were no serious adverse events, and inhalations were well tolerated. Echocardiograms were performed before, during, and after the first inhalation and demonstrated normal estimated pulmonary pressures. Heart rate, respiratory rate, oxygen saturation, and blood pressure were recorded at 5-minute intervals throughout inhalations and 30 minutes after cessation. The patient did not experience any hemodynamic instability or significant hypoxia with treatments. Nitric oxide oxidizes ferrous (Fe2+) hemoglobin into the ferric state (Fe3+), known as methemoglobin. Methemoglobin levels were continuously monitored during inhalations using a peripheral pulse co-oximeter (Masimo Rainbow SetTM Technology, Irvine, CA) and never surpassed our safety threshold of 5%. Specifically, at the end of the 30-minute and 60-minute inhalations, the highest recorded methemoglobin levels were 3.1% and 4.1%, respectively, and returned to baseline prior to subsequent treatments (). Additionally, the patient received 125 mg of ascorbic acid by mouth daily (on treatment days) to enhance methemoglobin reductase activity [].
Sputum was collected prior to (days 1 and 16), midcycle (days 3 and 23), and on completion (days 12 and 28) of each NO cycle (). Colony forming units (CFU) were calculated using sputum solubilized with Sputolysin® (MilleporeSigma) and plated on Burkholderia cepacia isolation agar. On days 1, 12, 23, and 28, B. multivorans grew from the patient's sputum, but the CFU count was low (). Early in therapy (day 3), the sputum culture yielded highly antibiotic-resistant B. multivorans, consistent with months before; however, by the end of the first week of therapy (day 16), isolated B. multivorans demonstrated susceptibility to trimethoprim-sulfamethoxazole and levofloxacin and intermediate susceptibility to ceftazidime, a susceptibility pattern not seen for months.
Fever, white blood cell count, and C-reactive protein all decreased with therapy (). The patient never manifested bacteremia or hemodynamic instability suggestive of cepacia syndrome—a dreaded complication of B. cepacia complex infection primarily linked to Burkholderia cenocepacia though also associated with B. multivorans []. The patient's international normalized ratio (INR) remained consistently below 1.2, and she never demonstrated evidence of platelet dysfunction, hemoptysis, or other bleeding. Her lung function improved from her baseline. Specifically, on day 1—before starting high-dose inhaled NO therapy and after recently completing a 16-day course of intravenous meropenem-vaborbactam two days before—the patient's forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were 1.60 L (49% predicted) and 2.05 L (56% predicted), respectively. Both measurements improved at the end of the second admission to FEV1 1.72 L (52% predicted) and FVC 2.36 L (64% predicted). The patient's baseline weight in the prior 6 months remained at the 10th percentile, and her BMI was consistently below 18 kg/m2. Her weight at the start of inhaled NO therapy was 48.4 kg (22nd percentile). It rose to a maximum of 50.3 kg (30th percentile) on day 16 but decreased to 48.9 kg (24th percentile) by day 24.


A 78 year-old woman with a history of kidney transplant on immunosuppression presented to our academic medical center with altered mental status and seizure-like activity in March 2020. The patient was observed at home to have sudden-onset uncontrolled limb movements with ocular deviation followed by several minutes of unresponsiveness. At her baseline, the patient lived independently and had no previous diagnosis of dementia or confusion. However, three days prior to admission, she was noted to have confusion and disorientation. In addition, she was noted to have fever and nasal congestion for 2 days prior to admission. The patient was known to be adherent with her medical care and medications including tacrolimus, mycophenolate mofetil, and lisinopril.
00Upon arrival the emergency department, the patient was febrile to 100.7 but was otherwise hemodynamically stable. On neurological examination, she was noted to be alert and oriented to be intermittently confused. She was tremulous, but there were no sensory or motor deficits, and cranial nerve functions were intact. The complete blood count was notable for a pancytopenia with a white blood cell count of 1.8 × 103/μL, hemoglobin of 10.8 g/dL, hematocrit of 37.4% and platelets of 130 mm3. Absolute neutrophil count was 0.9 ×103/μL and absolute lymphocyte count was 0.6× 103/μL. The basic metabolic panel was notable for normal serum electrolytes and stable renal function. Alkaline phosphatase was slightly elevated to 139 U/L but hepatic function was otherwise unremarkable. Thyroid-stimulating hormone was elevated to 8.1 mIU/L, but thyroxine (T4) was within normal limits. Tacrolimus level was 3.1 mcg/L (lower than therapeutic range). Procalcitonin was 0.5 μg/L and her respiratory viral panel was negative. Two sets of blood cultures did not grow any organisms. EKG showed normal sinus rhythm. Chest X-ray (, left) did not reveal any focal consolidation, pulmonary edema, pleural effusion or pneumothorax.
The patient was admitted to the general medicine floor for further work-up of her altered mental status. She underwent an electroencephalogram that demonstrated mild generalized slowing, and an MRI with contrast that revealed generalized atrophy and patchy periventricular and subcortical white matter hyperintensities, which were interpreted as sequelae of small vessel ischemic disease ().
She subsequently underwent lumbar puncture, which revealed CSF that was clear in appearance with no xanthrochromia. The CSF analysis revealed 350 red cells/uL, 1 white blood cell/uL, 75% lymphocytes, 25% monocytes, glucose 67 mg/dL and protein 43 mg/dL. The CSF HSV and VZV PCR were negative. The plasma CMV and adenovirus testing were negative by PCR, and serologies indicated prior EBV and Parvovirus B19 infection. On hospital day 3, the patient had persistent fevers and developed cough with dyspnea requiring oxygen supplementation. A chest X-ray revealed bilateral pulmonary infiltrate (, right). She therefore underwent SARS-CoV–2 PCR testing using a nasopharynx swab and was found to be positive. Sequencing of this SARS-CoV– 2 isolate revealed a virus similar to other SARS-CoV–2 circulating in the region ().
Further investigation of the CSF was done following the patient’s COVID–19 diagnosis. Inflammatory cytokines were measured in CSF and plasma using a multiplex cytokine assay. This patient’s CSF and plasma were tested alongside CSF and plasma specimens obtained from three healthy control volunteers: Female age 63, Female age 45, and Male age 62. (). These control samples were collected during the last year for unrelated studies and were kept frozen until the current cytokine assays, when they were run in parallel with this patient’s sample. Levels of IL–6, IL–8, and IP–10 appeared to be elevated in both CSF and plasma of this patient compared to control, with a unique MCP–1 signature found only in CSF and not plasma.
The patient’s CSF was next tested for the presence of SARS-CoV–2 by several methods and was negative. First, qRT-PCR was performed using the US CDC SARS-CoV–2 assay. Sequencing of SARS-CoV–2 in the CSF was then attempted using both targeted (tiled PCR-amplicons) and unbiased (“shotgun” metagenomic) approaches. From the targeted sequencing, 316,111 reads were generated from the sample and a total of 60 reads aligned to SARS-CoV–2, which was not above background. From the unbiased sequencing approach, about 40 million reads were generated and none aligned to SARS-CoV–2 or any other respiratory pathogen. Finally, culturing of SARS-CoV–2 was attempted from the CSF supernatant, and after 4 days of culture, SARS-CoV–2 by PCR was not detected.
summarizes the patient’s laboratory findings at the time of diagnosis of COVID–19 and the follow-up course. Based on the patient’s age and co-morbidities, she met criteria for treatment initiation per our academic center treatment protocol. The patient received hydroxychloroquine 400mg twice daily for one day followed by 200mg twice daily for nine additional days. Her confusion slowly improved. However, on hospital day 13, she had worsening of her mental status and became hypoxemic, with chest X-ray showing worsening bilateral infiltrates. She was therefore treated with the IL–6 inhibitor, tocilizumab, with overall improvement in her confusion and respiratory status. The patient was able to be weaned off oxygen and discharged home safely after one month of hospitalization. She remained in good condition at the time of this case report.


A 34-year-old nulliparous woman presented with increased serum human chorionic gonadotropin level in the second-trimester Down syndrome screening, and amniocentesis showed normal karyotype. The anomaly scan was normal. Ultrasound was performed at 36 weeks of gestation for increased symphysial fundal height (42 cm), which showed the fetus in breech presentation with polyhydramnios. She underwent Cesarean section at 36 weeks due to rupture of membranes and 2,700 ml of liquor was noted during delivery. The female baby weighing 2,178 g was born apneic and hypotonic. Multiple abnormalities were noted including increased head circumference, bilateral ptosis, no spontaneous limb movements, multiple joint contractures, and bilateral humeral and femoral fractures. Deltoid muscle biopsy indicated NM. The nerve conduction study showed markedly reduced amplitude due to diminished motor response of atrophic muscles. The baby required ventilation support and tube feeding. The baby passed away at 7 months of age as a result of sudden desaturation and bradycardia.


A 26-year-old nulliparous woman experienced persistently reduced fetal movement. Noninvasive prenatal testing was normal. The anomaly scan showed bilateral clubfeet. Increased head circumference was noted from 26 weeks of gestation. She had spontaneous preterm labor at 31 weeks and the baby was delivered in extended breech presentation vaginally. The female baby weighing 1,440 g was born apneic and flaccid, and had multiple anomalies including disproportionately large head, bilateral ptosis, paralytic hypotonia, abnormal posture with bilateral humeral fracture, lax hip joints, and bilateral clubfeet. Thigh muscle biopsy confirmed NM. Sural nerve biopsy was unrevealing. The baby required high-flow oxygen ventilation due to carbon dioxide retention, and passed away at 49 days of age due to sepsis.


A 26-year-old, gravida 2, and para 1 woman experienced subjectively reduced fetal movement compared with her previous pregnancy. The anomaly scan at 20 weeks of gestation showed a female fetus with abnormal posture, including persistently extended legs, closed hands, flexed wrists, and bilateral clubfeet (Figure ). Liquor volume was normal. Karyotype and chromosomal microarray of amniocytes were normal. Following termination of the pregnancy, posture of the abortus confirmed the prenatal sonographic findings. Autopsy did not reveal additional structural abnormalities (Figure ). Muscle biopsy was not performed as a fresh specimen was not available.


A 37-year-old woman had two unaffected children with another partner. In the index pregnancy, amniocentesis was performed for a positive first-trimester screening for Down syndrome, which showed normal karyotype. The anomaly scan was normal. She had spontaneous onset of labor at 38 weeks of gestation. The baby was delivered by ventouse extraction, and 4,000 ml amniotic fluid was released upon rupture of membranes. The female baby weighing 2,335 g was born hypotonic with poor respiratory effort. Multiple anomalies were noted including arthrogryposis multiplex congenita, fractured left humerus and right femur, generalized hypotonia, absent spontaneous limb movement, paucity of extraocular muscle movement, and congenital chylothorax. The baby required ventilation support and total parental nutrition. A chest drain was inserted for the chylothorax with a persistently high output. The baby subsequently passed away at 60 days of age.


A 47-year-old Chinese female patient presented with facial pruritic, erythematous papules since the last 8 months. The lesions were symmetrically distributed over the nose, cheeks, forehead, and mandible. They were scattered erythematous papules with a diameter of 0.3 to 1 cm, and a few papulopustules were observed. Radial stripes were observed around the mouth. The patient felt that the facial skin was dry, tight, hot, and itchy, and it was difficult to open the mouth. No obvious abnormalities were found in other skin mucosal tissues (Fig. A). The patient did not have any symptoms, such as fever, night sweats, and cough. The patient was physically healthy. She denied any history of tuberculosis and did not have any obvious abnormalities in the other systems. She was diagnosed with skin tuberculosis at another hospital. She was given oral isoniazid tablets (300 mg per day), rifampicin capsules (450 mg per day), pyrazinamide tablets (1.5 g per day), and ethambutol tablets (750 mg per day) for 8 weeks, followed by isoniazid and rifampicin for 16 weeks. However, the treatment was not efficacious, and the skin lesions did not subside and they progressively worsened. Because of nausea, vomiting, and other symptoms after medication, the patient discontinued the drugs for 8 weeks. The skin lesions gradually spread over the entire face.
A skin biopsy showed the presence of a Demodex mite inside the pilosebaceous unit surrounded by chronic inflammatory tissues in newly developed lesions (Fig. ). Caseation necrosis in the dermis was observed in mature lesions. Caseation necrosis showed the following 3-layer structure: central foci of caseation necrotic area, a middle layer of tuberculous granuloma formed by epithelioid cells and multinucleated giant cells, and an outer layer of lymphocytic infiltration (Fig. ), Acid-fast staining was negative. Demodex mites were observed in the secretion of sebaceous glands attached to the hair follicles in lesions (Fig. ), On the basis of clinical manifestations, laboratory tests, and pathological features, a diagnosis of Demodex-induced LMDF was established. On the basis of our previous study,[ the patient was given ornidazole tablets (500 mg twice a day) to fight against Demodex and recombinant bovine basic fibroblast growth factor gel (0.2 g/cm2 twice a day) for the repair of the inflammatory granuloma for an 8-week period. Five weeks after treatment, the lesions gradually improved and the patient reported a reduction in itching (Fig. B–F). Eight weeks after the treatment, the facial erythematous papules were improved, and the symptoms of dryness, tightness, burning, and itching were alleviated. No new skin lesions were observed (Fig. G). At the 6-month follow-up, the original lesions had completely resolved; there was no facial dryness, tightness, burning, and itching, and no new skin lesions were observed (Fig. H).


A 31-year-old, otherwise well female, with a body mass index of 26.2 kg/m2, presented with a locally advanced, mismatch proficient rectal cancer. She had had 12 months of symptoms, including altered bowel habit, rectal bleeding and increasing obstructive-type symptoms. Her initial staging with MRI and chest-abdomen-pelvis computed tomography (CT) showed a bulky mucinous rectal cancer with invasion of the posterior vaginal wall and possibly the cervix (). Locoregional lymph nodes were enlarged, including pre-sacral and external iliac nodes. There was no evidence of further distant disease.
The patient was re-staged 4 weeks after completion of chemoradiotherapy with a fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT and MRI. An exam under anaesthesia was also performed to assess vaginal involvement. These results confirmed an anteriorly based tumour, 6 cm from the anal verge with posterior vaginal wall invasion and potential cervical invasion, enlarged right pelvic side-wall lymph nodes and no further distant disease.
A discussion at the exenterative multidisciplinary team meeting suggested utilising a robotic approach from above and taTME approach from below as a combined two-team approach.


A 66-year-old Asian man who had hypertension for which he had been receiving medication for 20 years presented to our hospital. He had been a heavy smoker and drinker for more than 30 years. He had experienced progressive swallowing difficulty for 3 months and a body weight loss of 5 kg in 1 month. Endoscopy disclosed that a huge tumor was occupying the esophagus 30 cm from the incisor to the esophagogastric junction, with a biopsy determining poorly differentiated squamous cell carcinoma. A whole-body PET-CT scan with 18F-FDG revealed a distinct FDG uptake in the lower esophagus (Fig. ), and clinical stage cT3N1M0 was subsequently categorized. A chemoport was inserted, and a percutaneous endoscopic gastrostomy was performed prior to neoadjuvant CRT. The patient underwent a two-cycle chemotherapy regimen with cisplatin and 5-fluorouracil, in combination with RT in 25 fractions at 5000 cGy, with no obvious side effects being noted. Following the feasibility of definitive surgery for esophageal resection and reconstruction, a PET-CT scan was performed again 6 weeks later upon completion of CRT in order to evaluate the effects of the neoadjuvant CRT (Fig. ). It was at this time when a new FDG-avid lesion at the caudate lobe was discovered, and a formal report was written to address the liver metastasis (Fig. ).
The tumor markers, including α-fetoprotein (5.74 ng/ml), carcinoembryonic antigen (3.27 ng/ml), and squamous cell carcinoma–related antigen (0.3 ng/ml), disclosed nothing remarkable. A further imaging survey was performed to clarify the new lesion. Liver sonography (Fig. a) showed focally mild prominence in S1 of the liver with a slightly hypoechoic appearance, and CT of the liver revealed focally less enhancement in S1 of the liver (Fig. b). Additionally, magnetic resonance imaging (MRI) of the liver showed a low signal intensity on T1-weighted images, along with a high signal intensity on T2-weighted images, over the caudate lobe (Fig. c, d). The liver MRI in the formal report indicated the new lesion at the liver over S1 as being due to postradiation liver inflammation change rather than liver metastasis from esophageal cancer. Excluding the possibility of distant metastasis, a thoracoscopic esophagectomy with cervical esophagogastrostomy via the retrosternal route, along with a feeding jejunostomy, was performed smoothly 2 weeks later. A liver biopsy for both frozen section and pathology was also conducted during the surgery. The pathology report revealed esophageal cancer, specifically poorly differentiated squamous cell carcinoma, pT3N1M0. A valuable photograph was taken during surgery that revealed inflammation of the caudate lobe. The photograph also showed a manifested dark red color due to liver congestion containing a soft, smooth surface without adherence to the surrounding tissue (Fig. a, b), with no palpable hard nodules being seen in the lesion. There was no obvious tumor metastasis or enlarged lymph node discovered in the abdomen during the operation. The histology elucidated sinusoidal congestion with attenuated hepatic cords, which were filled with erythrocytes. However, there was no evidence of liver metastasis (Fig. c, d). The patient recovered uneventfully and was discharged with his oral intake performing smoothly, and a stable condition was observed during 12 months of outpatient department follow-up.


A 44-year-old male health care worker presented to the emergency department of a hospital in Tehran, Iran. The hospital was a designated coronavirus referral center at the time. He described a history of rib fracture due to falling about two weeks ago and complained of local tenderness and pain that was not responsive to over-the-counter painkillers. Upon admission to the emergency room, vital signs were within normal ranges. He reported no underlying medical conditions, and the patient was otherwise healthy.
A chest CT scan was performed (), which revealed left 8th and 9th ribs fracture along with an ill-defined patchy ground-glass opacity in the upper lobe of the right lung. Due to high suspicion of SARS-CoV-2 infection, an upper respiratory tract swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was obtained, and a positive real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay confirmed the diagnosis of COVID-19 infection.
Based on the Iranian interim guideline for "clinical management of COVID-19" published in February 2020, the decision for the use of antiviral and antimalarial therapy was made considering the patient’s diagnosis of SARS-CoV-2 infection []. Oseltamivir 75 mg every 12 hours, and hydroxychloroquine 400 mg stat was initiated despite no clinical signs. After three days of the treatment, fever and dyspnea developed, and the patient’s oxygen saturation values dropped to 93% while he was breathing room air.
The treatment regimen was changed to a more focused antiviral therapy with oseltamivir 75 mg and lopinavir/ritonavir (Kaletra), 400/100 mg every 12 h []. After approximately 24 h, the patient’s clinical condition started to improve; fever abated, dyspnea decreased, and O2 saturation increased to 97% on room air. On the fifth day of admission, the patient became asymptomatic.


A 34-year-old male patient with an unremarkable medical history consulted his local emergency department for intractable emesis for the past 48 h. The day before, he had been given a diagnosis of hand, mouth and feet syndrome with a possible cross-transmission from his 4-year-old daughter. He had a single bout of non-bloody diarrhea. Notable clinical signs consisted in elevated blood pressure (167/98 mmHg), purpura of the lower limbs and papulovesicular acrodermatitis of both hands and wrists. Prominent biological abnormalities consisted of KDIGO stage 3 AKI (Blood urea: 30 mmol/L plasma creatinine: 497 μmol/L) and hematological thrombotic microangiopathy (TMA) (hemoglobin levels: 13.1 g/dL, platelets: 47000 / mm3, haptoglobin levels < 0.20 g/dl, greatly elevated LDH levels: 1843 UI/L and schistocytes were detected). Proteinuria was in the nephrotic range (6 g/24 h), consisted primarily of albumin (66%) and was associated with microscopic hematuria upon urine culture. The patient was referred to an intensive care department and was started immediately on plasma exchange (PE). Neurological examination was normal. After two rounds, PE were discontinued owing to normal ADAMTS13 activity (113%). Additional etiological workup included negative HIV, HBV, HCV testing, unremarkable lymphocyte immunophenotyping and normal levels of C3, C4 and CH50. He was next referred to our renal intensive care unit. Quantitative explorations of the alternate complement pathway (ACP) disclosed normal levels of MCP, Factor H and Factor I and negative testing for anti-FH antibodies. Accordingly, renal biopsy identified double contours and several foci of mesangiolysis as well as focal segmental glomerulosclerosis of the tip variant affecting one glomerulus (Fig. ). Following supportive care with rehydration and blood pressure control, signs of peripheral TMA resolved while plasma creatinine levels declined to 350 μmol/L. The presence of shigatoxin (stx2b) and hemolysin (ehxa) were detected via PCR assessment in the stool samples and stool culture confirmed the presence of the enterohemorrhagic O128 Escherichia coli clone. Together these results ruled in favor of STEC-HUS. One month later the patient was readmitted in our unit owing to the recurrence of peripheral thrombotic microangiopathy (platelets: 130000/mm3, Hemoglobin: haptoglobin < 0.01 g/dl, schistocytes: 1%, LDH: 740 UI/L) and AKI with a creatinine level of 470 μmol/L. Repeated stool culture did not find evidence for the persistence of the predetermined E. coli clone or shigatoxin. Due to gradual worsening of the kidney function and platelet levels the patient was empirically started on eculizumab pending genetic findings. In the course of 15 days, creatinine levels gradually decreased from 630 μmol/L to 193 μmol/L and signs of TMA resolved. Genetic testing revealed that the patient was a heterozygous carrier of a CFHR1/CFH hybrid gene demonstrated to be associated with aHUS []. An attempt to discontinue eculizumab therapy 9 months after its initiation resulted in a second recurrence with an increase of creatinine levels to 430 μmol/L along with overt signs of peripheral TMA. After resuming eculizumab therapy, TMA resolved once again and creatinine levels fell back to baseline levels.


A 44-year-old male patient presented to the emergency department with fever and skin lesions. His only past medical history consisted of IV drug abuse, discontinued for several years and under substitution therapy by buprenorphin. He reported over the past 2 weeks fever, emesis, myalgia, ankle arthralgia, headache and asthenia. Clinical examination noted a purpura located on the feet and distal legs (Fig. ). Blood pressure was 120/86 mmHg. First blood tests only revealed mild thrombocytopenia (120,000/mm3) and creatinine levels were normal (98 μmol/L). He was referred to our nephrological department 4 days later due to the subsequent development of a rapidly progressive acute kidney injury. Upon admission he presented KDIGO stage 3 AKI (serum creatinine: 404 μmol/L, BUN: 43 mmol/L) with microscopic hematuria and glomerular range proteinuria (2 g/24 h) and signs of hematological TMA (Platelets 71,000 /mm3, hemoglobin level: 10 g/dL, haptoglobin < 0.08 g/L, LDH 864 U/L, detection of schistocytes 1.7%, reticulocytes 12,000/mm3). Blood pressure remained normal, as well as neurological examination. No diarrhea was reported. Platelet levels spontaneously normalized within 24 h. A renal biopsy was performed, showing marked glomerular endotheliosis without evidence of microthrombi; no cellular proliferation was noted.
Other biological investigations included negative testing for HIV, HBV, and HCV, mildly decreased levels of C3 (0.8 g/L) and C4 (0.19 g/L) serum complement levels, and negative ANCA. Owing to the aregenerative character of anemia, a bone marrow exam was performed; it showed erythroblastopenia and no other cytological abnormality. A skin biopsy was also realized and revealed purpuric capillaritis without vasculitis. Parvovirus B19 was detected both in the plasma (6.07 log) and in the bone marrow biopsy. Parvovirus B19 serology disclosed positive anti-B19 IgM (34 UI/L) and IgG antibodies (23 UI/L).
Taken together the clinical and biological presentation was suggestive of Parvovirus B19 primo-infection. However, stool sample culture found the presence of enterohemorragic O26 Escherichia coli confirmed by PCR which was positive for stx1b (shigatoxin gene), eae (adhesion gene) and ehxa (hemolysin gene). The patient spontaneously and rapidly improved with normalization of platelets within 7 days. One month later, patient had clinically fully recovered, hemoglobin and platelets levels were normal, serum creatinine was 58 μmol/L with no significant proteinuria; isolated microscopic hematuria persisted.


Case 1: A 75-year-old man complained of dropped head and neck pain without neurological abnormalities. The patient’s activity of daily living was severely impaired by his dropped head. Physical therapy including cervical spine traction and training of neck extensor muscles was not effective. Cervical spine radiograph showed apparent kyphosis (, Case 1). Magnetic resonance imaging (MRI) revealed no spinal cord compression.


Case 2: A 66-year-old man suffered from dropped head for one year. His dropped head was passively reducible with his hand. He had no traumatic history. Neurological examination did not reveal abnormalities at all. Conservative therapies such as wearing a collar and medication using non-steroidal anti-inflammatory drugs (NSAIDs) and an extract isolated from inflamed skin of rabbits inoculated with vaccinia virus (neurotropin) were not effective. A whole-spine radiograph in standing position revealed cervical kyphosis with mild degenerative change and lumbar hyperlordosis (, Case 2). MRI showed no spinal canal stenosis.


Case 3: An 81-year-old woman presented dropped head for 7 years. Osteoporosis was diagnosed previously. Her dropped head particularly deteriorated in the evening. This was considered attributable to fatigue due to reduced endurance of extensor muscles. Conventional conservative therapy did not improve her symptom. The neurological examination was almost normal. A radiograph image in standing position obtained a relatively normal cervical alignment. Her dropped head was reducible for a moment while taking the radiograph (, Case 3, left). However, it deteriorated by continuous walking (, Case 3, right).
All three patients were Japanese inhabitants of Japanese origin categorized as Asians. . shows the patients demography, anthropometrics, and radiograph parameters at the time of inclusion.


A 70-year-old Caucasian female presented to the emergency department complaining of right-sided weakness. The patient described the weakness as progressive in nature that had begun two weeks prior. One week after the onset of her initial weakness, she had begun to suffer from minor falls due to the right hemiparesis. Her family was present at the bedside and noted that they had observed a mild left-sided facial droop and slurred speech several days before. She denied any head trauma or confusion; however, she admitted to mild right-hand tremors that had started one month prior. Her past medical history was significant for RA, non-insulin-dependent diabetes mellitus, hyperlipidemia, and hypertension. She was on chronic therapy for RA with methotrexate (7.5 mg PO once every week) and infliximab (3 mg/kg IV every eight weeks) for the past two years. Her family and social history were noncontributory, apart from her owning a cat.
On physical examination, she was alert and oriented to person, place, and time. Cranial nerves II-XII were intact, and pupils were 3 mm and reactive. Both upper and lower extremity motor strength was 5/5 on the left and 4/5 on the right. There were no tremors or facial droop noted at the time of the exam.
The patient’s complete blood count revealed a white blood cell count of 8,000/uL, platelet count of 266,000/uL, and hemoglobin level of 12.7 g/dL. Her blood chemistry lab work revealed sodium of 143 mEq/L, potassium of 4.2 mEq/L, chloride of 105 mEq/L, carbon dioxide of 27 mEq/L, blood urea nitrogen (BUN) of 24 mg/dL, and creatinine of 0.68 mg/dL. Her glucose level was 91 mg/dL. The patient underwent a head CT without contrast, which demonstrated bilateral edema and lesions throughout the basal ganglia (left greater than right) with mild mass effect on the left ventricle as shown in Figure .
MRI of the brain with and without contrast revealed bilateral ring-enhancing lesions in the basal ganglia (left larger than right) with surrounding vasogenic edema and mild mass effect on the left lateral ventricle from the larger lesion as shown in Figures , . CT of the chest, abdomen, and pelvis with and without contrast was performed and was negative for primary malignancy.
Due to the characteristics of the lesions on MRI, there was high suspicion for brain metastases, which prompted a brain biopsy of the left intracranial intraparenchymal mass for diagnosis. The tissue specimen showed necrotic brain tissue with patchy marked inflammatory changes as well as structures morphologically compatible with tachyzoites of toxoplasmosis. Special stains for gram-positive and gram-negative bacteria, fungi, acid-fast bacilli, cytomegalovirus, and herpes simplex virus 1 and 2 were all negative. Immunohistochemistry for toxoplasma was positive and a diagnosis of cerebral toxoplasmosis was made. Serology revealed that the anti-toxoplasma immunoglobulin G was >400 IU/mL (positive). The patient had a negative human immunodeficiency virus (HIV) antigen and antibody screen as well as a normal T cell count (T cell total 1,499 and CD4 786). The patient was started on dexamethasone due to cerebral edema and her immunosuppressive medications were discontinued. As pyrimethamine was unavailable, treatment began with high-dose TMP-SMX (400 mg q12h). Due to an unfortunate post-biopsy hemorrhage, the patient’s neurologic status after treatment initiation was unable to be accurately monitored. The patient was stabilized and transitioned to a long-term acute care hospital with a six-week total course of high-dose TMP-SMX.


An 82-year-old female, non-smoker, with a history of arterial hypertension, was admitted to our hospital with symptoms of fever and general fatigue that had lasted 7 days. She had a positive IgM test for COVID-19 (Anachem Diagnostics-Ref B251C) prior admission. On admission, she was febrile (Θ°C = 37.8°C), hemodynamically stable (BP = 130/60 mm Hg, HR= 88 bpm), and her oxygen saturation was 97% (FiO2: 21%). She was alert and awake, with no signs of respiratory distress. Lung auscultation did not reveal abnormal sounds. Laboratory tests showed normocytic, normochromic anemia (Ht = 28.2%), leukocytosis (white blood cells = 16.12 K/μl), high levels of C-Reactive Protein (CRP = 29.91 mg/dl), and mild renal impairment (urea = 61 mg/dl, creatinine = 1.3 mg/dl). High Resolution Chest Computed Tomography (HRCT) depicted multifocal consolidative opacities, including one cavitary lesion in the right lower lobe. The cavitary lesion was initially considered as an air-bubble sign, a sign previously described in patients with COVID-19 infection (). Subtle areas of ground glass opacities across the bronchovascular bundle in both lower lobes were also noticed (). Treatment with hydroxychloroquine 200 mg thrice a day, ceftriaxone 2 g once daily, and azithromycin 500 mg once daily was commenced. An upper respiratory nasopharyngeal swab sample was obtained at day 1 and an RT-PCR test was negative for SARS-CoV-2. Over the following 2 days, her renal function further deteriorated (creatinine = 2.0 mg/dl), while hematuria and proteinuria with active urinary sediment developed. The patient progressed to respiratory failure as indicated by SaO2 = 94%, FiO2: 36%. Two more nasopharyngeal samples were obtained, and RT-PCR tests returned as negative for SARS-CoV-2. Based on high clinical suspicion for ANCA-associated vasculitis, we performed a complete immunologic profile which revealed positive c-ANCA (immunofluorescence) with elevated titers of anti-PR3 (300 IU), at day 4. Laboratory tests for other pathogens, including Influenza A and B, Streptococcus pneumoniae, and Legionella, were negative. Procalcitonin levels were mildly elevated (procalcitonin = 0.41 ng/ml). Based on a compatible radiological and laboratory pattern, the diagnosis of GPA was set. Pulses of methylprednisolone for three days (1 g per day), along with cyclophosphamide (1 g), were applied. Despite appropriate treatment, only minor radiological improvements were noticed, while oxygenation and renal function continued to deteriorate (SaO2 = 94% with FiO2: 60% compared to SaO2 = 94% with FiO2: 36%, blood creatinine levels = 2.0 compared to 3.1) (day 8). Treatment with diuretics commenced, due to the development of a pulmonary edema. Two more pulses (1 g) of methylprednisolone were applied, followed by maintenance doses of 1 mg/kg. At day 10, treatment response was noticed as indicated by respiratory and renal function improvement (SaO2 = 98% with FiO2: 36%, reduction in blood creatinine levels 2.4). During the following days, the patient remained clinically stable under a maintenance dose of corticosteroids. Post-treatment HRCT depicted mild improvement of the radiographic appearance of the lesions. Small bilateral pleural effusions were shown, indicating possible fluid overload ().


A 62-year-old man underwent an electrophysiology and ECGi study 21 weeks after the implantation of a St Jude Quadra Assura MP CRT-D system (St Jude Medical, Inc, St Paul, MN). This was implanted following a new diagnosis of heart failure during a hospital admission for breathlessness and syncope. Admission electrocardiogram showed sinus rhythm with left bundle branch block (LBBB) and a QRS duration of 170 ms. Transthoracic echocardiogram showed a dilated left ventricle with severely impaired systolic function (ejection fraction 25%), normal right ventricular (RV) function, and mild mitral regurgitation. He underwent a coronary angiogram, which showed unobstructed coronary arteries. He underwent cardiac magnetic resonance imaging, which confirmed the diagnosis of nonischemic cardiomyopathy with no evidence of scar on late gadolinium enhancement. The patient had a background of treated prostate cancer, hypertension, and hypercholesterolemia.
The electrophysiology and ECGi study were performed as part of a mechanistic cohort study ( identifier ). The patient provided written consent for the study, which was conducted in accordance with the Declaration of Helsinki and approved by the local ethics committee. The patient was fitted with a 252-electrode CardioInsight Sensor Array Vest (Medtronic, Minneapolis, MN) before the procedure and underwent a low-dose computed tomography scan to obtain electrode and cardiac positions, as previously described. Conventional CRT was delivered through the implanted CRT-D device. Temporary His bundle pacing was achieved using a high right atrial quadripolar catheter for atrial pacing and a roving decapolar catheter (6F Livewire 115 cm, St Jude Medical, Inc, St Paul, MN) to locate and pace the His bundle. Endocardial CRT was performed using the high right atrial quadripolar catheter, a roving decapolar catheter at the RV apex, and a second roving decapolar catheter (6F Livewire 115 cm, St Jude Medical, Inc) at the basal lateral wall of the left ventricle, via femoral arterial access with a retrograde aortic approach. Left bundle branch pacing was performed using the high right atrial quadripolar catheter and the roving decapolar catheter in the left ventricle by locating a left bundle signal on the septum. Fluoroscopy images of catheter positions are shown in . All temporary pacing was performed at 10 beats per minute above intrinsic rate with a fixed output of 5 V at 0.5 ms and an atrioventricular delay of 100 ms.
Activation maps were created using the ECSYNC CardioInsight software (Medtronic, Minneapolis, MN) and the following activation parameters were calculated:Global right/left ventricular electrical synchrony (VVsync): the difference between the mean RV activation time and the mean LV activation time. Global biventricular total activation time (VVtat): a measure of the total time required for both ventricles to activate. Global left ventricular total activation time (LVtat): a measure of the total time required for the left ventricle to activate. Global left ventricular dispersion time (LVdisp): the standard deviation of LV activation times; a measure of dyssynchrony within the left ventricle.
These measures have been previously validated in patients undergoing ECGi assessment during CRT.,,
The activation maps and activation parameters are displayed in . The maps demonstrate different activation patterns between different modes of CRT delivery. Baseline intrinsic conduction shows an LBBB pattern with slow conduction across the anterior wall and late activation of the basal lateral wall (seen in blue). A similar activation pattern is seen in RV pacing. All 4 methods of CRT resulted in reversal of LBBB. The activation maps for conventional CRT and endocardial CRT demonstrate early activation (seen in red) at the RV apex and in the mid lateral and basal lateral LV walls, respectively. In contrast, His bundle and left bundle branch pacing show early activation in the septum with rapid activation across the LV, which is consistent with recruitment of the His-Purkinje network.
As expected, intrinsic (LBBB) conduction showed dyssynchronous late activation of the left ventricle compared to the right ventricle, demonstrated by a very negative VVsync. All methods of CRT improved right/left ventricular synchrony, with VVsync having values closer to zero. In addition, all methods of CRT improved biventricular total activation (VVtat) and left ventricular activation (LVtat) times as well as dyssynchrony within the left ventricle (LVdisp). Interestingly, in this patient the improvement in VVtat, LVtat, and LVdisp was greater with endocardial CRT, His bundle pacing, and left bundle branch pacing, compared to conventional CRT.


A 68-year-old man with a history of a distal right femoral diaphyseal fracture that resulted in malunion and right varus knee deformity previously treated with a high tibial osteotomy (HTO) presented with severe osteoarthritic pain of the right knee. The patient had a distal femur fracture at the age of 18 years and was treated conservatively which resulted in malunion and shortening of the leg. At the age of 44 years, he was diagnosed with osteoarthritis and underwent a high tibial osteotomy. However, knee pain continued to get progressively worse especially for the last few years. The patient's social history included using an assisted walking device, being an active cigarette smoker, and combating chronic hypertension. Clinical evaluation and radiographic imaging confirmed the diagnosis of severe bone-on-bone tricompartmental osteoarthritis (). The patient's knee range of motion was significantly restricted from full extension to further flexion of only 90 degrees. The patient previously failed various conventional nonsurgical treatments and wanted to proceed with TKA. Given the complexity of this case, the RATKA MAKO-Stryker surgical arthroplasty system was advised as the surgical method in order to plan for implants that would better fit this patient's specific geometric bony anatomy with the plans of bringing the mechanical axis within 3 degrees of neutral biomechanical alignment. A thorough discussion of the risks and benefits of the surgical procedure and preoperative 3-D computed tomographic images of his knee was performed.
The surgical planning included obtaining a MAKO protocol CT scan. The robotic software converts CT images to a virtual model where a surgeon can plan on implant size, positioning, and joint alignment. As demonstrated from images, this patient had a distal femur fracture, which had resulted in malunion. Because of malalignment, the patient had recurvatum deformity. The use of the anatomical axis and jig-based technique would have resulted in the positioning of the knee implant into hyperextension. Also, it would have been difficult to use the jig-based technique in the setting of severe deformity of the distal femur. Also, deformity in the proximal tibia due to a previous high tibial osteotomy would have resulted in difficulties in establishing the mechanical axis. Because of robotic software, we were able to plan the implant position in a way that it would restore the mechanical axis.
After exposure, femoral and tibial trackers were applied. The hip center of rotation was registered followed by medial and lateral malleolus registration. Bony landmark registration was done. Now, we proceeded with removing all the visible osteophytes and remaining ACL. Often times, it is difficult to remove the PCL completely without making the tibial cut in tight knees with longstanding deformities.
We next proceeded with identifying the existing deformity without any correction and with corrective maneuver and checking the balances on the medial and lateral side (). With the planned tibial cut of 7 mm from the highest point of the medial tibial condyle with 0-degree varus, we were looking at an extension gap balance of 19 mm laterally and 18 mm medially. This was enough to accommodate an at least 9 mm poly liner. However, in flexion, this gap was 12 mm and 15 mm on the lateral and medial side, respectively. But often, making a cut on the tibia removes the tight PCL and opens up the flexion gap. Also, we all know that tibial cut symmetrically affects the flexion and extension gap. So, we decided to proceed with this tibial cut first.
Next, appropriate tibial cut was made. The previous existing hardware was removed. With the help of the lamina spreader, the balance of the ligament was checked again in extension and flexion. We were able to open up the flexion gap more. Moving the planned femur implant anteriorly and thereby planning to remove more bone posteriorly, we were able to get the numbers closer to the extension gap as evidenced by .
Now, as evidenced by this figure, on the right bottom corner, the extension gap is 19 and 18 mm and the flexion gap is 19 mm laterally and 22 mm medially. At this point of time, the femoral implant is in 1° external rotation. So now, we needed to close down the medial gap in flexion. We were able to do this by pinning the femoral implant laterally and internally rotating the femoral component. By this maneuver, we were able to predict almost equal gaps in both flexion and extension. We proceeded with the femoral cuts. Trial implants were positioned.
The patient remained in the hospital for 2 days to ensure that adequate pain management was obtained prior to being discharged home. He returned for a follow-up visit in 3 weeks postoperatively (). During this visit, his range of motion was recorded as 0° to 95° flexion, with stable varus/valgus stress testing, negative anterior/posterior drawer signs, palpable distal pulses, and great strength within the quadriceps muscle group. At this point, the patient's knee replacement was deemed clinically stable and the patient was advised to return for a 2-month follow-up.


A 48-year-old man of African descent was brought to our emergency department, unresponsive, following an episode of a generalized tonic-clonic seizure. On initial physical examination, he was comatose. Blood pressure revealed a reading of 178/121 mmHg, a heart rate of 105 beats/minute, and a respiratory rate of 18 breaths/minute. His Glasgow Coma Scale was recorded as 3 out of 15, which required intubation and admission to the intensive care unit.
Further history revealed no recreational drugs exposure, no tobacco smoking, and no alcohol consumption; he had no previous history of epilepsy or head trauma. He was not known to have any cardiac comorbidities such as ischemic heart disease or congestive heart failure. His past medical history is remarkable for resistant hypertension; he was on four anti-hypertensive agents but was non-compliant in taking them: atenolol 50 mg, spironolactone 100 mg, amlodipine 10 mg, and valsartan 160 mg. He was first diagnosed as having hypertension 20 years ago. He takes sulfonylurea for type II diabetes mellitus. His family history is remarkable for hypertension in both parents. His family history is negative for the presence of renal diseases, adrenal tumors, or any syndromes associated with adrenal tumors.
He had a body mass index (BMI) of 31. A thyroid examination was consistent with a normal size gland with no nodules and a visual field examination by confrontation to exclude multiple endocrine neoplasia (MEN) syndromes was normal. He did not appear to have cushingoid or acromegaly features.
Initial investigations showed a potassium level of 2.6 mmol/L (normal, 3.6–5.1 mmol/L), a creatinine level of 113 micromole/L, and a blood gas analysis consistent with metabolic alkalosis. His urea level was 5.70 mml/L (normal, 2.8–8.1 mmol/L) and creatinine kinase level read 2.2 mcg/L (normal, < 4.9 mcg/L). Urine analysis was negative for leukocyte esterase and nitrites. A chest X-ray showed no findings of congestive heart failure. A 12-lead electrocardiogram (ECG) showed a sinus rhythm. Troponin-T level was 0.014 mcg/L (normal, < 0.014 mcg/L) and brain natriuretic peptides (BNP) level was 25.9 ng/L (normal, 0–121 ng/L). Calcium level revealed a result of 2.46 mmol/L (normal, 2.23–2.58 mmol/L). A computer tomography (CT) scan showed no brain lesions that could explain the decreased level of consciousness. A magnetic resonance imaging (MRI) of his brain was performed next day and showed no features suggestive of a mass-occupying lesion (Fig. ). An electroencephalogram was performed and it read normal. Further investigations (Table ) revealed a potassium level of 2.6 mmol/L (normal, 3.6–5.1 mmol/L) and an aldosterone level of 36.2 ng/dL (normal, 2.8–15.8 ng/dL) with a renin level of less than 0.081 ng/dL (normal, 0.4–2.3 ng/dL). Results of a 24-hour urine analysis ruled out Cushing’s disease and pheochromocytoma (Table ). Renal ultrasound and cardiac echography results excluded the presence of renovascular and cardiac causes for secondary hypertension.
Labetalol was initiated in the intensive care unit which controlled our patient’s severe hypertension. He was extubated 2 days later and transferred to a regular care unit sustaining no neurological deficit. Blood pressure was controlled at 122/83 mmHg on amlodipine 10 mg daily, valsartan 160 mg daily, spironolactone 100 mg daily, and metoprolol 100 mg twice daily. Potassium and magnesium required replacement to maintain levels within the normal range.
An abdominal CT (Fig. ) revealed a well-defined left adrenal gland lesion with an absolute washout time of 85% and a relative washout time of 50%. The lesion measured 12 × 16 × 15 mm in its largest dimensions.
He stayed in our hospital until time of surgery because he lived far away from the hospital and because he was at high risk for uncontrolled severe hypertension. He needed to come off spironolactone for 4 weeks before we performed case detection tests. His potassium level was normalized afterward at 3.9 mmol/L (normal, 3.6–5.1 mmol/L), before performing another set of tests. His aldosterone level remained at 35.3 ng/dl (normal, 2.8–15.8 ng/dL) and renin measured less than 0.08 ng/dl (normal, 0.4–2.3 ng/dL). Aldosterone to renin ratio (ARR) result was consistent with a level above 40 ng/dL per ng/mL per hour (or 3.1 pmol/L per minute). A saline load confirmatory test was not performed as he presented with the following: spontaneous hypokalemia, plasma renin level measuring below detection levels, and a plasma aldosterone level above 20 ng/dL.
Selective simultaneous non-stimulated adrenal venous sampling was performed and it lateralized the lesion to the left adrenal (Table ). Adrenal vein (AV) to inferior vena cava (IVC) cortisol ratio on both sides was 19 and 15 for left and right AV, respectively (diagnostic cut-off > 5:1), which indicated successful catheterization. Aldosterone level in the left AV was 28,346 nmol/L compared to the right AV, which was 3070 nmol/L. Aldosterone to cortisol ratio of the left AV was significantly higher than that of the right one and it measured 8.7:1 (diagnostic cut-off is > 4:1).
His blood pressure was controlled on atenolol 50 mg, amlodipine 10 mg, and valsartan 160 mg once a day and potassium supplementation while waiting for surgery. He underwent a unilateral left laparoscopic adrenalectomy.
A histopathologic examination of the adrenal gland showed an enlarged adrenal gland weighing 20 g, with a discrete, bright golden yellow, ovoid nodule measuring 1 × 1 cm across. Light microscopic examination demonstrated a demarcated adenomatous nodule with a compressed pseudo-capsule, comprising a proliferation of zona glomerulosa-like cells arranged in small nests and cords (Fig. ).
His postoperative period was uneventful; his blood pressure reading recorded 140/87 mmHg while on three anti-hypertensive agents and his potassium level was 3.9 mmol/L (normal, 3.6–5.1 mmol/L) on no supplementations. At 3-month follow up, his blood pressure read 135/88 mmHg, while being on three anti-hypertensive agents (atenolol 50 mg, amlodipine 10 mg, and valsartan 160 mg), and his potassium level was at 3.8 mmol (normal, 3.6–5.1 mmol) without being on supplements. Baseline aldosterone and renin levels were 13.2 ng/dL (normal, 2.8–15.8 ng/dL) and 0.9 ng/dL (normal, 0.4–2.3 ng/dL), respectively. At 12 months follow up, his blood pressure was recorded as 123/86 mmHg while being on only one anti-hypertensive agent: amlodipine 10 mg daily. Potassium normalized at 4.1 mmol/L (normal, 3.6–5.1 mmol/L) while on no supplementation. Aldosterone and renin levels were at 11.4 ng/dl (normal, 2.8–15.8 ng/dL) and 0.8 ng/dl (normal, 0.4–2.3 ng/dL), respectively.
Summarizing his postoperative course: a 3-month visit showed a reduction in blood pressure and normalization of potassium level while on three antihypertensives. At 12-month visit, his blood pressure was controlled on only amlodipine 10 mg once daily with normalization of potassium level. A timeline of events is shown in Fig. .
Of note, there were no financial, language, or cultural challenges faced in this case.


A 44-year-old female with a medical history of hypertension and gastric sleeve surgery presented to the emergency department complaining of generalized abdominal pain. She had recently undergone a SAL of her abdomen and bilateral flanks eight days prior to evaluation. Associated symptoms included fever, nausea, and multiple episodes of vomiting. Review of systems was otherwise unremarkable.
Initial vital signs were notable for a temperature of 100.4°F, a blood pressure of 92/50 mm/Hg, a respiratory rate of 24 breaths per minute, a heart rate of 126 beats per minute, and an oxygen saturation of 99% on room air. On physical examination, there was diffuse abdominal tenderness with rebound and voluntary guarding, but the overlying skin was unremarkable for bullae or skin necrosis. However, there was mild crepitus throughout the abdominal wall. She had multiple surgical incisions across her bilateral flanks and abdominal wall draining minimal serosanguinous fluid.
Labs were significant for a white blood cell count of 17.1 x 103/mcL, hemoglobin of 7.9 g/dL, creatinine of 1.57 mg/dL, and lactic acid of 2.9 mmol/L. Arterial blood gas revealed a primary respiratory alkalosis with secondary metabolic acidosis. The patient's pH was 7.52, with PCO2 of 22 mmHg, PO2 of 162 mmHg, and HCO3 of 17. Due to her physical examination findings and recent abdominal surgery, a CT scan with intravenous contrast of the abdomen and pelvis was ordered, which demonstrated fluid collections measuring approximately 21 x 3.8 x 12 cm on the right flank and 15 x 2.4 x 15.5 cm on the left flank (Figure ), as well as an intrapelvic fluid collection anterior to the uterus measuring 5.3 x 3.0 x 6.9 cm (Figure ). Other findings included diffuse subcutaneous emphysema and soft tissue stranding of the abdominal wall overlying the fascial planes (Figures , ).
Based on the initial physical examination, hemodynamic instability, and recent abdominal surgery, broad-spectrum antibiotics were administered intravenously due to concern for necrotizing soft tissue infection (NSTI) before imaging was obtained. At this time, the patient received 2 liters of lactated ringers, with improvement in blood pressure and heart rate. Acute care surgery team was consulted and the patient was taken for exploratory laparotomy, which confirmed the diagnosis of necrotizing fasciitis as well as several mesenteric abscesses and seven small bowel enterotomies. Extensive debridement was performed with abscess drainage, enterotomy repairs, and an abdominal washout, followed by temporary closure and close monitoring in the surgical intensive care unit. Final abdominal wall and flank abscess wound cultures grew pan-sensitive E. coli. She underwent several follow-up surgeries for further debridement and abdominal washout followed by wound vacuum placement during her complicated 31-day hospitalization.


An eight-day-old ex-full-term boy presented to the ER of an outside hospital for poor feeding. His mother had initially sought medical attention for her own mastitis, but she also informed providers that the child had not fed well that day and had decreased wet diapers. She denied the baby having any fevers, vomiting, rashes, diarrhea, and abnormal movements. Initial assessment revealed an ill- and gray-appearing infant with a temperature of 35.9°C, heart rate 201, respiratory rate 60, blood pressure 90/50, and oxygen saturation of 95% in room air. Given overall appearance and periods of apnea, the infant was intubated shortly after arrival. A full evaluation for sepsis was initiated, which was significant for a cerebrospinal fluid (CSF) white blood cell count of 139 cells/mm3 and a Gram stain showing Gram-positive cocci in clusters. He received 40 mL/kg of fluid resuscitation and was initiated on ampicillin and gentamicin before being transferred from the outside hospital ED to our pediatric ICU (PICU).
The infant had been born full-term via waterbirth to a G1P1 mother with negative prenatal GBS testing. As such, no perinatal antibiotics had been given. Prenatal labs and ultrasounds were unremarkable, and there were no noted complications with the pregnancy, delivery, or postpartum stay.
Upon admission to the PICU, the patient became hypotensive and was initiated on an epinephrine infusion. His blood and CSF cultures from the outside hospital returned positive for GBS within 12 hours. Given abnormal movements, a video electroencephalogram was placed and demonstrated frequent seizure activity. Seizures were treated with administration of phenobarbital, levetiracetam, and eventually continuous midazolam infusion. He continued to have refractory status epilepticus, and pentobarbital was initiated for burst suppression. Over the next few days, he stabilized and total parenteral nutrition, along with trophic feeds of maternal breast milk, was initiated. The patient’s mother continued to suffer from mastitis despite antibiotic therapy and therefore maternal breast milk cultures were sent. These cultures also returned positive for GBS, and enteral breastmilk feeds were discontinued.
On hospital day (HD) five, the patient developed significant endocrinopathies, including diabetes insipidus, cerebral salt wasting, hypothyroidism, and adrenal insufficiency. Head ultrasound was concerning for a large fluid collection. He underwent brain MRI to assess the fluid collection, which showed striking loss of brain tissue and severe changes throughout, suggestive of liquefactive necrosis (Figure ).
On HD 16, enteral formula feeds were advanced to goal, and the patient clinically decompensated with large volume emesis and seizure activity. He became tachycardic and hypotensive, and subsequently developed a worsening metabolic acidosis. Feeds were stopped. Abdominal X-ray obtained showed portal venous gas but no pneumatosis (Figure ).
The patient was emergently taken to the operating room (OR). He was noted to have necrosis of bowel in an atypical distribution thought to be secondary to infarct. He had approximately 117 cm of bowel resected and the bowel was left in discontinuity. Hypercoagulable workup showed no significant findings. Two days later, the patient returned to the OR, and the remaining small bowel was noted to be necrotic and nonviable. After discussion with the family, life sustaining measures were withdrawn, and the infant passed away shortly thereafter. Autopsy and further hypercoagulable workup were unrevealing for any other contributing abnormalities. On autopsy, the bowel showed evidence of necrotizing enteritis but no evidence of direct bacterial invasion and was negative for mesenteric thromboemboli.


A 58-year-old man with liver cirrhosis and ulcer of the stomach in his medical history was found to have a T3N1M0 squamous cell carcinoma in the floor of the mouth between teeth 33-43. The tumor was surgically resected, and the patient was reconstructed with a free anterior lateral thigh (ALT) flap. At the same procedure, a neck dissection region 1-5 right side and region 1 left side was carried through since fine needle aspiration cytology had confirmed a regional metastasis in region 1, right side. The patient received antibiotics the same day as the surgery and regularly the days after surgery. However, the patient developed a redness on the neck and on the flap donor site 5 days after surgery, and pus started to leak from the neck wound.
Three years previously, the patient had been diagnosed with left-sided tonsil cancer and ipsilateral metastases on the neck. He then received full-dose (68Gy) radiotherapy. At the 3 months follow-up, a CT scan was routinely done and showed remaining lymph nodes with suspicious appearance. A neck dissection of the ipsilateral side regions 1-5 was carried out. Three days after surgery, a redness and suspected infection on the neck was found and clindamycin was ordinated. The patient was dismissed from the hospital but returned 13 days after surgery since the neck did not improve (Figure ). The neck showed alarming redness and the surgical wound was purulent. The patient was put into the ward and ordinated intravenous cefotaxime and later, cloxacillin, since a swab showed s aureus. Despite adequate antibiotics, a flap necrosis developed, and the neck was closed a month after the neck dissection with a transposition flap. The flap area got red after surgery, and a local swab showed presence of enterococcus and coagulase-negative staphylococcus. The patient was treated with several courses of antibiotics, and the flap eventually healed without necrosis about a month after the flap surgery (Figure ).
After the recent surgery for the cancer in the floor of the mouth, the flap of the neck eventually developed necrosis. The donor site on the thigh ruptured and started to show signs of a superficial infection and the edges developed necrosis, exposing the muscles underneath (Figure ,B). Treatment with antibiotics continued although no local swabs showed presence of any bacteria. Thirteen days after surgery, the diagnosis PG was suggested. A dermatologist confirmed the diagnosis clinically, and biopsies from the thigh were congruent with the diagnosis PG. The biopsies showed no bacterial structures but intradermal inflammation with abscess reaching to the deep dermis. The patient begun treatment with oral prednisolone 40 mg daily. The wounds were taken care of daily, and the thigh, concluded to be the most affected area, received vacuum-assisted closure therapy. The patient got gradually better and 21 days after surgery, prednisolone was reduced to 35 mg daily (Figure ,D). One and a half month after the primary surgery, the wound on the leg was covered with a partial skin graft. However, the graft had difficulties to attach and it was eventually rejected (Figure ,F). The neck and the thigh healed secondary at last, about 2 and 4 months after surgery, respectively (Figure , H). Four months after primary surgery, the dose prednisolone was reduced by 5 mg every other week.


A 50-year-old man was admitted to our dermatology clinic at our teaching hospital. He presented with erythematous nodular penile lesions of 4 months' duration. There was no history of fever, weight loss, or any other symptoms. He also denied any history of systemic disease. Our patient was married with no history of extramarital relationship.
In his physical examination, there were some reddish, nontender nodules of 5-10mm on the ventral and dorsal sides of glans penis (Figure ). No other skin lesion was observed on his skin. There were no palpable lymph nodes in the inguinal region.
Then skin biopsy was taken from the lesion, and the histopathology examination revealed atypical spindle cell proliferation, forming slit-like vessels grouped in bundles and RBC extravasation (Figure ). Furthermore, the immunohistochemical study was performed and the pathology confirmed the diagnosis of KS based on a positive HHV-8 immunostaining (Figure ).
All of his laboratory tests including HIV viral serology were negative. His chest X-ray was normal. No enlarged lymph nodes were found in his abdominopelvic ultrasonography. In addition, the patient was evaluated for the presence of any other systemic involvement and the result was negative. Our patient underwent cryotherapy for 3 courses with complete disappearance of penile lesions, and no local recurrence occurred after one year (Figure ).


Ms. A was a 65-year-old African American woman with a history of breast cancer, diabetes and hypertension who presented with shortness of breath and sharp left-sided chest pain. She had been in contact with her neighbor who was infected with COVID-19. In the emergency department (ED), Ms. A had a temperature of 36 degrees Celsius, a heart rate (HR) of 86 beats per minute (BPM), blood pressure (BP) of 78/58 mmHg and oxygen saturation of (SpO2) 94% while breathing ambient air at a respiratory rate (RR) of 25 breaths per minute (Table ). She had bilateral crackles on auscultation, extremities were cool to touch and her mentation was preserved. Her electrocardiogram (EKG) showed ST-segment elevations in leads I, II, III and aVF with ST-segment depressions in leads V1-4 (Figure ). Laboratory data were significant for a positive COVID-19 ribonucleic acid polymerase chain reaction (RNA PCR), lymphopenia (500/mL), highly elevated cardiac troponin I (cTnI) at 88 ng/mL and elevated inflammatory markers (Table ).
Coronary angiography and ventriculogram depicted mild luminal irregularities (Figure ) and a left ventricular ejection fraction (LVEF) of 25% (Figure ), a significant decrease from the 60% reported by echocardiogram five months prior. Right heart catheterization was notable for a pulmonary capillary wedge pressure (PCWP) of 39 mmHg with a cardiac index of 2.0 L/min/m2, after which an intra-aortic balloon pump (IABP) was placed.
Her chest x-ray showed diffuse bilateral multilobar airspace opacities (Figure ). Over the following hours, Ms. A became progressively hypoxic and hypotensive requiring intubation and escalating inotropic and vasoactive support. Her cTnI and high-sensitivity C-reactive peptide (hsCRP) levels increased to >200 ng/mL and 119 mg/L, respectively. Her cardiac index fell to 1.2 L/min/m2 despite IABP and four high-dose inopressors. In the context of an institutional scarcity of available mechanical circulatory support (MCS) resources amidst this pandemic, as well as her age, history of diabetes and breast cancer, escalation of MCS to extracorporeal membrane oxygenation (ECMO) was not pursued [,]. Ms. A ultimately passed away approximately 24 hours after presentation.
Ms. B is a 34-year-old previously healthy Hispanic woman who presented to the ED with shortness of breath, diffuse left-sided chest pain and weakness. After initial triage and EKG (Figure ), she left the facility without evaluation. She returned to the ED on the following day with worsening symptoms and new subjective fever and chills. The EKG at that time showed a significant reduction in voltage and subtle PR-segment depressions in leads II, III and aVF (Figure ). Vital signs in the ED were HR 141 BPM, BP 111/67 mmHg, RR 24 breaths per minute and SpO2 100% on room air (Table ). On examination, her extremities were cold to the touch and she was tachypneic and tachycardic without jugular venous distension. Her chest x-ray depicted a normal cardiac silhouette and did not show any pulmonary infiltrate or pleural effusions (Figure ). The laboratory data were notable for a positive serum COVID-19 RNA PCR, mildly elevated cTnI (0.55 ng/mL), elevated serum lactic acid level (4.8 mmol/L) and unremarkable inflammatory markers (Table ). A cardiac ultrasound demonstrated a large pericardial effusion with right ventricular diastolic collapse and severe global biventricular systolic dysfunction with an LVEF of 20%.
Ms. B became progressively hypotensive despite initial intravenous fluid administration. Emergent pericardiocentesis was performed, yielding 280 mL of serous fluid. A pulmonary arterial catheter was placed, demonstrating a PCWP of 32 mmHg and a cardiac index of 2.5 L/min/m2. Initially, her serum lactic acid levels normalized; however, over the following hours she developed progressive signs of cardiogenic shock. Her cardiac index declined hourly as her lactic acid increased despite escalating inotropic and vasoactive support. Considering Ms. B’s young age, isolated cardiac involvement and absence of comorbidities, support was escalated to cannulation for veno-arterial ECMO (VA-ECMO). She was treated with colchicine and intravenous pulse-dose steroids, and was successfully decannulated from VA-ECMO four days later after demonstrating modest cardiac recovery. Thereafter, she was discharged with six weeks of colchicine therapy and on follow-up her echocardiogram revealed recovery in LVEF to 60% and an absence of pericardial effusion.


BN is a 22 year-old transgender male and was just about to start hormone therapy. He works night shifts and notes, “I just don’t eat what I should.” BN is hopeful that his diet and exercise will improve moving forward and that “testosterone’s going to help weight distribution and things like that.”
BN has a BMI of 45 kg/m2, body fat percentage of 40% and waist circumference of 56 in., indicating class III obesity and central adiposity. He has a low risk of eating disorders (5/26 on the EAT-26) and yet a low degree of eating competence (16/48 on the ecSI-2). His dietary pattern includes 3–4 eating instances per day at home, work, or fast food restaurants. BN consumes 0–1 servings of fruits and vegetables per day and has a high intake of added sugars in the form of sodas, sweetened tea, and ice cream.
BN’s diet analysis was characterized by low energy (59% kcal needs), appropriate saturated fat (10% kcal intake), low fiber (45% AI) and high sodium (149% DGAs limit). His macronutrient intake was 48% carbohydrate, 37% fat and 15% protein, or within recommended AMDR ranges. BN’s micronutrient intake reflect low calcium (40% RDA), vitamin D (3% RDA), potassium (36% AI) and marginally high iron intake (114% RDA).


CE is a 27 year-old transgender male. He gained 40 lbs. when starting hormone therapy 18 months ago. CE reported that he “tried really hard for like, about 6-8 months to lose it, and then I was getting nowhere. So, I just kind of gave up.” He also described himself as a picky eater and “weird about textures,” but that he is starting to try new foods that his boyfriend prepares.
He has a BMI of 33 kg/m2, body fat percentage of 34% and waist circumference of 41 in., indicating obesity class I and central adiposity. He has a low risk of eating disorders (6/26 on the EAT-26) and yet a low degree of eating competence (24/48 on the ecSI-2). CE’s dietary pattern includes 2–4 eating instances per day at home and work. He consumes 0–1 servings of vegetables per day and a high intake of added sugars in the form of sodas, iced coffees and energy drinks.
His diet analysis was characterized by low energy (74% kcal needs), appropriate saturated fat intake (10% kcal intake), low fiber (41% AI), and high sodium (206% DGAs limit). His macronutrient intake was 63% carbohydrate, 23% fat and 14% protein, or within recommended AMDR ranges. CE’s micronutrient intake reflected adequate calcium (105% RDA), low vitamin D (48% RDA), low potassium (40% AI), and marginally low iron (84% RDA).


VK is a 29 year-old transgender male and has been on hormone therapy for 5 years. He noted that although he has “always struggled with food and weight and body image,” that his relationship with food and exercise started improving when he came out. He now approaches food as “more of a tool and a strengthening thing.”
VK has a BMI of 35 kg/m2, body fat percentage of 35% and waist circumference of 40 in., indicating obesity class II and central adiposity. He has a low risk of eating disorders (16/26 on the EAT-26) and yet a low degree of eating competence (30/48 on the ecSI-2). His dietary pattern includes 4–5 eating instances per day at home and fast food restaurants. VK consumes 2–3 servings of fruits and vegetables daily and added sugars in the form of sweetened coffee drinks and energy bars.
VK’s diet analysis was characterized by low energy (58% kcal needs), high saturated fat (29% kcal intake), low fiber (32% AI), and marginally high sodium (117% DGAs limit). His macronutrient intake was 21% carbohydrate, 55% fat and 24% protein, or lower in carbohydrate and higher in fat than the AMDR ranges. VK’s micronutrient intake reflected high calcium (124% RDA), low vitamin D (7% RDA), low potassium (16% AI) and adequate iron (102% RDA).


MR is a 30 year-old transgender male and has been on hormone therapy for just over 1 year. He reported gaining 15 lbs. of mostly muscle mass during the first 2 months of hormone therapy and then losing weight after a reconstructive chest surgery, or top surgery. He notes, “I don’t necessarily want to be thinner.” MR is somewhat conscientious of his kcal intake but is primarily driven by the feeling: “I still want to have a lot of fun, and I want to be myself.”
He has a BMI of 25 kg/m2, body fat percentage of 19% and waist circumference of 32 in., indicating an overweight BMI and yet overall healthy body weight and composition given the additional anthropometric measures. He has a low risk of eating disorders (3/26 on the EAT-26) and yet a low degree of eating competence (29/48 on the ecSI-2). MR’s follows a mostly vegetarian dietary pattern with 3–4 eating instances per day at home and at restaurants. He consumes 2–3 servings of vegetables and fruits daily, very little added sugars, and 1–4 alcoholic drinks/day.
MR’s diet analysis was characterized by marginally low energy (84% kcal needs), appropriate saturated fat (8% total kcals), low fiber (71% AI), and high sodium (134% DGAs limit). His macronutrient intake was 32% carbohydrate, 33% fat, and 22% protein, or lower in carbohydrate than the AMDR ranges. Additionally, 13% of his kcals were derived from alcohol. MR’s micronutrient intake reflected high calcium (132% RDA), low vitamin D (53% RDA), low potassium (47% AI) and high iron intake (171% RDA).


CA is a 31 year-old transgender male. He started hormone therapy and had top surgery over 3 years ago. CA was motivated to lose weight in order to be eligible for top surgery, but didn’t feel comfortable going to the gym without wearing a binder, or a compression undershirt worn to flatten breasts, which he knew was not safe. CA also had gastric sleeve surgery after his top surgery “just because I wanted to take care of my health more.” He notes, “I feel like I made the right choice in doing top surgery first, and then that lead me to take care of myself more.”
CA has a BMI of 33 kg/m2, body fat percentage of 41% and waist circumference of 44 in., indicating class I obesity and central adiposity. He has a low risk of eating disorders (3/26 on the EAT-26) and yet a low degree of eating competence (23/48 on the ecSI-2). He follows a vegetarian dietary pattern with 5–6 eating instances per day at home and fast food restaurants. CA consumes 2–3 servings of fruits and vegetables daily and added sugars in the form of breakfast cereals, muffins, and sweetened tea.
CA’s diet analysis was characterized by low energy (77% kcal needs), marginally high saturated fat (13% total kcals), low fiber (69% AI) and high sodium (154% DGAs limit). His macronutrient intake was 47% carbohydrate, 37% fat and 15% protein, or slightly higher in fat than the AMDR ranges. CA’s micronutrient intake reflected adequate calcium (90% RDA), low vitamin D (11% RDA), low potassium (15% AI) and high iron (199% RDA).


GT is a 32 year-old transgender male. He has been on hormone therapy for over 10 years and recalls initially gaining approximately 40 lbs., which he lost slowly over time. GT and his partner are now into ayurvedic cooking, though he still enjoys “going to get a burger across the street.” GT is physically active with drumming, biking and rock climbing.
He has a BMI of 25 kg/m2, body fat percentage of 15% and waist circumference of 35 in., indicating an overweight BMI and yet overall healthy body weight and composition given the additional anthropometric measures. He has a low risk of eating disorders (2/26 on the EAT-26) and yet a low degree of eating competence (30/48 on the ecSI-2). GT’s dietary pattern includes 5–7 eating instances per day at home, a friend’s home, or restaurants. He consumes 3–6 servings of fruits and vegetables daily and sugar-sweetened foods and beverages in the form of coffee drinks, cookies and candy. His beverage intake also includes 0–4 alcoholic drinks per day.
GT’s diet analysis was characterized by marginally high energy (119% kcal needs), marginally high saturated fat (14% total kcals), low fiber (59% AI) and high sodium (221% DGAs limit). His macronutrient intake was 43% carbohydrate, 36% fat and 16% protein, or slightly lower in carbohydrate and higher in fat than the AMDR ranges. Additionally, 5% of his kcals were derived from alcohol. GT’s micronutrient intake reflected adequate calcium (98% RDA), low vitamin D (3% RDA), marginally low potassium (89% DI) and high iron (263% RDA).


CM is a 33 year-old transgender male and has been on hormone therapy for over 5 years. He experienced an initial weight gain of approximately 60 lbs., both due to an increase in appetite and a genuine desire to have a larger body size. He describes this as, “I’m not going to blow over and am just more rugged, solid, stocky.”
CM has a BMI of 51 kg/m2, body fat percentage of 46% and waist circumference of 57 in., indicating class III obesity and central adiposity. He has a low risk of eating disorders (12/26 on the EAT-26) and a high degree of eating competence (35/48 on the ecSI-2). CM’s dietary pattern includes 5–6 eating instances per day at home, work, or fast food restaurants. He consumes 1–2 servings of vegetables per day and added sugars in the form of candy, energy drinks, and ice cream. His beverage intake also includes 0–2 alcoholic drinks per day.
CM’s diet analysis was characterized by adequate energy (102% kcal needs), marginally high saturated fat (14% total kcals), low fiber (71% AI) and high sodium (228% DGAs limit). His macronutrient intake was 42% carbohydrate, 41% fat and 15% protein, or lower in carbohydrate and higher in fat than the AMDR ranges. Additionally, 2% of his kcals were derived from alcohol. CM’s micronutrient intake reflected high calcium (167% RDA), low vitamin D (11% RDA), low potassium (37% AI) and high iron (149% RDA).


SB is a 37 year-old transgender male and has been on hormone therapy for just over 1 year. He was highly motivated to improve his diet prior to starting hormone therapy. He noted, “… the things I was able to eat, in my mind, were helping me to get ready for the medical transition.” He had also sought out foods that had been purported to increase natural levels of testosterone, though he noted he doesn’t know if they actually worked or simply helped him to feel more mentally prepared.
SB has a BMI of 21 kg/m2, body fat percentage of 13% and waist circumference of 31 in., indicating a healthy body weight and body composition. He has a low risk of eating disorders (7/26 on the EAT-26) and a high degree of eating competence (48/48 on the ecSI-2). SB follows a gluten-free dietary pattern with 4–7 eating instances per day at home or work. He consumes 2–4 servings of fruits and vegetables per day and minimal added sugars in any form.
SB’s diet analysis was characterized by adequate energy (109% kcal needs), appropriate saturated fat (7% total kcals), low fiber (75% AI) and high sodium (169% DGAs limit). His macronutrient intake was 44% carbohydrate, 38% fat and 18% protein, or slightly lower in carbohydrate and higher in fat than the AMDR ranges. SB’s micronutrient intake reflected low calcium (53% RDA), low vitamin D (20% RDA), low potassium (39% AI) and high iron (197% RDA).