The patient was a 58-year-old woman with past medical history of hypothyroidism that was stably controlled on a stable dose of levothyroxine, hypertension, osteoarthritis, chronic pain on methadone, and bipolar disorder who presented with fatigue, nausea, vomiting, confusion, and generalized weakness for 7 days. She was hospitalized a week prior to developing symptoms for an infected right knee arthroplasty with subsequent removal of hardware and placement of antibiotic spacer and beads ~ 1 week prior and was discharged on intravenous (IV) vancomycin via peripherally inserted central catheter (PICC line). She had been doing well until 2 days after discharge and had then progressively become more lethargic.
In the Emergency Department, the patient was confused with tenderness to light palpation of epigastrium. She was hypertensive to 177/65 with heart rate of 57 and normoglycemic with point-of-care glucose of 105 mg/dL. She was found to have severe hypercalcemia of up to 21.2 mg/dL with ionized calcium level of < 2.5 mmol/L and albumin 3.0 gm/dL, acute renal failure with creatinine of 1.6 mg/dL, and pancreatitis with lipase of 3,430 U/L. Other lab results were notable for low parathyroid hormone (PTH) of 14.9 pg/mL, 1,25-vitamin D of < 5 pg/mL, and 25-OH vitamin D of 9 ng/mL. The suppressed parathyroid hormone level made secondary hyperparathyroidism less likely, despite the presence of vitamin D deficiency in this case.
Parathyroid hormone-related peptide (PTHrP) level was within normal limits at < 2.5 pmol/L. Chest X-ray performed on this admission also was normal without any mass. Serum protein electrophoresis showed hypoproteinemia with hypoalbuminemia without a monoclonal protein (M-protein) spike. Urine protein electrophoresis showed protein of 8 mg/dL with albumin as predominant protein. Both anti-nuclear antibody (ANA) and complement levels (C3, C4) were unremarkable. According to these lab values, primary hyperparathyroidism, hypervitaminosis D, paraneoplastic syndrome, granulomatous disease, and multiple myeloma were ruled out. She was given methylprednisolone 4 mg IV once, furosemide 40 mg IV every 6 hours (given development of hypervolemia as per guidelines) [], normal saline at 250 cc/hour, pamidronate 90 mg in normal saline 500 mL Intravenous Piggy Back (IVPB) once, and calcitonin injection 285 units (for 48 hours). Due to her acute renal failure, her antibiotic regimen was also changed from vancomycin to daptomycin 6 mg/kg every 2 days.
Prior to this episode, the patient had no prior history of renal dysfunction (baseline creatinine 0.8 – 0.9 mg/dL and estimated glomerular filtration rate > 60 mL/min/1.73m2), malignancy, or recent change in medication that could be the culprit of her calcium level. Her pre-operative medication included biotin 10,000 μg) daily, duloxetine 60 mg daily, quetiapine 25 mg every night, amlodipine 10 mg daily, carisoprodol 350 mg 3 times a day, diclofenac sodium 50 mg 3 times a day, fenofibrate 134 mg daily, gabapentin 800 mg 3 times a day, lamotrigine 200 mg every morning and 250 mg every night, levothyroxine 88 μg) every day, methadone 10 mg every 4 hours if needed, methocarbamol 750 mg 3 times a day, multivitamin 1 tablet daily, orphenadrine 100 mg twice a day, oxycodone 15 mg every 4 hours if needed, tizanidine 4 mg every 6 hours, and triamterene-hydrochlorothiazide 37.5 – 25 mg capsule daily. Post-operatively, she was started on aspirin 325 mg daily, intravenous cefazolin 2 g every 8 hours, dilaudid injection 0.5 mg every 3 hours as needed, and morphine injection 2 – 4 mg every 2 hours as needed. She had a history of hypothyroidism but was well-controlled on the same dose of levothyroxine. Also, her bipolar disorder was controlled with duloxetine, quetiapine, and lamotrigine without the need for lithium. Within the next 3 days, she markedly improved as her calcium level came down with the above treatments. On discharge, her calcium was at 10.1 mg/dL with creatinine back to baseline (). Her most recent calcium level after discharge was 8.8 mg/dL, and subsequent urinalysis was unremarkable. She had no further event of hypercalcemia or acute renal failure after this hospitalization.
The acute time course and rapid recovery indicated an iatrogenic cause of her symptomatic hypercalcemia. In examining her hospitalization to treat her infected right knee arthroplasty, it was found that Stimulan was used, which is composed of calcium sulfate. When her infected joint was washed out, antibiotic-loaded acrylic cement, 9 L of triple antibiotic sterile saline solution and chlorhexidine lavage, and 50 mL of Stimulan containing 1 g of vancomycin and 240 mg of tobramycin per 10 mL were used to attempt to clean the knee replacement to salvage artificial joint. Cortisol levels were not measured, but opioid-induced hypocortisolemia may have played some role with regard to lethargy. It is unlikely, however, that they directly contributed to hypercalcemia since patient was not hypotensive or hypoglycemic and without any other signs of hypocortisolemia.


A 40-year-old man presented to the emergency department with the chief complaints of uneasiness in the chest, breathlessness, and dyspnea on exertion for 1.5 months. His symptoms exacerbate on climbing stairs and lifting heavy objects. No co-morbid conditions were noted. He is a current smoker and drinks alcohol socially. On general examination his pulse - 66/min, blood pressure (BP) - 130/90 mm of Hg, respiratory rate (RR) - 18/min, jugular venous pressure (JVP) - normal, peripheral capillary oxygen saturation (SpO2) - 98%. The cardiac, respiratory, and abdominal examinations were unremarkable. Electrocardiogram (ECG) was performed which showed S wave in Lead I and T wave inversion in Lead II, III, aVF, V3, V4, V5 (Figure ). The chest X-ray appeared normal. Initial laboratory findings are noted in Table . As the classic retrosternal chest pain was not present and the serum troponin T level was normal, 2-D colour Doppler echocardiography was performed. It showed that the right atrium and right ventricle were dilated, left ventricular ejection fraction (LVEF) was 60%, moderate to severe tricuspid regurgitation (TR) was present, right ventricular systolic pressure (RVSP) was 70 mm of Hg, inferior vena cava (IVC) was dilated (2.5 cm) and non-collapsing and no regional wall motion abnormality (RWMA) was seen at rest. He was further investigated by computed tomography pulmonary angiogram (CTPA) which showed a large hypo-dense defect involving the left main pulmonary artery extending into the left anterior segmental artery and apical branches of the left upper lobar and left inferior lobar artery along with an eccentric hypotenuse filling defect involving the right inferior lobar artery (Figure ). Hence, subacute massive pulmonary embolism was confirmed.
The patient was admitted to the intensive care unit and was started on Streptokinase 250,000 IU IV diluted over 30 minutes then 100,000 IU/hr infusion for 24 hours. The treatment was then shifted to IV heparin 3000 IU 8 hourly for three days along with oral dabigatran, aspirin, clopidogrel, rosuvastatin, sildenafil citrate, and ivabradine. A venous Doppler study of both lower limbs was performed which showed normal venous flow without Doppler evidence of deep vein thrombosis. After clinical recovery, the patient was discharged with oral medications - dabigatran, sildenafil citrate, aspirin (75 mg), and diuretics. On advice, the patient quit smoking and alcohol intake.
The patient came for regular follow-up and was clinically stable without any complaint. Repeat CT pulmonary angiography at the one-month follow-up showed a significant reduction in the extent of thromboembolism but chronic partially occlusive thrombus was still noted (Figure ). Repeat 2D echocardiography at three months showed pulmonary artery hypertension (PAH) of 35-40 mm of Hg. The patient was advised for pulmonary thromboendarterectomy due to presence of chronic thrombus and pulmonary artery hypertension but he refused to undergo surgery. Repeat CT pulmonary angiography at seven months of follow-up showed a minimal reduction in the extent of thromboembolism compared to the previous CT scan (Figure ). The patient is currently being managed medically and is clinically stable with no chief complaints.


A 67-year-old female with a past medical history of multiple myeloma status postautologous stem cell transplant 4 years prior with evidence of stringent complete response and maintained on lenalidomide presented with wrist pain, fevers, and altered mental status. The patient had been well until two days prior when she fell at home. She was found by a home aide to be confused, febrile, and with a swollen right wrist. Significant surgical history included bilateral knee surgeries, left shoulder arthroplasty, and right total hip arthroplasty. She reported living with a roommate and numerous domestic cats and dogs.
In the emergency department, presenting vital signs revealed blood pressure 86/44 mmHg, temperature 101.1 F, heart rate 128, and oxygen saturation 94% on 3 liters nasal cannula. Examination of the patient revealed her to be alert and oriented only to herself. Respiratory examination revealed good air movement and normal breath sounds. The ulnar aspect of her right wrist revealed a small abrasion with mild erythema. The right wrist was edematous and tender to palpation. She had decreased strength and range of motion in the right wrist, but normal elbow and shoulder joints. There were no signs of otherwise broken or punctured skin. The remainder of her musculoskeletal examination was unremarkable.
Initial complete blood count revealed a white blood cell count of 5.0 Th/mm3 (normal limit 4.0–11.0 Th/mm3), hemoglobin 10.4 g/dL (grams/deciliter) (normal limit 12.0–16.0 g/dL), platelets 132.0 Th/mm3 (normal limit 150–400 Th/mm3), and 21% bands (normal limit 3–5%). Complete metabolic panel was significant for sodium 126 mMol/L (millimoles per liter) (normal limit 136–145 mMol/L), AST 213 IU/L (international units per liter) (normal limit 8–20 IU/L), ALT 57 IU/L (normal limit 8–20 IU/L), and alkaline phosphatase 479 IU/L (normal limit 20–70 IU/L). Erythrocyte sedimentation rate and C-reactive protein were 104 mm/hr (normal limit 0–20 mm/hr) and 237 mg/L (normal limit < 10 mg/L), respectively. Procalcitonin was 5.48 ng/mL (normal limit < 0.05 ng/mL). Urinalysis returned negative for leukocyte esterase and nitrite, and moderate blood was noted. Blood, urine, and stool cultures were obtained. Lumbar puncture was attempted twice unsuccessfully. Aspiration of the right wrist resulted in a dry tap. Empiric antibiotic coverage with vancomycin and ceftriaxone was initiated. illustrates lab values from the patient's admission.
Radiographs of the chest as well as the right wrist (), elbow, and humerus were obtained. Computed tomography (CT) of the head, abdomen, and pelvis were also obtained. Right upper extremity radiographs revealed no acute osseous or soft tissue abnormalities, and chest radiograph revealed clear lungs. CT imaging revealed no intracranial abnormalities but did note fluid levels in frothy secretions in the paranasal sinuses, as well as nonspecific perinephric edema and thickening of the renal pelvis bilaterally.
The patient's blood cultures grew Pasteurella multocida in both sets of bottles. Susceptibilities included amoxicillin-clavulanate, ampicillin, ceftriaxone, levofloxacin, penicillin, and tetracycline. The organism was noted to be resistant to trimethoprim-sulfamethoxazole. Respiratory, stool, and urine cultures were negative. Antibiotic therapy was deescalated to monotherapy with ceftriaxone. Repeat blood cultures were obtained on hospital day four and were without growth.
On hospital day seven, the patient reported worsening left shoulder pain, the site of her previous left total shoulder arthroplasty. Magnetic resonance imaging (MRI) () revealed the presence of a small perihardware collection. Aspiration was performed, revealing approximately 70,000 white blood cells without crystals, and no subsequent growth on either aerobic or anaerobic cultures. Arthroscopy revealed purulent drainage from the anterior left shoulder, and subsequent lavage was performed by orthopedics out of concern for septic arthritis. Thick, purulent material was noted intraoperatively, but cultures remained without growth.
On hospital day ten, the patient reported an acute worsening in pain and feeling overall unwell. Physical exam revealed extreme point tenderness to palpation of her cervical and lumbar spine. MRIs of the spine () revealed multilevel osteomyelitis and septic arthritis of the facet joints L3-S1 bilaterally, as well as edema of the paraspinous soft tissues with epidural abscess. Laminectomy with incision and drainage was performed, and subsequent cultures revealed no growth. Additional imaging with contrast further demonstrated septic arthritis and epidural abscess.
The patient was able to be successfully discharged to a rehabilitation facility with the follow-up arranged with infectious disease and orthopedic specialists. She was continued on levofloxacin at discharge to complete a total of 6 weeks of therapy.


A 61 year-old man presented with several one month-old erythematous to brownish papules and nodules on the back and both legs (a,c). He had diabetes mellitus. The initial clinical suspicion was prurigo nodularis and punch biopsy was done. Microscopic examination showed hyperkeratotic epidermis with acanthosis and parakeratosis. Elongated and irregular rete ridges were observed with dense dermal perivascular infiltration (a,b). The final diagnosis was prurigo nodularis. Initially, he was treated with oral cyclosporine 100 mg/day for 4 weeks. However, relief of the symptoms was insufficient and oral alitretinoin was started at a dose of 30 mg/day. After 4 weeks of alitretinoin treatment, symptoms and skin lesions were improved, and with 8 weeks of treatment (b,d), he stopped medical treatment and achieved complete remission without recurrence.


A 65 year-old man had developed multiple, scattered, itchy excoriated erythematous papules on both arms starting 2 years prior. He had no underlying disease. The biopsied skin lesion showed hyperkeratotic epidermis with acanthosis. Elongated and irregular rete ridges were observed. The final diagnosis was prurigo. He was treated with oral cyclosporine (25 mg/day) and naltrexone (50 mg/day), and there was no improvement in the symptoms within 2 years. Therefore, the oral alitretinoin treatment (30 mg/day) was started. After 3 weeks of alitretinoin treatment, the patient achieved partial remission. The skin lesions and itching sensation were improved and the patient stopped medical treatment.


A 75 year-old man presented with multiple scattered nodules and excoriated patches with crusts on the trunk, both arms, and both legs that were two weeks old. He had no underlying disease. The initial clinical diagnosis was prurigo nodularis and treatment was started. Despite treatment with oral cyclosporine (100 mg/day) for 3 years, his symptoms and skin lesions waxed and waned. After that, the treatment was changed to oral alitretinoin in a dose of 30 mg/day. Within 12 weeks of treatment, pruritus had improved and treatment with oral alitretinoin was stopped with partial remission.


A 41 year-old woman presented with localized brownish papules and patches with crust and a scaly skin lesion. She had chronic kidney disease. Her skin lesion was diagnosed as prurigo nodularis. Because of her impaired kidney function, medication that might impair renal function was limited. Treatment with oral alitretinoin was selected in a dose of 30 mg/day. Within 4 weeks of treatment, the symptoms had improved compared to conventional treatment. She continued treatment with oral alitretinoin during which the symptoms waxed and waned.


A 42 year-old man presented with multiple scaly erythematous itchy papules on the whole body that were 12 months old. He had hypertension and diabetes mellitus. The clinical diagnosis was prurigo nodularis and treatment was started. Despite taking oral antihistamine and cyclosporine (200 mg/day) for 4 weeks, the patient’s symptoms were not improved. Medication was changed to oral alitretinoin in a dose of 30 mg/day. Within 5 weeks of treatment, symptoms had improved. The treatment of oral alitretinoin was continued for 12 weeks until complete remission and was stopped afterward without recurrence.


A 78 year-old man diagnosed with prurigo nodularis had itchy multiple erythematous to brownish papules on both flanks, chest, and back that were 6 months old. He had no underlying disease. Oral cyclosporine (50 mg/day) was taken for 1 year. His symptoms waxed and waned. In our study, oral alitretinoin (30 mg/day) was started. Within 2 weeks of treatment, the skin lesions and pruritus had improved. The patient was treated with oral alitretinoin for 14 weeks until complete remission and then the treatment was stopped without recurrence.


A 54 year-old man presented with multiple, 1 month-old, itchy erythematous maculopapular patches on both legs, both arms, and back, which were diagnosed as prurigo nodularis. He had no underlying disease. Treatment with oral cyclosporine (50 mg/day) was started. However, his blood pressure exceeded the hypertension borderline after 8 weeks of treatment even though he had no underlying hypertension. Therefore, the treatment was changed to oral alitretinoin (30 mg/day) for 2 weeks. His itching sensation was reduced after the treatment without recurrence.


A 54 year-old man had developed several scattered, itchy, excoriated erythematous papules on both the arms and back (5 years previously). He had no underlying disease. The clinical diagnosis was prurigo nodularis and treatment was started. Oral cyclosporine (200 mg/day) was taken for 1 year, but his symptoms waxed and waned. Treatment was changed to oral alitretinoin (30 mg/day). Within 16 weeks of treatment, the symptoms and skin lesions had improved more than with previous treatment. His treatment with oral alitretinoin continued for 3 years without progression or any side effects.


A 56 year-old man presented with 2 year-old, itchy, erythematous to brownish papules with silver scales on both legs. He had hypertension and diabetes mellitus. The clinical diagnosis was prurigo nodularis and punch biopsy was done. Microscopic examination showed a pronounced granular layer and numerous lymphocytic infiltrations of the papillary dermis with mild spongiosis (c). The final diagnosis was Kyrle’s disease with prurigo nodularis. He was treated with cyclosporin (100 mg/day) and narrowband ultraviolet-B(NB-UVB) twice/week for 12 weeks. However, there was no improvement of symptoms. Therefore, oral alitretinoin (30 mg/day) was started. After 16 weeks of treatment, skin lesions and pruritus were improved. His score on the visual analog scale for pruritus improved (from 6 to 3). His treatment with oral alitretinoin continued for 19 months and he successfully achieved complete remission without recurrence.


A 41 year-old woman presented with multiple, 2 year-old, scattered erythematous to brownish papules with pruritus on both legs. She had diabetes mellitus. The initial clinical suspicion was reactive perforating collagenosis and punch biopsy was performed. Atrophic and ulcerative epidermis was observed. There was cup-shaped invagination of the epidermis associated with a keratin plug containing inflammatory debris and collagen fibers (d,e). Reactive perforating collagenosis and prurigo nodularis were finally diagnosed. After the use of oral cyclosporine (100 mg/day) for 4 weeks without improvement, oral alitretinoin (30 mg/day) was started. Within 5 weeks of alitretinoin treatment, her pruritus and skin lesions improved. After that, she stopped medical treatment without progression or recurrence.


Case 7: This 1-year-old female was referred to paediatric surgery for clitoromegaly and fused labia minora. At that time, ultrasound was not conclusive and abdominal and pelvic MRI showed a small vagina (3.2 cm) without fallopian tubes. Karyotype was 46,XY. Basal hormonal testing indicated slightly reduced FSH (1.23 U/L) while LH was elevated (0.56 U/L). Testosterone levels were in the normal female range, and AMH was increased (40.3 ng/mL). After stimulation with hCG, testosterone increased highly (8.0 ng/dL), while DHEA-S levels remained in the normal range for age and female sex. During genitoplasty, the absence of a uterus and ovaries was confirmed. When the patient was 3 years old, a structure of 3 cm was seen by ultrasound, most likely corresponding to a vaginal pouch. Recent laboratory results at 7 years of age showed normal values for age and sex ().


The patient was a 35-year-old Indian male with no significant medical history. He was born in Tamil Nadu, India, and emigrated to Singapore six years prior to presentation. He returns to India annually to visit friends and relatives, both in small towns and villages in rural areas with farms housing farm animals. He drank well water and ate local food during these trips back to India. He had no known personal or contact history of tuberculosis.
He presented to medical care after a first-onset seizure which was witnessed by his wife. The seizure was described as jerking movements of all four limbs, associated with uprolling of eyeballs, and a transient loss of consciousness lasting ten minutes. There were no preictal symptoms. Postictally, he was drowsy for another ten minutes and was unable to recall the events upon regaining consciousness. Prior to this seizure, he was generally well and did not report any constitutional symptoms such as fever, night sweats, weight loss, or anorexia.
On examination, he had a low-grade temperature of 37.8 degrees centigrade. Blood pressure, heart rate, and oxygen saturation were normal. Neurologic examination did not reveal any focal neurologic deficits, and there were no localising signs of infection. Laboratory investigations were significant for leukocytosis with a white blood cell count of 18.4 × 109/L. There was no peripheral eosinophilia. Renal and liver function tests were normal, as were routine biochemistry and serum electrolytes. Noncontrasted computed tomography scan of the brain revealed an ill-defined eight-millimetre hypodense lesion with a hyperdense rim in the left basal temporal region, with mild surrounding vasogenic edema. MRI of the brain further delineated this as a solitary ring-enhancing lesion measuring 1.2 by 1 centimetre (). Postcontrast images showed thick smooth peripheral enhancement, but no clearly-defined scolex or mural nodule consistent with a typical viable cyst of neurocysticercosis. Skull base artefacts limited assessment of the contents on diffusion-weighted images.
Human immunodeficiency virus serology was nonreactive. Two sets of blood cultures were negative, as was serum Cryptococcal antigen. Three sets of stool microscopy for ova, cyst, and parasites did not pick up any parasites. As there was no available serologic test for cysticercosis at our centre, a serum sample was sent to an overseas reference centre for serologic testing with an antibody-detecting ELISA-based assay.
After discussion with the managing neurosurgical team, the patient opted for brain biopsy for definitive diagnosis, in view of the broad range of differential diagnoses based on the neuroradiologic features. A left minicraniotomy was performed and identified a slightly hardened pale white to yellow lesion, with a milky white exudate upon breaching the lesion capsule. The entire cyst was excised and sent for histology and microbiologic evaluation.
Histology demonstrated granulomatous inflammation featuring aggregates of epithelioid histiocytes and multinucleated giant cells lining the fibrous cyst wall, accompanied by a mixed inflammatory infiltrate and necrosis. Features characteristic of a cysticercus were absent, and no viable larva was identified (). No fungi or acid-fast bacilli were found on Gomori methenamine silver (GMS) and Ziehl–Neelsen histochemical stains, respectively, and no Toxoplasma organisms were identified on immunohistochemical staining.
Microbiologic testing did not identify causative organisms on Gram stain, aerobic and anaerobic culture, fungal smear, acid-fast smear, and GeneXpert MTB/RIF assay (Cepheid Inc, Sunnyvale, CA, USA).
In view of nonspecific histologic and radiologic features, no definite diagnosis was made at this point. As histology showed granulomatous inflammation, and tuberculosis is endemic in the region, empiric combination ant-tuberculous therapy and a tapering corticosteroid regimen were initiated after discussion and shared decision-making between the patient and medical team while awaiting further diagnostic tests.
While awaiting ELISA serologic assay results, which later returned positive for cysticercosis, residual brain tissue was sent to the National Public Health Laboratory, a tertiary reference laboratory, for further molecular diagnostic testing. 25 milligrams of brain tissue was minced on dry-ice, lyzed in ATL buffer with proteinase K, and DNA was extracted using QIAmp® DNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. A Taenia solium-specific PCR targeting the pTsol9 repeat element based on a previous paper by Almeida and colleagues [] and a pan-Cestoda PCR targeting a fragment of the mitochondrial ribosomal RNA (16S rRNA – 12S rRNA) genes based on a paper by Le and colleagues [] were attempted. Capillary electrophoresis on QIAxcel® Advanced System (Qiagen, Hilden, Germany) equipped with DNA Fast Analysis Kit displayed multiple bands of expected sizes (120 bp, 280 bp, and 440 bp), corresponding to the amplification of 1, 2, and 3 repeat unit(s) of the pTsol9 element, respectively () and a single band of 810 bp for the 16S rRNA-12S rRNA genes. Purification, bidirectional Sanger sequencing, alignment, and cross-checking of the sequences were performed as previously described [] for the 16S rRNA-12S rRNA PCR products. A consensus fragment of the 16S rRNA-12S rRNA genes (808 bp) was obtained, compared by Basic Local Alignment Search Tool (BLAST) against GenBank (NCBI, Bethesda, MD, USA), showed 99.6% similarity (805/808) with sequence [AB086256], and thus ascertained that detected DNA was from T. solium. The sequence has been deposited in GenBank under the accession number (MT772182).
Upon molecular confirmation of neurocysticercosis, antituberculous therapy was stopped. The patient completed 14 days of oral albendazole together with a rapid taper of corticosteroids and has remained well since on subsequent follow-up.


A 63-year-old man with a history of transurethral resection of prostate and a ballistic lithotripsy of bladder stone 15 years ago, presented with low urinary tract symptoms and hematuria. Cystoscopy showed multiple bladder stones and a bulky tumor mainly intradiverticular (). Partial resection of the tumor was done and pathology concluded on a squamous cell invasive bladder carcinoma. Since staging showed no metastatic lesion, a cystoprostatectomy was decided. Its execution was delayed because of a pulmonary embolism treated with curative anticoagulation and a severe paraneoplastic hypercalcemia treated with Zoledronic acid and veinous hydration on hospitalization. At Day 10 from admission and Day 60 after endoscopic resection of the tumor, the patient complained of abdominal pain, with diffuse tenderness and fever. Biology shows biologic inflammatory syndrome and kidney failure. Peritonitis was suspected and CT-scan showed a perforated bladder diverticulum with intraperitoneal effusion (). An emergency surgical investigation was executed, objecting a peritoneal cavity filled with nauseating hematic urine derived from a 2 cm disruption at the level of a posterolateral bladder diverticulum (). Radical cystectomy was performed. The patient was in severe septic shock requiring catecholamines and the procedure had to be shortened. No pelvic lymphadenectomy was done and bilateral ureterostomy was chosen as urinary diversion. The intervention lasted 2 h and there was no significant blood loss.
Postoperative course was marked by an aggravation of the septic shock, multiorgan failure, and death of the patient at Day 2 after surgery. Pathological examination concluded a pure SCC that massively invades the bladder muscle and perivesical fat (–).


A 43-year-old female sought medical attention due to her complaints of frequent urinary voiding dysfunction requiring intermittent catheterization, and lower abdominal pain during micturition for a period of two years. She was first diagnosed with right hydroureteronephrosis and treated with the placement of a ureteric stent, without any relief of the urinary symptoms. Her past surgical history was significant for the exeresis of an endometrioma of the right ovary, 18 years before.
Her general physical examination as well as her per-abdominal, and per-vaginal examinations were normal. An abdominal CECT showed the right moderate hydroureteronephrosis with a double J (DJ) stent in situ. The uterus was bulky and heterogeneous, with the presence of few hypodense lesions within the uterine wall. A well-defined heterogeneous oval lesion of 2.1х3х3.2cm in the right lateral and posterior wall of the cervix, along with few foci of calcifications were found. The bilateral adnexa were normal. She subsequently underwent trans-vaginal USG-guided FNAC of the uterine cervical mass that was suspected to be malignant. A Papanicolaou smear test from the cervix was normal.
With the working diagnosis of a complicated uterine leiomyoma having chances of suspicious malignant transformation, the patient underwent total abdominal hysterectomy (TAH), right salpingo-oophorectomy (Right SO), pelvic lymph-nodal sampling, peritoneal cytology and ureteric stent replacement. Intraoperatively, a tumor with size of 4x4 cm was identified in the right broad ligament, posterolateral to the cervix. There was no ascites. Both the ovaries as well as the fallopian tubes were grossly normal. No lesions consistent with endometriosis or disease dissemination were found.
A gross examination of the surgical specimen showed a normal appearance of the uterus measuring 8х6х6 cm. However, a bulging mass of the right broad ligament measuring 2.5x1.5x2cm was attached to it. Post serial slicing, a single well-circumscribed, grey-white, firm tumor was identified in the broad ligament. The endometrial cavity, the endocervical and ectocervical mucosal surfaces, the right ovary and the fallopian tubes were all unremarkable. On microscopic examination the broad ligament mass showed adenomyoma with focal areas of malignant transformation. The tumor cells were arranged in the form of nests, glands and trabeculae, infiltrating the smooth muscle and reaching just beneath the ectocervix (). Three internal iliac lymph nodes were sampled that were free of tumor.
An immunohistochemistry (IHC) showed positivity for CK7 in the cytoplasm of the tumor cells, membranous positivity for vimentin and nuclear positivity for Estrogen (ER) and Progesterone Receptors (PR). IHC results for p16, CEA, CK20 and WT1 were negative ( and).
The peritoneal washing done intraoperatively was suggestive of metastatic adenocarcinoma. The final histopathological diagnosis was endometrioid adenocarcinoma, grade I, arising from broad ligament adenomyoma, FIGO-IC.
The patient received adjuvant treatment with six cycles of paclitaxel and carboplatin chemotherapy, followed by hormonal therapy with tamoxifen 20mg daily. She completed five years of hormonal therapy during her latest visit, and is completely disease free clinically and radiologically. She is currently on a six-monthly clinical follow-up routine with yearly ultrasonography of the abdomen and the pelvis.


A 42-year-old previously healthy male was referred to our tertiary center complaining of high-grade fever accompanied by chills over the last 20 days. He also complained of progressively increasing breathlessness, nonproductive cough, and right-sided chest pain. There was no history of weight loss or abdominal pain. He denied smoking tobacco. On arrival at our center, he was found to be febrile and dyspneic. His pulse was 120/min, respiratory rate 28/min, and SP02 was 95% at room air. The systemic examination of the chest revealed decreased breath sounds in the right lower zone and coarse crackles in the right infrascapular region. No peripheral or deep chain lymphadenopathy was detected on physical or imaging examinations. The hematological workup showed a leukocyte count of 18,000/µl (reference range [RR]; 4000-12000/μL) with 80% polymorphs. Liver and renal function tests were within normal limits. The serum lactate dehydrogenase (LDH) was 1650 U/L (RR; 150-250U/L). The chest X-ray revealed a heterogeneous opacity in the right pulmonary lower lobe and pleural effusion, which showed to be hemorrhagic after diagnostic thoracocentesis (A). The computed tomographic (CT)-guided Tru-cut biopsy attempted in the original-attending hospital showed necrotic tissue. The thoracic CT scan after the second hospitalization revealed a well-defined irregularly, marginated, complex, non-enhancing mass in the right lung, likely pleural based with thickened visceral pleura causing collapse and consolidation of the right lung (B). The radiological differentials comprised malignant mesothelioma versus a synovial sarcoma.
A new CT-guided biopsy was attempted and showed atypical cells consistent with an underlying malignant lesion (A). The thoracocentesis revealed an exudative and hemorrhagic pleural effusion without malignant cells.
Meanwhile, the patient’s clinical condition deteriorated, he became tachypneic and developed puffiness of the face and altered sensorium and a clinical diagnosis of superior vena cava obstruction was made. He was kept on an antibiotic regimen with Piperacillin-Tazobactam, corticosteroids and controlled ventilation. Bedside 2D echocardiogram failed to evidence a pericardial tamponade, but the mass was seen compressing the right atrium and superior vena cava. On the eighth day of hospitalization, his general condition suddenly worsened, and he expired. Immediately. the autopsy was performed with the working diagnosis of a right lung mass with SVC syndrome, probably due to malignant mesothelioma or a high-grade sarcoma.


A 58-year-old woman with known cases of SLE, Addison’s disease, type 2 diabetes, and fibromyalgia presented to the clinic for the first time with concerns of polyuria, nocturia, abnormal sweating, excessive fatigue, hair thinning, heat and cold intolerance, and progressive darkening of the skin for the last few months. She was diagnosed with SLE at age 19 when she presented to her rheumatologist with concerns of polyarthralgia, hair loss, facial rash, rash on hands, weight loss, fatigue, headache, seizures, and photosensitivity, for which glucocorticoid therapy was initiated. The patient remained stable on glucocorticoid therapy, and there was no flare of the disease since then. At the age of 35, she was diagnosed with Addison’s disease and type 2 diabetes when she presented to the emergency department with hypoglycemia and an associated episode of loss of consciousness. A review of the patient's medication revealed that she was taking oral prednisone 2.5 mg, four times daily for Addison’s disease and SLE. A review of her family history showed that her aunt also had SLE. Physical examination showed vital signs within reference limits; her body mass index was 17.8 kg/m2, and she had epigastric tenderness and swollen gums. Based on the initial evaluation, laboratory tests were ordered consisting of anti-thyroglobulin antibodies, anti-microsomal antibodies, high-resolution computed tomography of the abdomen without contrast, and thyroid ultrasound. Moreover, hydrocortisone 10 mg twice per day was added to prednisone as part of the initial management.
Investigation results showed an increase in the size of the thyroid gland (an approximately 0.7-mm increase in the thickness of the left thyroid lobe) without any echogenicity or nodules and bilateral atrophic adrenal glands without discrete nodules. Thyroid-stimulating hormone (TSH) levels were in the high normal range (3.518 IU/L), serum antibody tests were positive for anti-thyroid peroxidase antibody and anti-thyroglobulin, and these tests, the patient’s symptoms, and other laboratory findings were all consistent with autoimmune thyroiditis. She was already diagnosed with Addison’s disease, and thus, she met the criteria for APS type II. Her oral, four times daily prednisone 2.5 mg tablet was discontinued, and she was advised to continue her oral, twice daily hydrocortisone 10 mg tablet. For the treatment of autoimmune thyroiditis, oral, once-daily levothyroxine was initiated (50 mcg tablet) in the morning, one hour before breakfast. The dosage of levothyroxine was later adjusted to optimize her TSH levels. The treatment regimen improved her symptoms and quality of life. Later, the patient complained of palpitations, tingling, and numbness. Therefore, to evaluate the patient’s concern, autonomic nervous system (ANS) testing was advised. The ANS test demonstrated abnormal responses to autonomic challenges (deep breathing, Valsalva, or standing), suggesting autonomic dysfunction (Figure ).
Based on the results of ANS testing, the diagnosis for the patient was autonomic dysfunction. The patient was then evaluated every three months, and a yearly review of her laboratory test results is shown in Table .
Due to her persistently decreased adrenocorticotropic hormone, her dose of oral hydrocortisone was decreased from two tablets to one tablet in the morning. Her type 2 diabetes was indicated by her C-peptide value and insulin levels in the reference ranges, and glycated hemoglobin slightly above the reference range (5.9% to 6.3%). The patient is subsequently being treated with dietary modification and exercise for type 2 diabetes. Other than this, throughout the course of the illness, the patient didn’t develop any signs or symptoms of other autoimmune manifestations of the disease; skin hypopigmentation (vitiligo), pernicious anemia (normal MCV and B12 levels), diarrhea (celiac disease), jaundice and abdominal pain (autoimmune hepatitis. Normal liver function tests), patchy hair loss (alopecia) and muscle weakness (myasthenia gravis), so further antibody workup for each of these systemic manifestations associated with APS type II was not done.


A 60-year-old Caucasian female with the unknown past medical history presented to the emergency department via her sister for evaluation of altered mental status. The patient was a poor historian, and most of the history was obtained from the patient's sister. As per collateral, the patient had been behaving "differently" for the past month. The patient was unaware of why she was in the hospital. She replied, 'does not know' to almost every question. She denied fever, headache, dizziness, nausea, vomiting, muscle weakness, sensory deficit, gait abnormality, hallucination, homicidal or suicidal ideation. She also denied smoking or any illicit drug use; however, her sister reported the patient has been inhaling heated vapours of heroin for an unknown duration.
On examination, she looked confused and restless, was alert and oriented to person and place but not to time, and intermittently laughing throughout the interview. CNS examination revealed normal strength and sensation in all extremities, including proprioception. No gait abnormalities or nystagmus was observed.
Laboratory investigations done on admission, including complete blood count and metabolic panel, were unremarkable; WBC 8.3 k/ul, Hb 13.3 g/dl, platelets 392 k/ul, creatinine (Cr) 0.7 mg/dl, sodium (Na) 135 mmol/l, potassium (K) 4.8 mmol/l. The urine drug screen was negative. The CT head was unremarkable. MRI brain without contrast showed diffuse symmetric increased intensity signals throughout the white matter (Figures and ). Lumbar puncture was also done, which was unremarkable. EEG revealed mild diffuse slowing with no lateralization.
The patient was started on Vitamin E 400 IU twice daily and was transferred to a rehab facility with following up neurology as an outpatient. She was counselled regarding abstaining from heroin.


A 20-year-old female presented with fatigue, low-grade fever, painless oral ulcers, a rash on face and back (Figure ), and gradually progressive shortness of breath with dry cough for one month. There was no history of orthopnea, paroxysmal nocturnal dyspnea, palpitations and swelling of lower limbs. There was no significant history, and she did not report having alopecia, photosensitivity, joint pains or stiffness, blue discolouration of fingers, dry eyes and mouth, tightening of skin or difficulty in swallowing. She had a blood pressure of 110/70 mm of Hg with a regular and good volume pulse, and JVP was elevated. Investigations revealed mild thrombocytopenia and lymphopenia with normal haemoglobin. Renal and liver function tests were normal, and urinary sediment was bland without significant proteinuria. An electrocardiogram was suggestive of sinus tachycardia, and there was no abnormality on chest radiograph and ultrasound of the abdomen. Specialized tests (Table ) confirmed the diagnosis of a lupus flare with absent antiphospholipid antibodies and cryoglobulins. The inflammatory markers and autoimmune antibodies were elevated, and serum complement level was reduced. The blood and urine cultures were sterile, and procalcitonin level was normal.
Echocardiography showed a thickened pericardium with effusion, and motion abnormalities consistent with CP. On M-mode echocardiogram, there was a slight lag between the onset of electrical depolarization and the motion of interventricular septum and the posterior left ventricular wall. The peak downward motion of the interventricular septum slightly preceded the peak upward motion of the posterior wall. In early diastole, there was a small downward movement of the septum (diastolic dip) as a result of early right ventricular filling that preceded the filing of the left ventricle. This is illustrated in figure . There were no valvular lesions, and the systolic function was normal with a left ventricular ejection fraction of 60%. Computed tomographic scan (Figure ) of the chest revealed pericardial effusion, pericardial thickening and normal lung parenchyma with mild bilateral pleural effusion. Analysis of the pleural effusion confirmed its sterile and transudative nature. Tuberculosis was ruled out by polymerase chain reaction, acid-fast staining and culture. Skin biopsy (figure ), taken from her back, revealed changes consistent with SLE. These included plugging of the hair follicles with keratin, homogenization of collagen and moderate perivascular and peri-appendiceal lymphomononuclear infiltrate in the dermis.
The patient was administered 750 mg of intravenous methylprednisolone for three days, followed by prednisolone 40mg once a day. She was also given hydroxychloroquine, proton pump inhibitor, calcium and vitamin D supplements. Improvement was noticed during the course of admission in terms of dyspnea, rash and general well-being. A repeat echocardiogram after three weeks demonstrated normalized motion of the ventricular septum and reduced respiratory variation in E-wave velocity. Prednisolone was gradually tapered and stopped entirely after four months without any relapse of the disease.


A 65-year-old pleasant gentleman presented to emergency department of our hospital complaining of malaise, shortness of breath and dry cough for 2 weeks. His past medical history was notable for hypertension, diabetes and paroxysmal atrial fibrillation on systemic anticoagulation. He denied having any anginal symptoms. Initial vitals were significant for blood pressure of 159/70 mmHg, respiratory rate of 23/min, temperature of 102.8 º Fahrenheit with oxygen saturation of 87% on 6L oxygen via nasal cannula. Chest x-ray was suggestive of multifocal pneumonia and initial electrocardiogram (ECG) showed normal sinus rhythm without any significant ST-T wave abnormalities (Figure ). He was noted to be progressively worsening over the next 24 hours resulting in sudden hemodynamic decompensation requiring ventilator support and vasopressors. Other pertinent lab results were ferritin 804 ng/mL, D-dimer 0.91 mcg/mL, C-reactive protein (CRP) 12.6 mg/L and normal troponin T (<0.01 ng/mL). He was found to be positive for SARS-CoV-2 through PCR testing and negative for influenza virus.
He received azithromycin, hydroxychloroquine and plasmapheresis, with good response and was eventually successful extubated. His blood cultures remained negative and transthoracic echocardiogram (TTE) checked during his critical illness was noted to demonstrate normal biventricular functions without any conduction abnormalities. As a part of our institutional protocol, daily troponin T were checked and remained negative (<0.01 ng/mL) until day 10, when it was noted to be elevated (peak of 0.61 ng/mL). Troponin elevation triggered an ECG which showed nonspecific ST-T wave abnormalities (QTc 420 ms, QTc 439 ms on admission) and TTE performed on the same day revealed new left ventricular (LV) regional wall motion abnormalities with hypokinesis of the basal to mid segments and hyperkinetic apical segments, suggestive of a reverse Takotsubo cardiomyopathy, likely in the setting of COVID-19 myocarditis (Figure ). Cardiac catheterization was considered, but given the patient's presentation, imaging and electrical data before and after the troponin elevation, ischemic heart disease was unlikely. Therefore cardiac catheterization was not performed to further limit the exposure to COVID-19. He was on 2L oxygen via nasal cannula but otherwise completely asymptomatic and denied having any anginal or cardiac symptoms. Unfortunately, he suffered pulseless electrical arrest 24 hour later with successful return of spontaneous circulation though comfort measure was pursued due to worsening clinical condition with development of multiorgan failure and eventually expired. Cardiac MRI was not performed due to acuity and rapid decompensation of the patient's clinical condition after the diagnosis of reverse Takotsubo Cardiomyopathy.


A 64-year-old female nursing home medical technician presented to the emergency department with fever and nonproductive cough of one-week duration. Her medical history was notable for venous insufficiency, vertigo, migraine headaches, hypothyroidism, and remote tobacco abuse. In the emergency department, she was febrile (38.2℃), with an otherwise preserved heart rate, blood pressure, and respiratory rate. Her oxygen saturation was 92% on ambient air. Initial, basic laboratory diagnostics were unremarkable, and SARS-CoV2 nasopharyngeal PCR was negative. Chest radiograph demonstrated patchy infiltrates in the right mid and lower lung fields. She was discharged home with recommendations for self-isolation. Over the course of the next 48 hours, she noted ongoing fevers and worsening shortness of breath, prompting a return to the emergency department where she was noted to be febrile (39.5℃) and hypoxic (90% on room air) requiring supplemental nasal cannula. Physical examination was unremarkable except for occasional, generalized scattered crackles and wheezes on lung auscultation. Laboratory diagnostics demonstrated a preserved white blood cell count (5.8 k/uL) with neutrophilic predominance (82.6%) and lymphopenia (13.4%), with an absolute neutrophil count (4.8k/uL) to absolute lymphocyte count (0.8 k/uL) ratio of 6, a preserved hemoglobin (14.1 gm/dL), and mild thrombocytopenia (142 k/uL). The metabolic panel demonstrated mild hyponatremia (130 mmol/L), a preserved creatinine (0.90 mg/dL), and mild elevation of the AST (56 units/L) with a preserved ALT (27 units/L). Inflammatory markers were remarkable for an elevated CRP (118 mg/L), LDH (460 units/L), ferritin (1,962.5ng/mL), and D-dimer (3.38 mcg/mL). Repeat SARS-CoV2 testing on re-presentation as well as one additional test during the course of her hospitalization were negative. Computed tomography was ordered in the setting of her worsening hypoxia and elevated D-dimer and demonstrated bilateral ground-glass opacities with crazy paving patterns worse on right than left, consistent with SARS-CoV2 infection, a left upper lobe pulmonary embolism with associated right heart strain, and an enlargement of the main pulmonary artery (Figure ). She was initiated on therapeutic anticoagulation with low molecular weight heparin (LMWH). Unfortunately, despite continued management of her pulmonary embolism and conservative management for presumed SARS-CoV2 infection, her clinical condition was complicated by progressive tachypnea and associated hypoxia, necessitating endotracheal intubation and mechanical ventilation. She received three doses of hydroxychloroquine and seven days of azithromycin. Antibiotics were discontinued as she had no evidence of secondary superinfection. Intriguingly, despite initially negative nasopharyngeal swabs, endotracheal sampling demonstrated SARS-CoV2 positivity. She remained on mechanical ventilation was subsequently extubated after seven days. She was transferred to the medical service where her clinical course remained stable and subsequently discharged home on apixaban.


A 77-year-old woman was referred to our hospital suspected of COVID-19 with a 4-day history of dyspnea. Eight days prior to the admission, she had a fever, cough, and sore throat. Her son was diagnosed with COVID-19 2 days before her admission. She had no history of diabetes, hypertension, and/or chronic kidney disease. On the day of admission, she was alert with a body temperature 37.7 °C, blood pressure at 114/66 mmHg, heart rate at 66 per minute, respiration at 24 per minute, and oxygen saturation at 96% (nasal cannula delivering oxygen 4.0 L per minute). The physical examination was unremarkable. The laboratory test revealed an increase in the C-reactive protein (CRP) level. The patient’s renal and liver functions were normal. Using a dipstick urinalysis, 1+ proteinuria and 1+ hematuria were detected. Chest CT without contrast showed ground-glass opacities in bilateral lower lobes. Ceftriaxone and azithromycin were started. Her respiratory condition gradually deteriorated. The SARS-CoV-2 PCR test performed on the day of admission returned positive 2 days later. On the sixth day of admission, she was intubated and received mechanical ventilation, and piperacillin-tazobactam (4.5 g every 6 h) and methylprednisolone (120 mg/day for 3 days) were started. On day 12, due to the possible superimposed infection with fever and increased white blood cell count, blood cultures were taken and vancomycin was administered (loading dose of 2 g and maintenance dose of 1 g twice a day), but it was discontinued on hospital day 15 with negative blood cultures. On hospital day 16, favipiravir was started because of deterioration confirmed by chest CT scan without contrast. On the same day, serum creatinine had started to elevate (trough vancomycin concentration 26.75 ug/mL), despite adequately maintained blood pressure with no clinical signs of hypotension and volume depletion. Urine microscopy detected massive granular casts and mild hematuria with no dysmorphic red blood cells (RBCs) (30–49 RBCs per high-power field [RBCs/HPF]) and a urine dipstick confirmed that there was no presence of proteinuria. The patient was suspected of vancomycin-associated acute tubular necrosis (ATN). Her respiratory condition remained unchanged; however, her serum creatinine level gradually decreased over the course of several days, with no appearance of granular casts and hematuria thereafter. She underwent tracheostomy on hospital day 26, and mechanical ventilation was withdrawn on hospital day 44.


A 45-year-old man was referred to our hospital with severe respiratory failure and a 10-day history of dyspnea. He had no history of diabetes, hypertension, and/or chronic kidney disease. He was smoking one pack of cigarettes per day. On the day of admission, he was alert with a body temperature of 37.7 °C, blood pressure at 154/110 mmHg, heart rate at 106 per minute, respiration at 36 per minute, and oxygen saturation at 70% with reservoir mask. The laboratory test revealed an increased CRP level. His renal and liver functions were normal. Using a dipstick urinalysis, 1+ proteinuria was detected with no hematuria. Chest CT without contrast showed ground-glass opacities with bilateral peripheral distribution and no pleural effusions. Patient was intubated and received mechanical ventilation, and piperacillin-tazobactam, azithromycin, methylprednisolone, and favipiravir were started empirically due to acute respiratory distress syndrome (ARDS). A SARS-CoV-2 PCR test was performed on hospital day five and returned positive. While the patient’s respiratory condition improved gradually, his high fever still remained with no elevation of white blood cell count or CRP level. On the fifth day of hospitalization, risperidone administration was initiated for delirium. On hospital day eight, a significant increase in serum creatinine kinase accompanying brown colored urine was observed. Using dipstick urinalysis, 2+ proteinuria and 3+ hematuria were detected. In microscopic urinalysis, a few red cells (1–4 RBCs/HPF), myoglobinuria (urine myoglobin concentration was 120,000 ng/mL), and massive granular casts were also detected. Risperidone was discontinued. On hospital day 11, the patient’s serum creatinine was further elevated, although his urine volume was adequately maintained with no significant hypotension and volume depletion. Additionally, he suddenly presented microscopic hematuria with no dysmorphic RBCs (> 50 RBCs/HPF). He was suspected of having heme pigment-associated ATN. His serum creatinine level gradually decreased (peaked at 8.13 mg/dL on hospital day 16), with an eventual disappearance of microscopic hematuria and granular casts. Regarding the pneumonia, the patient discontinued mechanical ventilation on hospital day nine and was discharged on day 33 following two negative PCR tests. After discharge, his renal function recovered to basal level.


An 80-year-old Japanese man hospitalized due to acute exacerbation stemming from asthma and COPD overlap presented with left-side pneumothorax caused by respiratory tract infection. Subsequently, a chest drain tube was inserted; however, a tumor suspicious for lung cancer was present at the entrance of the left upper lobe bronchus. The lung could not be sufficiently expanded, and an air leak was present. We performed pleurodesis twice (first: 200 mL of autologous blood and 4 g of talc; second: 200 mL of autologous blood), but the air leak persisted. Since surgical treatments were considered high risk for this patient due to poor lung function, we decided to treat by bronchial occlusion with EWS. Under bronchoscopy, a tumor was observed with a smooth surface at the entrance of the upper left lobe (Fig. ). A balloon occlusion test was performed using a balloon catheter (Edwards Lifesciences Corporation, Irvine, CA, USA) with a diameter of 4 Fr and an inflated balloon diameter of 9 mm, to determine the affected bronchi. After the entire left lower lobe bronchus was occluded by the balloon, the air leak ceased. Subsequently, bronchography was performed to identify the affected bronchi at the subsegmental bronchial level. The catheter was inserted into the subsegmental bronchus, and a contrast medium (iopamidol 5 mL and saline 15 mL) was injected from the tip. The contrast medium was injected from the left B8a and left B8b bronchi (Fig. ). Fluoroscopy confirmed contrast leakage from the left B8b bronchus into the thoracic cavity, and we suspected major leakage at the bronchi leading from the left B8b and the left B6 bronchi (Fig. ). We then successfully inserted a medium-sized EWS into the left B8b bronchus. Subsequently, we attempted to insert a large-sized EWS into the left B6 bronchus, but the fitting was difficult. Thus, we cut the end of the EWS to size and inserted it into the left B6a bronchus. After EWS insertions, the air leak clearly decreased. Finally, occluding the left B6 and left B8 bronchi by balloon catheter, we confirmed a slight but further decrease in air leakage. Therefore, we judged the remaining air leak to be minor. After bronchial occlusion, we performed pleurodesis twice (first: Picibanil (OK-432) 5 KE; Chugai Pharmaceutical Co. Ltd, Tokyo, Japan, minocycline 300 mg; second: 50% glucose solution and 120 mL of autologous blood), and the air leak ceased completely. The chest drain tube was successfully removed. Several days later, he was diagnosed with pyothorax. The empyema cavity was confined to a small area, and it was difficult to puncture. Therefore, we treated with antibiotics (tazobactam-piperacillin 4.5 g 4 times a day). After 4 weeks of antibiotics therapy, he was transferred to a rehabilitation hospital.


A 16-year-old boy was received at the outpatient department with a history of intermittent fever and inflammatory arthralgia. The arthritis appeared over a period of three years and was evolving by thrust. Arthritis appeared symmetrically within the metacarpal joints of the upper extremities, the phalangeal joints of the wrist, and knees. This condition worsened gradually with occurrence of temporomandibular arthritis which induced permanent constriction of the jaws. This patient had no history of diarrhea. A family history of rheumatic diseases and psoriasis was not found. At admission, the patient had a temperature of 39.5°C, heart rate of 120 beats/minute, blood pressure of 120/90 mmHg, and breathing rate of 24 cycles/minute. A musculoskeletal examination showed synovitis of his wrists and knees (Figure ). The clinical examination also found multiple enlarged lymph nodes (inflammatory lymphadenopathy). He had no sacroiliitis, enthesitis, or rash.
This polyarthritis occurred in a context of hypogonadism marked by gynecomastia, a high-pitched voice, a delay in the development of secondary sexual characteristics, and pre-pubertal testicles Tanner classification stage P2G2 (Figure ). He exhibited a failure to thrive characterized by a height of 145 cm, which corresponded with -2.5 standard deviation (SD) for his age, and a weight of 23 kg or -3 SD. The rest of the clinical examination was within normal limits; notably, there was no anosmia or hyposmia.
Laboratory tests indicated a biological inflammatory syndrome and hyperferritinemia with collapsed glycosylated ferritin at 11%. The transferrin saturation was less than 20% (14.14%). Laboratory data is summarized in Table . Hormonal evaluation found low blood testosterone (0.08 mg/L) and pituitary hormone levels attesting to the hypogonadotropic hypogonadism diagnosis (Table ). The other pituitary hormonal sectors were normal (Table ).
Screening for infection included the Plasmodium falciparum thick blood test, blood cultures, cytobacteriological examination of urine, acid-fast bacillus test (for Mycobacterium tuberculosis), human immunodeficiency virus serology, and hepatitis B/C serology. The immunological assessment included profiling of antinuclear antibodies, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. All these tests were negative (Table ).
Standard radiography showed bilateral wrist carpitis (Figure ).
Facial computed tomography showed destructive temporomandibular arthritis with bilateral ankylosis (Figure ).
The olfactory bulb was present and normal by magnetic resonance imaging (Figure ). There were no signs of hypophysitis. Furthermore, MRI found a pituitary microadenoma.
The diagnosis of sJIA associated of hypogonadotropic hypogonadism was retained. The activity of the disease was classified as high based upon the Juvenile Arthritis Disease Activity Score - 10 joints (cJADAS-10).
Initial treatment was based on corticosteroid therapy with prednisone at 1 mg/kg per day. The clinical course was marked by a clear improvement in the symptomatology, with stable apyrexia, arthritis regression (visual analog scale changed from 8/10 to 2/10), a C-reactive control protein level of 15 mg/L, and a hemoglobin level of 10.2 g/dl obtained after one week. For endocrine damage, hormone replacement with testosterone (injections of testosterone enanthate every three weeks) was used. On discharge, degression doses of corticosteroid was initiated after one month of treatment along with methotrexate at 25 mg/day. A follow-up three months later, with a good adherence and tolerance of the treatment (patient self-assessment), showed a complete regression of arthritis and biological inflammatory syndrome, and elevated residual testosteronemia.


A 17-year-old Hispanic Colombian boy from a rural area, troubled by familial and financial issues, tried to kill himself by allegedly consuming 28 mL of PQ (Gramoxone SL 1 L, 200 g/L ion PQ), equivalent to a high dose of approximately 80 mg/kg of PQ ion []. Shortly after the ingestion he experienced a repulsive taste, severe odynophagia, dysphagia, stomach pain and vomiting. He was given kitchen oil and panela by his mother. Two hours had already passed when the patient arrived at the emergency department of a local hospital. Gastric lavage was done with activated charcoal. The patient also received vitamin E and N-acetyl cysteine (NAC). He was then referred to the Hospital San Vicente Foundation (Medellin, Colombia) for further management.
On arrival 9 hours post-ingestion, the patient had arterial pressure of 123/65 mmHg, pulse rate of 78 per minute, respiratory rate of 16 per minute and 100% oxygen saturation. The following treatment was ordered: NAC 1.8 g in 500 mL of 5% dextrose to infuse over 1 hour, vitamin E 400 mg orally every 12 hours, propranolol 40 mg orally every 8 hours, methylprednisolone 1 g intravenously every 24 hours, cyclophosphamide 900 mg in 500 mL of 5% dextrose to be infused over 1 hour, and omeprazole 40 mg intravenously every 12 hours. Laboratory tests showed a white blood cell count of 11,750/mm3 (80% neutrophils), hemoglobin 16.6 g/dL and hematocrit 50%, platelets 428,000/mm3, prothrombin time 7 seconds, and activated partial thromboplastin time of 42 seconds. Electrocardiogram, liver enzyme and kidney function tests were normal. UDT showed a dark blue color at 12 hours post-ingestion (Fig. ). Considering the large amount of PQ ingested, the positive UDT and the unavailability of hemoperfusion, the family was informed of the patient’s poor prognosis. Based on reports of thrombotic microangiopathy as the primary systemic pathological event in PQ poisoning, a single dose of enoxaparin (60 mg subcutaneously) as an extraordinary measure was offered, to which the patient consented. As severe gastroesophageal chemical burns were found by endoscopy 84 hours post-ingestion (Fig. ), the oral route was stopped for a week. There were no signs or symptoms of pulmonary compromise during the hospital stay, but thoracic high-resolution computerized tomography showed minimal and unspecific atelectatic changes. A second endoscopy at day 14 after PQ ingestion was normal, showing no residual stenosis, and the patient was discharged in good condition at day 21. The patient was doing well at his 1-month health follow-up appointment.


A previously healthy, 4 week old, Caucasian boy was brought to the emergency department by his mother because he had accidentally been given the mothers’ dose of citalopram. Instead of the vitamin D drops she intended to give him, she accidentally switched bottles of the citalopram and vitamin D. These bottles are similar, as shown in Fig. . The mother noticed the incorrect medication bottle around 30 min later and immediately presented the infant to the emergency department. She administered 10 drops of citalopram, corresponding to 20 mg. With a weight of 3355 g corresponding to a dose of around 6.0 mg/kg.
Upon first physical examination we saw an extremely jittery, agitated infant with an evident opisthotonos, as shown in Fig. . Vital signs were stable, the patient had a respiratory rate of 50/min and an oxygen saturation of 100% in room air. At presentation the patient showed an isolated systolic hypertension. Blood pressure was 110/38 mmHg (reference value p95 for systolic pressure 105 mmHg), with a regular heart rate of 190 beats per minute []. An electrocardiogram showed sinus tachycardia with normal intervals. A nasogastric tube was inserted to empty the stomach; activated charcoal and sodium sulfate were administered over a 2 h period to prevent any possible further absorption of the citalopram. Furthermore, an intravenous cannula was placed with maintenance fluid and secure intravenous access.
The patient was transferred to a neonatal intensive care unit (NICU) for intensive monitoring, concerning the possible risk of cardiac rhythm disturbances and convulsions. Laboratory testing was performed including a complete blood count, infection parameters and electrolyte concentration, all results were within normal limits. Because of the risk of convulsions and intracerebral hemorrhage, amplitude-integrated electroencephalography (aEEG) and cerebral ultrasound were performed, which showed no abnormalities.
After 16 h the patient was transferred back to the medium care neonatal ward. In the following days he continued showing signs of extreme jitteriness and increased muscle tone. After 4 days these symptoms were found to be acceptable enough to discharge the patient. Before, during and after admission the patient was only fed formula feeding, breast milk was not used.
During several weeks, at ambulant follow-up, the patient showed persistent signs of increased muscle tone for at least 1 month after discharge. Furthermore, he showed signs of agitation and gastro-oesophageal reflux. Treatment was started with esomeprazole to counteract the effect of the gastro-oesophageal reflux. After 7 months patients symptoms disappeared completely and the patient was discharged from further ambulant follow-up.
To assess pharmacokinetic parameters as well as to predict time to improvement of symptoms, citalopram and the active metabolite desmethylcitalopram concentrations were measured in the serum of the patient. Citalopram and desmethylcitalopram concentrations were analyzed using a validated UPLC-MS-MS method at the Onze Lieve Vrouwe Gasthuis hospital in Amsterdam, the Netherlands. Two hours after ingestion, the citalopram plasma concentration was 77 μg/l with no detectable desmethylcitalopram concentration. Fifty-four hours after ingestion, citalopram serum level decreased to 33 μg/l and desmethylcitalopram increased to a concentration of 43 μg/l.
To objectify the severity and clinical course, Finnegan scores were randomly measured during the course of admission (Additional file ) []. Fig. shows the course of the known Finnegan scores, citalopram and desmethylcitalopram serum levels. Finnegan scores were as follows: 2 h after ingestion 11, 24 h after ingestion 8, 46 h after ingestion 6, 66 h after ingestion 3, more elaborate data is shown in Additional file . Unfortunately during the time of admittance at the NICU, Finnegan scores were not measured.


A 65-year-old Caucasian female presented with a three-week history of a moderately painful erythematous and pustular skin rash on the posterior head, extending to the posterior neck, right ear, and right shoulder (Figure ). She has a past medical history of childhood chickenpox and current chronic lymphocytic leukemia (CLL) of B cell type which was last treated six-weeks ago with a chemotherapy regimen, bendamustine and rituximab.
The patient was given a 10-day course of doxycycline after being seen in the ED three-weeks prior to arrival. Two days later, her primary care provider diagnosed her with herpes zoster virus (HZV) due to its dermatological distribution. She was given a 14-day course of valacyclovir (1 g, three times a day) and instructed to continue (500 mg, twice per day) for prophylaxis. Two weeks later, via telemedicine, there was an improvement in the appearance of her rash but she reported pain on the right side of her neck. A timeline of her disease course is shown in Figure .
Five days later, the patient presented to the ED due to a new pustular eruption along upper cervical dermatomes on the posterior neck and right shoulder indicating multiple sensory ganglia involvement (Figure ). She noted that the rash was pruritic, painful, and easily aggravated by light touch and air. Her auditory and visual sensations were intact and no facial paralysis was observed. The diagnosis of bacterial furunculosis was made.
The patient was admitted to the inpatient service and was started on vancomycin, ceftriaxone, morphine, and diphenhydramine. Allodynia and pruritus may be severe in some presentations, which can be explained by WIR having involvement with the peripheral sensory fibers []. Moreover, her white blood cell count was 4.2 x 103/μL, which was monitored during her hospital stay (Figure ). A CT scan of the head and cervical spine, and X-ray of the chest showed no acute findings. The oncology and infectious disease specialists were consulted. The oncologist recommended transfusing the patient with one unit packed red blood cells if her hemoglobin fell below 8.0 g/dL. This was done once at the beginning of her hospital stay. The infectious disease physician suggested switching ceftriaxone to cefepime. However, the cefepime was later discontinued after wound cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin was continued.
On day six of her hospital stay, the patient reported a sudden worsening of her pain. She was started on valacyclovir (1 g, twice a day). A brain MRI without contrast showed concern for possible inflammation of the right facial nerve. The suspicion for Ramsay Hunt syndrome (RHS) (herpes zoster oticus) led to a consultation with an otolaryngologist, ruling out the diagnosis due to no evidence of facial nerve paralysis.
Eventually, the patient’s rash appeared to be improving and no purulent drainage was observed (Figure ). Given her older age, complex history, and no complete resolution of her skin condition, the patient was discharged to a long-term acute care facility and her medications were transitioned from intravenous to oral route. She was instructed to continue valacyclovir for prophylaxis.


Case 1 A 60-year-old Caucasian female patient was admitted to the hospital in March 2020 for suspected pneumonia. She had a history of hypertension and was otherwise healthy. Her oral medication contained an angiotensin receptor blocker (candesartan cilexetil 8 mg twice daily). She had no history of smoking, but did occasionally consume alcohol. She was working as a secretary in a company specialized in processed food supply. She had lived for the last 17 years with her husband in an urban area in the vicinity of our hospital. She reported fever, shivers and cough for 7 days and a change in her sense of taste. The probable time of infection was 8 days prior to the onset of symptoms, when she was in an airport in Austria with many people who were leaving the area after ski vacations. Two days prior to admission, she was given an oropharyngeal and nasopharyngeal swab test by her general physician, which was negative for SARS-CoV-2. The swab test was repeated in our hospital after her admission with a confirmation of the negative result. RT-PCR was conducted according to the TIB MOLBIOL cycling parameters on a Roche LightCycler 480 []. At this time, her body temperature was 37.4 °C, blood pressure 128/78 mmHg and heart frequency 61 beats per minute. The physical and neurologic examination was unremarkable, except for her taste loss. Computed tomography showed ground-glass opacities with the beginning of consolidation (Fig. a). Bronchoscopy was performed to obtain bronchoalveolar lavage (BAL) fluid, which finally tested positive for SARS-CoV-2. She was provided with subcutaneous antithrombotic prophylaxis (enoxaparin 40 mg once daily). Her laboratory findings are reported in Table . Aerobic and anaerobic blood cultures remained sterile, and no fungi were detected.


Case 2 A 83-year-old Caucasian male presented to our hospital for a red swollen lower leg. Moreover, he reported having fever and a mild cough for 4 days. He had a history of diabetes with peripheral artery disease, coronary heart disease and hypertension. The antidiabetic oral medication consisted of metformin (1000 mg twice daily), empagliflozin (10 mg once daily), combined with valsartan (160 mg once daily), amlodipine (10 mg once daily), acetylsalicylic acid (100 mg once daily) and atorvastatin (40 mg once daily). A widower and former employee of a large brewery, he had moved to a retirement home 4 years ago. He had no recent travel history. On physical examination he showed a one-sided diabetic foot syndrome with erysipelas, presenting as a sharply demarcated, hyperthermic and swollen erythema. His temperature was 38.9 °C and blood pressure 134/88 mmHg with a heart frequency of 94 beats per minute. Pulmonary auscultation and the remaining physical examination were unremarkable. No neurologic deficit was detected. Laboratory findings showed a C-reactive protein value of 6.5 mg/dl, lactate dehydrogenase of 237 IU/l and elevated leukocyte count (19.0/nl). Blood cultures did not reveal any pathogens.
In addition to antithrombotic prophylaxis with enoxaparin (40 mg once daily), antibiotic treatment with ampicillin/sulbactam was initiated for erysipelas. His home medication was continued during his hospital stay. Due to the reported cough, a pharyngeal swab test was performed, which was positive for SARS-CoV2. Cough and fever disappeared within the first day after admission, and the erysipelas and general condition gradually improved. At day 5, the pharyngeal swab test was repeated and was negative. A final swab test was scheduled for the next day, and discharge was prepared in case of a negative finding. At this time, however, the patient rapidly developed hypoxia. Computed tomography showed bilateral ground-glass opacities (Fig. b), and a BAL was obtained. Both the final pharyngeal swab test and the BAL fluid were negative for 2019 novel coronavirus. Microbiologic examination of the BAL did not detect any coinfection either. Besides a slight lymphopenia (1063 cells/µl) and moderate NK cytopenia (26.4 cells/µl), the cellular immune profiling performed at detection of pneumonia revealed normal absolute and relative numbers of CD4+ and CD8+T cells, B cells, monocytes (including intermediate, classical and non-classical monocytes) and NKT cells. The patient required oxygen supply, but did not need intensive care support. He recovered gradually from the SARS-CoV-2 pneumonia and was discharged 15 days after admission. Both patients had an ambulatory follow-up after 6 months and had recovered completely from their COVID-19-associated symptoms.


In October 2019, a 31-year-old male amateur bodybuilder approached the authors with the complaint of fatigue for unknown reasons, numbness of the palms and soles, irritability, frequent headache, mental dullness, generalized pain, muscle weakness and tingling, as well as twitching and shaking of the legs while sleeping. A detailed patient history revealed that the patient had been taking herbal supplements for the last three years. The patient consulted a general practitioner who referred him for testing at a private pathology laboratory in New Delhi. Test results revealed that his blood lead level (BLL) was 59.43 μg/dL. Thereafter, he contacted the National Referral Centre for Lead Projects in India (NRCLPI), King George's Medical University, Lucknow, India. The examination at NRCLPI showed that his BLL was 78.4 μg/dL. In addition, it was also observed that the patient had an elevated serum creatinine level (between 1.8 to 2.1 mg/dL) and he reported having foamy urine over the previous one month. The complete analysis results are shown in .
Blood analyses revealed that the hemogram, liver and renal function tests of the patient were normal except for a few parameters. Metal analysis was carried out by inductively coupled plasma-optical emission spectrometry (ICP-OES) after microwave digestion of samples as described by Ansari et al., 2015 with a slight modification. Briefly, whole blood and different types of herbal supplements were acid digested in a microwave reaction system with a temperature and pressure sensor (Multiwave 3000, Anton Paar, Perkin Elmer, USA). The resultant clear solution was analyzed by ICP-OES using a low flow aqueous system (Perkin Elmer, Optima, 8000, USA). On metal analysis his BLL was found to be 78.40 μg/dL (Normal: <5 μg/dL). We also investigated the lead content of different herbal supplements which the patient was taking for over three years and the results are summarized in .
After the patient reported to NRCLPI and his BLL was found to be 78.4 μg/dL, he was directed to immediately stop the consumption of all herbal supplements.
Overall, the patient's BLL trended down over time after proper nutritional uptake and stopping of herbal supplementation. After stopping the consumption of herbal preparations, beginning a diet rich in fruits and vegetables, and beginning adequate supplementation of iron, zinc and calcium, the patient's BLL came down to 15 μg/dL. This level does not require any chelation therapy. Chelation at first instance was not advised due to known adverse effects of chelation therapy. His symptoms resolved after six months of diet modification and essential mineral supplementation, and his last BLL was 15 ug/dl. The heavy metals investigation of these supplements showed that one of the formulations had a very high lead concentration (9265.97 ppm) ( The patient reported using 16 different types of formulations for approximately three years as health supplements.


A 55-year-old man with a pancreatic mass on contrast-enhanced computed tomography (CT) performed due to acute alcoholic pancreatitis was admitted to our hospital. His serum cancer antigen 19-9 level was mildly elevated at 54 U/mL (normal range, 0–37 U/mL). Abdominal CT revealed a 40-mm heterogenous mass with a clear boundary in the tail of the pancreas (Fig. ). Pancreatic cancer, neuroendocrine neoplasm (NEN), solid pseudopapillary neoplasm (SPN), and inflammatory change were considered in the differential diagnosis. Endoscopic ultrasound (EUS) showed a heterogenous hypoechoic mass with partial necrosis (Fig. ). Histological examination of an EUS-guided fine-needle aspiration (EUS-FNA) specimen revealed the presence of tumor cells with round nuclei and eosinophilic vesicles. Immunohistological staining was positive for BCL-10. The patient underwent distal pancreatectomy. The resected specimen showed two white–grayish masses in the pancreatic tail (Fig. ) and pancreatic body (Fig. ), and normal pancreatic tissue was found between the two tumors. Histologically, tumor cells similar to acinar cells with round nuclei, eosinophilic vesicles, and a solid growth pattern were found in the two lesions (Fig. ). Both lesions were positive for BCL-10 and were diagnosed as synchronous pancreatic acinar cell carcinoma (PACC). S-1 was administered as postoperative chemotherapy.
Ten months after the surgery, abdominal CT demonstrated a 20-mm hypovascular mass in the remnant pancreas, and EUS-FNA revealed the presence of PACC. The patient underwent total remnant pancreatectomy. The histological features of the tumor in the remnant pancreas resembled the PACC histology of the first resected mass. No tumor cells were found in the resection margin. Finally, the patient was diagnosed with synchronous and metachronous PACC.


A 17-year-old girl presented on January 2, 2014 with multiple skin lesions. The lesions were reported to be present at birth on the right scalp, face, neck and trunk. Café-au-lait patches appeared in both arms and gradually coalesced. The lesions on the head and neck were characterized by warty protuberances whereas the lesions on the right face were thickened, with new protruding nodules.
Past history included febrile convulsion, right lateral canthus soft tissue tumor at 12, worsening exotropia of the right eye, and social communication disorder. Family history was unremarkable.
Physical examination revealed large nevus sebaceous on the scalp, oral and nasal cavity, neck, and chest, and generalized nevus spilus on the arm, shoulder, and back (Fig. ). Strabismus and ptosis were noted. Optical coherence tomography scan showed reduced diameter of the right optic disc. Plain orbital MRI scan demonstrated abnormal intensity signals, 18 mm in diameter, in the right lacrimal sac. T1WI showed hyperintensities whereas T2WI revealed hypointensities (Fig. a, b). The right orbital and ethmoid bone were partially destroyed. Orthopantomography showed poor development of the right upper and lower jaw bones, as well as alveolar bones (Fig. c). H&E staining of skin lesions in the head and face revealed epidermal hyperkeratosis, acanthosis, papillomatous hyperplasia in the epidermis, numerous mature or immature sebaceous glands in the dermis, and sparse ectopic apocrine sweat glands (Fig. a). Lesions on the chest showed an increased number of nevus cells in the basal layer and numerous mature or immature sebaceous glands in the dermis (Fig. b). A diagnosis of LNSS was made.
The skin lesions was resected on January 16, 2014. Post-operative recovery was unremarkable except for mild scar hyperplasia at the surgery sites. At the time of drafting this manuscript, no recurrence was reported.


A 63-year-old woman presented with a one-week history of atraumatic lower back pain and fever. Given her past medical history of valvular heart disease, a bacterial infection such as infectious endocarditis was suspected. She had a bilateral lower-extremity weakness (grade 3/5) and was unable to walk. The deep tendon reflexes of both lower limbs were absent, and the pathological reflex was not detected. Her severity was in stage Ⅲ. Laboratory examination showed that white blood cell count and CRP level were 14,980/µL and 13.66 mg/dL, respectively, and MSSA was detected from cerebrospinal fluid culture. Sagittal T2-weighted MRI showed extensive epidural phlegmon throughout the lumbar spine with a capsule-like rim of low signal intensity along the periphery of the phlegmon. The axial views showed compression of the dural tube (). Four days after admission, the patient was diagnosed with SEA and underwent posterior surgical decompression of the lumbar spine and drainage of the abscess. Intravenous antibiotics (ceftriaxone 2g IV q12h, vancomycin 0.5g IV q6h) was administered for 8 weeks. Postoperatively, a return of the strength (grade 4/5) of the iliopsoas and anterior tibialis muscles was noted bilaterally, but hypesthesia in both lower extremities persisted. She became able to walk with the assistance of a cane after rehabilitation. In this case, the neurological symptoms have not worsened despite the diagnostic delay, so surgical treatment could lead to neurological recovery. We initially suspected that the symptoms were possibly due to Guillain–Barré syndrome, so lumbar puncture was performed. As mentioned earlier, a lumbar puncture generally should be avoided after SEA has been ruled out. Once SEA is clinically suspected, a diagnostic procedure, particularly Gd-enhanced MRI, should be done urgently, and the treatment should be initiated promptly.


A 54-year old man with a history of lumbar spinal stenosis presented with a five-day history of severe low back pain, fever (temperature, 39°C), and vomiting. His limb weakness was not noted. His severity was stage Ⅰ. White blood cell count and CRP level were 7,850/μL and 28.2 mg/dL, respectively. MSSA was detected from blood culture. A linear lesion that appeared to be an epidural abscess was found along the dorsal side of the lumbar vertebral bodies on T2-weighted MRI (). Subsequently, intravenous antibiotics (ceftriaxone 2g IV q12h, vancomycin 0.5g IV q6h) was administered for two weeks. However, paraplegia developed suddenly, and his severity abruptly became stage III. The patient then underwent emergent anterior lumbar discectomy and fusion. He became almost completely paraplegic (Stage Ⅳ) and showed no improvement after rehabilitation. He could not void and was discharged with a urinary catheter. In this case, although he was diagnosed with SEA in the early stage and treated with antibiotics alone, the timing of the operation may have been delayed. If the symptoms are in stage I at the time of diagnosis like in this case, the progression to subsequent stages is difficult to predict. In addition, the deterioration of neurological deficits in SEA can be sudden. Thus, clinicians should be aware of these features to prevent delay in surgical intervention.


A 60-year-old male came to the emergency department of a tertiary care hospital, in Pakistan, with complaints of fever for one week, cough, and shortness of breath for two days. He was tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before admission. The polymerase chain reaction (PCR) test came positive and chest X-ray revealed bilateral infiltrates as shown in Figure . The patient was diagnosed with severe COVID-19 infection and was admitted to our dedicated COVID-19 ICU. His past medical history included essential hypertension for the past 10 years, which was in control by his medication.
Examination at the time of admissions showed a regular heart rate of 100 beats per minute, non-invasive blood pressure (NIBP) of 155/88 mmHg, temperature 37.5°C, respiratory rate of 30 breaths per minute, and pulse oximeter showed 80% saturation on room air. The patient was immediately given non-invasive 100% FiO2, which improved saturation to 95%. Continuous monitoring of vitals was done using the Life Scope VS BSM-3000 series monitor (Nihon Kohden, Tokyo, Japan) for NIBP measurement, pulse oximetry, and electrocardiogram.
Initial lab investigations showed an elevated white blood cell (WBC) count of 13.9×109/L, elevated neutrophil percentage of 91%, decreased lymphocyte percentage of 6%, and a decreased platelet count of 95×109/L. The biochemical examination displayed normal serum creatinine 0.7 mg/dL, slightly elevated blood urea nitrogen 25 mg/dL, serum lactate dehydrogenase 1397 U/L. C-reactive protein (CRP) was markedly increased with a level of 82.5 mg/L, and procalcitonin was normal at 0.3 ng/mL. Coagulation function displayed an elevated D-dimer level of 1.96 mg/L, normal prothrombin time of 14.2 seconds, elevated international normalized ratio of 1.35, and elevated activated partial thromboplastin time of 28.4 seconds on Day 1. Arterial blood gases showed a slightly alkalotic pH of 7.48, decreased pCO2 of 27 mmHg, decreased pO2 of 60.7 mmHg, and increased lactate level of 3.2 mmol/L. His laboratory findings are shown in Table . However, one of the limitations to this study is that his complete cytokine assay was not performed.
The patient's treatment plan included antibiotics, prophylactic enoxaparin, 40 mg subcutaneous once daily, symptomatic, and supportive treatment, including steroids and vitamins. The patient was also found to have CRS by aggravated inflammatory markers, for example, CRP levels []. Intravenous TCZ 6 mg per kg was given on the day of admission. Oral feed along with oral and intravenous hydration was continued.
On the third day of admission, the patient's oxygen requirements decreased. The WBC count increased to 45×109/L, pO2 increased to 82 mmHg, and inflammatory markers were reduced. Chest X-ray also showed improvement. On the same day, the patient began complaining of pain in the right lower limb. A physical examination revealed hypothermia, numbness, and mild blackening of the right foot as shown in Figures , . Peripheral pulses of the right foot were not palpable. The vascular ultrasound of lower limbs showed no vascular flow in the popliteal, anterior tibial, posterior tibial, and dorsalis pedis artery. A severe arterial insufficiency was diagnosed, and the Vascular Surgery department was consulted immediately. They declared the limb unsalvageable and counselled for right limb above-knee amputation after the patient's condition had stabilized. Administering a therapeutic anticoagulant dose to prevent any other athero-embolic event was also suggested. Enoxaparin was then increased to 80 mg subcutaneous twice daily. Broad-spectrum antibiotics were added for the raised white cell count. On the ninth day of admission, the patient was maintaining oxygen saturation of 94% on room air. Chest X-ray showed a significant reduction in bilateral patchy infiltrates as shown in Figure . The right foot was blackened and atrophied, which extended up to the knee. No progression in ischemia was noted. The patient was stepped down to high dependency unit (HDU) and was placed on the vascular surgery operating room list for above-knee amputation. The surgery took place under spinal anesthesia. After all aseptic measures, fish-mouth incision was given at the mid femur level through the skin, superficial fascia, and subcutaneous tissue. Deep tissue dissection and muscle transection was done. Neurovascular structures were identified, ligated, and transected. Lastly, the bone was lacerated, hemostasis was secured, and the wound was closed. Aseptic pressure dressing was applied, and the patient remained hemodynamically stable. Postoperatively, the patient was monitored in the HDU for 48 hours. The patient was then discharged and advised tablet rivaroxaban 10 mg once daily for one month.


A 43-year-old Caucasian female presented with multiple episodes of loose, watery, dark stools. Her presentation was associated with gradual onset, colicky, lower abdominal pain since the previous day. She otherwise denied any fever, nausea, or vomiting, history of ill contact, or any history of travelling or taking outside food. No one within her household had similar symptoms.
The patient had been diagnosed several years earlier with multiple sclerosis (MS) and is wheel-chair-bound due to that disease. She had been prescribed alemtuzumab in a clinical trial 10 years preceding this presentation and had used teriflunomide for one year prior to being prescribed ocrelizumab by her neurologist—she had received two doses six months apart. She denied any prior history of inflammatory bowel disease or bowel cancer.
Upon examination, it was noted that she was afebrile and was haemodynamically stable. Examination of the abdomen revealed a soft abdomen with tenderness at the suprapubic and iliac regions with increased bowel sounds but no evidence of peritonism or organomegaly. Digital per rectal examination established an empty rectum.
The patient was ordered a range of initial laboratory and imaging investigations and follow-up diagnostics based on those findings (Tables and ). The abdominal X-ray () demonstrated a classical thumbprinting sign that was nonspecific but suspicious for clostridium difficile infection. Empirical antibiotics IV metronidazole and oral vancomycin were commenced for presumed clostridium difficile infection while awaiting for laboratory tests and histology results.
The patient's venous blood gas showed lactate of 4 mmol/L (normal range, 0.6–1.8 mmol/L) which prompted a CT abdomen. The CT demonstrated a pronounced colitis extending from the transverse colon to the sigmoid colon. When the patient did not respond to IV metronidazole and oral vancomycin, a flexible sigmoidoscopy was undertaken and showed nodular mucosa with white-yellowish adherent plaques with increasing severity from the rectosigmoid to the sigmoid (Figures and ). The histology from biopsies taken from various parts of the left colon was negative for cytomegalovirus (CMV) and clostridium difficile infection, but suggestive of biological medication effect.
Accordingly, the patient was treated as ocrelizumab-induced colitis and commenced on intravenous hydrocortisone. Her CRP was downtrending on hydrocortisone. However, serial abdominal X-rays demonstrated ongoing gaseous distension, and she continued having watery bowel motions. The patient was referred to a tertiary hospital and colorectal surgeons for medication-resistant biological medication-induced colitis. She subsequently underwent a total colectomy and ileostomy formation.


A 23-year-old man, without any past medical history, underwent open reduction, and internal fixation for a radial neck fracture and left olecranon fracture (Fig. ) sustained during a fall. He was referred to the rehabilitation department due to pain and a limited range of motion (ROM) of his left elbow 2 months following the injury. Physical examination of the left elbow in the clinic of the rehabilitation department revealed an active ROM of 40° to 60°, passive ROM of 40° to 60°, supination of 0° to 20°, and pronation of 0° to 30°. Physical therapy was arranged with therapeutic exercises including joint mobilization, stretch exercises to help increase elbow extension, as well as elbow flexion and extension with a sand bag and wrist supination and pronation with a stick following 15 minutes of infrared therapy.
After approximately 6 months of physical therapy, the pain and ROM in the elbow improved, with an active ROM of 40° to 100°, passive ROM of 5° to 110°, supination of 0° to 30°, and pronation of 0° to 35°. He was admitted again 9 months after surgery to undergo removal of the internal fixation, and was discharged home after 2 days. During admission for removal, an X-ray taken showed bony union of the fracture site and smooth cortical bone without obvious fractures around the previous injury site or the drill holes (Fig. ). After discharge, the patient remained under the rehabilitation program at our department and the symptoms gradually improved.
However, on 1 day, 5 months after removal of the internal fixation, the patient complained of left elbow tenderness with a “breaking” sound occurring during physical therapy. He was promptly sent to emergency room in our hospital and the results of a subsequent X-ray revealed a greenstick fracture of the left ulnar shaft (Fig. ). After discussion with our orthopedic department, a cross-elbow splint was applied. Two months after splinting, the tenderness and numbness of the elbow was alleviated, and callus and increased density of the ulnar shaft was identified on subsequent X-rays (Fig. ).