A 68-year-old male with an extensive medical history of alcohol and tobacco use, medication non-compliance, Graves’ disease treated with radioiodine ablation and resulting hypothyroidism, chronic obstructive pulmonary disease, hypertension, deep venous thrombosis with inferior vena cava filter placement, and bipolar disorder presented to the emergency room with alcohol intoxication and cough. The patient also reported subjective fever and chills at the time of presentation along with history of previous incarceration, shelter living, and homelessness. His initial chest x-ray showed probable pericardial effusion, which was later confirmed on chest CT scan (Figure ) and bedside echocardiography (Figure ). Chest CT scan also showed ground glass opacities in the bilateral lower lobes. The evaluation of patient’s presenting complaint of cough guided the way for the incidental finding of pericardial effusion on chest x-ray. Bedside ultrasound in the emergency room ruled out right ventricular collapse. Transthoracic echocardiography demonstrated early tamponade physiology, and the patient was hemodynamically stable. Based on the presentation, we suspected tuberculosis (TB) as the cause of his chronic cough. The patient was transferred to a negative pressure room for infectious evaluation. TB was ruled out after a negative purified protein derivative and QuantiFERON gold test. He was instead found to have been suffering from aspiration pneumonia after his sputum culture came back positive for Klebsiella and Serratia extended-spectrum beta-lactamase producing species. Poor dentition and usual alcohol intoxication made the patient at risk of recurrent aspiration of the oral bacteria.
The patient was prescribed levothyroxine 25 mcg daily for hypothyroidism in the past but he had run out of his medication several months ago. His TSH level of 31.42 μIU/mL (normal range: 0.4-5.5 μIU/mL) with undetectable free T4 and previous history of thyroid disease pointed towards uncontrolled hypothyroidism as the likely cause of his moderate pericardial effusion. The patient’s hemodynamic stability did not qualify him for the indication of pericadiocentesis. He was prescribed levothyroxine 150 mcg daily which resulted in the reduction of the TSH level to 14.17 μIU/mL in less than two weeks. The pericardial effusion was followed up with serial transthoracic echocardiogram, and the patient was discharged on the advice to follow-up with primary care physician.


In August 2018, a 10-year-old male Pomeranian–mixed breed dog from Pattani, a southern province of Thailand, was referred from a local animal clinic to our hospital at Prince of Songkla University (PSU) in Hatyai, Songkhla Province. At admission, the owner reported that seven days earlier, the dog had run away from home at night and probably got hit by barbed wires at a nearby army camp. In the morning, the dog was found with large dirty wounds around its neck and back. The dog was immediately taken to a local animal clinic for primary care. The dog was admitted and then given primary treatment as well as wound dressing daily. The primary treatment included oral amoxicillin–clavulanic acid (30 mg/kg) twice daily and oral carprofen (4 mg/kg) once daily. Four days later, the wounds got worse with progressive purulent discharge and odor. An additional antibiotic, metronidazole (18 mg/kg), was then given twice daily. The blood profile examined on that day showed a high number of white blood cells (22,400 cells/mL) and low platelets (33 × 109 PLTs/L). After seven days of treatments, the wounds continued to expand. The dog was then transferred almost 100 miles to PSU Animal Hospital, a teaching hospital in the region, for proper laboratory diagnosis and appropriate treatment.
At the second admission, a physical examination and laboratory testing were conducted. The physical examination revealed that the dog was slightly depressed with a high body temperature of 102.8 ๐F (despite treatment with the anti-inflammatory drug from the previous hospital), pale mucus membranes in its mouth, and severe seropurulent discharge around its large cervical wounds (A). Blood profile analysis revealed leukocytosis (35,940 WBCs/mm3), severe anemia (14.1% hematocrit), extremely severe thrombocytopenia (22 × 109 PLTs/L), slightly increased liver enzyme (ALP 192 U/L), and positive serological detections of two common bacterial pathogens, Ehrlichia canis and Anaplasma platys, by a rapid test SNAP 4Dx Plus (IDEXX Inc., Westbrook, ME, USA). The dog was then intravenously treated with enrofloxacin (10 mg/kg) once daily, aiming to kill the blood parasites as well as providing broad-spectrum antibacterial activity while awaiting the results from culture and biochemical tests. Three days later, a second complete blood count was suggested since clinical signs persisted. The blood profile still showed progressive severe leukocytosis (74,580 WBCs/mm3), thrombocytopenia, and increased liver enzymes. The culture results from the wound swabs revealed the presence of Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli, all of which were resistant to both previously used antibiotics, while the hemoculture grew Burkholderia pseudomallei (B), the causative agent of melioidosis.


An 85-year-old male patient with known history of severe coronary arterial disease presented for planned repair of his enlarging ductus arteriosus pseudoaneurysm. A previous computed tomography (CT) of the thorax (GE Brightspeed 16 slice Multi Detector CT (MDCT)) from December 2010 demonstrated the pseudoaneurysm which measured 3.6 cm × 3.3 cm in diameter. A follow-up CT angiogram of the chest (GE Lightspeed VCT 64 slice MDCT) in February 2016 demonstrated interval enlargement to a diameter of 6.1 cm × 5.5 cm (Fig. ). This included the peripheral thrombosed aspect of the pseudoaneurysm as well as the flowing opacified central portion. The flowing central aspect of the pseudoaneurysm measured 2.3 cm. The diverticulum component had a wide neck (1.6 cm) and created obtuse angles with the thoracic aorta (Fig. ). This diverticular aneurysm was oriented towards the left pulmonary artery, demonstrating that this was indeed a ductus arteriosus pseudoaneurysm. CT angiography (CTA) of the abdomen and pelvis performed concurrently showed severe iliofemoral tortuosity and advanced atherosclerotic calcific burden (Fig. ). A 5.1 cm infrarenal abdominal aortic aneurysm (AAA) that was directed towards the origin of the left common iliac artery was also demonstrated (Fig. b, c).
Endovascular stent graft repair was attempted. The preoperative CTA of the chest suggested that the proximal landing zone of the stent graft would quite likely include the origin of the left subclavian artery. Therefore, a left common carotid to subclavian arterial bypass with interposition ProPaten Graft (Gore, Flagstaff, AZ) was performed to avoid the probable left subclavian artery occlusion.
After the left carotid to left subclavian arterial graft was successfully placed, the right common femoral artery was exposed through a surgical cutdown and the vessel was accessed in a retrograde fashion. This access was to be used for insertion of a 24 French (Fr) introducer sheath used for the introduction of the Medtronic Talent thoracic aortic stent graft system (Minneapolis, MN, USA). Percutaneous access of the left common femoral artery was also obtained for the placement of a 5 Fr flush catheter for the purposes of angiographic control. However, given the previously described advanced common and external iliac tortuosity and severe calcific nature of these vessels combined with the AAA, the 24 Fr introducer sheath could not be successfully navigated distally into the abdominal aorta (Fig. d).
Endovascular coil embolization was performed two days following attempted TEVAR placement. Using right common femoral artery access, a 5 Fr flush catheter (Omni Flush, AngioDynamics, Queensbury, NY) was placed and thoracic angiography was performed. The DAD with its inferior extension of the large pseudoaneurysm component was well visualized (Fig. a). A 4 Fr directional catheter (MeritMedical, South Jordan, Utah) was then introduced into the pseudoaneurysm. Given the wide-neck characteristics of the DAD relative to the thoracic aorta, the junction of the diverticulum and the pseudoaneurysm was used as the “neck” and platform for stable endovascular coil placement. A series of eleven Azur 35 detachable coils (Terumo, Somerset, NJ) were placed in the following order: one 20 mm/50 cm framing coil (Fig. b), two 20 mm/39 cm coils, two 16 mm/32 cm coils, two 13 mm/24 cm, one 12 mm/30 cm, two 10 mm/19 cm and one 8 mm/13 cm. The loop of the initial framing coil slightly protruded into the diverticulum forming a “bridge” across the junction of the diverticulum and pseudoaneurysm. Follow-up thoracic angiography demonstrated no further flow into the pseudoaneurysm of the DAD (Fig. c).
The patient had no immediate complications from the coil embolization. He was taken to the operating room later that night for repair of a right groin hematoma. Ultimately, the patient recovered well and was discharged from the hospital on post-embolization day six. The patient did not return for a recommended three-month-follow-up CTA of the chest. He did, however, present to our facility over a year after the coil embolization, at which point his only concern was a non-healing foot ulcer. He died twenty-one months after the embolization from an acute myocardial infarction with severe underlying coronary artery disease.


A 48-year-old man (158 cm, 65 kg, BMI 26.04) who had undergone clipping after subarachnoid hemorrhage was hospitalized for convulsions at 5 months following initial surgery. VP shunt operation was scheduled. Chest CT showed no pulmonary bullae or blebs before surgery.
Induction of general anesthesia was uneventful. At 140 min, the anesthesiology resident noticed an increase in airway pressure (AP) (to 25 cmH2O) and the attending decided to proceed with anesthesia since no abnormalities on the patient side (change in pulse oximetry readings or abnormal sounds on auscultation) or on the circuit side (endotracheal tube occlusion, kinking, anesthetic machine malfunction) were found. Arterial blood gas analysis showed pH 7.444, PaCO2 35.2 mmHg, PaO2 147 mmHg, and SaO2 98.4%. Peak pressure stayed at 25–29 cmH2O. The attending concluded that increased AP was caused by patient’s position and/or patient’s body weight.
The surgery ended 40 min later and the asymmetrically deformed patient’s chest with distention on the right side was noticed after removal of surgical drapes. Soon after returning the patient’s head into the straight position, bucking occurred. The AP immediately increased and oxygen saturation dropped to 70%. The attending suspected tension pneumothorax, confirmed the diagnosis by absence of lung sliding on ultrasonography, and performed needle thoracentesis with an 18-G intravenous catheter under ultrasound guidance (Fig. a).
Following decompression, oxygen saturation returned to 100%. A chest X-ray taken a few minutes later revealed massive subcutaneous emphysema, right pneumothorax, and mediastinal shift to the left (Fig. b, c). After insertion of a chest drainage tube, the patient was extubated and transferred to the intensive care unit. Continuous air leakage was observed for few days postoperatively indicating intra-operative iatrogenic pleural and lung injury. The chest tube was removed on POD7. The patient was discharged and transferred to a rehabilitation hospital for further treatment on POD15.


An 83-year-old male patient with a medical history of benign prostate hyperplasia was admitted with left inguinoscrotal pain and swelling. Physical exam revealed a large left-sided irreducible inguinoscrotal hernia (ISH). A non-contrast abdominopelvic computer tomography showed a left hydroureteronephrosis with a dilated ureter included in a paraperitoneal ISH associated with left nephroptosis. Renal function was normal, with a creatinine level of 0.92mg/dl.
Subsequent surgical repair by hernioplasty with a synthetic mesh placement was performed in a multidisciplinary approach. Intraoperatively, we found a large paraperitoneal ureteral ISH with dilated gonadal vessels. Patient was discharged after 3 days without complications. The patient is free of symptoms after 3 months of follow-up and the IVU showed hydroureteronephrosis resolution.


A 29-year-old black African woman presented to the emergency department with headache and fever for 5 days. Brain imaging was normal, and lumbar puncture for cerebrospinal fluid (CSF) analysis showed a raised white cell count (WBC) of 31/mm3 with 95% lymphocytosis, elevated CSF protein, and borderline high CSF adenine deaminase levels of 18.1 U/L. CSF Ziehl–Neelsen stain, GeneXpert, and culture for Mycobacterium tuberculosis (TB) were negative. Blood tests are in accordance with . Her headache and fever resolved with oral paracetamol, and she was discharged with a diagnosis of aseptic meningitis.
However, she was readmitted with worsening neck pain and headache 2 weeks later and was found to have significantly enlarged cervical lymph nodes. Further evaluation with an MRI scan of the neck showed features in keeping with TB lymphadenitis. A repeat of laboratory workup (refer to ) remained negative. She also had a positive EBV IgG but with a negative serum IgM. A cervical lymph node was biopsied. Histopathological examination revealed necrotizing lymphadenitis with no granulomas (Figures and ). Since the histologic appearance was indistinguishable from that of TB lymphadenitis, the patient was commenced on TB treatment (ATT) and was reviewed in a clinic 3 weeks later and found to have improved significantly.
The slides were sent for a second opinion overseas (USA), where the cervical biopsy was noted to show marked architectural effacement with large areas of necrosis containing abundant apoptotic debris. The adjacent viable areas contained numerous histiocytes, small lymphocytes, occasional plasma cells, and immunoblasts (Figures and ). Hematoxylin bodies were not identified. Immunohistochemistry performed on the slides was CD20/PAX5 (B-cell marker)-positive, CD68 (histiocyte marker)-positive, and CD123 (plasmacytoid dendritic cells)-positive with a Ki of 67–60%.
These findings were in keeping with a diagnosis of histiocytic necrotizing lymphadenitis likely secondary to either KFD or SLE. However, given the patient was responding well to the TB therapy and she had screened negatively for SLE, she was continued on the treatment. Three months into her TB treatment, she was found to have an elevated thyroid stimulating hormone (TSH) of 47 pg/ml with low thyroxine and thyronine levels and positive antithyroid peroxidase and thyroglobulin antibodies in keeping with Hashimoto's thyroiditis. The patient completed 12 months of TB treatment and remained well and was discharged.
However, 5 months later, she presented to the infectious disease's clinic with a 1-month relapse of the same symptoms. She reported a history of travel to a malaria-endemic region 2 weeks prior and had taken a complete course of self-prescribed antimalarial medication with no resolution of symptoms. On examination, she had a temperature of 38°C but otherwise normal vital signs and large >1 cm bilateral nontender nonmatted upper cervical lymphadenopathy, but otherwise a normal physical examination with no meningism.
Investigations on this occasion are summarized in .
Interestingly, the repeat autoimmune screen revealed ANA positive with titers of 1 : 320 and a speckled pattern. Her ENA anti-SS-A/RO-52 was also positive. The remainder of her evaluation was unremarkable except for persistent leucopenia, anemia, and thrombocytopenia.
She was reviewed by the rheumatologist and diagnosed as a case of systemic lupus erythematosus after she met 4 components of the SLICC criteria which included thrombocytopenia, leucopenia, arthritis, and positive ANA. Her Anti-Ro antibody was also positive and even though not part of the SLICC criteria is still in keeping with the diagnosis of SLE. While in hospital, her fevers settled spontaneously with antipyretics. At the time of discharge, she was initiated on prednisolone, azathioprine, and hydroxychloroquine which she is currently on and is asymptomatic. She currently remains on follow-up in the Rheumatology clinic.


The patient is a 27-year-old male who was suffered from a traffic accident that fell into the ditch from the motorcycle. He was brought to the emergency department with severe right thigh pain. Physical examination revealed right thigh tenderness and limited range of motion of the right hip. Radiography with a plain view of the right femur and CT of the abdomen showed ipsilateral femoral middle shaft fracture AO 32B3 and Garden type II, Pauwel’s classification type III (73°), AO31B2.3, femoral neck fracture (Fig. a, b).
Surgical intervention of open reduction and internal fixation (ORIF) with PFNA II (10 × 380 mm; blade, 95 mm) was performed. (Fig. c, d) Fluoroscopic view during operation revealed well alignment of both femoral neck and shaft fracture. After a few days of observation in ordinary ward, the patient was discharged successfully.


The patient is a 67-year-old female who was a motorcyclist and crashed with a car. There was a loss of consciousness initially. She was brought to ER and an initial brain computed tomography scan revealed Subarachnoid hemorrhage at the right pre-pontine and Sylvian cistern. Besides, for right thigh deformity, radiography was performed and found the right femur middle shaft wedge fracture AO 32B2 with ipsilateral femoral neck fracture Garden type IV, AO31B2.3 and Pauwel’s classification type III (65°) (Fig. a).
Due to the traumatic SAH, she was intubated and admitted to NSICU for further close observation and management. After her clinical condition was stable, ORIF with long PFNA II (10 × 340 mm) was performed on day 7 after the traffic accident. Fluoroscopic view during operation revealed well alignment of both femoral neck and shaft fracture (Fig. b, c).


The patient is a 30-year-old male who had traumatic event of traffic accident. Radiography and CT of the pelvis were arranged and showed the right femur middle shaft transverse fracture AO 32A3 with ipsilateral femoral neck fracture Garden type III and Pauwel’s classification type III (72°), AO31B2.3. Besides, the right patella subluxation was also found (Fig. a, b).
Surgical intervention of ORIF with PFNA II (10 × 380 mm; blade,110 mm) was performed for the ipsilateral femoral neck and shaft fracture on the day of the trauma. Fluoroscopic view during operation revealed well alignment of both femoral neck and shaft fracture (Fig. c,d).


A 55-year-old Nepalese woman was admitted to our hospital with cholangitis. She had undergone surgery 11 years earlier for cholelithiasis, when a laparoscopic procedure was converted to an open one. Her postoperative course was complicated by biliary peritonitis, for which she underwent reoperation. Eleven years later, the patient presented with fever as well as pain over her right upper quadrant with jaundice for the last 4 weeks. Initially, she was admitted and managed conservatively with symptomatic relief. On further evaluation, she was icteric with moderate dilation of intrahepatic biliary ducts (IHBDs) and the common hepatic duct (CHD) with nonvisualization of the common bile duct (CBD) by ultrasonography. Magnetic resonance cholangiopancreatography (MRCP) revealed severe stricture at the CHD (CHD stump length 1.4 cm below hilar confluence) with grade II dilated IHBDs (Fig. ). Endoscopic retrograde cholangiopancreatography (ERCP) revealed a nondilated CBD with complete cutoff and no passage of contrast or guidewire above the stricture level, likely representing CHD stricture.
The patient underwent percutaneous biliary drainage (Fig. ), following which full symptomatic relief was achieved with resolution of cholangitis, including normal biochemical and hematological parameters (except alkaline phosphatase of 457 U/L and cancer antigen 19.9 of 86.7 U/mL). A diagnosis of Bismuth type II biliary stricture (Strasberg bile duct injury E2) was made, and bilioenteric anastomosis was planned.
The operative findings were dense adhesions with 15-mm-long remnant CHD (Fig. ) and small hepatoduodenal fistula, and the liver was grossly normal. A Roux-en-Y hepaticojejunostomy (HJ) was made in a single-layer duct to mucosa in a continuous manner using polypropylene 5-0 suture (Figs. and ). The postoperative period was uneventful with a normal T-tube cholangiogram (Fig. ), following which the abdominal drain was removed, and the patient was discharged on the sixth postoperative day. Six weeks after surgery, the T-tube cholangiogram was repeated, which showed a well-functioning HJ, and the tube was removed with normal liver function tests. The patient was doing fine through 10 months of follow-up.


A 53-year-old white man presented to our hospital with a 3- to 4-day history of progressive epigastric and right upper quadrant pain. He had chills but no fever, nausea, or vomiting. His past medical history was significant for hypertension, borderline diabetes, chronic obstructive pulmonary disease, and sleep apnea. His past surgical history included umbilical hernia repair. His family history was significant for bladder and colorectal cancer. He smoked one pack of tobacco per day for many years but did not use alcohol or recreational drugs. He had no known environmental exposures, and he was currently unemployed. Upon admission, his blood pressure was 97/71 mmHg, heart rate was 67 beats/minute, temperature was 97.8 °F, and weight was 285 pounds.
A detailed physical examination did not demonstrate any abnormalities in the cardiovascular, pulmonary, neurological, and musculoskeletal systems but was significant for tenderness in the epigastrium and right upper quadrant of the abdomen, which was itself soft and rotund with obesity. The patient’s white blood cell count was 15,700/mm3. His hemoglobin, platelets, chemistries, and liver panel results were all normal, as was his urinalysis.
Computed tomography (CT) showed fat stranding extending from the umbilical fissure, along the course of the falciform and round ligaments, anteriorly to the abdominal wall and inferiorly toward the umbilicus (Fig. ). Ultrasound (US) showed cholelithiasis without signs of cholecystitis or biliary dilation. A hepatobiliary scan showed a low ejection fraction (2%) of the gallbladder and a patent common bile duct. Esophagogastroduodenoscopy (EGD) showed only mild erythema of the proximal body and greater curvature.
Upon admission, the patient was treated empirically with piperacillin and tazobactam 3.375 g intravenously every 6 hours, and in addition, he was given intravenous hydromorphone and ondansetron as needed for pain and nausea, respectively.
Given his progressively worsening symptoms, he was taken for laparoscopic exploration. At operation, the falciform and round ligaments were severely inflamed and thickened, with adherent omentum (Fig. ). The falciform and round ligaments and a small portion of involved omentum were resected. His gallbladder was distended but not inflamed and otherwise grossly normal. Given his low ejection fraction and gallstones, his gallbladder was removed to prevent future gallstone disease.
Pathologic examination revealed hemorrhagic fat necrosis and fibrin thrombi of the omentum, with hemorrhage and inflammatory changes of the falciform and round ligaments. The gallbladder pathology revealed only minor, microscopic evidence of chronic inflammation and cholesterolosis.
The patient’s postoperative outcome was good, and he was discharged on the second postoperative day. He failed to return for a postoperative follow-up visit, but 1 year later, he presented to the emergency room of our hospital with unrelated complaints but no abdominal pain.


A 17-year-old girl, with Evans syndrome history (autoimmune hemolytic anemia and immunological thrombocytopenic purpura) treated with oral prednisone and IV immunoglobulins, presented with papulo-erythematous squamous, crusted and pruriginous skin lesions of the scalp, the trunk, the back, the arms, and the face with peri-orifical distribution (Figure ). She also had relapsing pustules of the legs and arms. A trunk lesion's biopsy showed spongiotic dermatitis. A pustule's histology showed ostio-suppurative folliculitis. Several pustule samples were positive for staphylococcus aureus and b-hemolytic-streptococci superinfection. Multiple antibiotic treatments improved skin lesions over short periods.
At the same time as Evans syndrome, she developed atypical colitis with a nonspecific lymphoid infiltrate on histology and anti-Saccharomyces cerevisiae antibodies positivity. Exhaustive immune explorations researching an immune deficiency or dysregulation syndrome type LRBA deficiency were negative. HTLV1 serology and PCR were negative.
Oral corticosteroids were started for skin lesions, colitis, and Evans syndrome and drastically improved these 3 conditions, but skin lesions relapsed below 15 mg prednisone/d.
For 7 years, eczematiform and pustular rashes persisted, punctuated by short courses of corticosteroids and antibiotherapies. When she was 24 years old, she presented isolated inflammatory polyarthralgia. Biological tests showed antinuclear antidouble stranded DNA (anti-dsDNA) antibodies and hypocomplementemia. She was diagnosed with SLE and hydroxychloroquine treatment was started (400 mg/d).
One year later, while she had stopped hydroxychloroquine, she had a SLE flare with hematological, cutaneous (Figure ), and articular involvement. In addition to previous immunological abnormalities, she had anti-Sm, RNP, ribosomal antibodies, and anticardiolipin antibodies and anti-beta-2-glycoprotein-1 antibodies. Skin biopsy of a fingertip lesion showed a vacuolar interface dermatitis consistent with acute lupus erythematosus. Combined treatment with corticosteroids (methylprednisolone dose iv 3 consecutive days, then prednisone 1 mg/kg) then oral corticosteroids and hydroxychloroquine (400 mg/d) plus low-dose aspirin (75 mg/d) induced complete remission. Steroids were progressively tapered, and the patient remained disease-free with 3 years follow-up.


The 63-year-old man was admitted for second opinion with the suspected diagnosis of a motor neuron disease. He was seen at three visits (July, August, and December 2018). The patient had been healthy until February 2018, but then developed progressive muscle weakness starting at his left proximal arm. In March 2018, he noticed ubiquitous fasciculations and generalized muscle wasting including his legs without paresis of lower extremities. In July 2018, that is, within six months, he developed paraparesis of both arms and also suffered from cramps in the shoulder girdle and hand muscles. By August 2018, the patient was severely impaired in everyday life activities. He had never experienced sensory symptoms or pain. The patient reported a tick bite in September 2017, however, without the development of an erythema migrans. Except for type II diabetes mellitus which was treated with metformin 1000 mg per day and a cervical spinal canal stenosis without signs of myelopathy, the patient did not have relevant diseases. No further regular medication was taken. The family history was uninformative with regard to neuromuscular diseases. He did not drink alcohol regularly and had stopped smoking 20 years ago.
At his first neurological examination, in July 2018 no relevant bulbar symptoms were found except for mild fasciculations of the tongue. Facial nerve functions and swallowing were normal. Tests for motor function revealed the following paresis according to the Medical Research Council Scale (MRC; results given as right/left side): head flexion 4/5, shoulder abduction 3-4/4−, shoulder adduction 4+/4+, shoulder internal rotation 4+/4−, shoulder external rotation 2-3/2-3, arm flexion 4+/4−, arm extension 4+/2-3, arm supination 4+/1-2, arm pronation 4+/4, hand flexion 5/5-, hand extension 5-/4+, finger extension 5-/4+, finger spreading 4+/4−, bilateral deficits in finger adduction and especially finger 5, thumb abduction 4/4, thumb adduction 5/5−, thumb flexion 5/4, and thumb extension 5/4−. So, asymmetric distal and proximal atrophic arm paresis (left > right) was found while the lower extremities were spared. Muscle tone was flaccid. Muscle atrophy was seen at the shoulder girdle and fasciculations at all four extremities. Deep tendon reflexes at the upper extremities were normal, while they were reduced at the lower extremities. Babinski's sign was negative. The sensory and coordination systems were spared. On the revised ALS Functional Rating Scale (ALS-FRS), the patient reached 43 (0-47) points.
Extensive laboratory tests were normal, except for mild increase in serum creatine kinase levels (224 [0-190] U/l). Diabetes mellitus was controlled with a current HbA1c of 7.2% (4%-6%) and mild glucosuria and ketonuria.
There was shown a motor and axonal neuropathy without conduction blocks. Axonal loss was found with reduction of CMAP amplitudes of the left ulnar nerve (distal stimulation: 11.0 mV, proximal stimulation below ulnar sulcus: 9.2 mV, and proximal stimulation above ulnar sulcus: 8.2 mV), left median nerve (distal stimulation: 2.9 mV and proximal stimulation: 2,7 mV), and left peroneal nerve (distal stimulation: 8.0 mV, proximal stimulation below fibular head: 3.7 mV, and proximal stimulation above fibular head: 3.4 mV). Distal motor latency and nerve conduction velocity as well as sensory nerve conduction studies were normal.
Electromyography (tongue, masseter, deltoid, interosseus dorsalis I, anterior tibial muscles, paravertebral muscles (th8 level), and femoral muscles) showed hints for chronic and acute denervation with spontaneous activity (fibrillations, positive sharp waves, and fasciculations; Figure ). The tongue was spared.
Motor evoked potentials did not show signs of pyramidal impairment or an involvement of the first motor neuron when obtained from the legs and the arms.
Cranial and spinal MRI did not show any definitive pathology. However, cranial MRI showed a slight increase in signal intensity along the pyramidal tract on the proton-weighted sequences. Additionally, the right median nerve was investigated using high-resolution ultrasonography (18 MHz probe, transversal plane) and showed normal cross-sectional area and echogenicity. All muscles investigated (biceps, triceps, flexor digitorum, and infra- and suprahyoidal muscles) ubiquitously showed deep and superficial fasciculations (Video ). Muscles of the upper extremities were atrophic and hyperechogenic.
Analysis of the cerebrospinal fluid (CSF) in August 2018 revealed a pleocytosis (27 [1-4] n/mm3) and increased protein (111 [0-50] mg/dL), albumin (89.3 [0-53] mg/dL), and lactate (2.7 [1.2-2.1] mmol/L) levels, as well as an increased albumin ratio (18.6 [9]). It is of note that the initial lumbar puncture was accidentally traumatic and hence showed erythrocyte contamination (43.200 [0-<1] n/mm3), which was first interpreted as causative for the pleocytosis. However, while virologic examination of CSF was normal, microbiological analysis surprisingly revealed positive IgM and IgG titers for antibodies against borrelia burgdorferi. Laboratory tests were performed in serum and CSF. First, an ELISA was done for screening and results were confirmed using an immunoblot. Serum tests (both with ELISA and immunoblot) were positive for IgG and negative for IgM. In line with recommended standards, the relevant antibody index was assessed, which was increased in terms of IgM antibody index 2.3 (<1.4)), while the IgG antibody index was normal. Furthermore, laboratory tests on VDRL, VZV, HSV1/2, and FSME were performed. Test results in CSF were each negative; in serum, a constellation indicative of past HSV and VZV infection was found and for FSME immunization, while results for serum VDRL were negative and therefore not further analyzed in CSF. Thus, the diagnosis of neuroborreliosis was made.


A 49-year-old caucasian female patient with a previous medical history significant for von Willebrand type one disease presented to a hand surgeon at our department of orthopedic surgery after sustaining a crush injury to her left fifth digit following a motor vehicle accident. Physical examination was notable for 30-degree flexion contractures of both the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the left fifth digit, associated with a substantial decrease in active and passive range of motion (ROM). The patient underwent an uneventful capsulectomy of the MCP and PIP joints with tenolysis of the flexor tendons of the left fifth digit. Given her adequate tolerance to the procedure, she was later discharged with an implanted infraclavicular PNC and a prescription for daily occupational therapy (OT), with the PNC being removed on the fifth day postoperatively.
At the sixth-week postoperative follow-up consultation, the patient described intense pain in her left fifth digit, which she characterized as often burning, sometimes aching and throbbing, with an average intensity of 7 out of 10 on the numeric rating scale (NRS). Additionally, she presented with diffuse edema of the whole fifth digit, did not show any improvements in passive ROM, and reported being unable to tolerate most exercises during OT sessions. At this time, passive ROM of her left fifth digit was still severely limited, being restricted to 30 degrees of flexion on the both the MCP and PIP joints. Additionally, she was unable to initiate active flexion of the MCP, while being able to perform an active flexion of 20 degrees of the PIP
After consulting with the regional anesthesia medical staff, a determination was made to submit the patient to a trial with an ulnar PNC, so as to assist with targeted pain relief and OT goals, as well as to ascertain for a possible CRPS type 1 diagnosis. The PNC was implanted under ultrasound guidance and was left in place for seven days. During the trial, the patient reported a decrease in the pain intensity score from 7 out of 10 to 0-1 out of 10 on the NRS.
Given the result of the trial, the patient was then submitted to a nuclear bone scan, which revealed increased radioactive tracer activity in the entire left fifth digit on blood pool and delayed imaging, which, in the context of her medical history, was consistent with a diagnosis of active CRPS type 1.
Given the patient’s medical history (symptoms and signs fulfilling the 2010 revised CRPS clinical diagnostic criteria proposed by the International Association for the Study of Pain), the successful trial with an implanted ulnar PNC, the anatomical region of radioactive tracer caption on the nuclear bone scan, and after consulting with the medical staff of our department of pain medicine, the patient was submitted to an uneventful ultrasound-guided implantation of a percutaneous PNS (Bioness StimRouter®, Valencia, CA) (Figure ) parallel with the trajectory of the left ulnar nerve just distal to the ulnar tunnel, with intraoperative stimulation of the nerve obtained at 1.0 milliamps [] (Figure ).
Two weeks after implantation of the PNS, the patient experienced a reduction in the pain intensity score from 7 out of 10 to 0-1 out of 10 on the NRS and was able to initiate pain-free active motion of her left fifth digit. At the 3-month follow-up consultation, the patient reported maintenance of the reduction of pain in her left upper extremity with the implanted percutaneous PNS, as well as improved performance in her daily activities.


A 74-year-old female patient presented to the hospital with a tumor on the posterior scalp that had grown rapidly within two months after a long-standing period over the past 10 years. Ultrasonography revealed a well-circumscribed solid mass with a diameter of 25 mm that was partly cystic with calcification. An excision biopsy was performed. Microscopic examination of the lesion revealed a well-demarcated but non-encapsulated dermal mass that had no contact with the superficial epidermis. The tumor showed two closely intermingled components composed of epithelial and mesenchymal malignant tissue (Fig. a–f). The epithelial components included basaloid tissue showing follicular differentiation where peripheral atypical basaloid cells transitioned to clear cells and showed degenerative substances at the center of the tumor (Fig. a). One area containing eosinophilic “shadow” cells surrounded by foreign body giant cells were observed with some foci of calcification, which was compatible with a remaining benign pilomatricoma (Fig. b). A cystic structure was present, which was focally covered with basaloid cells (Fig. c). The epithelial component was also admixed with areas of keratinizing atypical squamous cells, indicating squamous cell carcinoma (Fig. d). In contrast, the macrophage-rich mesenchymal components included pleomorphic spindle tumor cells as well as multinucleated pleomorphic giant cells (Fig. e), which was consistent with undifferentiated pleomorphic sarcoma. Part of the sarcomatous lesion also showed features of giant cell tumor showing elongated mononuclear cells and osteoclast-like multinucleated giant cells which resembled a giant cell tumor of the bone (Fig. f). The average mitotic indexes were 14 in one high-power field in the carcinomatous area, and 12 in 10 high-power fields in the sarcomatous areas. Atypical mitotic figures were observed frequently in the sarcomatous area. Vascular or perineural invasion was not observed. The restriction margin was negative.
The results of immunohistochemistry are shown in Fig. and Table . Both epithelial and mesenchymal components tested positive for P53 (Fig. a). The epithelial component tested positive for AE1/AE3 (Fig. b), CK5/6, and P40 (data not shown). The nuclear expression of P63 was intense in basaloid cells and showed partial staining in squamous cells (Fig. c). The mesenchymal tumor stained diffusely positive for vimentin (data not shown) and partially positive for SMA (Fig. d). P63 and AE1/AE3 also stained sparsely positive in the spindle cell element. Macrophages and osteoclast-like giant cells, but not tumor cells stained positively for KP1. A few tumor cells in both epithelial and mesenchymal components stained positively for S100. Based on the above findings, the epithelial component was consistent with pilomatrical carcinoma and the mesenchymal component had features consistent with undifferentiated pleomorphic sarcoma. Consequently, the tumor was diagnosed as one of a pilomatrical CS. The patient has been well without recurrence or metastasis for 45 months.
For further analysis, we investigated β-catenin and LEF-1 expressions via immunohistochemistry and exons 3, 4, and 5 of the CTNNB1 gene via polymerase chain reaction assay and sequencing. Cytosolic and/or nuclear staining of β-catenin, termed ‘abnormal type β-catenin expression’ in this study, was partially observed in both components, apart from the sarcomatous tumor component which showed a giant cell tumor pattern (Fig. a). LEF1 expression was oberved in nuclei of sarcomatous components but very few in carcinomatous components, which may be transitional cells between basaloid to squamoid (Fig. b). A CTNNB1 mutation was not detected in exons 3, 4, or 5 of the CTNNB1 gene. Both carcinomatous and sarcomatous components stained diffusely positive for P16 (Fig. c). Fluorescence in situ hybridization (FISH) analysis (Fig. , Table ) revealed an increase in the copy number of chromosomes 9p21 (CDKN2A, p16 gene), 3, and 7 in both components. A gain in the copy number of chromosome 17 was present in the sarcomatous lesion, whereas the change was minimal in the carcinomatous area, showing a pattern similar to the normal epithelium surrounding the tumor.


A 44 years old male presented with 4 weeks of fever, breathlessness. There was no weight loss (90 kg). Physical examination showed tachycardia 125 beats per minute, tachypnoea (36/minute), normal blood pressure (110/80 mmHg). Soft systolic murmur was heard in left parasternal space.
There was no obvious pericardial rub. Lungs had few rales. Abdomen was soft with no organomegaly. Hemoglobin was 11.9 gm/dl (range 12–16 gm/dl), WBC 7800/ µl (6000-10000/µl); platelets 414000/ µl (150000-450000/ µl); LDH (lactate dehydrogenase) 200 U/L (100-250); Blood Widal test excluded enteric fever. Sputum for AFB (acid fast bacilli) was negative for tuberculosis. Sonography showed bilateral pleural effusions, small pericardial effusion. There was no evidence of deep vein thrombosis on color doppler scan. FDG PET CT was performed using 7.7 mCi of 18F- fluorodeoxyglucose on 6 hours empty stomach. Scanning was done at 60 minutes using Siemens Horizon 16 slice PET CT system. The pericardium showed intense uptake of FDG in the anterior, inferior and right lateral walls. The anterior wall showed FDG avid thickening measuring 10×81mms standardized uptake value (SUV) 7.74. The inferior wall of pericardium showed thickening of 107×13mms with SUV value of 12.07. Few mediastinal lymph nodes were noted as follows: subcarinal node 17×13 mms SUV 3.86, left internal mammary node 17×6 mms SUV 2.58, right internal mammary node 8 mms SUV 2.81, left paratracheal 10 mms SUV 1.80, right paratracheal 10 mms SUV 3.24. Left supraclavicular node 19 mms SUV 2.53. Right level IV neck node 16 mms SUV 2.26 (). Bilateral moderate pleural effusions and small ascites were noted. The myocardium did not show focal increased FDG uptake (). Cardiac MRI was performed using T2 spin echo and TRUFI sequence on 1.5T Siemens Sempra MRI system. Sequential fusion of PET and MRI data was done on station. MRI revealed diffuse asymmetric pericardial thickening hyperintense on T2W corresponding to PET CT ().
In view of these findings a diagnosis of granulomatous disease involving the pericardium was made. Serum ACE (angiotensin converting enzyme) was recommended. The value was 72 U/L (normal 50). Tuberculin test was negative. Histology (pericardial window) showed non- caseating Granulomas, multinucleated Langhan’s giant cells and lymphocytic infiltrates ().
Steroids and empirical antitubercular treatment were initiated. Myocardial biopsy was not performed as FDG PET CT of myocardium was normal.


The proband is female, aged 2 years and 8 months, and is the only daughter of nonconsanguineous parents. The 35-year-old father and the 29-year-old mother reported gestation with high blood pressure and cesarean section with a gestational age of 41 weeks. The girl was born with a weight of 2860 g, length of 45 cm, and cephalic perimeter of 33 cm. The first convulsion of the child was manifested at 15 days of life as a generalized epileptic crisis, which was repeated 24 hours later. At 21 days, new seizures were characterized as focal seizures with secondary generalization and treatment with phenobarbital. The first neuropediatric assessment occurred at 4 months, showing delayed neuropsychomotor development, mild hypotonia, low weight gain, and cephalic perimeter of 36 cm (<−3 Z scores). The electroencephalogram, cranial resonance, and screening tests for inborn errors of metabolism were unchanged. The child was referred for genetic evaluation. At the age of examination, the patient showed some facial dysmorphic features as enlarged nasal dorsum, bulbous nasal tip, short columella, and long nasolabial filter. The treatment with phenobarbital was efficient with control of the epileptic seizures for approximately 1 year, when it presented decompensation of the convulsive conditions, making it necessary to change the anticonvulsant to oxcarbazepine and levetiracetam. The child started walking independently at 26 months, and at 2 years and 6 months of age, the child presented delayed motor development and language and high cognitive deficit.
Karyotyping from the proband was performed on metaphase spreads prepared from peripheral blood samples. The chromosomal analysis was conducted after GTG banding at 550-band resolution, and at least 100 cells were analysed (A). The karyotype showed results 46,XX,r(20). The parental karyotype was normal. At least 100 cells from each individual were analyzed. The DNA sample from the child was investigated using chromosomal microarray analysis (CMA) with a 60-mer oligonucleotide-based microarray with a theoretical resolution of 40 kb (8 × 60 K, Agilent Technologies Inc., Santa Clara, CA, USA). The images were analyzed using Cytogenomics v 2.0 and 2.7 with the statistical algorithm ADM-2 and a sensitivity threshold of 6.0 (B). It is recommended to provide confirmation of CMA results with other methods such as FISH or real-time PCR, especially for the refinement of breakpoints of structural chromosomal abnormalities. The authors pursued to perform it; but unfortunately, there is no sample left of this patient anymore, and the family is not available to obtain a new sample. The protein-protein interaction (PPI) metasearch engine STRING 10.0 () was used to create PPI networks based on 40 genes and gene predictions located in the deleted region from our patient (A). The list of genes was obtained from CMA analyses and subsequent research into the human assembly of February 2009 (GRCh37/hg19) [, ]. The parameters used in STRING were (i) degree of confidence, 0.400, with 1.0 being the highest level of confidence; (ii) 500 proteins in the 1st and 2nd shell; and (iii) all prediction methods enabled, except for textmining and gene fusion. The final PPI network obtained through STRING was analyzed using Cytoscape 3.5 []. The MCODE tool was used to identify densely connected regions in the final Cytoscape network. The PPI modules generated by MCODE were further studied by focusing on major biology-associated processes using the Biological Network Gene Ontology (BiNGO) 3.0.3 Cytoscape plugin []. The degree of functional enrichment for a given cluster and category was quantitatively assessed (p value) using a hypergeometric distribution. Multiple test correction was also implemented by applying the false discovery rate (FDR) algorithm [] at a significance level of p < 0.05. Finally, two major parameters of network centralities (node degree and betweenness) were used to identify hub-bottleneck (H-B) nodes from the PPI network using the Cytoscape plugin CentiScaPe 3.2.1 [].


The first admission
A 57-year-old man, with a history of hypertension, diabetes mellitus type 2, gout and chronic alcohol abuse, presented to the emergency department with lethargy, dysarthria and lack of coordination. He had been passing loose stools recently. His outpatient medications consisted of rosuvastatin, metformin, enalapril, amlodipine and hydrochlorothiazide. The patient was not evidently dehydrated on physical examination. Laboratory tests revealed hyponatremia (105 mmol/L) with low urine sodium and acute kidney injury (Table ). Potassium and glucose were within normal range.
At this point, we considered the symptoms to fit with symptomatic hyponatremia due to poor intake and hydrochlorothiazide use. We started an isotonic saline infusion and discontinued the hydrochlorothiazide. Serum sodium increased gradually (Figure ); we adjusted the infusion rate in response to fluctuations in the correction speed according to the European guideline []. The acute kidney injury restored fully.
During admission, the patient became increasingly confused, which we deemed to be an alcohol withdrawal delirium after ceasing to drink three to four beers per day. We treated the delirium with haloperidol and lorazepam. The neurologist’s examination revealed no abnormalities, aside from a slight tremor. Magnetic resonance imaging (MRI) of the brain showed no significant abnormalities (Figure ). Four days after attaining a serum sodium within the normal range, the symptoms of the delirium had improved substantially, and the patient was self-sufficient in activities of daily living. He was discharged with a three-day supply of haloperidol and lorazepam.
The second admission
The patient returned to the emergency department one week later. His confusion had worsened substantially since discontinuing the medication; he was agitated and hallucinating. He now required assistance with all activities of daily living. However, he had not consumed alcohol since before the previous admission.
The patient appeared apathetic, responded incoherently to questions and sometimes spoke unintelligibly. His vital parameters were normal, and the laboratory tests were unremarkable aside from an isolated elevation of gamma-glutamyl transferase of 201 (<55 U/L). His serum sodium was 143 mmol/L at this point. Under the preliminary diagnosis of persistent delirium resulting from premature discontinuation of haloperidol and lorazepam, we restarted haloperidol and lorazepam and admitted the patient for observation.
The patient deteriorated despite the medication. He fell twice during the night and developed myoclonus and dysphagia. Contrary to the first admission, neurological symptoms were clearly present at this point: ataxia, an abnormal plantar reflex (Babinski sign), dysarthria and possibly aphasia, indicating a disorder in the central nervous system. Because of the preceding severe hyponatremia and alcohol abuse, our differential diagnosis now included ODS and Wernicke’s encephalopathy. We excluded the latter when several days of high-dose intravenous thiamine failed to improve the neurological symptoms.
A few days later, the patient developed an aspiration pneumonia due to dysphagia, and he had to be transferred to an intensive care unit (ICU).
A second MRI of the brain (Figure ) was performed to look for ODS. In stark contrast with the first MRI, the second MRI revealed a markedly increased signal intensity in the pons characteristic for ODS. When the patient was ready for discharge, his dysarthria and dysphagia had improved substantially. He was transferred to a rehabilitation facility for further recovery.


The patient is a 34-year-old morbidly obese female with a 2.4-cm symptomatic gastric diverticulum confirmed by both esophagogastroduodenoscopy (EGD) and upper gastrointestinal series (UGI). The patient reports chronic gastroesophageal reflux disease (GERD), which is resistant to treatment with proton pump inhibitors. She weighs 260 pounds and is 5 foot 3 inches tall, with a body mass index (BMI) of 46. The patient has obesity-related comorbidities including hypertension, hypercholesterolemia, and fatty liver disease. She has a history of previous abdominal surgeries including a laparoscopic cholecystectomy and a laparoscopy for gynecologic evaluation. She has a family history positive for hypertension. She has no history of smoking, alcohol, or recreational drug use.
Preoperative workup included several studies such as a UGI, EGD, and an abdominal CT with contrast. She had Helicobacter pylori testing, routine preoperative blood work including a complete blood count (CBC) and complete metabolic panel, as well as cardiac, dietary, psychiatric, and pulmonary evaluation and clearance.
The preoperative UGI revealed a small hiatal hernia and a 2.4-cm gastric diverticulum as seen in Figures and 2. EGD confirmed the gastric diverticulum as well as findings of mild antral erythema with mild chronic gastritis (photos not available). The patient’s CT scan was unremarkable as evidenced in Figures and 4. Testing was negative for Helicobacter pylori. Routine blood work results were unremarkable.
The patient lost 20 pounds following a very low calorie liquid diet two weeks prior to surgery. On the day of surgery, the patient received antibiotic prophylaxis with 2 g cefazolin IV 60 minutes prior to surgery. Deep vein thrombosis (DVT) prophylaxis involved administering with 5,000 units of heparin prior to anesthesia, as well placing sequential compression device (SCD) boots bilaterally.
General endotracheal anesthesia was induced with the patient supine. The patient was then prepped and draped, and concurrent diverticulectomy and sleeve gastrectomy were performed in the following way: The abdomen was accessed by placing a Veress needle in the left upper quadrant. Insufflation was created to 15 mmHg. The Veress needle was removed and replaced with a 5 mm trocar and 30 degree laparoscope was placed. Under direct visualization, additional trocars were placed (right and left 5 mm lateral trocars, right and left 15 and 12 mm supraumbilical trocars). The surgeon was positioned on the patient’s right with the assistant on the patient’s left side.
The operating table was placed in reverse Trendelenburg position. The left lobe of the liver was retracted cephalically using a Nathanson. An orogastric calibration tube was then placed, the stomach was decompressed, and the orogastric calibration tube was removed and discarded. An Ethicon Harmonic scalpel was used to incise the peritoneum over the cardia. The plane between the cardia and the left crus of the diaphragm was bluntly dissected to expose the left diaphragmatic crus. The area was examined, and it was determined that no hiatal hernia was present. The Harmonic scalpel was then used to open the bare area over the liver. The lesser curvature of the stomach was examined; no abnormality was seen.
The vessels along the greater curvature of the stomach, including the short gastric vessels, were ligated creating a window of visualization of the posterior wall of the fundus. The 2.4-cm gastric diverticulum was identified 3 cm distal to the angle of His, oriented with the base towards the greater curvature of the stomach, favorable to resection concurrent with a sleeve gastrectomy as seen in Figure .
The stomach was marked 6 cm proximally to the pylorus. The vessels along the greater curvature of the stomach were dissected and sealed using a Harmonic scalpel. The stomach was lifted and all posterior attachments to the pancreas were sharply divided as seen in Figure . A 42-French bougie was placed. The stomach was stapled and divided using Ethicon Flex triple staple line power stapler with one black and four green 60 mm Gore bioseamguard reinforced staple loads to resect the greater curvature and fundus of the stomach including the gastric diverticulum and a 3-cm margin of unaffected tissue as seen in Figures -. The 15 mm trocar and specimen were removed. The bougie was removed and an intraoperative endoscopy was performed using a 5 mm Olympus Ultrathin gastroscope, revealing no areas of stenosis, leak, bleeding, or staple malfunction.
The trocars were removed, and the 15-mm incision was closed laparoscopically. Local anesthetic was injecting at the port sites. The skin was closed with staples, and sterile dressings were applied. The patient tolerated the procedure well, and there were no postoperative complications.
The patient’s postoperative course included pain management and DVT prophylaxis including heparin administration, SCD boots, and ambulation every four hours. On postoperative day 1, the patient underwent a UGI, which revealed normal gastric emptying without evidence of obstruction or extravasation as evidenced in Figure .
The patient was discharged on postoperative day 1 with no complications. One week after the discharge, the patient followed up in office with no complaints. She was tolerating liquids, taking her antacids as prescribed, and attending appointments with a registered dietician. Two weeks later, the patient returned to the office with no postoperative complaints or complications. At the three-month post-surgical appointment, the patient was tolerating regular diet and no longer requiring proton pump inhibitors. She lost 45 pounds since her consultation, currently weighing 215 pounds with a BMI of 38. The patient is scheduled for a six-month postoperative appointment at which she will obtain routine postoperative labs including a CBC, liver function test, kidney function test, vitamin B6, vitamin B12, folate, albumin, and prealbumin levels. At this appointment, she will also be counseled on discontinuing her antacids and encouraged to continue taking vitamin supplementation daily.


A 68-year-old, never-smoking woman with a history of pancreatic cancer and diabetes mellitus was referred for further evaluation of multiple ground-glass nodules (GGNs) on chest computed tomography (CT). She had been diagnosed with stage III pancreatic cancer and diabetes mellitus seven months before her initial visit to our department. She had undergone chemotherapy with the modified FOLFIRINOX regimen for four months. One month after the termination of chemotherapy, chest CT showed multiple new GGNs, some of which had pleural tags (Fig a,b). After a two month observation period, the GGNs had not improved. Moreover, positron emission tomography showed accumulation of 18F-fluorodeoxyglucose in several GGNs (Fig a–d). Lung metastases from pancreatic cancer was suspected.
The patient was asymptomatic and physical examination was unremarkable. On laboratory examination, serum C-reactive protein and KL-6 levels were not elevated. Transbronchial biopsy specimens of the right GGNs showed mild fibrosis and infiltration of lymphocytes, but no malignant cells (Fig a). Immunohistochemical analysis of the specimens showed that the lymphocytes consisted of more CD4+ than CD8+ cells (Fig b,c). The CD4+ cells did not include FOXP3+ regulatory T cells (Fig d). Bronchoalveolar lavage (BAL) fluid from the right middle lobe confirmed the increase in total cell number (23.5 × 104/mL), lymphocyte composition of 18% with no eosinophils or neutrophils, and a high CD4+/CD8+ ratio of 7.4 (Fig ). There was no evidence of other interstitial pneumonia and infectious diseases.
The patient reported that an oral probiotic supplement of L. paraplantarum had been taken since the diagnosis of pancreatic cancer along with vildagliptin. A drug-induced lymphocyte stimulation test, although considered a complementary examination, was 270% for vildagliptin and 560% for the probiotic supplement (reference, <180%). The GGNs disappeared shortly after both agents were discontinued (Fig c–f). She was diagnosed with vildagliptin-induced IP, possibly affected by the Lactobacillus probiotic supplement. Subsequently, the IP has not recurred for seven months. Written, informed consent for the publication of this case report was obtained from the patient.


A 17-month-old Japanese female was hospitalized due to high fever lasting for 4 days in August 2018. The present patient was born to non-consanguineous healthy parents as an extremely premature infant at 26 weeks of gestation with a birth weight of 956 g. She was well-developed after discharge from the neonatal intensive care unit. On admission, her height and weight were 75.0 cm (0.2 standard deviation [SD] for corrected age) and 9.3 kg (0.3 SD for corrected age), respectively. She was not on any medications. She had no contact with potential sources of infection in the 2 weeks prior to her admission. Her family members had been all well during the period. At the initial visit, she showed high fever of 40.4°C with infection ruled out as a cause. She displayed severe sunburn on large area of her body; first- and second-degree thermal skin injuries accounted for 32 and 29% of her body, respectively (). Brunet sunburn marks along lines of clothes were left on the skin of body trunk and face. The patient's skins where small bullae had been existed were peeling. Her mother mentioned that she had the sunburn following a 3 h outdoor play on the bathing beach without sunscreen 5 days ago. Maximum ultraviolet index on the day was 9 (very high). She did not receive any treatment for the sunburn. Blood examination showed a white blood cell (WBC) count of 14.0 × 109/L, with 68.0% segmented neutrophils and C-reactive protein (CRP) concentration of 15.3 mg/dL. Urinalysis and abdominal ultrasonography results were normal and rapid diagnostic test for adenovirus was negative. She was hospitalized and received intravenous cefotaxime, but symptoms did not improve. On the next day of hospitalization (5th day of illness), conjunctival hyperemia, erythema of the trunk of the body, redness of the lips, strawberry tongue, cervical lymphadenopathy, and redness at the Bacille Calmette-Guérin inoculation site emerged (). Fulfillment of the diagnostic criteria of KD prompted us to start 2 g/kg of IVIG and oral aspirin. Single dose IVIG led to a prompt response with defervescence. She was discharged from the hospital on the 15th day of illness without coronary artery lesions (CALs) (). Nose, throat, blood, urine, and stool cultures identified no causative bacteria. After her discharge, we measured the HMGB1, as a representative for DAMPs, in the conserved sera using an ELISA kit (HMGB1 ELISA kit II; Shino-test Corporation, Tokyo, Japan). As shown in , serum levels of HMGB1 were elevated during acute phase and continued to decrease during subacute phase; these results were consistent with the previous reports (, ).


A 4-year-old Bengali girl with no significant past medical history was brought to our emergency department with a 2-week history of right inferior eyelid oedema and hyperemia, treated firstly with dexamethasone and netilmicin by eye drops, and then with per oral amoxicillin clavulanate. Despite this treatment her symptoms rapidly worsened: on evaluation she had a voluminous and erythematous, fluctuant warm mass localized inferiorly to the medial canthus of the right eye, without purulent drainage by applying pressure over the lacrimal sac area or signs of conjunctivitis (Fig. a). She was in good general conditions and she had neither fever nor impairment in visual and ocular motility. No history of previous signs of NLD obstruction or facial trauma was reported. Ultrasound examination showed a well-circumscribed round lesion (dimensions 2,9 cm × 1,2 cm × 2,2 cm) filled by anechoic fluid with punctate echoes, confirming the diagnosis of PAD complicated by lacrimal abscess (Fig. b). White-cell count was 7810 per cubic millimeter (reference range, 7500 to 15,500); C-reactive protein and procalcitonin were in the normal range. Parents refused a head CT, so that we could not investigate the presence of conditions causing NLD obstruction. She was immediately treated with intravenous teicoplanin (20 mg/kg in the first day, followed by 10 mg/kg/day), and piperacillin/tazobactam (100 mg/kg/day). However, 3 days later the lesion showed a rapid and progressive colliquation with skin fistula and leakage of abundant purulent material. Culture of the drainage fluid grew methicillin-sensitive Staphylococcus aureus. On 5th day from admission, open DCT was performed with good esthetical result (Fig. ). Anatomopathological examination of surgical specimen ruled out tumors and malformations. She was discharged on postoperative day 6 on a 7-day regimen of per oral clindamicin (30 mg/kg/day). Follow up 2 weeks and 2 months after surgery revealed no swelling recurrence.


A 4-year-old boy was admitted to our hospital on July 20, 2021, because of recurrent abdominal pain and distention. He had scattered papules with central ivory atrophy or scabs on the trunk, lower extremities, and genital areas. The patient underwent partial resection of the small intestine due to small bowel perforation 1 month prior to hospitalization. At the same time, erythematous papules occurred. One week after the surgery, his abdominal symptoms recurred and worsened over time. Physical examination revealed scattered scarring papules of a mung bean size with central porcelain-white depression over the trunk, lower extremities, and genital areas, sparing the palms and face (). An esophagogastroduodenoscopy detected multifocal raised nodules in the duodenal bulb without significant abnormalities in the esophagus, cardia, gastric fundus or corpus, stomach angle, gastric antrum, and pyloric region (). And a biopsy of duodenal bulb demonstrated focal gland dilatation and inflammatory cells infiltration with focal deposits of mucin (). Biopsy of a characteristic lesion revealed thickened vascular wall with fibrinous necrosis and perivascular lymphocytes infiltration without mucin deposition in the dermis (). Autoimmune antibodies tests found antinuclear antibody and anticardiolipin antibody were positive. Dermoscopy of atrophic papules revealed a central white structureless area surrounded by hairpin vessels ().
Based on these findings, a diagnosis of pediatric MAP was established. The child began treatment with low-dose subcutaneous heparin (5,000 IU/day) and some symptomatic treatments. During the hospitalization, his digestive manifestations were relieved, while the skin lesions only improved slightly. One month later, the patient was lost to follow-up.


The patient was a Japanese woman in her 50s (). Previous screening mammography showed abnormalities, so she visited our hospital. In our mammography, we found an irregular mass at 4 o’clock and grouped amorphous calcifications having a background density at 2 o’clock in her left breast. Although the mass was identified by US, the calcifications were not. Vacuum-assisted biopsy for the mass revealed ductal carcinoma, and a breast marker (SenoMark™, Medicon, Osaka, Osaka, Japan) was inserted near the mass. Magnetic resonance imaging (MRI) showed a 6-mm oval mass with a breast marker at 4 o’clock in her left breast and a 9-mm linear enhancement at 2 o’clock in her left breast. 18F-FDG PET/CT performed for staging also showed two breast lesions, and the maximum standardized uptake values were 1.4 for the 4 o’clock lesion and 1.0 for the 2 o’clock lesion, which were visually higher than those of normal mammary glands.
The calcifications were also suspected to be malignant. Because the two lesions were in close vicinity of each other, the surgeons decided to skip the biopsy of the calcifications and remove them all at once by partial mastectomy. Although stereotaxic guidance for the purpose of marking was an alternative to localize the calcifications, this procedure has the drawbacks of patient posture and exposure to repeated mammography. Virtual navigator real-time US fusion imaging with 18F-FDG PET/CT was selected as a more noninvasive option compared with stereotaxic guidance. We imported the 18F-FDG PET/CT data into the US instrument (Aplio i900, Canon Medical Systems, Otawara, Tochigi, Japan). The breast marker inserted at the time of biopsy was used as the reference. The site corresponding to the accumulation of PET was apparently normal on US, but the morphology was suitable on CT, and we were convinced that it was consistent with the lesion. After placing skin markers on the surface of this lesion and the biopsied mass, a mammogram showed that these two lesions were correctly marked. Mammography of the surgical specimen did show that the two lesions had been successfully resected. Histologically, two non-consecutive invasive ductal carcinomas were found.


A 61-year old woman presented to our Department of Ophthalmology with complaints of floaters in the left eye for a week, with no complaints in the right eye. She denied remarkable systemic, ocular or familial history and was not taking any medication. She reported no symptoms of night blindness. The best corrected visual acuity was 20/20 in both eyes. Her extraocular motility and external examination were unremarkable. An anterior segment exam was normal in both eyes, without any signs of inflammatory responses of the retina and vitreous body. The intraocular pressure was 12 mm Hg in both eyes.
Ultra-wide field fundus photography revealed grayish retinochoroidal atrophic and pigment clumping lesions along the retinal vein and the fundus periphery, bilaterally. No changes were observed in both optic nerve heads and in the caliber of the retinal vessels (A). FA showed transmitted hyperfluorescence consistent with retinal pigment epithelium (RPE) degeneration in both eyes, with more extensive areas of choriocapillaris atrophy and blocked fluorescence in the pigment accumulation areas (B). ICGA showed a window defect with visualization of choriocapillary vessels and hypofluorescence corresponding to atrophic lesions (C). Spectral domain optical coherence tomography (SD-OCT) of PPRCA-associated lesions documented outer retinal thinning and intraretinal hyperreflective foci with underlying shadowing corresponding to the pigment clumps. Macular SD-OCT imaging revealed no abnormal changes. The circumperipapillary retinal nerve fiber layer was preserved. Wide-field fundus autofluorescence showed increased fluorescence with a crescent-like distribution surrounding the area of RPE atrophy along the retinal vein and a decreased fluorescence pattern spreading in a fin shape into the peripheral area, bilaterally. She had normal visual evoked potentials (A). The results of a pattern electroretinogram (ERG) were normal. A multifocal electroretinogram (mfERG) showed a markedly generalized reduced response density in the right eye and reduced amplitude paracentral areas in the left eye (B,C). The visual field and OCTA revealed no significant abnormalities (A,B).
The patient did not undergo any specific treatment for RPE or choriocapillaris atrophy. After a one-year follow-up, no clinical progression or changes were recorded in the fundus lesions.


A 64-year-old male was followed in our center for ITP diagnosed in 2002. His past medical history was remarkable for arterial hypertension, requiring treatment, and he had a peptic ulcer; there was no familiarity for hematological diseases.
At ITP onset, he showed severe thrombocytopenia; the increase in megakaryocytes in the bone marrow (BM) and the negativity of other tests, including the autoimmunity profile, allowed the diagnosis of ITP. He was treated with steroids, a first line with dexamethasone and a second line with prednisone, enabling only a partial response to be reached. Because of steroid dependency and multiple relapses, he started eltrombopag in September 2011, initially at the dose of 50 mg/day, then reduced to 25 mg/day. In May 2017, he showed hyperleukocytosis; the hemogram profile revealed a white blood cell (WBC) count of 25.9 × 109/L, consisting of 82% neutrophils, 11% lymphocytes, 4% monocytes, 2% basophils, 1% eosinophils, a hemoglobin level of 15.1 g/dL, and platelet count of 800 × 109/L, and the physical examination was negative and no hepatosplenomegaly was observed. After exclusion of infectious origin, he performed second-level exams. The BM smear showed increased cellularity, with a high number of megakaryocytes without blast cells (). The BM biopsy revealed a marrow cellularity of 90%, with markedly increased granulocytic series, normal megakaryocytes and reticulin staining. The karyotype was 46, XY, t (9;22) (q34;q11) in all the 10 metaphases analyzed. The real-time quantitative polymerase chain reaction showed the presence of the transcript p210 b3a2. Analysis of JAK2 V617F revealed a positivity of 0.7%, and the screening for CALR and cMPL mutations was negative. Therefore, a diagnosis of chronic-phase CML was made, with low Sokal (0.73), Hasford (695.51) and EUTOS (14) scores, and an intermediate ELTS (2.1065) score. The patient started treatment with imatinib, without cytoreduction and with hydroxyurea.
In the first phase, a balance of the two treatments, imatinib and eltrombopag, was necessary to normalize the platelet count. Eltrombopag was initially discontinued and then when the platelet count fell to 60 × 109/L, it was restarted at 25 mg every other day for the first week, and then a daily dose of 25 mg was able to reach and maintain a platelet count of around 150 × 109/L. The profile of WBC and platelets from diagnosis to complete hematological response with treatment is shown in . The patient continued treatment with imatinib and eltrombopag, and he reached cytogenetic remission and major molecular remission at 6 months. Following cytogenetic analysis, he showed a normal karyotype (46,XY), except for a deletion of chromosome Y in 3 cells out of 20 in September 2020. Since May 2018, the patient showed molecular remission (sustained MR ≥4, at last follow-up in June 2021 MR 5). Molecular analysis confirmed a low positivity for JAK2 (2.7%) in September 2017, which was reduced to 0.02% in December 2017, and then it remained negative (0%) thereafter. The results of the molecular analysis of bcr-abl and JAK2 are shown in . No adverse events were observed during the follow-up at 4 years. The platelet count was in the normal range, with eltrombopag 25 mg/day, until October 2021 when we tried to suspend it; the first week after the discontinuation of eltrombopag, the platelet count reduced, and in the following week it failed at 51 × 109/L. Therefore, the patient had to restart therapy with eltrombopag at the same dosage of 25 mg/day, obtaining normalization of the platelet count in two weeks this way.


A 16-year-old male patient had no significant past medical history. Ten days after receiving the second dose of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech, New York, NY, USA; EE.UU. & Mainz, Alemania), he began to have symptoms characterized by odynophagia, dry cough, and myalgia. He consulted an outpatient physician, and symptomatic treatment associated with prednisone 20 mg daily for five days was indicated, with a partial response to therapy. Two weeks later, he had oppressive chest pain to an intensity of 10/10, associated with nausea, vomiting, and palpitations, for which he consulted the emergency department. Upon admission, he was subfebrile (37.6 °C), tachycardic (112 beats per minute), and had high blood pressure (146/99), without other significant findings on physical examination. The study was complemented with an electrocardiogram without ischemic or rhythm alterations, ultrasensitive troponin I of 65 ng/L with a rise at two hours to 147 ng/L (upper normal limit less than 11 ng/L), and negative test for respiratory virus panel (including SARS-CoV-2). The patient was hospitalized with suspected myocarditis in this context, so he was admitted to the coronary unit for monitoring and further tests. Treatment was started with intravenous ketoprofen (50 mg every 8 h) and oral colchicine (0.5 mg every 12 h), with which there was progressive improvement in chest pain. Ultrasensitive troponin I continued to rise to a maximum of 6614 ng/L on the second day after admission, with a progressive decrease to 471 ng/L on the fourth day ( shows the progression of ultrasensitive troponin I levels).
The patient did not present electrocardiographic disorders during hospitalization. A transthoracic echocardiogram showed right and left ventricular function without segmental wall motion abnormalities, left ventricular ejection fraction of 60% (preserved ejection fraction), and valve disorders of the pericardium without effusion. Subsequently, cardiac magnetic resonance imaging was performed (a,b), which showed a slight increase in T1 times of the inferolateral and lower walls of the basal third of the left ventricle (on average 1150 ms), without alterations in myocardial perfusion in the sequence first step. In inversion recovery sequences after the administration of intravenous gadolinium, delayed subepicardial enhancement was observed in the inferolateral and lower walls of the basal third of the left ventricle (segments 4 and 5), in addition to a mild pericardial effusion. The findings described were compatible with myocarditis.
The diagnosis of myocarditis secondary to the administration of the anti-SARS-CoV-2 vaccine was made by adding elements of the medical condition and the findings in the laboratory tests. He was maintained with the initial symptomatic treatment and was discharged on the fifth day after admission, with ketoprofen 50 mg every 12 h orally and colchicine 0.5 mg every 12 h orally. At the outpatient check-up one month after discharge, he was in good condition with complete resolution of symptoms.


A 56-year-old woman with well-controlled hypertension presented with 20 lbs weight loss over the preceding three months, and on workup was found to have a large left renal mass in the renal hilum with multiple regional lymph node enlargement and bilateral pulmonary nodules (Figure ).
Her lab testing was significant for anemia with a hemoglobin of 9.1 g/dL. Her Karnofsky Performance Status score was 50. Renal and liver functions were normal, and calcium level was within the normal limits. Percutaneous biopsy of the renal mass was consistent with RCC with clear cell histology and no sarcomatoid variant. Using the Memorial Sloan Kettering Cancer Center (MKSCC) prognostic model for kidney cancer, she was found to be in the poor risk group. She was not offered CN and was started on systemic therapy with sunitinib. She tolerated sunitinib well and was compliant, but despite four months of systemic treatment, she continued to lose weight and on repeat imaging, the renal mass was shown to be enlarging, suggesting refractory disease (Figure ).
Her treatment was switched to temsirolimus and after two months of treatment, she presented to the emergency department with complaints of abdominal pain and distention, nausea, and vomiting of three days of duration. Repeat imaging indicated massive gastric distention and an increased size of the previously seen renal mass with a substantial central necrotic component (Figure ).
There was new direct infiltration of the renal mass into the stomach. Oral contrast was noted to extravasate from the stomach to the necrotic renal mass (Figure ).
The patient was unable to tolerate oral diet and opted for comfort care. She died in hospice care one week later.


A 65-year-old woman with severe, symptomatic aortic stenosis was admitted to a hospital for a TAVI. Her past medical history included type 2 diabetes mellitus, hypertension, diabetic chronic kidney disease, and dyslipidemia. The patient was well known to have a bicuspid aortic valve and had been followed up by echocardiography for 20 years. She complained of exertional dyspnea for the last three months and was admitted with severe pulmonary edema. Following careful assessment, it did appear that the primary precipitant for refractory pulmonary edema is severe aortic stenosis. The aortic valve area of a heavily calcified valve was only 0.3 cm2. Aortic valve replacement was a necessary therapeutic strategy to achieve hemodynamic stability and reduce in-hospital mortality.
Contrast-enhanced computed tomography (CT) scan was contraindicated because of her renal impairment. Noncontrast computed tomography would not have added significant diagnostic information to influence the treatment plan. Catheterization with limited contrast injections for coronaries, aortic root, and peripheral bed had provided the required details to plan the procedure with less contrast than computed tomography with contrast. In addition, noninvasive imaging with echocardiography has been used pre and postprocedure.
Coronary angiography was normal but revealed a single right coronary artery, with the left main coronary artery arising from the proximal right coronary artery (). This is a very rare congenital malformation which can be a lethal obstruction of the orifice of the right coronary artery occurring secondary to stenosis or because of coronary emboli during the deployment of a new aortic valve.
The distance of the single coronary artery to the bicuspid aortic valve was >12 mm and to the annulus of the valve was >20 mm, and to S5 was 25 mm ().
Echocardiography showed a severe bicuspid aortic valve stenosis with a gradient of 80/50 and a valve area of 0.3 cm (). Mild mitral regurgitation was observed, but there is no aortic regurgitation.
An electrocardiogram showed a normal sinus rhythm.
The patient was informed by the cardiac team, and it was agreed to proceed with an urgent TAVI procedure.
A direct implantation of Evolut Pro, 26 mm valve from Medtronic, was performed using a right femoral artery approach. Close monitoring of the single coronary artery with coronary angiography revealed no complications (). The left main coronary artery took its origin from the proximal right coronary artery. 2Proglide was used on the right-hand side, with 6F Angioseal on the left side; a hundred mL contrast medium was used.
The procedure was performed in the cardiac catheter laboratory under local anaesthesia plus sedation, and the patient remained hemodynamically stable throughout.
The patient was then transferred to the intensive care unit for observation and was discharged to the ward the following day. The patient remained in sinus rhythm and did not require a pacemaker postoperatively.
The post TAVI echocardiography showed a well-functioning aortic valve with trivial paravalvular leakage and no pericardial effusion. Ejection fraction was 70% with a peak and mean gradient after TAVI of 10/4. The mild mitral valve regurgitation apparent before the procedure remained unchanged.
The patient was asymptomatic and consequently discharged home after 3 days. The two-week follow-up showed a well-functioning valve with similar echocardiography. The electrocardiogram confirmed normal sinus rhythm, and the patient remained asymptomatic.


The patient is a 73-year-old female, the only child born to non-consanguineous parents, who presented with a history of late adulthood-onset PEO. At 60 years old, she underwent corrective strabismus surgery but complained of diplopia post-surgery. She also reported mild bilateral ptosis at 69 years old. Upon clinical examination she had marked PEO with subtle asymmetry, mild asymmetric ptosis (right>left), exotropia of the right eye and mild orbicularis oculi weakness (Figure A). Mild facial and proximal muscle weakness (MRC 4+/5) were also noted. Brain MRI was normal but there was no comment on the extraocular muscles. There was no reported family history of any eye movement or neuromuscular disorder. She has three asymptomatic children.


On October 17 and 18, 2018, a man aged 55 years who lived in Utah sought chiropractic treatment in Idaho for neck and arm pain thought to be caused by a recent work-related injury. On October 19, he was evaluated in the emergency department of hospital A for continued neck pain, nuchal muscle spasms, burning sensation in his right arm, and numbness in the palm of his right hand. He had no fever, chills, or other symptoms of infection. Dehydration was a concern because the patient reported he was unable to drink liquids because of severe pain and muscle spasms. The patient received a prescription for a steroid for muscle spasms and decreased sensation in the right arm and was discharged home.
Two days later, on October 20, the patient developed shortness of breath, tachypnea, and lightheadedness and reported he had not been able to sleep for 4 days; he was transported by ambulance to hospital B. The patient continued to have right upper extremity pain and severe esophageal spasms, causing him to refuse oral fluids. Because of his worsening symptoms and acute delirium, he was transferred to hospital C.
On October 21, the patient was intubated for airway protection. His symptoms worsened, with fever to 104.7°F (40.4°C), and he became comatose on October 25. Additional exposure history collected from family members included ownership of two healthy dogs and a healthy horse, and a recent grouse-hunting trip where the patient had dressed and cleaned the birds while wearing gloves. High-dose corticosteroid treatment was initiated for presumed autoimmune encephalitis. Because of refractory seizures beginning on October 26, he was transferred to hospital D on October 28, where steroids were continued. On November 3, an infectious disease physician was consulted at hospital D who noted that the patient’s symptom of spasms when swallowing suggested a possible diagnosis of rabies. When specifically questioned about the patient’s exposure to wild animals, family members reported extensive contact with bats that had occupied the patient’s home in the weeks before illness onset. The physician notified UDOH, which recommended collecting clinical specimens, including skin, saliva, cerebral spinal fluid (CSF), and serum. Rabies PEP was not indicated because of the advanced state of disease (). The patient continued to decline, supportive care was withdrawn, and he died on November 4, 19 days after symptom onset.
On November 7, antemortem specimens (serum, CSF, skin biopsy, and saliva) were sent to CDC for testing. CDC reported detection of rabies immunoglobulin M and immunoglobulin G in the CSF by indirect immunofluorescence assay. Rabies virus neutralizing antibodies were detected in serum (titer = 1:5,400; 43.2 IU/ml) and in CSF (titer = 1:250; 2.0 IU/ml), by rapid fluorescent focus inhibition test. No rabies virus antigen was detected in skin biopsy by direct fluorescent antibody (DFA) test, and no viral RNA was detected in skin and saliva by real-time reverse transcription–polymerase chain reaction (RT-PCR) (,).
CDC confirmed the presence of rabies virus antigen and RNA in postmortem brain stem tissue and cerebellum specimens by DFA and real-time RT-PCR, respectively. Antigenic typing with monoclonal antibodies to the rabies virus nucleoprotein, and phylogenetic sequence analysis indicated that the virus identified in the patient’s specimens was consistent with that of a rabies virus variant associated with Mexican free-tailed bats (Tadarida brasiliensis).


A 72-year-old male was admitted to our hospital after experiencing 2 months of intermittent fever, fatigue, and full-body discomfort. He was treated with antibiotics at a local hospital, but there was no improvement in his symptoms. The fever was apparently unprovoked. He had no known personal or family history of renal dysfunction. Physical examination indicated his blood pressure was 137/74 mmHg, heart rate was 100 beats/min, and cardiopulmonary and neurological functions were normal, with no costovertebral knocking tenderness. A urinalysis performed upon admission showed 3+ occult blood and his 24-hour urine protein level was 1.24 g. Serum biochemistry revealed the following: creatinine, 233.9 μmol/L; MPO-ANCA, 203.45 AU/mL, p-ANCA, 1:32, IgG, 22.90 g/L; IgG4, 7.230 g/L; complement C3, 0.82 g/L, erythrocyte sedimentation rate (ESR), 120 mm/h; and C-reactive protein (CRP), 141 mg/L. Routine blood analysis revealed the following: white blood cells, 11.45 x 109/L; hemoglobin, 72 g/L, and platelets, 400 x 109/L. Abdominal CT results were normal. A bone marrow smear showed signs of hyperplastic anemia. Granulocyte-poisoning particles in peripheral blood, vacuole degeneration, and, occasionally, late granulocytes were also present.
Among sixteen glomeruli examined in a renal biopsy, one had glomerular sclerosis, and eight had cellular crescent formations, we observed 2 cellular fibrinous crescents, and one renal bulb with segmental celluloid necrosis. Furthermore, there was evidence of local mild edema and diffuse inflammatory cell infiltration into the renal stroma, predominantly lymphocytes and plasma cells, macrophages, a small number of neutrophils and eosinophils, in addition to stromal foci with mild fibrosis. Immunofluorescent staining of three glomeruli indicated that these were highly C3-immunoreactive yet negative for IgA, IgM, IgG, C4, and complement F. Immunohistochemical analysis demonstrated that most of the IgG-positive infiltrating inflammatory cells were IgG4 immunoreactive, accounting for over 40% of the IgG-positive cells.
Our patient was admitted due to intermittent fever and fatigue. Upon admission, further testing revealed albuminuria, hematuria, elevated serum creatinine levels, serum IgG4 antibody levels three-fold higher than typical healthy values, and MPO-ANCA-positive serum. These serological indicators are characteristic of IgG4-TIN and ANCA-GN. The pathological results from a renal puncture indicated that 67% of the glomeruli were marked by crescent-shaped scars with segmental cellulose-like necrosis, with no obvious immune deposits, which is in line with the pathological characteristics of ANCA-GN (Fig. A). The renal stroma was slightly fibrotic with IgG4-positive plasma cell (representing more than 40% of IgG-positive cells) and mild eosinophil infiltration, which is in accordance with the diagnostic criteria for IgG4-RD (Fig. B–D). Additionally, immunofluorescence revealed diffuse granular mesangial deposition of C3 (Fig. E) and electron microscopy showed electron-dense sediment deposition in the subepithelial intramembranous and mesangial regions of the kidney (Fig. F). Therefore, the patient was finally diagnosed with ANCA-GN and IgG4-TIN with C3GN.
We prescribed methylprednisolone and cyclophosphamide (Fig. ). The patient had a history of tuberculosis and, therefore, rifampicin and isoniazid were also prescribed to prevent its reactivation and dissemination. Additionally, the patient was treated with Adalat, a calcium antagonist used for the treatment of hypertension, to manage his blood pressure and Recombinant Human Erythropoietin to improve anemia.
He continued with these treatments and received regular follow-up care at our hospital. The monthly follow-up showed downward trends in MPO-ANCA, 24-hour urine protein, IgG4, CRP, and ESR, but creatinine remained around 170 μmol/L (Fig. ). Due to eye discomfort, the patient stopped taking methylprednisolone 6 months after initiating treatment. In the seven month follow-up period, no recurrence of the disease was observed.


An 18-year-old woman visited our hospital with a 1-year history of TA with intermittent claudication of the left leg. She presented with low-grade fever in 1 month prior to the current visit. There was no history of dyspnea, palpitations, dizziness, visual disturbances or carotidynia. She visited a local hospital and also reported claudication of the left leg. Clinical examination revealed bruits over the left femoral arteries, and laboratory data indicated increased levels of C-reactive protein (CRP). She was diagnosed with TA according to the European League Against Rheumatism (EULAR) criteria for TA.[ Initially, she was treated with oral prednisolone (PSL) (40 mg/day) and the increased levels of CRP were normalized. Finally, PSL was tapered to 10 mg/day. She was referred to our hospital for maintenance therapy due to movement problems. In the first visit to our hospital, intermittent claudication improved partially, however she recognized claudication symptoms after walking more than 100 m.
Upon physical examination, the pulse rate was 88 bpm. Radial pulses were normal and equally palpable on both sides. A bruit was audible over the inguinal region on the left side without any carotid, renal or abdominal bruits. Hematology and biochemistry (Table ) revealed no abnormality except increased serum amyloid A (SAA) (53.4 μg/mL) and CRP level (1.26 mg/dL). Antinuclear antibodies (ANAs) were positive with low titers (1:80), and anti-neutrophil cytoplasmic antibodies (ANCAs) were negative. Enhanced computed tomography (CT) showed the stenosis of the left femoral artery (Fig. , case 1).
Owing to sustained intermittent claudication and relapse of increased levels of CRP, additional immunosuppressive treatments were required. We decided to increase the dose of PSL (10 mg/day → 20 mg/day), and the increased levels of CRP fell to within normal ranges. However, intermittent claudication was not controlled completely by GCs therapy, and elevated levels of SAA (20.7 μg/mL) were still observed. Hence, we introduced TCZ treatment in combination with maintenance GCs therapy. We tried to taper the PSL dose under the concomitant TCZ treatment with stable dose (subcutaneous injections, 162 mg/week). Serum levels of SAA were normalized (<2.5 μg/mL) within 3 weeks from the start of TCZ treatment. During this treatment periods, PSL dose was gradually tapered. Six months after starting TCZ, contrast-enhanced CT revealed a marked reduction of stenosis in the left femoral artery. Also, the ankle–brachial index (ABI) showed an increase in blood pressure of the lower extremities (Fig. , case 1). One year after starting TCZ treatment, the patient remained asymptomatic even after walking >2 km and there are no relapsing signs of TA. Serum levels of interleukin (IL)-6 (measured using a Human IL-6 ELISA kit; R&D Systems, Minneapolis, MN) showed high levels (27.5 pg/mL) before initiation of TCZ treatment. Serum levels of IL-6 increased transiently, but declined to the lower levels (10–20 pg/mL) at 12 weeks from the start of TCZ treatment (Fig. ). TCZ treatment had been continued and there was no TCZ-related adverse effect at the time of this writing. Doses of PSL were tapered gradually to the maintenance dose (11 mg/day), which was accompanied without disease flare.


A 16-year-old woman presenting with low-grade fever, general fatigue, headache and intermittent claudication was referred to our hospital. One year before the current episode, she had suffered from headache, increasing weakness, and claudication in both legs. She had visited a local hospital, and the increased levels of erythrocyte sedimentation rate and CRP were pointed out. Ultrasonography of the cervical region was undertaken to look for inflammatory changes. It revealed a characteristic, homogeneous and circumferential thickening of the wall of the entire left common carotid artery. She was referred to our hospital for further examination.
Upon admission, physical examination revealed discrepancies in blood pressure (in mmHg) in the right arm (129/53), left arm (136/58), right leg (54/27) and left leg (53/37). Laboratory data (Table ) revealed anemia (Hemoglobin 10.5 g/dL) and increased CRP concentration (4.1 mg/dL). ANAs were positive with low titer (1:160), but ANCAs were not detected. Enhanced CT revealed significant thickening of the aortic-artery wall and both carotid arteries. Also, there was severe stenosis of both femoral arteries (left >right) originating from intermittent claudication (Fig. , case 2).
The patient was diagnosed as TA according to the EULAR criteria for TA.[ She was started on PSL (50 mg/day) and antiplatelet therapy (cilostazol, 200 mg/day). The CRP concentration and ESR returned to normal values, and her intermittent claudication was improved partially. However, serum levels of SAA were not normalized (11.3 μg/mL). Therefore, we started TCZ (subcutaneous injections, 162 mg/week) therapy in combination with GCs treatment. After TCZ therapy, the increased levels of SAA declined to <2.5 μg/mL. Repeated imaging revealed significant improvement in the luminal diameter of the both femoral arteries, and arterial stenosis was decreased significantly. Also, the ABI showed an increase in blood pressure of the both lower extremities (Fig. case 2). TCZ treatment had been continued with same dose, which permitted tapering of PSL to the maintenance dose (13 mg/day) over 17 months. There was no TCZ-related adverse effect at the time of this writing. Similar to case 1, elevated circulating IL-6 was declined (21.8 pg/mL → 3.2 pg/mL) at 12 weeks after the start of TCZ.