A 76-year-old woman was diagnosed with complete infra-Hisian heart block by an electrophysiology study and underwent dual-chamber pacemaker implantation. Three years later, she presented with sudden cardiac arrest (in the setting of preserved LV systolic function) that was attributed to possible long QT syndrome. At that time, her pulse generator was upgraded to a dual-chamber implantable cardioverter-defibrillator (ICD). Nine years later, the patient developed heart failure symptoms including dyspnea on exertion and lower extremity edema. A year prior, she had been diagnosed with breast cancer and completed a course of doxorubicin chemotherapy. Her echocardiogram demonstrated a LV ejection fraction (LVEF) of 35%. She was placed on guideline-directed medical therapy for heart failure including beta blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists. She continued to have reduced LV systolic function but deferred to undergo upgrade to cardiac resynchronization therapy (CRT) owing to chronic right ventricular (RV) pacing.
Three years later, she presented to the Emergency Department with lightheadedness on activity. Her electrocardiogram demonstrated bradycardia with complete AV block with a right bundle branch block pattern escape rhythm (A). Further workup revealed that the patient’s RV lead had fractured, resulting in failure to capture. She had a slow escape rhythm requiring emergent transvenous ventricular pacing overnight. On telemetry, she had no intrinsic AV conduction prior to RV lead revision and her prior device checks had shown no intrinsic AV conduction.
Given the presence of complete infra-Hisian AV block on prior study, heart failure with reduced ejection faction in the setting of wide left bundle branch RV pacing morphology (B), it was decided to upgrade her pulse generator to a biventricular ICD via HBP. His-bundle mapping was performed using a C315 His sheath and a 3830 pacing lead (Medtronic, Minneapolis, MN). Non-selective HBP was achieved at an output of 1 V @ 1 ms (C). The His bundle lead was connected to the LV port and the RV single-coil ICD lead was connected to the RV port. LV-to-RV offset was programmed to 80 ms to promote HBP while minimizing the possible effects of fusion. The patient reported significant improvement in her symptoms (from NYHA class II to class I), and a repeat cardiac echocardiogram 3 months later demonstrated normalization of LV systolic function (echo prior to RV lead revision had demonstrated an LVEF of 35%). Owing to the rapid reversal of LV systolic dysfunction, it was felt that her cardiomyopathy was primarily related to pacing-induced cardiomyopathy. Several months later, she remained symptom-free, with no functional limitations. During routine device check, RV pacing inhibition demonstrated 1:1 AV conduction with the presence of a LBBB (D). She maintained 1:1 AV conduction with LBBB during her subsequent device checks over the next 2 years.


A 51-year-old woman with a past medical history of hypertension and diabetes mellitus presented with shortness of breath and leg swelling. She was diagnosed with idiopathic non-ischemic cardiomyopathy at that time after undergoing cardiac catheterization and genetic testing. Her LVEF progressively deteriorated over subsequent years to 20%. She was also noted to have wide LBBB (>150 ms) (A). The patient’s NYHA class II heart failure symptoms never improved despite being managed with optimal guideline-directed medical therapy for several months, which led to the decision of pursuing a CRT defibrillator in the setting of a LVEF <30% and wide LBBB. She had declined a CRT defibrillator for 3 years prior to agreeing to undergo device implantation.
After discussing her options, she agreed to undergo HBP with the hope of recruiting her underlying LBBB. During the procedure, a C315 His sheath was advanced to the tricuspid annulus and His bundle mapping was performed. This demonstrated excellent His bundle recordings with normal AH and HV intervals. The pacing lead was screwed into place with excellent selective HBP and complete recruitment of the intrinsic LBBB at 0.6 V at 1.0 ms (B). On follow-up, the patient reported significant improvement in her symptoms (from NYHA class II to class I), and a repeat cardiac echocardiogram 3 months later demonstrated normalization of her LV systolic function. Pacing thresholds remained stable after 3 months at 0.5 V at 1 ms. During her 1-month follow-up post implantation, pacing inhibition demonstrated an intrinsic narrow QRS complex with 1:1 AV conduction (C). In addition, burst atrial pacing and atrial extrastimulus testing through the device did not induce rate-related LBBB (D).


A 41-year-old Latina woman with severe HS for more than a decade presented with a flare of her vulva, perianal, and perineal regions. The patient was a smoker and had a disease of the axillae, abdomen, groin, and labia treated with infliximab (treatment with adalimumab having failed), spironolactone, dapsone, intralesional triamcinolone, and aggressive surgical intervention of her axillae and panniculectomy. Physical examination revealed extensive erythematous, edematous plaques involving the vulva, consistent with chronic HS. Deep fissures with a gelatinous pseudomembrane extended along the inguinal folds. Erythematous, scaly patches of the lower abdomen and medial thighs were also noted (), consistent with erythrasma. Wood's lamp revealed coral-red fluorescence of the lower abdomen and medial aspect of thighs. The erythrasma resolved with topical application of clindamycin, twice daily.


A 20-year-old Black woman with HS since 3 years presented with an active disease of her suprapubic area, labia majora, and medial aspect of the left thigh. The patient had a disease of the axillae, buttocks, and breasts treated with aggressive surgery, doxycycline, chlorhexidine wash, topical clindamycin, intralesional triamcinolone, and adalimumab. Physical examination revealed draining sinus tracts in the left thigh, suprapubic area, and labia majora with granulating ulcers of the sacrum and right buttock. Erythematous, scaly plaques were noted on the medial aspect of the left thigh (, A). Wood's lamp revealed coral-red fluorescence (, B) of the medial aspect of the left thigh, consistent with erythrasma. The erythrasma responded to oral erythromycin base 500 mg that was administered 4 times daily for 7 days, after failing a course of topical clindamycin and benzoyl peroxide combination gel.


A 23-year-old Black woman presented for a follow-up of severe HS of many years. The patient had a disease of the axillae, inguinal folds, abdomen, labia majora, and perineum that had been managed with secukinumab (after failing treatment with infliximab and adalimumab), intralesional triamcinolone, and aggressive surgical debridement. Physical examination revealed ulcers of bilateral inguinal creases (consistent with erosive HS) and well-defined erythematous scaly plaques of the lower abdomen and inguinal folds (), consistent with erythrasma. Wood's lamp revealed coral-red fluorescence. The erythrasma responded to clindamycin 1% lotion, applied twice daily for 1 month.


A 37-year-old Black man presented for consultation of HS of many years. The patient had a disease of the groin and axillae that had been managed with adalimumab and surgical debridement. Physical examination revealed multiple draining sinuses and nodules in the groin and axillae, and erythematous scaly plaques of the axillae (). Wood's lamp was performed for the axillae, revealing coral-red fluorescence.


A 59-year-old woman underwent transfemoral cerebral angiography (TFCA) for a follow-up evaluation of previously treated intracranial aneurysms. She had a history of SAH secondary to the left posterior communicating artery (PCOM) aneurysm that was treated with coil embolization 7 years prior. One year later, she underwent the surgical clipping of a right PCOM aneurysm and fully recovered without any neurological deficit. In brain computer tomography angiography, before TFCA, there was no definite chronic degenerative changes or focal lesion in the brain parenchyma. On TFCA, the blood flow of the ophthalmic artery was normal, and the previously clipped aneurysm was noted on the right PCOM (A). Additionally, an intact choroidal blush was observed during the late arterial phase (B). The morning after TFCA, she complained of visual disturbance of her superior visual field. The patient presented no headaches, diplopia, or jaw claudication. Ophthalmic examination revealed that her visual acuity was 20/20 in the right eye. There was no limitation or pain with extraocular muscle movement, and the relative afferent pupillary defect (RAPD) was negative. She promptly underwent brain DWI and it showed multiple focal scattered acute infarctions, possibly due to embolic events (C,D).
Fundus examinations revealed inferior sectoral optic disc swelling and small cotton wool spots (CWS) in the peripapillary area of the right eye. Fluorescein angiography (FA) showed early filling defects in the inferior segment of the optic nerve’s head and late leakage from the optic disc. A Humphrey visual field 24-2 showed a superior altitudinal deficit that corresponds with inferior sectoral papilledema (). We assumed the diagnosis of acute nonarteritic anterior ischemic optic neuropathy (NAION) caused by posterior ciliary artery occlusion from micro-embolism after TFCA. Orbit MRI was also performed to exclude optic neuritis, and optic nerve was not enhanced. Carotid ultrasonography revealed mild stenosis on the right distal common carotid artery (22%) and right carotid bulb (28%). Two days after onset, prednisolone (1000 mg/day) was intravenously administered for 3 days as steroid pulse therapy. Papilledema had gradually improved except for the inferior temporal sector, but the visual field defect remained with no significant change up to 7 days after the start of the treatment. One month later, most papilledema and peripapillary CWS were resolved on fundus photography. However, narrowed inferior neuroretinal rim and peripapillary retinal nerve fiber layer (RNFL) thinning was observed in the corresponding quadrant on SD-OCT (). Although the visual field slightly improved, superior nasal quadrantanopia still remained.


A twenty-month-old male presented to his pediatrician’s office with a chief complaint of delayed walking milestone. The child was born vaginally following an uncomplicated pregnancy and breastfed until twelve months of age when he was transitioned to whole cow’s milk and continued solids. Postnatal screening was unremarkable. The child was twentieth percentile for length, thirtieth percentile for weight, fortieth percentile for occipital-frontal circumference, appeared pleasant while seated, and vitals were within normal ranges. Physical exam revealed bilateral valgus knees and a pain response while standing. The abdomen was soft, round, free of masses and the child soiled four to five diapers per day and had a daily bowel movement. Family history was unremarkable. Laboratory studies indicated elevated serum levels of FGF23, hypophosphatemia, normocalcemia, and low serum levels of 1,25-dihydroxyvitamin D (1,25-vitD) and hyperphosphaturia was noted via urinalysis. Genetic testing revealed a loss-of-function mutation in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) which led to a diagnosis of the metabolic bone disease X-linked hypophosphatemia (XLH).


An 83-year-old man with a past medical history of sick sinus syndrome status post pacemaker placement, essential tremor, and an isolated episode of aseptic meningitis three years prior presented with a two-day history of fever, generalized weakness, and worsening essential tremor of the right hand. He reported usual health until two days prior to admission, at which time he developed sudden-onset severe generalized weakness that was followed by low grade fever over the next 24 hours. At baseline, per family report, the patient was an otherwise healthy, independent, and pleasant gentleman. Home medications prior to admission included: propranolol, primidone, rosuvastatin, digoxin, melatonin, acetaminophen, and alprazolam, without any recent medication changes or use of over the counter or herbal supplements. There was no noted recent travel, sick contacts, or additional exposures. On presentation he was febrile at 102°F and hypertensive at 161/84 mmHg with a regular heart rate (69 beats per minute) and preserved oxygen saturation on room air. Physical examination was notable for a pronounced oropharyngeal tic that abated with tongue protrusion and speech and fine bilateral distal upper extremity intention tremor. Muscular strength of the bilateral upper and lower extremities was nevertheless preserved (5 out of 5) and sensory function remained intact. Reflexes were brisk (2+) in all extremities and Babinski sign was negative bilaterally. In general, he remained awake, alert, and oriented to person, place and time with no focal neurologic deficits; however, he had fluctuating episodes of confusion and agitation during admission.
Initial diagnostic evaluation included a complete blood count which demonstrated a preserved white blood cell count (6.6 k/uL) with a normal differential, hemoglobin (13.2 gm/dL), and platelet count (219 k/uL). Serum chemistries were within normal limits. Urinalysis and urine toxicology were unremarkable. Diagnostic imaging including a chest radiograph, computed tomography (CT) of the chest with contrast, and CT of the head without contrast (Figure ) were unremarkable. COVID-19 and influenza virus testing were negative. Blood cultures were drawn and empiric therapy with vancomycin and piperacillin-tazobactam was initiated, with subsequent transfer to the medicine wards.
Of note, the patient had a similar presentation to our facility three years prior in 2017, presenting with fever, generalized weakness, and delirium. At that time, symptoms also commenced two days prior to admission with flailing myoclonic-like arm movements, culminating in a mechanical fall. At that time, he was empirically started on acyclovir and ceftriaxone for altered mental status and fever along with azithromycin (with concurrent ceftriaxone) for possible left lower lobe pneumonia. Lumbar puncture (LP) was performed with CSF analysis consistent with aseptic meningitis (Table ), and acyclovir was stopped upon CSF studies, including HSV-1 and HSV-2 PCRs, returning negative (Table ). He showed symptomatic improvement by the sixth hospital day and was discharged to subacute rehabilitation where he recovered to his functional and neurological baseline.
Throughout the current hospitalization, the patient remained hemodynamically stable. Laboratory diagnostics failed to demonstrate leukocytosis. Empiric antibiotics were discontinued on the second day of hospitalization and his blood cultures remained negative. In the setting of his presentation, physical examination, and unremarkable initial work-up, a presumptive working diagnosis of meningitis was made. A lumbar puncture was performed and CSF analysis once again demonstrated pleocytosis, elevated protein, and a normal glucose consistent with aseptic meningitis (Table ). Neurology recommended acyclovir for empiric therapy of HSV encephalitis until viral PCR and CSF cultures returned, however acyclovir was deferred given high clinical suspicion of Mollaret’s meningitis. CSF viral PCRs, including HSV-1 and HSV-2, and serologies returned negative and cultures remained negative (Table ). Head CT with contrast was performed (due to pacemaker-related MRI incompatibility) that demonstrated a stable, unchanged meningioma, previously seen on imaging (Figure ). To further evaluate for a potential underlying malignancy contributing to a paraneoplastic disorder, CT imaging of his neck and abdomen, and bilateral renal ultrasound were performed, demonstrating the presence of only benign bilateral renal cysts, further lowering the suspicion for a paraneoplastic disorder. Additional investigation into autoimmune etiologies was deferred given his positive CSF findings consistent with aseptic meningitis and clinical improvement with conservative management by the fourth day of his hospitalization. Of note, the patient sustained a mechanical fall during hospitalization; however, thorough neurologic exam and CT imaging without contrast of the head following the fall event were benign. In the setting of his recurrent presentations, CSF studies demonstrating aseptic meningitis, and the low concern for an underlying infectious etiology, the diagnosis of Mollaret’s meningitis was made.
Similar to the 2017 admission, the patient’s presenting symptoms of fever and neurologic dysfunction resolved by the end of the hospital admission. Furthermore, the patient no longer demonstrated episodes of fluctuating cognition and returned to his baseline aware and pleasant demeanor. Given his significant clinical improvement by day four of admission without any neurologic sequalae, the patient was discharged to subacute rehabilitation for lingering weakness. On follow-up two months later, his next of kin shared that the patient had passed away at home from unrelated causes following return from subacute rehabilitation.


A 45-year-old male who tested positive for SARS-CoV-2 was presented to the emergency department (ED) with persistent non-productive cough, severe dyspnea, fever, chills, and intermittent diarrhea. His comorbidities include diabetes mellitus, hypertension, and morbid obesity (BMI 44.7 kg/m2). The patient's symptoms started eight days prior to his presentation to the ED. He experienced gradual worsening dyspnea at rest and daily fevers up to 105 °F. He denied loss of taste or smell. He also denied any history of alcohol, tobacco, or illicit drug use. On presentation, his vital signs included a blood pressure of 127/70 mmHg, respiratory rate of 24 per minute, fever of 103.6 °F, and oxygen saturation of 89% on room air. His physical examination was notable for tachypnea and bibasilar crackles.
Chest X-ray revealed diffuse bilateral airspace opacities most prominent in the right upper lobe (Figure ). Laboratory testing was significant for leukocytosis of 12,000 cells/µL, elevated absolute neutrophil count of 10,400 cells/µL (normal range =2500-7500 cells/µL), elevated D-dimer of 415 ng/mL (normal range <250 ng/mL), and elevated ferritin of 3329 µg/L (normal range = 20-300 µg/L). Serology was negative for antibodies to SARS-CoV-2 via an enzyme chemiluminescence assay (manufactured by Roche-Elecsys, Indianapolis, IN).
During the initial resuscitation in the ED, the patient’s oxygen saturation improved to 94% on 4 L/min of supplemental oxygen via nasal cannula. Additionally, he was given a single dose of dexamethasone 10 mg intravenous (IV), remdesivir 200 mg IV, and enoxaparin 40 mg subcutaneously (SQ) in the ED. After admission to the inpatient unit, he was continued on once-daily administration of dexamethasone 6 mg IV, remdesivir 100 mg, and enoxaparin 40 mg SQ.
Due to the patient’s complicated medical history, comorbidities, and risk of progressing to severe COVID-19 pneumonia, pulmonology/critical care and infectious disease specialists were consulted and recommended the administration of REGN-COV2. The consideration for IV infusion of REGN-COV2 via off-label use was based on the recently reported studies suggesting a significant reduction in viral load for seronegative patients on low-flow supplemental oxygen [,]. The risks, benefits, and alternatives for the antibody cocktail infusion were discussed with the patient, and he ultimately consented to the recommended treatment. Subsequently, he received a 2.4 g IV infusion of the antibody cocktail the evening of the first day of hospitalization. On the second day, his respiratory rate normalized, and his supplemental oxygen requirements decreased to 2 L/min. By the third day of his hospital course, the patient was only intermittently requiring supplemental oxygen while ambulating. The patient was ultimately discharged home with supplemental oxygen to be used as needed after five days of hospitalization. The patient experienced no further complications since his discharge from the hospital.


A 69-year-old Caucasian male who was a former alcoholic and former smoker presented to the emergency department with a chief concern of right lower back pain radiating down the right thigh to the level of the knee for three weeks. There was no history of trauma or recent illness. However, the patient had received a routine dental cleaning 17 days prior to the onset of symptoms. Vital signs at index were remarkable for tachycardia and hypertension. Physical exam revealed diffuse swelling of the right thigh, pitting edema of the extremity, and some erythema and warmth over the medial thigh. No crepitus was noted. Range of motion was normal at the right hip and knee.
Plain radiographs of the right femur were unremarkable. Upon hospital admission, laboratory studies revealed leukocytosis, elevated alkaline phosphatase, elevated liver transaminases, low albumin, elevated C-reactive protein, and elevated erythrocyte sedimentation rate. Two blood cultures were obtained, and intravenous (IV) vancomycin was begun empirically.
A contrast enhanced magnetic resonance image (MRI) of the right thigh demonstrated a large, irregular, peripherally enhancing fluid collection centered within the vastus intermedius muscle in the mid to distal right thigh. The fluid collection wrapped around the anteromedial cortex of the femur with associated signal change within the femur (). IV cefepime and clindamycin were started, and vancomycin was continued. Interventional radiology successfully placed an image guided percutaneous drainage catheter into the abscess cavity. Cultured abscess fluid resulted negative, but blood cultures obtained at admission grew S. anginosus. The patient was discharged with a peripherally inserted central catheter for daily outpatient administration of 2 g IV ceftriaxone.
Three months after discharge, the patient returned with worsening symptoms and inability to bear weight on the right leg. Radiographs revealed a pathologic fracture of the right mid-shaft femur through the site of prior diaphyseal osteomyelitis (). He was subsequently transferred to a tertiary university affiliated care center for further multi discipline management. An attending physician specialized in orthopaedic oncology attempted surgical stabilization with a lateral 8-hole 4.5 mm locking compression plate with bicortical 4.5 mm screws (DePuy Synthes). Open biopsies and cultures at that time did not demonstrate any recurrent organisms, and the final histology showed no evidence of neoplasm. The patient was discharged home to be followed by a local community orthopaedic surgeon.
Five months post-operatively the patient began experiencing sharp pain in the right thigh and decreased function. Plain radiographs demonstrated catastrophic hardware failure with breakage of the proximal three screws, varus collapse of the femur, and an oligotrophic nonunion of the right femur (). At this time, he was referred to a local orthopaedic oncologist and traumatologist at a regional hospital. Inflammatory markers were within normal limits and his surgical wounds were completely healed without evidence of a sinus tract or drainage. Considering the patient's previous S. anginosus osteomyelitis, single- and two-stage procedures were discussed, and the patient elected to proceed with a single-stage procedure. The procedure was performed by the attending orthopaedic oncologist/traumatologist at the regional hospital. The patient was optimized for surgery by nil per os.
Intraoperatively, the previous lateral thigh incision was used and a trans vastus lateralis approach to the femoral diaphysis was performed (). The previous plate and screws were removed. Significant scar tissue and fibrinous material at the nonunion site and hypertrophic anterior and medial calluses were observed. No gross purulence or abscess was seen. The hypertrophic calluses were removed with an osteotome and rongeur. The reamer-irrigator-aspirator (RIA) device (DePuy Synthes) was used to complete endosteal preparation of the femoral canal. Given the capacious medullary canal, a 12 mm titanium intramedullary nail was selected to allow room for a coating of antibiotic-impregnated cement. Two batches of regular viscosity bone cement (Palacos) were hand mixed with 2 g of vancomycin powder and 2.4 g of tobramycin powder. The antibiotic cement delivery device was then hand placed around the exterior of the nail (). Iliac crest cancellous autograft was used for major bone grafting of the osseous defects at the site of nonunion. In total, the operation lasted about 90 minutes. There were no intraoperative complications or otherwise difficulties to cause deviation from the pre-operative surgical plan. The patient was discharged home one day postoperatively and advised to continue once daily 81 mg aspirin for venous thromboembolism prophylaxis.
Post-operatively, weightbearing was permitted as tolerated under the guidance of physical therapy. An ambulatory gait aid was used for mobility assistance. Wound healing was uneventful. Clinical and radiographic healing were achieved approximately 6 months following this revision procedure. At 12-month final follow-up, the patient was pain free, functional, and able to perform his activities of daily living without the use of a gait aid. There was no evidence of infection recurrence or implant failure ().


A 31-year-old Chinese female presented to the ophthalmic clinic of our hospital and complained of persistent blurred vision in her right eye for 1 day immediately after a lumbar spine magnetic resonance imaging (MRI). As a routine procedure, she was asked before the scan if she had any contraindications to the MRI scan. At that time, she denied any metallic foreign body or surgical devices. After the MRI scan, she noticed blurred vision in her right eye immediately, but she did not take it seriously until her symptoms persisted for one day.
On initial examination, the uncorrected visual acuity in the right eye was 20/80, the manifest refraction was −1.00 DS–1.50 DC×160, the best-corrected vision acuity (BCVA) was 20/40, and the intraocular pressure was 11.6 mm Hg. Slit-lamp examination of the right eye showed a 2 mm linear corneal scar on the nasal side of the pupil (Fig. A) and a metal particle embedded in the iris root at 7 o’clock with the pigmentation of the adjacent limbus (Fig. B). Brownish spots were observed on the anterior lens capsule at the pupil area (Fig. A). No corneal edema but mild anterior chamber inflammation was observed. The examination of the left eye was unremarkable. Further detailed history revealed a previous ocular injury concerning an undiagnosed IOFB 15 years earlier while her father was pounding metal against metal with a hammer. After intravenous antibiotic therapy at a local clinic, she did not feel any discomfort; thus, she was never referred to an ophthalmologist. She noticed an abnormality in the appearance of her eye in the mirror but thought it was a scar on her cornea and ignored it.
Fundus examination and photography showed no pigmentary retinal degeneration, optic disc swelling, or hyperemia (Fig. C). Ultrasound biomicroscopy showed that the foreign body was lodged near the anterior chamber angle (Fig. D). A non-contrast computerized tomography scan of the orbits confirmed a radiopaque foreign body embedded in the anterior chamber, and no other foreign body was detected. Corneal endothelioscopy revealed decreased corneal endothelial cell density and percentage of hexagonal cells compared with the contralateral eye (Fig. ). The posterior segment swept-source optical coherence tomography examination revealed inner retinal degeneration at the peripapillary area despite an intact and normal microstructure of the foveal region (Fig. ). Electroretinogram (ERG) examination was not performed because of the poor toleration and cooperation of the patient at that time. Thus, she was diagnosed with anterior chamber IOFB (ACFB) and OS.
IOFB extraction was advised for this patient. The surgery was performed under topical anesthesia. A limbal incision was made with a 3.0 mm slit knife at 11 o’clock. An ophthalmic viscosurgical device was refilled to stabilize the anterior chamber and protect the corneal endothelium. A pair of tying forceps with 0.3 mm wide tips, 5 mm tying platforms, and 10 mm angled shafts from tips to bend (Fig. A) was used to extract the IOFB. The IOFB was successfully isolated from granulation and adjacent tissues and then extracted from the eye (Fig. B). The ophthalmic viscosurgical device was aspirated with irrigation-aspiration. The limbal wound was sealed by hydration. The foreign body was a 0.5 mm × 0.5 mm × 1.5 mm brown iron particle (Fig. C). Levofloxacin eye drops (Cravit, Santen, Japan) and tobramycin/dexamethasone eye drops (Tobradex, Alcon) were applied four times a day postoperatively. The uncorrected visual acuity in the right eye was 20/40, and the manifest refraction was −1.25 DS/−2.00 DC∗160 with a BCVA of 20/20 the next day. Anterior chamber inflammation was mild, and a small iris defect near the limbus was noticed, which may account for the photophobia of the patient (Fig. D). No postoperative complications were observed during a 3-month follow-up. There was a 12% decrease in the “b” wave and a 91% decrease in the “a” wave in the ERG three months postoperatively (Fig. ).


A 38-year-old female with a medical history of Graves' thyrotoxicosis presented to the emergency department (ED) complaining of generalized weakness that started several days prior to her presentation. It was associated with nausea, vomiting, and weight loss. She denied diarrhea, pain, or shortness of breath. Her only medication was methimazole 10 milligrams twice daily which she had been taking for three years with intermittent compliance. She was alert and oriented to person, place, and time. Her vitals on presentation were blood pressure of 127/80 mmHg, heart rate of 80, respiratory rate of 22, and temperature of 98.4°F. Neurological exam yielded intact cranial nerves with no sensory deficit. However, she had diffuse weakness in all extremities with strength of 2/5 in the lower extremities and 2/5 in the upper extremities. The rest of the physical examination showed no abnormalities.
Workup in the ED revealed multiple lab abnormalities including hypokalemia, a nonanion gap metabolic acidosis, and hyperthyroidism (). Her EKG showed changes consistent with hypokalemia including a QTc interval of 686 milliseconds (). A chest X-ray and computed tomography of the head without contrast showed no acute abnormalities. Renal ultrasound and abdominal X-ray were negative for hydronephrosis or kidney stones.
The patient was given intravenous potassium in the ED and transferred to the intensive care unit (ICU) with continuous cardiac monitoring. The endocrinology team recommended starting propranolol and increasing her dose of methimazole. She was treated with additional intravenous and oral potassium supplementation in the ICU. The potassium level was checked frequently due to concern for rebound hyperkalemia. Based on the patient's acute onset of diffuse weakness without cranial nerve dysfunction or pain, hypokalemia, elevated free T4, and low TSH, a presumptive diagnosis of thyrotoxic periodic paralysis was made.
The patient's potassium was gradually corrected with subsequent resolution of her paralysis and decrease of her QTc interval. However, she continued to have a nonanion gap acidosis. Urine studies showed a urine pH of 8 (normal range 4.5–8), urine chloride of 105 mmol/L (normal range 55–125 mmol/L), urine potassium of 39.8 mmol/L (normal range 12–62 mmol/L), and urine sodium of 90 mmol/L (normal range 20–110 mmol/L) resulting in a positive urine anion gap of 24.8. This was attributed to renal tubular acidosis (RTA) type 1. The patient was started on sodium bicarbonate in addition to her oral potassium supplementation. These medications were gradually titrated and later discontinued as her labs normalized ().
Further history revealed intermittent dry eyes, dry mouth, and recurrent dental carries. This prompted additional workup which was significant for positive ANA, SS-A, and SS-B. The patient was eventually referred to rheumatology for further evaluation and management of Sjögren's syndrome. She was started on hydroxychloroquine. With this treatment, her RTA completely resolved, and she no longer required potassium or bicarbonate supplementation. The patient maintained follow-up with endocrinology, and she preferred to continue antithyroid medications rather than pursue radioactive iodine ablation.


A 57-year-old man presented with right lower extremity pain and light headedness when standing up. He had no related family history or medical history. His right leg pain gradually worsened and movement became difficult over a period of 4 months, so he was transferred by ambulance. On admission, he was aware and conscious, and complained of nervous pain in the right lower leg. Physical examination found mild paralysis of manual muscle test 4/5 and increased deep tendon reflex in the left half of the body. Orthostatic hypotension was observed in which systolic blood pressure decreased to approximately 70 mmHg when sitting. In addition, mild urination and defecation disorders were noted. Cerebrospinal fluid examination indicated elevated initial pressure of 27 cmH2O and high protein level of 605 mg/dl. No tumor cells were detected in the cerebrospinal fluid, and collagen-related antibody levels were normal. Magnetic resonance imaging revealed contrast-enhanced lesions at the posterior intramedullary C2 and high C6 levels, left posterior intramedullary Th12 level, medullary cone surface, and left middle cerebellar peduncle (Fig. ).
On the day after admission, the patient suddenly lost consciousness and systolic blood pressure rose to around 230 mmHg, with marked facial sweating, upper conjugate deviation of the left eye, ankylosis of both upper and lower limbs, and dilated pupils. His head was immediately elevated and head computed tomography/magnetic resonance imaging was performed but found no abnormalities. Intravenous injection of nicardipine hydrochloride was performed to reduce his blood pressure, but his blood pressure was refractory and difficult to reduce immediately. This neurological symptom could not be explained by a transient ischemic attack, so antithrombotic therapy was not started. Epileptic seizures were suspected, and diazepam (10 mg) and fosphenytoin sodium hydrate (750 mg) were administered intravenously. Conjugate deviation of the eye and ankylosis in both upper and lower extremities were alleviated, but the hypertension, facial sweating, and dilated pupils showed almost no improvement. However, these symptoms gradually disappeared after approximately 30 min to one hour, and the patient’s consciousness disturbance was ameliorated. Such attacks repeatedly occurred 1 to 5 times daily and were mainly triggered by pain during physical activity and daily nursing care. Electroencephalography in the resting state recorded on day 2 showed α waves predominantly originating from the occipital lobe at 8–10 Hz, but no laterality was observed. Complex partial epileptic seizures were suspected, so oral administration of lacosamide (100 mg/day) was initiated on the same day for prophylaxis. However, the frequency of seizures remained unchanged.
Sudden onset of symptoms of sympathetic hyperactivity accompanied by consciousness disorder triggered by pain indicated AD associated with an intramedullary tumor. Initially, the number of therapeutic agents was increased and more care was taken to minimize the stimulation caused when changing postures and moving the bed, which acted as triggers. However, non-steroidal anti-inflammatory drugs had little analgesic effect on the resting right lower extremity pain, so oral administration of carbamazepine 400 mg/day was initiated, together with administration of tofisopam (150 mg/day) and gabapentin (1200 mg/day). The patient had presented with bladder-rectal disorder at the time of admission, so catheterization of the urethra was performed and oral administration of laxatives and prokinetic agents for constipation was initiated. However, the seizures repeatedly occurred, so early treatment was planned. Tumor biopsy was performed at the Th10-11 level on hospital day 3.


A 65-year-old female with a prior history of B-cell lymphoma status post-chemotherapy in 2016 and currently in remission presented to the pulmonary clinic for further evaluation of an abnormal CT chest in comparison to prior scans four months prior. Her new CT scan showed a previously noted spiculated nodule that has changed in configuration, measuring 39 x 11 x 8 mm (Figure ) as compared to 14 x 12 x 12 mm seen prior. She underwent an electromagnetic navigational bronchoscopy (ENB) with transbronchial biopsies taken from the abnormal lesion localized to the superior segment of the lingula under fluoroscopy guidance. The procedure was completed without procedural complications, and the patient was transferred to the post-anesthesia care unit.
Assessment
A post-bronchoscopy chest X-ray (CXR) (Figure ) showed small new opacities in the lingula, expected of the procedure, but no pneumothorax was appreciated. Shortly afterward, the patient started to experience mild dyspnea and left scapular pain, therefore, a bedside point-of-care ultrasound (POCUS) was performed, which revealed normal lung sliding over the right upper lobe but the absence of lung sliding over the left upper lobe. M-mode on ultrasound was utilized, which showed a “seashore sign” over the right upper lobe and a “barcode/stratosphere sign” over the left upper lobe (Figure ). A repeat CXR did not demonstrate findings of a left pneumothorax (Figure ); therefore, a right lateral decubitus CXR was performed, which successfully demonstrated radiographic findings of a left pneumothorax (Figure ).
Diagnosis
The patient was diagnosed with a small iatrogenic left pneumothorax.
Management
Supplemental oxygen was administered via a non-rebreather mask with 15 liters of O2 per minute to help accelerate pneumothorax reabsorption, and the patient was admitted overnight for observation. Repeat chest radiograph the following morning revealed a stable left pneumothorax, and the patient’s symptoms of dyspnea and scapular pain had resolved. She was discharged home with instructions to return to the clinic to review her bronchoscopy pathology results.


A 45-year-old man presented with dark urine that had lasted for 3 months in September 2019. The main clinical manifestations were hematuria, backache and occasional activity chest tightness. He presented no symptoms related to urinary irritation. Back in December 2010, the patient had symptoms of lower extremity edema and heavy proteinuria with 24-h urinary protein of 20.6 g and serum albumin of 15.4 g/L, and was diagnosed with “nephrotic syndrome”. The white blood cell (WBC) count was 14 × 109/L, with 34% eosinophils. He had good response to corticosteroid therapy. After 1 week of prednisone treatment, urinary protein decreased to 1.02 g/day, and eosinophil decreased to 2.19%. However, the patient experienced frequent relapse of nephrotic syndrome and eosinophilia, when prednisone was reduced to 10 mg/day. He repeatedly refused renal biopsy. Additional use of tripterygium wilfordii was ineffective. Proteinuria decreased rapidly in 1–2 weeks when prednisone was increased to more than 30 mg/day. He presented with symptoms of itchy skin and rash of limbs, and was diagnosed with “allergic dermatitis” in October 2012. Swelling of neck lymph node was first noted in 2013. Ultrasound detected found that the largest lymph node in the left neck was 1.6 × 0.7 cm. He rejected lymph node biopsy. Prednisone was reduced and stopped gradually, proteinuria remained negative since 2014.
On admission, blood pressure was 151/92 mmHg. Enlarged lymph nodes with clear boundary and good range of motion was noted in the neck, supraclavicular, and inguinal region. The mass of right retroauricular was circular, soft, no-tender with a moderate range of motion, and measured about 2 cm in diameter. The WBC was 24.54 × 109/L, with 20.4% neutrophils, 9.3% lymphocyte and 67.3% eosinophils. Urinary red blood cell (RBC) count was 760,500 cells/ml with mixed type of predominant dysmorphic RBC. 24-h urinary protein was 0.36 g and serum albumin was 43.8 g/L. The serum creatinine level and estimated glomerular filtration rate (eGFR) were 88 μmol/l and 90.99 mL/min per 1.73 m2, respectively. The serum IgE level increased to 1735 KU/L (reference value: < 60 KU/L). Sensitive troponin I was elevated to 0.0907 ng/ml. There were no abnormalities in liver function, coagulation function and urine culture. No evidence of infectious disease, connective tissue disease, and malignant tumor was found in the laboratory examinations. Ultrasound detected no abnormalities in urinary system, while lymph nodes enlargement was found in the neck, supraclavicular, subclavian and inguinal regions. The largest lymph nodes were 1.4 × 1.0 cm in the neck, 1.8 × 1.1 cm in left subclavian, and 2.0 × 0.8 cm in inguinal region, respectively. Computed tomography (CT) showed multiple enlarged lymph nodes in mediastinum, bilateral axillary and retroperitoneum. Electrocardiogram revealed left ventricular hypertrophy with strain and unusual Q waves in V2-V3. Echocardiography showed left ventricular dilation and dysfunction, and significantly decreased systolic activity of the inferior wall of left ventricle. Left ventricular ejection fraction (EF) was 30%. Coronary CT angiography (CTA) did not detect significant stenosis of each branch.
To identify the cause of eosinophilia, bone marrow puncture and renal biopsy were performed. Bone marrow cell morphology indicated eosinophilia with 9% myelocyte, 1% metamyelocyte, 8% stab granulocyte, and 20% segmented granulocyte. Eosinophilic interstitial nephritis was diagnosed by renal biopsy (Fig. ). Light microscopy showed multifocal and patchy infiltration of eosinophils (about 70% area) in interstitium, granular degradation and tubular vacuolization of renal tubular epithelial cells, thickening and narrowing of arteriolar wall, while no significant proliferation of mesangial cells and matrix or thickening basement membrane was observed. Immunofluorescence of IgG, IgA, IgM, C3, C1q, Fib, IgG1, IgG4, and phospholipase A2 receptor (PLA2R) were negative. Electron microscope showed diffuse foot process fusion and only a few electron dense deposits in the mesangium region. Based on results from cervical lymph node biopsy that histological examinations showed eosinophil hyperplasia, destruction of germinal centers by eosinophils (Fig. ), final diagnosis of KD was made.
The patient was treated with oral prednisone therapy (60 mg/day) on October 10, 2019. Because of 2019 novel coronavirus, the patient didn’t return visit. After 7 months of treatment with prednisone, the subcutaneous masses in forehead and right retroauricular regressed. Meanwhile, eosinophil count, serum IgE, and urinary RBC count decreased. However, hematuria and eosinophilia recurred when prednisone gradually reduced to 10 mg/day. The patient was given prednisone at 25 mg/day on May, 2020 and decreased to a maintenance dose of 12.5 mg/day. Eosinophil count, urinary RBC count, and IgE reduced, while EF increased to 44% (Fig. ). He kept normal renal function (serum creatinine 88 μmol/l, eGFR 90.35 mL/min per 1.73 m) during follow-up.


A 69-year-old man was seen at our Dermatology Department with complaints of blistering disease on his right leg. The complaints had started 2 to 3 weeks after knee replacement surgery on the right knee. First, small vesicles had appeared on his knee. These, however, continued to multiply and became larger in the following weeks. The blisters progressed and after few weeks resulted in large erosions that were resistant to treatment with local corticosteroids.
Skin biopsies, direct (DIF) and indirect immunofluorescence (IIF), and salt-split skin results were all consistent with BP. Except for the right leg, there was no other skin or mucous membrane involvement.
Six months after the surgery, complaints gradually disappeared. No relapse appeared in the following year. The patient had no change in systemic medication in this period as a possible explanation of this cure. Because of the atypical course of his disease and at his specific insistence, he was referred for patch tests.
Patch tests were performed on the upper back with the European baseline series, a local extension of the baseline series, an acrylate series, and a metal series. Allergens were tested using van der Bend test chambers (Brielle, the Netherlands) applied on the upper back and covered with Fixomull stretch (BSN Medical, Hamburg, Germany). Readings were performed on day (D) 2, D4, and D7 according ESCD criteria. Tests were positive for 2-hydroxyethyl methacrylate 2.0% pet. (D2: ?+, D4: +, D7: +), methyl methacrylate 2.0% pet. (D2: ?+, D4: +, D7: +), ethylene glycol dimethacrylate 2.0% pet. (D2: -, D4: +, D7: +), triethylene glycol dimethacrylate 2.0% pet. (D2: ?+, D4: +, D7: ?+), and tetrahydrofurfuryl methacrylate 2.0% pet. (D2: ?+, D4: ?+, D7: +).
Contact sensitization to several methacrylates was regarded as being of probable clinical relevance for the complaints of the patient. Prior to the knee replacement procedure, the patient had no contact with methacrylates as far as could be determined that could have caused sensitization.


The first patient treated with HP was a 55-year-old male, who had undergone lung transplant due to a congenital bullous emphysema and was under therapy with oral glucocorticoids and Tacrolimus. He had previously suffered from diffuse alveolar damage, leading to lung fibrosis and Aspergillus fumigatus infection in the transplanted lung. He had tested positive for SARS-CoV2 in April 2020, despite the presence of IgG, which were found to be non-neutralizing (titer< 1/20). Further tests after two months evidenced a persistent positivity of nasopharyngeal swab (E Ct 17.5, RdRp Ct 18.3 and N Ct 18.2). Lymphocytes subpopulation evidenced very low levels of B cells (28/ul, normal value 90–660). In June, he was treated with two administrations of HP compatible for ABO and RhD grouping and neutralizing titer of 1/80. Seven days since the second infusion, he had eventually tested negative for SARS-CoV-2.


The second patient, a 77-year-old female suffering from mild symptoms (ageusia, anosmia, fever) had tested positive in April. Her previous medical history evidenced gastric follicular lymphoma, in treatment with Rituximab and Bendamustine, and ulcerative colitis, for which the patient was assuming Mesalazine. After 6 months, further nasopharyngeal swabs displayed a persistent positivity (E Ct 31.6, RdRp Ct 34 and N Ct 32.2) and no specific IgG or IgM antibodies were developed. Total serum IgG and IgM were below normal values, too. For these reasons, the patient underwent two administrations of HP ABO and RhD grouping and neutralizing titer of 1/80. She was discharged with low viral load and eventually tested negative 7 days later.


The third and last patient of our case series was a 60-year-old male, affected by stage IV chronic lymphocytic leukemia and in treatment with Bendamustine, Cotrimoxazole and Aciclovir. He had been admitted to our COVID Unit with a diagnosis of bilateral interstitial pneumonia and blood examination revealed leukopenia and thrombocytopenia.
After two months, the patient did not develop any specific antibody response against SARS-CoV-2 and his nasopharyngeal swab was persistently positive (E Ct 24.3, RdRp Ct 24.3 and N Ct 23), thus he was treated with two administrations of HP ABO and RhD grouping and neutralizing titer of 1/100. The patient was subsequently discharged and he had eventually tested negative after two weeks.


A 13-year-old girl without a previous medical problem was brought to the emergency department for nausea, persistent nonbloody vomiting, and abdominal pain for the last two days, along with one episode of loose stool. Abdominal pain was sudden in onset, progressive, and located in the epigastrium. She also had a mild cough and fever for the last week. She was previously healthy with no history of fever and ill contacts. Initial evaluation revealed a temperature of 100°F, tachypnea (31/minute), tachycardia (103/minute), and borderline oxygen saturation (93%). On clinical examination, she looked ill, and her lungs were clear with reduced breath sounds in the lower lobe of the right lung. Abdominal examination was unremarkable except for tenderness in the epigastrium. A nasal swab for COVID-19 polymerase chain reaction was done as part of the regular screening which was positive. Initial laboratory investigations revealed elevated serum lipase, amylase, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) (Table ).
Abdominal ultrasonography was nonsignificant with no evidence of gallstone, and the pancreas was not visualized. Abdominal computed tomography (CT) was performed, which revealed diffuse inflammation of the pancreas with peripancreatic edema without necrosis, consistent with acute pancreatitis (Figure ). Her chest X-ray demonstrated diffuse infiltrates and pneumonic patches in the lower lobe of both lungs (Figure ).
Diagnostic workup for infection, including blood culture and sputum culture, were negative. She had no history of previous pancreatitis and no recognized risk factors such as family history, trauma, gallstone, alcohol consumption, or medication exposure. Due to the lack of any identifiable risk factor, she was diagnosed with acute pancreatitis and pneumonia due to COVID-19. She was admitted to the gastroenterology ward to treat acute pancreatitis, and infectious disease consultation was taken to manage COVID-19 pneumonia.
Her initial management included bowel rest, dietary restrictions, intravenous fluids, antiemetics, and analgesics. For COVID-19 pneumonia, she was commenced on intravenous remdesivir (5 mg/kg) and azithromycin (20 mg/kg) with supplemental oxygen. Her abdominal symptoms started improving on day two; however, her respiratory system worsened with a gradual drop in oxygen saturation to 85%. She was shifted to the intensive care unit for aggressive management. She was commenced on dexamethasone (0.15 mg/kg) in addition to azithromycin and remdesivir, and she required oxygen at 3 L/minute by nasal cannula. She was stable on day four of hospitalization and was symptom-free on day six except for a mild cough. She received seven days of treatment and was discharged on day eight with follow-up. She was doing well on her recent visit seven days later. Her laboratory investigations on day one and day six are shown in Table .


The patient was a 24-year-old male with a past psychiatric history of schizophrenia who was seen in the outpatient clinic due to hypersexuality after starting aripiprazole. The patient had no known health problems. He had no history of head trauma, seizures, sexually transmitted disease, or significant substance abuse problems. He was first diagnosed with schizophrenia at the age of 19 years and was started on olanzapine, which he responded well to for years. The patient was living with his mother and had completed 11th grade level education. He did not have any history of developmental or intellectual difficulties. He was working part time in a fast food restaurant when he started to have the decline. He was single, never married, and had no significant other. The patient did not have very many acquaintances and led a quiet life. He has no known legal issues so far. The patient used cannabis occasionally when he was 17, but denied any use now. He did not have any problems with alcohol and or other illicit substances. He did not have any history of tobacco use. There was no known family history of mental illness.
The patient was previously stable on olanzapine 20 mg/day for four years and then became noncompliant due to unclear reasons, leading to worsening of psychotic symptoms. He was switched to oral aripiprazole 15 mg/day with a plan to switch to a long-acting injectable due to possible nonadherence. During the initial oral one-week trial, the patient became increasingly unstable, with physical and verbal altercations with his mother. The patient also ran away from home and lost his job due to public masturbation at his workplace. His mother also noticed that the patient was increasingly flirtatious and inappropriate in public with females, which were behaviors he had never displayed previously. Given his worsening behaviors, the patient was admitted to the inpatient unit and was switched to intramuscular injection (IM) of aripiprazole 400 mg, assuming that he would benefit from a long-acting injectable and that he could be non-adherent with the oral medication. He became increasingly sexually aroused and was acting inappropriate in the days following. During the hospital stay, there was an instance where he had sex with a female peer and had to be placed on 1 : 1 observation, i.e., one staff was assigned to continuously observe the patient. After discharge from the hospital, the patient needed constant reminders in his group home to keep his hands out of his pants. Despite these attempts to reduce the inappropriate behavior, the patient endorsed that his sexual arousal was more than normal after starting the aripiprazole. At this point in time, the patient had received two doses of aripiprazole 400 mg IM. While on aripiprazole, he did not show any gambling urges and or other impulsivity other than the sexual preoccupations. The sexual preoccupations started within a week of starting with aripiprazole. Further aripiprazole injections were discontinued, and the patient was again prescribed olanzapine 20 mg/day given his previous good response. In the group home, the patient continued to remain occasionally agitated with outbursts and required constant redirection about appropriate sexual behaviors in public. He also continued to display sexually inappropriate behaviors towards females in a day program and was banned from attending the program until he was able to behave appropriately. Although he had reduction in the intense sexual behaviors four weeks after stopping the aripiprazole injections, he did not completely return to baseline. Given his ongoing sexually inappropriateness and possible reports of being internally stimulated, he was started on paliperidone 6 mg/day for augmentation and with plan to taper and stop olanzapine. The patient started to have fewer outbursts and was noted to be in much better mood after three to four weeks of starting the paliperidone. He was noted to be less sexually preoccupied and with reduction in inappropriate behaviors in public. When writing this report, the patient was on both olanzapine 20 mg/day and paliperidone 6 mg/day, with the goal of attaining paliperidone monotherapy, initially oral and subsequently long-acting injections. The patient continued to live in the group home to learn social skills before moving into independent housing. After 12 weeks of paliperidone use, the patient was completely free from hypersexual thoughts and behaviors.


A female, 47-year-old patient underwent treatment for nasolabial folds. Polymethylmethacrylate (PMMA) 10% was injected with a 22 G microcannula. Local anesthesia of lidocaine 2% was administered, then the cannula was introduced through the right oral commissure. At that moment, the patient moved abruptly and reported feeling pain. Although the cannula had already been inserted, the filler had not yet been injected. A retrograde injection of 0.4 mL of PMMA in total was administered. As soon as injected, when removing the cannula, the responsible doctor noticed edema in the region of the nasolabial folds, which spread to the malar region, and the patient reported discomfort at the site. Then, the immediate formation of a small hematoma was observed in the cannula path and, after five minutes, the skin presented a livedoid aspect in the entire cheek region. The protocol for treating occlusion, which consists of severe massage in the region, application of hot compresses, prescription of acetylsalicylic acid (ASA) 300 mg, prednisone 20 mg and prophylactic antibiotic, was started at this moment. The doctor massaged vigorously the region and applied hot compresses. After action was taken, the patient remained in the clinic under observation for approximately one hour. As the patient reported that the pain had ceased, and a relative improvement was observed; she was prescribed antibiotics and sent home.
On the following day, the doctor asked the patient for a photo of the affected region; it looked better, but there was still quite a significant edema. On the second day after the procedure, there was an improvement of the edema, and the patient reported being happy with the evolution of the case. On the third day following the procedure, the patient progressed to develop pustules in the nasal ala, which is compatible with tissue distress and epidermolysis. The patient was then immediately seen by the doctor, who continued with the protocol and prescribed acetylsalicylic acid (ASA) 300 mg and prednisone 20 mg daily. On clinical examination, ischemic right buccal mucosa and hyperemic skin were observed from the right upper lip, nasolabial fold, nasal ala, up to the glabella; delimiting the region of the angular branch of the facial artery. In addition to the traditional protocol for the treatment of arterial occlusion, the patient started oxygen therapy in a hyperbaric chamber, accompanied by the doctor responsible for the filling procedure and the one in charge of the oxygen therapy. The patient started the treatment on the third day after the procedure, being subjected to a pressure of 2.4 atm in a multi-place chamber with 100% oxygen inhalation for 90 min, and reported relative improvement. The treatment was carried out daily for another six days, following the recommendation of the doctor responsible for the oxygen therapy. In the daily monitoring of the patient by the doctor, a significant improvement between each session of the hyperbaric chamber could be seen. In the fifth session (on the eighth day after the procedure), the doctors responsible for the injection and the oxygen therapy observed that the patient's skin had already recovered approximately 100%, with no signs of scarring. The patient underwent two more sessions and then the doctor at the oxygen therapy service considered the treatment to be successfully completed, as it had reversed 100% of the arterial occlusion with total restoration of the affected skin and tissues ().


A female, 39-year-old patient had a prosthesis in her chin, which was insufficient to satisfy her desire. In the medical evaluation, filling with PMMA was indicated to fill the region. After the consent form was signed by the patient, the procedure was performed. Local anesthesia with lidocaine 2% was administered in the mental region, and a 22 G microcannula was inserted through the entry point to inject PMMA 10%. The correction of a depression caused by a prosthesis on the left side of the chin started, however, when 0.3 mL of PMMA 10% was injected, a hematoma and cyanosis were observed on the chin. The patient remained under observation for approximately five minutes by the responsible doctor. Hyperemia extending from the side of the chin, in the mandibular region, to the nasal ala on the left side was observed, which is very characteristic of the occlusion of the facial artery. Thereby, the doctor started the occlusion protocol, massaging the site and applying hot compresses.
At no time the patient reported feeling pain. She remained under observation for another hour at the clinic. The doctor, in suspecting arterial occlusion, followed the treatment protocol and prescribed antibiotics, corticosteroids 20 mg, and acetylsalicylic acid (ASA) 300 mg per day before discharging the patient. Twelve hours after the procedure, the doctor requested the patient to send a photo of the affected area. The patient had more intense hyperemia in the region of the facial artery and a significant hematoma in the chin, which led the doctor to the diagnosis of vascular occlusion. Therefore, the doctor referred and accompanied the patient to a hyperbaric oxygen therapy center. The treatment, overseen by the doctor responsible for the oxygen therapy, was carried out to reverse the region's arterial suffering. The patient was subjected to 2.4 atm of pressure in a multi-place chamber with 100% oxygen inhalation for 90 min. On the third day of treatment, despite the external part of the mucosa appearing cyanotic, there was a significant reduction in both the hematoma and the hyperemia in the region. On the fifth day of the therapy, that is, the sixth following the procedure, the patient presented recovery of 100% of the blood flow rate, as monitored by the doctors responsible for the procedure and the oxygen therapy treatment.
After the fifth session of oxygen therapy, the patient was discharged. Seven days after the procedure, she contacted the doctor once more to report wellness during a car trip and 100% of the region healed, without any visible scarring ().


We present a 44-year-old Caucasian man with crops of red-brown papulovesicles on his trunk and upper extremities, which had been present for 2 weeks (). Palms and soles were not involved. Lymphadenopathy was not present. He denied pruritus, fevers, chills, purulent drainage, or any other current symptoms. He denied a history of chancre or new sexual partners. His past medical history included hypertension and hyperlipidemia. He was currently taking amlodipine, gemfibrozil, hydrochlorothiazide, and simvastatin. Although the differential was broad, the clinical presentation was concerning for lymphomatoid papulosis. Punch biopsies of the epigastric skin and left ventral forearm lesions were performed. Both specimens demonstrated a dense superficial and deep perivascular and periadnexal dermal infiltrate comprised mostly of small lymphocytes, some medium-sized lymphocytes, and a few plasma cells and histiocytes (). Immunoperoxidase analysis of the infiltrates showed predominantly CD20/CD79a+ B-cells, associated with a background of CD3+ T cells with a normal CD4:8 ratio. There was variable bcl-2 reactivity, while bcl-6 and cyclin D1 were negative. CD30 immunoperoxidase analysis was also negative. Both biopsies showed polyclonal results via kappa and lambda in situ hybridization studies.
Given the dense lymphocytic infiltrate on microscopy and the clinical concern for cutaneous lymphoma, both specimens were submitted for T- and B-cell gene rearrangement studies. The epigastric specimen exhibited positive T-cell receptor beta and gamma gene rearrangements. The forearm specimen exhibited negative T-cell receptor beta gene rearrangement; however, the biopsy was positive for T-cell receptor gamma gene rearrangement (demonstrating the same clonal pattern as that observed in the epigastric skin biopsy). B-cell clonality studies were negative for both specimens. These molecular findings raised concern for a T-cell lymphoproliferative disorder, although a reactive clonal expansion could not be completely ruled out. Further workup included an oncology consultation and subsequent dermatology follow up. Medical therapy was not initiated at this time, as the patient was asymptomatic, and as the diagnosis was still in question. Early blood work revealed an unremarkable complete blood count, comprehensive metabolic panel, and protein electrophoresis.
The oncology team in conjunction with the dermatology team requested additional biopsies prior to initiating any therapy. Upon the follow-up visit with dermatology, 7 weeks from the initial visit, the patient showed a more generalized papulosquamous rash () on the trunk and extremities (but not palms and soles). A re-biopsy was performed, which showed mild epidermal hyperplasia, with a less dense lymphoplasmacytic perivascular and periadnexal dermal infiltrate. Treponema pallidum immunoperoxidase analysis revealed spirochetes in the dermis, supporting a diagnosis of secondary syphilis (). In addition, T. pallidum immunoperoxidase analysis was performed in retrospect, in the previous 2 biopsies, and both exhibited spirochetes. HIV and hepatitis panels were negative. A rapid plasma reagent test was positive at a titer of 1:128, and a fluorescent treponemal antibody absorption test was also positive.
The patient was sent to the health care department for further therapy. After antibiotic therapy with 28 days of oral doxycycline, the eruption resolved. Lymphoproliferative disorders were ruled out given the prompt resolution of the eruption, clarity on secondary biopsies, and lack of recurrence at the 6-month follow-up. The identical T-cell clonality in the 2 initial biopsies was attributed to a reactive process.


A 48-year-old male with a past medical history of hypertension and diabetes presented to the emergency room (ER) with left lower quadrant stabbing pain which was intermittent, moderate to severe with no worsening or relieving factors. He denied any fever, chest pain, shortness of breath, nausea, vomiting, dysuria, hematuria, diarrhea, or constipation. His last bowel movement was on the day of the admission. The patient was a nonalcoholic and a nonsmoker. There was no family history of any pancreatic or gastrointestinal cancers. The pain was present for one year before the admission and had worsened two days before the ER visit. Vital signs on admissions were: temperature 97.9°F, heart rate 84 beats/min, blood pressure 170/92 mmHg, respiratory rate 14/min, and oxygen saturation 99% on room air. On physical examination, the abdomen was soft, nontender, and nondistended without any guarding or rigidity. There was no evidence of swelling or mass. Digital rectal examination was negative for any signs of blood. Laboratory studies including lipase, amylase, and lactate were normal. CT scan of the abdomen with IV contrast showed a 1.5 cm mass in the proximal loop of the jejunum with contrast enhancement (Figures -). His abdominal pain was thought to be due to the mass. The pain resolved in few hours and he was discharged with an outpatient follow-up with the gastroenterology team for a single balloon enteroscopy to further investigate the mass. He underwent a single balloon enteroscopy with the gastroenterology team a few days later. The scope was advanced to the distal jejunum and then pulled back while carefully examining the folds of the jejunum. A 1-2 cm subepithelial lesion was identified in the proximal jejunum with a small umbilication on top of the lesion (Figure ). He underwent a biopsy of the mass. Biopsy results showed preserved small bowel villous architecture without any evidence of inflammation or malignancy. His abdominal pain reappeared and resection of the unexplained mass was considered by the surgery team. A repeat CT scan of the abdomen was performed, which showed the jejunal mass in the same location without a change in size. His carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9) levels were normal. Chromogranin A levels were elevated to 318.1 ng/mL. He was, therefore, scheduled for the laparoscopic resection of the mass. He underwent laparoscopic resection of the small bowel mass (Figures -). We used indocyanine green (ICG) dye as the mass looked hypervascular on the CT scan images. Though, in ICG dye images we did not see any difference between the mass and the surrounding structures suggesting that the cells of the lesion had a similar blood supply and metabolism as the surrounding tissues. It did help to show a more circular lesion (Figure ) compared to the image without the dye where the margins of the mass look very irregular (Figure ). A small segment of the small bowel which had the mass was removed by segmental resection and side-to-side anastomosis was performed with a stapler. Histopathological analysis showed the mass as the ectopic pancreatic tissue (Figure ). He was started on a liquid diet the next morning and was discharged a day later. At his last follow-up one month after the surgery, he remained symptom-free. His chromogranin A levels declined to 156.8 ng/mL. Currently, he is being followed by a general surgery team with repeat measurements of chromogranin A levels every month to ensure normalization of the chromogranin A levels.


A 35-year-old female came to the primary care center complaining of acute lower abdominal pain with a history of amenorrhea for two months and spotting per vaginum. Upon presentation, the abdominal pain was of sudden onset, not radiating, continuous, and not relieved by oral analgesics. There was no history of vomiting or fever. Her blood pressure (arterial blood pressure, ABP) was 105/75 mmHg, with a pulse of 70 beats/minute. Clinical examination revealed a soft abdomen and mild tenderness in the right iliac fossa.
A pregnancy test was requested and revealed a positive result with elevated human chorionic gonadotropin β (β-hCG) titer (30000 units/mL). The patient was referred to the obstetric department at the referral hospital, in which she reported an obstetric score of gravida 3 para 2a with normal past obstetric history. Per vaginal examination revealed right cervical tenderness. Pelvic ultrasonography showed a 4.5 cm x 3 cm swelling adjacent to the right ovary with a gestational sac containing a viable gestational sac with active heartbeats and body motions, a gestational age of 10 weeks, and a uterus within the normal size. Hemoglobin level was 10.5 g/dL, other routine hematology and biochemistry examinations were within normal ranges.
The patient was primarily diagnosed clinically with ruptured ectopic pregnancy. Explorative laparoscopy was performed and a ruptured mass was detected in the ampulla of the right fallopian tube. A little free fluid collection in the Douglas pouch was also seen. Right salpingectomy was performed and sent to the histopathology laboratory in a formalin fixative fluid.
Grossly, the content of the fallopian tube consisted of a lump of blood clots in which edematous-looking villi and fetal tissue measuring 4.5 cm were seen. Upon microscopic examination by the senior pathologists, polar proliferated syncytiotrophoblastic and cytotrophoblastic cells were noted with irregular shape and edematous stroma with fetal tissue. The hydropic appearance was mild to moderate. Histological features are consistent with a non-invasive molar pregnancy, the complete mole was excluded due to the presence of fetal parts, the patient was advised for karyotype analysis, and the final diagnosis was confirmed as a partial hydatidiform molar pregnancy. Follow-up with β-hCG serum level was done and a gradual decline of the hormone level was recorded without noted complications (Figures -).


A 10-year-old male patient was referred to orthodontic traction of an impacted right lower first molar (tooth 46). During clinical examination, no alteration was noted except the absence of tooth 46. No abnormalities were detected in previous medical history. A cone-beam computed tomography (CBCT) showed the presence of a radiolucent image measuring <1 cm located between teeth 46 and 48, which was initially interpreted as a dental germ (). The patient was submitted to surgery under local anesthesia to achieve tooth crown exposure and bonding of an orthodontic device to traction of its right lower first molar. Six months after the procedure, in a routine panoramic radiograph during orthodontic treatment, a well-defined radiolucent image with radiopaque foci was identified in the region of the suggestive dental germ. Additionally, an increasing volume with cortical expansion and fenestration was observed in a CBCT investigation ().
Thereby, a provisional diagnostic hypothesis of odontogenic lesions was made, suggesting adenomatoid odontogenic tumor and COC. The chosen clinical conduct was the surgical enucleation of the lesion. A straight incision was made in the alveolar ridge with flap detachment to facilitate access to the lesion, and an aspiration puncture was performed revealing a liquid content (). During surgery, the lesion was completely detached from the mandibular bone, allowing visualization of a capsule with a cystic aspect (). The specimen was sent for histopathologic examination, and the microscopic findings revealed a cystic cavity lined by a thin odontogenic epithelium with ameloblastomatous features. Ghost cells and calcification foci were also observed. Furthermore, the formation of dentinoid matrix, immature enamel, and fibrous connective tissue was noticed. Therefore, the diagnosis of COC associated with odontoma was established (Figures and 3(b)). One year later, no signs of recurrence were observed and a CBCT revealed new bone formation in the region (). Currently, the patient is undergoing clinical and radiographic follow-up with pediatric dentistry specialists and orthodontists for adequate establishment of occlusal dynamics.


A 56-year-old Chinese man was diagnosed with colonic carcinoma with liver and lung metastases (T2N0M1b, stage IV). His family history and social history were noncontributory. He underwent Hartmann operation in November 2016. The patient’s tumor tissue was classified as wild-type genotypes of dMMR, KRAS, NRAS, and BRAF. Then he was treated with 12 cycles of XELOX chemotherapy combined with cetuximab. The patient underwent hepatectomy at Mayo Clinic in the United States in December 2017 after treatment with a single 6 Gy dose of local liver radiation for six times. Afterward, he underwent folinic acid–fluorouracil–irinotecan (FOLFIRI) combined with panitumumab chemotherapy for seven cycles after the operation. Because chest and abdomen computed tomography (CT) scan revealed new lesions in the liver and lungs in November 2018, he received six cycles of immunotherapy with nivolumab (140 mg daily), an anti-PD-1 antibody, within 3 months. His myocardial enzymes and echocardiography were normal before nivolumab treatment. He presented progressive chest tightness and pain after 1.5 months of taking nivolumab. Laboratory tests after admission to hospital revealed elevated serum NT-proBNP (180.40 ng/L, normal < 125 ng/L), CK-MB (8.99 ng/mL, normal < 4.87 ng/mL) and troponin T (0.23 ng/mL, normal < 0.014 ng/mL). Transthoracic echocardiography showed a left ventricular ejection fraction (LVEF) of 50%. Electrocardiogram reported sinus bradycardia and inverted T wave in lead II, III, and aVF. Three days later, these laboratory tests showed further increased NT-proBNP (612.30 ng/L), CK-MB (12.33 ng/mL), and troponin T (0.49 ng/mL). Coronary artery CT angiography revealed no coronary artery lesions. The serological analysis of antiviral antibodies did not suggest myocarditis-associated viral infection. Considering the relation of onset time and the drug therapy, the most likely diagnosis was fulminant myocarditis secondary to nivolumab administration.
The patient rapidly experienced cardiogenic shock and was transferred to intensive care unit after cardiopulmonary resuscitation and tracheal intubation. He revived within half an hour with blood pressure of 89/52 mmHg on the support of 8 µg/kg/minute dopamine and 0.12 µg/kg/minute epinephrine. NT-proBNP was higher than 15,000 ng/L (Fig. ). Electrocardiogram showed a heart rate of 108 beats/minute with wide QRS and arrhythmia. Echocardiography revealed declined movement of the left ventricle multisegments and the right ventricle free wall, and LVEF was 25% (Fig. ). The patient was unconscious and exhibited hypotension, tachycardia, high lactic acid, and anuria. Then, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was used to support his circulation. After 24 hours, the patient regained consciousness, and the urine output was 15–30 ml/hour. Also, the blood lactate concentration and heart rate were decreased. Dopamine and epinephrine were continued (8 µg/kg/minute dopamine and 0.08 µg/kg/minute epinephrine). Intravenous methylprednisolone (160 mg/day) was used for the first 3 days, followed by a dose of 80 mg/day, and intravenous immunoglobulin therapy at 25 g/day for 5 consecutive days. In addition, the patient developed severe pneumoniae caused by Klebsiella pneumoniae. We used the antibiotics based on the drug susceptibility testing. NT-proBNP, CK-MB, and troponin T levels were decreasing gradually. Echocardiograms showed the LVEF improved gradually (Figs. , ). The patient regained consciousness, command action, and sinus rhythm. ECMO flow rate was gradually decreased to 1.5 L/minute. Respiratory and circulatory function was clinically stable. The 24-hour urine volume was 2400 ml. After 8 days support, he was successfully weaned from ECMO. At this moment, transthoracic echocardiography revealed an abnormal echo in the right atrium (considering thrombosis or neoplasm), about 19.0 × 7.3 mm, attached to the interatrial septum, while left ventricular ejection fraction is 33%. Therefore, oral anticoagulation warfarin (2.5 mg/day) was used. During the following days, marked clinical and laboratory improvement was observed. Steroids were then gradually tapered. The patient was transferred to the ward on day 14. The further clinical course was uneventful. Finally, the patient was discharged on day 45 without complication, with LVEF of 42% (Fig. ). Also, he took some medications (methylprednisolone 36 mg daily orally, metoprolol succinate 23.75 mg twice daily orally, pantoloc 40 mg daily orally) according to the doctor’s prescription when discharged from hospital. Through follow-up by telephone, we learned that the patient died from an unknown reason 1 month after being discharged from the hospital.


A 39-year-old African American female with 20-year history of HIV infection and hypertension presented with complaints of abdominal pain and decreased urinary output of 2 weeks duration. She had sustained a mechanical fall 2 weeks prior to presentation and had taken ibuprofen for pain control. Initial evaluation revealed a serum creatinine 5.5 mg/dL. Her baseline serum creatinine 3 months prior to presentation was 0.91 mg/dL. Urinalysis showed 3+ proteinuria and microhematuria, without microscopic casts. Urine protein-to-creatinine ratio was > 10 g/g. CD4 count was 267/µL and HIV viral load by PCR revealed viremia with 1,220 copies/mL. She was compliant with antiretroviral therapy (ART) consisting of bictegravir, emtricitabine, and tenofovir alafenamide (Biktarvy), and lisinopril 10 mg daily for hypertension.
Non-contrast computed tomography (CT) scan of the abdomen and pelvis showed mild bilateral hydronephrosis, marked diffuse irregular bladder wall thickening and ascites. Bladder cystoscopy revealed no evidence of ureteral obstruction but showed diffuse nodules throughout the bladder wall; multiple bladder biopsies were obtained. Given her renal insufficiency, tenofovir was stopped and ART was changed to renally adjusted dolutegravir, rilpivirine, and lamivudine. Serologic workup, including complement C3 and C4, antinuclear antibodies, hepatitis C antibody, hepatitis B surface antigen, anti-neutrophil cytoplasmic autoantibody (ANCA) titers, and anti-GBM antibody, were negative. Serum protein electrophoresis was consistent with acute inflammatory stress response, with no evidence for a monoclonal protein. However, serum free κ light chains were elevated at 1,988 mg/L, with serum free κ/λ ratio 36.4. Urine immunofixation revealed monoclonal free κ light chains. Attempted bone marrow biopsy was unsuccessful. Diagnostic paracentesis was negative for malignancy. Hemodialysis was initiated on hospital day 6 because of progressive renal failure and uremic symptoms.
Bladder biopsy revealed high-grade plasmablastic lymphoma (). Histopathology showed large plasmablastic cells diffusely positive for CD138, MUM-1, and negative for PAX-5, CD20, BCL-6, and BCL-2. Cell proliferation marker Ki-67 approached 100%. Tumor cells were positive for EBER1. Additional immunostains revealed that the plasmablastic lymphoma cells were κ light chain-restricted and positive for CD56, CD10, and c-MYC. They were negative for λ light chain, CD30, and AE1/AE3.
Diagnostic kidney biopsy, performed 9 days after presentation, revealed focal atypical κ-restricted tubular casts with diffuse acute tubular injury and 30% interstitial inflammation and edema, consistent with κ light chain cast nephropathy (). There was no evidence of glomerular disease by light microscopy, immunofluorescence, or electron microscopy.
Chemotherapy was initiated 2 weeks after initial presentation with bortezomib and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). She received 1 dose of intrathecal methotrexate, cytarabine, and hydrocortisone followed by 3 doses of intrathecal methotrexate alone to prevent central nervous system (CNS) relapse, which is common in patients with HIV-associated lymphoma []. She was maintained on ART during this period and started on trimethoprim-sulfamethoxazole and acyclovir for opportunistic infection prophylaxis.
Seven weeks after initial presentation, renal function recovered, and hemodialysis was discontinued. Eleven weeks after presentation, the patient achieved complete remission by imaging (PET). Her chemotherapeutic induction regimen was then switched to bortezomib with ifosfamide, carboplatin, and etoposide (ICE) as CHOP is considered insufficient treatment for PBL []. Six months after presentation, repeat bladder biopsy showed no evidence of PBL and additional testing including PET and bone marrow biopsy were negative confirming complete remission. Seven months after presentation, she underwent modified BEAM (BCNU, etoposide, cytarabine, melphalan) followed by autologous hematopoietic cell transplant. At last follow-up 8 months after autologous hematopoietic cell transplant, her renal function remains stable (creatinine 1.07 mg/dL) with minimal proteinuria (urine protein-to-creatinine ratio 0.36 g/g), normal plasma free light chains, and improved HIV viral load (364 copies/mL). She tolerated chemotherapy well, except for peripheral neuropathy and onychodystrophy which were attributed to her chemotherapy.


A 19 months old female patient was referred to our department because of developmental delay, hypotonia and mild ataxia. She had an unremarkable family, perinatal and personal history with normal developmental milestones until the age of 11 months and an otherwise normal physical examination (Head Circumference [HC]: 45.5 cm, 10th-25th percentile). The initial laboratory and metabolic work-up was normal, while a brain MRI showed delay in myelination (Figure ). Important developmental regression at the age of 2 years (loss of speech and imitation, aggravation of ataxia, loss of standing position and fine motor skills as independent eating, appearance of autistic behavior) was followed 2 months later by onset of several daily clusters of epileptic spasms and abnormal EEG background activity (Figure ). The HC was still in the normal range (47 cm, 10th to 25th percentile).
The epileptic spasms were drug-resistant, and the patient also presented other seizure types within few months, only partially responding to antiepileptic treatment (Table /). Ketogenic diet (KD), initiated 3 months after seizure onset as an add-on treatment to valproate and topiramate, resulted in a further 50% reduction of seizure frequency (approximately 10 episodes per day reduced to 5 per day) and severity with a significant improvement in the patient's daily life. Meanwhile, the repeat of the metabolic work-up with CSF organic acids, amino acids, and neurotransmitters (without 5-MTHF) was nonconclusive. Folic acid in plasma was measured at lower normal levels (4.5 ng/mL) and per os supplementation with folic acid at a daily dose of 1 mg had a beneficial effect on patient's development, according to the parents. After suspicion of CFD due to delayed myelination, ataxia, and epilepsy, folinic acid was also administered at a daily dose of 3 mg/kg/d per os with clinical improvement in social interaction and motor skills. Whole Exome Sequencing revealed two compound heterozygous mutations in the FOLR1 gene, ΝM_016725: c.195C > G (p.Cys65Trp) and c.427 T > A (p.Trp143Arg). Both parents were carriers of a single variant and the patient's older asymptomatic sister had only inherited the paternal mutation. Because of the low CSF age-related 5-MTHF levels (19 nmol/L, normal range 44-122 nmol/L) and the incomplete clinical response to per os folinic acid administration at a dose of 3-5 mg/kg/d for 3 months, along with, 3 day regimens of IV calcium folinate (10 mg/kg/day) were administered weekly under careful laboratory and clinical monitoring. The patient showed immediate clinical improvement with diminution of seizures (ca. 1 per day) and regained walking with support, imitating, eye contact and some verbal communication within 2 months. No acute adverse effects were reported during IV administration but mild leucopenia (~3.500-4.500 leukocytes, neutrophils 900-1100) was probably linked to the treatment, after a negative extended etiological work-up. As no effect on epilepsy was observed by any other intervention apart from KD and folinic acid, the attempt to slowly discontinue all the antiepileptic drugs was successful, with no change in seizure frequency, type, and duration. After 4 months of IV calcium folinate administration, the patient was slowly but constantly progressing (regained walking with support, use of some words), the seizures were stabilized (<1 per day), the brain MRI at the age of 2.5 years confirmed hypo-myelination with no further findings (Figure ) and CSF 5-MTHF levels were augmented to 52 nmol/L.
Compound heterozygous mutations of FOLR1 gene were also detected in the patient's younger brother; 5-MTHF levels in CSF were measured at 49 nmol/L at diagnosis (normal range for age: 63-122 nmol/L). His development was considered within the normal limits until the age of 1 year, although concerns were raised with regards to some involuntary movements and relevant stagnation of development around that age. He was immediately administered per os calcium folinate (initially 2 mg/kg/d). By the age of 18 months, dyskinetic and stereotypic features were apparent but he walked without assistance, followed simple orders, used a few words and had a good nonverbal communication. He never experienced epileptic seizures. His baseline EEG was normal, but his brain MRI at diagnosis had already extended delay in myelination (Figure , Table ). Per os calcium folinate was elevated to 6 mg/kg/d according to clinical response and repeat of CSF 5-MTHF levels were found within normal limits for this age (71 nmol/L, normal range: 44-122 nmol/L).
Both siblings have to date a normal growth, normal HC and no abnormal ophthalmological and hearing findings. They are under clinical and biochemical monitoring every 3 months.


A five-year-old female Cameroonian patient, born in January 2007, was referred to the Stomatology and Maxillofacial Surgery Department, in August 2012, for a painless swelling of the floor of the mouth. This swelling had been evolving for one week, accompanied by deglutition problems, without fever or any other clinical manifestation. Except for a Bactrim allergy, the patient did not present any known medical history, especially no growth retardation and no history of recurrent or severe infections nor any hospitalization or blood transfusion. No HIV checkup had ever been performed on the child, even though both parents were HIV positive.
The clinical examination showed a painless blue swelling of the floor of the mouth that had appeared one week before. The biological analysis only identified abnormal coagulation results. The clinical diagnosis concluded to a ranula. A marsupialization was proposed. However, the treatment was postponed until complete hemostasis work-up. The patient travelled back to Cameroon and came back a year later with the same lesion. In July 2013, coagulation was within normal range with no other biological abnormality observed, and the marsupialization of the ranula was performed. Postoperative follow-up was uneventful. One month later, the patient presented a pulmonary infection requiring hospitalization and underwent a complete checkup, including routine blood tests as well as microbiological test (tuberculin intradermo reaction, serology for Mycoplasma pneumoniae and Chlamydia pneumoniae, and nasopharyngeal aspiration with testing for common epidemic viruses). After a thorough anamnesis, the patient's mother recounted that her daughter presented a chronic cough for a long time. During the medical investigations, HIV serology was performed, demonstrating an HIV infection. The patient had 172 CD4 cells/mm and a viral load of 64000 copies/mL at the time of diagnosis. An opportunistic infection was suspected, and however, no germs were highlighted. The patient was immediately treated with highly active antiretroviral therapy (HAART). In August 2014, the patient came back to the department with a right submandibular swelling that had been evolving for six months. The clinical examination revealed a massive and slightly painful swelling in the right submandibular region. A radiography, an ultrasound, and a CT-scan (Figures and ) were undertaken, confirming the presence of a liquid cyst of 25 × 35 × 29 mm, located in the right submandibular region and pushing back the homolateral submandibular gland. Subsequently, the excision of the cystic lesion associated with the resection of the sublingual and submandibular glands was performed. The postoperative course was favorable. Since then, no ranula recurrence has been observed and the patient comes back every year to Belgium for her HIV follow-up. The patient is now 14 years old and is being treated with anti-HIV tritherapy. The last blood sample showed an undetectable viral load. No opportunistic infection has occurred. The anatomopathological examination of the two fragments, of, respectively, 3 × 2 × 1.3 cm and 3.8 × 2.5 × 2.5 cm, revealed cellular tissue containing a few lymphoid isles, with rare images of lymphoepithelial complexes and the presence of an extensive cavity full of mucin. This cavity was delimited with a fibrous deepithelized wall. The anatomopathological results confirmed the diagnosis of a ranula.


A thirteen-year-old female Congolese patient, born in August 2000 and living in Belgium since the age of four, was referred to the Stomatology and Maxillofacial Surgery Department, in January 2014, for swelling of the floor of the mouth associated with a submandibular mass. Both appeared a few days previous, along with dysphagia. The patient had no other symptoms. The patient was in good health, height and weight were in the normal percentile range, and she presented no medical history, nor allergies. The patient had never been hospitalized, never had a severe or recurrent infection, nor received a blood transfusion. The clinical examination showed a soft painless blue swelling of the left side floor of the mouth. Except for the left submandibular mass, no cervical lymphadenopathy was palpated. Medical imaging, including an ultrasound and magnetic resonance (), was performed confirming the presence of a cystic lesion of 31 × 31 × 17 mm. The patient's father was HIV positive, and the mother was HIV negative in 2012. The patient has four brothers, all HIV negative. A preoperative HIV serology was performed, due to the familial context and clinical presentation, and led to the diagnosis of an HIV infection. The patient had 477 CD4 cells/mm and a viral load of 8310 copies/mL at the time of diagnosis. No HIV treatment was prescribed at that time. A marsupialization of the lesion was performed. Unfortunately, relapse of the lesion occurred three months later. The patient benefited from a resection of the cystic lesion and the sublingual gland. The anatomopathological examination of the 4.5 × 1.5 × 1 cm fragment revealed a seromucous salivary gland characterized by canals dilatation, containing mucin and a discreet chronic inflammatory infiltrate without lymphoid formation that could fit in a mucocoele context. The postoperative follow-up was uneventful. No recurrence of the lesion was observed since then. Since 2017, the patient has been treated with anti-HIV tritherapy. The last blood sample showed an undetectable viral load. The patient is currently treated with an integrase inhibitor.


The patient is a 56-year-old Caucasian male (height: 173 cm, weight: 53 kg) with a history of visual impairment on the right eye since childhood, bilateral hypoacusis, and cholecystectomy. At age 42 years, he presumably experienced the first SLL in the right parieto-occipital area manifesting with a transient flickering of the left eye, quadrantanopia to the lower left, left-sided ataxia, depressive mood, multimodal memory deficits, and a holocrane headache. Echocardiography revealed concentric thickening of the left ventricle in the absence of arterial hypertension. Mild hyperCKemia and hyperlipidemia were noted for the first time.
At age 49 years, the patient was admitted for a presumed second SLE manifesting with recurrent, focal myoclonic seizures, right-sided hemiparesis, gait disturbance, memory deficits, and dysarthria. Cerebral MRI showed a T2-hyperintense, cortical, and subcortical lesion in the left parieto-occipital area. Cerebrospinal fluid (CSF) investigations revealed elevated protein and lactate exclusively. Immune-encephalitis was suspected. To exclude paraneoplastic syndrome, a whole-body 18F-FDG-PET was performed. Interestingly, 18FDG-PET revealed hypometabolism in the left>right occipital lobes (Figure ). The PQ-interval was shortened. Neuropsychological testing revealed a dysexecutive syndrome. Corticosteroids and anti-seizure drugs (ASDs) (levetiracetam, lamotrigine, oxcarbazepine, and valproic acid) were started. Since then, lactate was recurrently elevated in the serum and CSF. Prediabetes under steroids developed. Protein-S deficiency was additionally found.
At age 50 years, the patient experienced a third SLE in the right parieto-occipital area, manifesting with weakness of the left lower leg and seizures. This time, a mitochondrial disorder (MID) was suspected, being confirmed by a muscle biopsy. Genetic workup revealed the MT-TL1 variant m.3243A>G in muscle (heteroplasmy 70%). Since the third SLE, he experienced gait disturbance, easy fatigability, progressive memory disturbance, difficulties in finding words, and recurrent panic attacks, triggered by fear from experiencing a seizure.
At age 56 years, the patient experienced a fourth SLE, manifesting as vertigo, confusional state, speech disturbance, and difficulties in finding words, starting two days prior to admission, in addition to ataxic gait and impaired concentration.
The family history was positive for diabetes (mother), valve replacement (mother), myocardial infarction (mother), and carcinoma (father, mother, sister). His medication included bisoprolol, clopidogrel, metformin, pantoprazole, levetiracetam, pregabalin, and ciprasidone.
Clinical neurologic exam revealed a weakness for head anteflexion (M5-), cerebellar speech, severe visual impairment bilaterally with only light/dark discrimination, severe hypoacusis, mild ptosis bilaterally, diffuse wasting of the upper limbs, bradydiadochokinesia bilaterally, wasting of the thighs, marked ataxia on the lower limbs, and reduced Achilles tendon reflexes. There was an ataxic stance, but he could walk with a walker. Blood chemical investigations revealed lactic acidosis, hyperuricemia, folic acid deficiency, and hyper-triglyceridemia. MRI of the brain revealed an SLL in the right parieto-occipital area (Figure ) and an asymptomatic T2-hyperintense cystic lesion in the right tongue root. Abdominal ultrasound revealed steatosis hepatic and benign prostate hypertrophy. Diabetes was excluded and metformin discontinued. Folic acid and ezetimibe were added.


A 56-year-old woman underwent an elective right L5 nerve root decompression for L5/S1 foraminal stenosis. Prior to the operation, she had a stable daily bowel habit. Her past medical history included a previous episode of ACPO following a redo lumbar spinal fusion approximately 1 year prior, depression for which she took mirtazapine regularly, and an intensive care unit admission related to Clostridium difficile infection and dilated cardiomyopathy following a posterior lumbar fusion 6 years earlier.
The operation was completed under general anesthesia without an epidural. There were no intraoperative complications. Patient-controlled intravenous oxycodone was used for initial postoperative analgesia and this was changed to oral oxycodone on the morning of the postoperative day (POD) 1. On POD 3, she developed abdominal pain and distension. She had not passed a bowel motion since prior to the operation. Abdominal radiograph and computed tomography (CT) showed ACPO and caecal dilatation to 9.8 cm, without the evidence of mechanical obstruction, ischemia, or perforation (Figure , Video ). Serum electrolyte concentrations (sodium, chloride, potassium, calcium, magnesium, and phosphate) were all within normal ranges. She proceeded for colonoscopic decompression on POD 4, which revealed a dilated colon with normal mucosa. Following decompression, a 36-sensor fiber-optic high-resolution (HR) manometry catheter was endoscopically inserted in the distal colon, as previously described (Figure ) (Vather et al., ). A flatus tube was not inserted.
Continuous HR manometric recordings were obtained for 24 h, after which the catheter was removed. During the recording period, the patient's abdominal pain had improved and she had no oral intake other than small amounts of clear fluids. She passed flatus on the morning following catheter insertion, but did not pass any further flatus or stool during the rest of the recordings. She received 10 mg of oral oxycodone during the first hour following catheter insertion and a further 5 mg dose at 11:50 a.m. the following morning. Recurrent symptoms on POD 6 required a further endoscopic decompression and a second insertion of the manometry catheter was not performed. The patient recovered well and was discharged on POD 11 without further intervention. Neostigmine was not given at any stage during the hospital admission.