A 26-year-old gentleman with a past medical history of HIV and schizoaffective disorder presented with left arm pain after a physical assault. He had been on antiretroviral therapy for one year with CD4 count 227 (500-1200 cells/m3) and an undetectable viral load. He had no recent sex partners in the last six months, no pets, and no recent travel. History was significant for a recent physical assault 16 days before this admission, resulting in a left forearm skin abscess. He underwent surgical irrigation and debridement of left forearm abscess and completed a two-week course of antibiotic treatment, initially intravenous vancomycin followed by oral trimethoprim/sulfamethoxazole. Then was transferred to a rehabilitation facility.
On the first day following discharge, the patient became septic again and was readmitted to the hospital. Initial vital signs on admission revealed hypotension with blood pressure 85/45 mmHg (90/60-120/80 mmHg), tachycardia with heart rate 123 bpm (60-100 bpm), and fever with temperature 39.1 C (36.5-37.2 C). Oxygen saturation was normal. Physical exam showed erythema around the surgical wound without purulence or fluctuance to suggest an abscess on the left forearm. A plain radiogram of the left forearm showed no evidence of fracture, Computed tomography (CT) was only suggestive of hematoma. Initial laboratory tests revealed a pancytopenia with hemoglobin 6.7 g/dL (13.5-17.5 g/dL), white blood cells 2.0/mm3 (4.5-11.0/mm3), and platelets 74 (150-400/mm3). Creatinine on admission was within the normal range, 1.05 mg/dL (0.6-1.2mg/dL).
The patient was initially started on cefepime and vancomycin for presumed sepsis secondary to the infected surgical wound on the left forearm. Despite the initiation of broad-spectrum antibiotics, he continued to experience spike high fevers >39C and developed septic shock requiring intensive care unit admission. Bacterial and fungal cultures from the blood and surgical wound were negative. COVID-19 polymerase chain reaction (PCR) was negative. Viral quantitative PCR testing for Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were negative, as was nasopharyngeal swab PCR for respiratory viruses including influenza, parainfluenza, and human metapneumovirus. A CT abdomen revealed mild hepatosplenomegaly. Rheumatological studies including anti-double-stranded DNA, antinuclear antibodies (ANA), antineutrophilic cytoplasmic antibody (ANCA), and extranuclear antibodies (Ro, Sm, RNP, La, Scl-70, Jo) were negative. Complement levels were reduced, C4 was 9 mg/dl (16-48mg/dl) and C3 was 46 mg/dl (80-160mg/dl).
The patient’s pancytopenia continued to worsen, and he was transfused multiple units of red blood cells. Given the continued pancytopenia of unidentified cause, bone marrow biopsy was performed. It revealed 80% cellular marrow with myeloid hyperplasia, plasmacytosis, dyserythropoiesis and erythrophagocytosis. Laboratory data at that time showed hemoglobin 6.7 g/L (13.5-17.5 g/dL), absolute neutrophil count 0.8 (3-5%), platelets 34 (150-400k/mm3), creatinine 2.1 mg/dL (0.6-1.2mg/dL), LDH 172 u/L (<150mg/dL), triglycerides 243 mg/dL (35-160mg/dL), D-dimer 23.43mg/L (<0.46mg/L), ferritin 8355 mg/dL (15-200 ng/mL), interleukin 2 receptor (CD25) 4370pg/mL (<2500pg/mL), and fibrinogen 337. Given this constellation of clinical symptoms, laboratory abnormalities, and bone marrow findings, the patient was diagnosed with HLH based on the HLH-2004 diagnostic criteria as demonstrated in Table [].
On day 17 of admission, HLH treatment was initiated with etoposide and dexamethasone as outlined in the HLH-2004 protocol. Cyclosporine had ultimately deemed a poor therapeutic option due to multiple comorbidities. The patient was severely cachectic and required enteral nutrition via tube feeds. His course was further complicated by hospital-acquired infections including Clostridioides difficile diarrhea and central line-associated bloodstream infection. Although the patient initially showed some clinical improvement after immunosuppression with declining ferritin, his pancytopenia subsequently worsened and he succumbed to his disease two months after he was admitted.


The patient was a 41-year-old woman with a height of 166 cm and a weight of 58 kg. In January 2019, she fell indoors and injured her face and visited a hospital for medical treatment. Her chief complaint was trismus. A close examination of the head at the head and neck surgery department showed no abnormal findings. She was referred to our department for detailed examination and medical treatment for a suspected mandibular fracture. Her first visit to our department was on the following day. Her family history was unremarkable. Facial findings on the first visit included mild swelling and reddening in the right preauricular region. The intraoral finding was displacement of the median line of the mandible to the right. The right molar was also in early contact, and the left molar had an open bite. Trismus was observed, and her mouth opening capacity was 10 mm between the upper and lower central incisors. A panoramic radiograph showed a right mandibular condylar base fracture (subcondylar fracture, Lindahl's classification []) (). An X-ray of the head (P-A) showed a right mandibular condylar dislocation fracture (displacement fracture, Maclennan's classification []) (). Computed tomography (CT) imaging showed a right mandibular condylar base fracture and lateral dislocation of the fracture fragment (). No fractures were observed elsewhere. No fractures of the teeth and of the alveolar bones of the upper and lower jaws were seen. Amoxicillin 750 mg/day was prescribed for 3 days to prevent infection, and acetaminophen 500 mg was prescribed for pain on an as-needed basis. Because she hoped for early functional recovery, open reduction and internal fixation, rather than a nonsurgical approach, were chosen. The patient was consulted on the treatment policy.
Nine days after the first visit, open reduction and internal fixation procedures were performed on the right mandibular condylar fracture under general anesthesia. During surgery, 1 g of cefmetazole sodium was administered to prevent surgical site infection. The skin incision was designed to be 5 mm caudal to the inferior margin of the mandible and 5 to 7 mm posterior to the posterior margin of the mandible to include the mandibular angle. The incision line extended more posteriorly than Wilk's skin incision [, ]. Thus, an incision line with a total length of approximately 5 cm was made (). Subsequently, a subcutaneous cut of approximately 2 cm was made in the skin along the platysma fascia. Delamination was performed between the subcutaneous and platysma fascia. The platysma was located and incised to the depth of the masseter fascia; the incision was 1 cm cranial from the mandibular margin in the anterior direction and 2 cm cranial from the mandibular margin in the posterior direction. Wilk and Biotchane [, ] made an incision up to the masseter muscle; however, in the present case, an incision was made only in the platysma muscle, and the masseter fascia was delaminated approximately 2 cm further cranially along the masseter fascia. The platysma was thin, with the masseter fascia immediately inside the platysma (). A buccal muscle branch that was running along the masseter fascia was found and retracted cranially to avoid injuring it. Next, the masseter fascia was delaminated towards the posterior margin of the ramus. While proceeding with the delamination towards the posterior margin of the ramus, the parotid gland was encountered, and delamination was performed between the parotid gland and the masseter fascia using a Metzenbaum scissor. A muscle retractor was applied to the anterior margin of the parotid gland to slight traction of the parotid tissue backward. The posterior margin of the parotid gland was located by inserting a reverse warping muscle retractor at the posterior margin of the ramus followed by a gentle displacement of the parotid gland posteriorly. A periosteal incision was made in the posterior margin of the ramus by a round-edged knife. Next, the periosteum on the medial and lateral surfaces of the ramus was delaminated by a periosteal elevator, and the fracture site was reached. A muscle retractor was inserted on the anterior side, and the masseter muscle was slightly extruded anteriorly to permit the localization and observation of the fractured site. A protector was inserted inside the mandibular ramus; a hole of approximately 2 cm was drilled from the lateral side on the caudal side of the fracture line by a steel bar. A 0.5-mm-diameter metal wire was passed through the hole (). An assistant attempted to reduce the fractured fragment by pulling the metal wire and the ramus downward (). After reducing the fractured fragment, plate fixation was performed. A MatrixMANDIBLE Subcondylar Strut Plate (Depuy Synthes, Switzerland), developed for mandibular condylar fractures was used for the fixation () []. The surgeon manually confirmed the patient's jaw movements. The surgeon manually opened and closed the patient's jaw. In addition, the surgeon manually moved the patient's jaw from side to side. And after confirming the absence of occlusion, a periosteal suture was placed with an absorbable thread. The platysma was also sutured, followed by the dermis. The skin was sutured with a nonabsorbable thread. Finally, Dual-Top anchor screws (Jeil Medical Corporation, Korea) were placed in the maxilla and mandible for postoperative intermaxillary traction, and that completed the procedure. There were no abnormalities during the surgical procedure.
Cefmetazole sodium 2 mg/day was administered for 48 hours after surgery to prevent postoperative infection, and acetaminophen 1000 mg was prescribed for pain on an as-needed basis. The reduction and fixation were confirmed on panoramic and head X-rays (P-A) a day after the surgery (Figures and ). No postoperative dysfunction such as facial paralysis was observed. From the day after surgery, elastic was used for intermaxillary fixation to control mouth opening. Two weeks after the surgery, the intermaxillary fixation was released. She started self-opening exercises involving daily horizontal movements of the lower jaw forward and to the left and right and vertical movements involving opening and closing of the mouth. Approximately one month after the surgery, her mouth opening capacity recovered to 30 mm between the upper and lower central incisors. By 2 months after the surgery, her mouth opening capacity had recovered to 40 mm. Three months after the surgery, she recovered and had no interference with her daily life. No facial deformity, wound infection, or scarring was observed.


A 59-year-old female nonsmoker presented with left-sided headache, disorientation, and confusion starting a few hours before presentation in the emergency department (ED). A week before that, she had abdominal pain, nausea, and multiple episodes of vomiting and diarrhea. A few days later she complained of frequent episodes of moderate left-sided throbbing headaches associated with nausea. In addition, her symptoms were unresponsive to analgesic medications including diphenhydramine and a combination tablet (aspirin/paracetamol/caffeine). She had gone to an outside hospital and had a computed tomography (CT) scan of head without contrast that was negative and then she was sent home. However, she continued to complain of headaches. In the morning on the day of presentation, her left-sided headache became more severe, and she became disoriented, confused, and off-balance. She denied any fever, seizures, loss of consciousness, shortness of breath, chest pain, or palpitations. She also denied any history of head trauma, coagulopathy, or intake of steroids or any contraceptive medications.
Her husband drove her to the ED where she was fully conscious, oriented with a Glasgow Coma Scale (GCS) score of 15 and her vitals were stable except for asymptomatic bradycardia. Her neurological examination didn’t show any speech, motor, or sensory deficits and her reflexes were equal bilaterally. She had head CT without contrast showing hyperdensity along the tentorium on the left with associated hypodensity in the posterior temporal lobe on the left as shown in Figure , and this raised a concern for small volume infarcts in the posterior left temporal lobe with possible underlying petechial hemorrhage. She had CT angiography (CTA) of the head that showed no evidence of large vessel occlusion, significant intracranial stenosis, aneurysm, or vascular malformation. She was admitted to the ICU.
The neurosurgery team was consulted that recommended CT venography (CTV) of head, which showed widely patent right transverse and sigmoid sinuses, while there was no contrast identified within the transverse or sigmoid sinus (Figure ). It also showed that the left transverse sinus is likely small in caliber as suggested by the somewhat small in caliber jugular canal (Figures , ).
The patient was started on a heparin drip; the six-hour follow-up head CT hadn’t changed, consistent with dural venous sinus thrombosis and associated developing left temporal lobe infarct. The 24-hour follow-up CT of head without contrast didn’t show any signs of hemorrhage. The patient was then started on warfarin and heparin drip for bridging until therapeutic international normalized ratio (INR) was established. Thrombophilia workup was ordered including lupus anticoagulant, factor V Leiden, factor II activity, protein S, and anticardiolipin Ab that were all within the normal ranges.
The five-week follow-up CTA/CTV of head showed re-canalized but diminutive left transverse sinus with a widely patent right transverse sinus and right sigmoid sinus. Also, it showed diffusely diminutive left internal jugular vein with dominant right internal jugular vein suggesting that the left transverse/sigmoid sinuses were chronically diminutive.


A 29-year-old male patient presented to the ED with migrated right sided abdominal pain for 2 days. He reported rigors and fever up to 39 °C (measured orally at home), nausea, and vomiting, but no change in defecation. His medical history was unremarkable and he took no medication.
On physical examination, there were no signs of acute distress. He had a temperature of 37.2 °C, heart rate of 95 beats per minute, a blood pressure of 130/80 mmHg and saturation of 99% on room temperature without tachypnea. There was local tenderness in the right upper abdominal quadrant upon palpation without guarding. No jaundice was observed, and no abnormalities were found on auscultation of heart and lungs. Laboratory results showed elevated infection parameters (leukocyte count 11.1 × 109/L, CRP 63 mg/L) and liver function tests (ASAT 208 U/L, ALAT 212 U/L, AF 50 U/L, GGT 93 U/L, total bilirubin 34 U/L, conjugated bilirubin 13 μmol/L). LDH was slightly elevated (305 U/L) and platelet count was slightly decreased (128 ×109/L). The estimated glomerular filtration rate was normal (eGFR 80 mL/min, creatinine 108 μmol/L) with a BUN of 8.7 mmol/L. Urinalysis was positive for albumin and urobilinogen. Otherwise, laboratory results were normal. An abdominal ultrasound showed an enlarged appendix with fat-infiltration without signs of perforation. The patient was started on ceftriaxone (2000 mg once daily) and metronidazole (500 mg three times daily) after three sets (aerobic and anaerobic) of blood cultures were obtained. A laparoscopic appendectomy was performed on the same day, where a gangrenous appendix localized on the inferior liver border was found (possibly explaining the elevated liver function tests).
One day after admission, all six blood cultures were found positive for both Klebsiella pneumoniae and Staphylococcus aureus (S. aureus) susceptible for ceftriaxone. Thorough re-assessment and physical examination revealed no other infectious focus, no clinical stigmata of endocarditis, and no new cardiac murmurs. Transthoracic cardiac ultrasound (TTE) showed no signs of valvular vegetation. On the second day after surgery, the fever increased (38.6 °C) and the patient reported increasing general malaise. The antibiotic regime was switched to meropenem 1000 mg three times daily after control blood cultures were drawn in order to cover potential extended spectrum beta-lactamase (ESBL)-producing bacteria. After this, the fever subsided, and the clinical condition improved. An abdominal ultrasound was performed on the 4th day after surgery without signs of complications. The patient was discharged in good condition on the 8th day after admission with continuous intravenous flucloxacillin (12 g/24 h) until 14 days after the control blood cultures, which were all negative. By then, the patient had made a speedy recovery and all laboratory results had normalized.


A 46-year-old Egyptian man presented to the emergency department with one-day history of epigastric and right upper abdominal pain, associated with nausea and vomiting. He denied any other associated gastrointestinal or urologic symptoms. Apart from being type 1 diabetic, he declared no other significant past medical history.
The patient presented in good shape, and there was no hemodynamic instability. He showed epigastric tenderness with no signs of peritonism with the rest of the abdomen unremarkable. White blood cell count (WBC) was 17.4 K/uL (4-10 K/uL). Liver function tests (LFTs) were abnormal: total bilirubin 47 umol/L (0-21 umol/L), direct bilirubin 35 umol/L (0-3 umol/L), ALT 156 U/L (0-40 U/L), and AST 182 U/L (0-41 U/L). Other results showed hemoglobin 14.4 g/dL (13-17 g/dL), platelets 190 K/uL (150-400 K/uL), lipase 106 U/L (13-60 U/L), CRP < 5 mg/L (0-5 mg/L), CA 19-9 303 U/ml (0-27 U/ml), and IgE 432 Ku/L (0-114 Ku/L). IgA and IgG4 were normal. Abdominal ultrasound (US) showed multiple GB stones with intrahepatic biliary dilatation and prominent common bile duct (CBD) measuring 7 mm. The rest of the examination showed no signs of acute cholecystitis and no bile duct stones. The patient was admitted as a case of obstructive jaundice for further work up. He later developed signs of sepsis (tachycardia and fever) for which blood cultures were taken. He was started on intravenous ceftriaxone and metronidazole. Endoscopic retrograde cholangiopancreatography (ERCP) showed purulent bile immediately following cannulation and failed to show any filling defects. Sphincterotomy and CBD stenting were done. ERCP procedure was not extraordinary in difficulty to suspect ampullary fibrosis or deformation. Magnetic Resonance Cholangiopancreatography (MRCP) later showed distended GB containing sludge and tiny stones, hyperenhancement of both GB and CBD walls, and mildly thickened GB wall in addition to pericholecystic edema and fat stranding, consistent with acute cholecystitis and cholangitis. There were no CBD stones nor thickening of the CBD wall. After stenting, the patient was kept on piperacillin/tazobactam. He improved clinically, and both his LFTs and inflammatory markers were trending down till the 4th day post-ERCP when he started to spike fever again. Septic work up was repeated, and endoscopic ultrasound (EUS) was done. This exam showed the stent in place. Both US and computed tomography (CT) showed a new lesion 5 × 4 × 5 cm in the segment IVb of the liver in continuation with the GB fundus (). The lesion was compatible with a newly developed liver abscess. A percutaneous aspiration was carried out under US guidance, during which 100 ml of pus was aspirated and sent for microbiology/culture. During the aspiration, the GB was noticed to be deflating which pointed towards continuity between the liver abscess and the GB. Cultures grew Klebsiella oxytoca and Escherichia coli. The patient responded well after aspiration and antibiotic therapy and showed improved inflammatory markers. He was discharged the next day on oral antibiotics with close clinic follow-up to arrange for interval cholecystectomy after ERCP and stent removal.
During follow-up visits, the patient was asymptomatic. ERCP was done 5 weeks after discharge and showed no filling defects in the CBD. The stent was removed. The patient travelled and was lost to follow-up for 5 months. When he came back, an MRCP showed complete resolution of the liver abscess. Multiple gall stones in GB were still demonstrated. He was booked for elective laparoscopic cholecystectomy. Intraoperative findings showed omental adhesions to the GB. The GB was also densely adherent to the liver. Despite the difficult dissection, the procedure was managed laparoscopically. Patient's postoperative course was unremarkable, and he was discharged next day after surgery. Histopathology of the gallbladder showed chronic cholecystitis, with granulomatous inflammation secondary to schistosomiasis ().


A 41-year-old woman with no significant past medical history presented to the hospital with complaints of nausea, vomiting, and generalized weakness over two weeks. The patient was doing well prior to her presentation and she assumed that her symptoms would resolve without seeking medical attention. The patient reported subjective fevers with severe back pain during this period. The patient often had mild back pain; this is usually controlled by naproxen over the counter but provides little relief during this episode. The patient felt progressively worse and lost her appetite; thus, her husband suggested drinking large volumes of fluids. The patient reported drinking a gallon of cranberry juice, six 16oz bottles of water, and four 12oz cans of Sprite, leading to severe diarrhea and further weakness. The patient reported that she had a tick bite around the time of her initial symptoms which stayed on her skin for an hour. She avoided seeking medical attention as this was a normal occurrence given where she lives in the country. The patient denied smoking or illegal drug abuse.
On examination, the patient was tachycardiac at 132 bpm and borderline hypotensive at 95/60 mmhg with normal oxygen saturations. The patient looked sick and lethargic with dry mucous membranes but otherwise appeared normal in the exam. Admission labs () were significant for leukopenia with white blood count (WBC) of 1.7 (4.5–11.0 K/uL), thrombocytopenia with platelets of 44 K (150–450 K/uL), hyponatremia at 125 (137–145 mmol/L), potassium of 3.7 (3.5–5.1 mmol/L), acute kidney injury with creatinine of 1.9 (0.7–1.2 mg/dL) (unknown baseline), and elevated liver enzymes with AST of 553 (14–36 U/L), ALT of 188 (0–34 U/L), and LDH 1120 (140–280 U/L). The thyroid function test was also normal. The acute hepatitis panel was negative. The urine drug screen was positive for amphetamines and marijuana. The computed tomography (CT) abdomen showed splenomegaly without any other abnormalities. Tick bite labs were sent including Ehrlichia, tularemia and Rocky Mountain spotted fever.
A urine drug screen was obtained for suspicion of drug abuse despite her initial denial. We discussed the findings with the patient, and she later admitted to using both amphetamines and marijuana. This led us to take a detailed social history that revealed an unexpected event. The patient raises horses at her ranch, one whom was in pain. The vet prescribed non-steroidal anti-inflammatory drug (NSAID) pain medication (phenylbutazone) for the horse, and she recognized that the horse had pain relief. The patient was frustrated as naproxen did not help her this time and took phenylbutazone to alleviate her pain. The patient admitted to taking three doses of a 400-pound horse equivalent dose of phenylbutazone about 3 days before the start of her symptoms.
Poison control and toxicology centers were notified but no antidote was recommended. Due to suspected acute liver damage from phenylbutazone, we decided to start an N-acetyl cysteine and sodium bicarbonate drip. She was three IV doses over the course of 21 h, a loading dose with 15 g over one hour, a second dose of 4 g over 4 h, and a third dose 8 g over 16 h. Patient also received two units of cryoprecipitate for suspected disseminated intravascular coagulation (DIC) as her fibrinogen was low at 80. Yet, her international normalized ratio (INR) and peripheral smear were normal. We also initiated empiric doxycycline to cover for tick-borne illness. The patient’s labs () improved during her 3 days stay and was clinically feeling better but unfortunately decided to leave the hospital against medical advice before complete recovery occurred.
One week after her discharge, tick titers came back abnormal for Ehrlichia with positive IgM and IgG. Numerous calls attempted to notify the patient but were unsuccessful.


Case 1: A 72-year-old Japanese woman with bilateral geographic choroiditis reported to our hospital for a follow-up visit with a complaint of blurred vision after starting nab-PTX. Two months prior, she started receiving chemotherapy with 310 mg nab-PTX (220 mg/m2 body surface area) every 3 weeks for breast cancer with bone, pulmonary, and lymph node metastases. She received three treatments with nab-PTX, and visited us 2 weeks after the last dose. She had a history of surgery for thyroid cancer at the age of 53 years and for breast cancer at the age of 58 years. There was no family history of cancer and hereditary ophthalmic disease.
Her best-corrected visual acuity (BCVA) declined from 1.2 to 0.9 (decimal visual acuity measured by Landolt C) in the right eye and from 1.0 to 0.4 in the left eye, as compared with the BCVA at the previous visit. The anterior chamber was clear bilaterally, and fundus examination showed no new geographic choroiditis lesions (Fig. ). OCT showed CME with loss of foveal depression. No obvious CME was seen at the previous visit (Fig. ).
Since she was treated with nab-PTX, taxane-related CME was suspected. After consultation with her oncologist, chemotherapy was terminated (Fig. A). Because CME persisted for 3 weeks (5 weeks since the last nab-PTX treatment) (Fig. B), topical 1% dorzolamide treatment three times daily in both eyes was initiated. CME nearly resolved within 6 weeks in the right eye and within 10 weeks in the left eye after starting topical dorzolamide treatment (Fig. C, D); the treatment was then discontinued. Our initial diagnosis of taxane-related CME was confirmed, since CME resolved without chorioretinal scaring and without the administration of immunosuppression therapy.
While BCVA was improved to 1.2 in the right eye and 0.7 in the left eye, en face OCT revealed residual parafoveal cystoid spaces in the left eye that persisted for 4 months after discontinuation of dorzolamide (Figs. A, A). Since these cystic spaces persisted for a prolonged duration of time and because there was a concern that they would affect vision, dorzolamide was resumed in the left eye, 1 year after the first course of topical dorzolamide treatment had ended (Figs. A, B). Three months after treatment, the cystoid spaces regressed, and the BCVA improved to 0.8 in the left eye (Figs. A, C). We ended treatment after 4 months. No recurrence was observed a year after the dorzolamide treatment ended, and BCVA improved to 1.0 in the left eye.


Case 2: A 70-year-old Japanese man was referred to us with a 1-week history of blurred vision. He had a history of surgery for rectal cancer at 63 years of age. Five months prior, he started receiving nab-PTX plus gemcitabine therapy for pancreatic cancer with hepatic and lymph node metastases. He received 210 mg nab-PTX (125 mg/m2 body surface area) and gemcitabine on days 1, 8, and 15, every 4 weeks. After receiving five cycles of nab-PTX plus gemcitabine therapy, nab-PTX was terminated owing to the occurrence of sensory disorder of the limbs; only gemcitabine treatment was continued. He visited us 3 weeks after the last nab-PTX treatment. BCVA was 0.3, and the anterior chambers were clear bilaterally. Fundus examination revealed bilateral CME, and neither retinal hemorrhage nor exudate were observed (Fig. ). Prominent CME was observed bilaterally on OCT (Fig. A).
We suspected taxane-related CME and initiated topical 1% dorzolamide treatment three times daily in both eyes. CME completely resolved bilaterally at his next visit at 5 weeks after starting dorzolamide treatment (Fig. B). Nine weeks later, his BCVA improved to 0.8 and 1.0, in the right and left eye, respectively. At this time, we terminated dorzolamide treatment. At the final visit, 2 months following discontinuation of dorzolamide treatment, there was no evidence of CME. We diagnosed this as a case of taxane-related CME, owing to the resolution of CME after cessation of nab-PTX without any treatment other than topical dorzolamide. He passed away 2 months after the final visit.


A 74-year-old man with esophageal cancer after thoracoscopic esophagectomy had high-output chylothorax from day 6 post-surgery. We performed total parenteral nutrition, right-side pleural drainage and continuous intervenous injection of Octreotide (150 µg/day) from day 7 post-surgery, but were unsuccessful. Since the amount of chylothorax (> 4000 ml/day) was very high and the albumin levels in the blood (1.2 g/dl) did not improve, we considered reoperation, but before that, we selected inguinal intranodal lymphangiography on day 13 post-surgery.
First, inguinal intranodal lymphangiography was performed using a 22-gauge cathelin needle (Fig. a, b). Puncture the superficial inguinal lymph node under ultrasound guidance and position the tip of the needle at the nodal hilum. Iodized oil (Lipiodol; Guerbet Japan, Tokyo, Japan) was gently injected manually at a rate of approximately 1–2 ml every 5 min under intermittent fluoroscopy. A total of 6 ml of Lipiodol was injected to opacify the lymphatic system up to the cisterna chyli, which was at the level of Th12/L1 disc.
Although the leak could not be identified, since Lipiodol was discharged into a vein at the left venous angle, we decided to perform transvenous retrograde thoracic duct embolization (Fig. a, b, c). A 4-F introducer sheath (Super Sheath; Medikit, Tokyo, Japan) was inserted in the left brachial vein. In the approach from the left brachial vein to the junction of the thoracic duct with the vein (JTV), a 4-F cobra-shaped catheter (ANGIOMASTER; Terumo, Tokyo, Japan) and a 1.9-F microcatheter (Prograteλ19; Terumo) were used to access the thoracic duct. A 0.014-in. microguidewire (ASAHI CHIKAI; Asahi Intecc, Aichi, Japan) and a 0.016-in. microguidewire (ASAHI Meister; Asahi Intecc) were used to seek the JTV and guide the microcatheter. A small amount of contrast was injected to confirm proper entry into the thoracic duct and also to verify the site of leakage. Iodinated water-soluble contrast medium (iopamidol, Iopamiron 370 Injection syringe; BAYER, Osaka, Japan) was used in all transcatheter contrast radiography. The leak could be accurately identified by being able to entry into the thoracic duct. Once the site of the leak was identified, the microguidewire and microcatheter were inserted beyond the suspected site of leakage and placed in the cisterna chyli, and microcoils were used to embolize the thoracic duct. The microcoils, including Target XXL 360 Detachable Coils and Target 360 soft (Stryker, Kalamazoo, MI) and Tornado Embolization Coil 4/2 mm and 3/2 mm (Cook Medical, Bloomington, IN) were placed from near the cisterna chyli to the cephalic side of the aortic arch (Fig. ). The time for all these procedures was 260 min. This procedure cost 29,000 Japanese yen. Although N-butyl-2-cyanoacrylate (NBCA) may be used in combination, it is often difficult to reuse the catheter, so only microcoils were placed.
Chyle output gradually decreased after TDE and stopped completely on day 20 post-surgery. The patient’s post-interventional course was uneventful (Fig. ).


A 70-year-old male patient was admitted to our hospital complaining of choking while eating for more than 1 month on March 20, 2019. CT showed tumor signs in the middle of esophagus on March 6, 2019. Esophagogastroduodenoscopy demonstrated the patient was suffering from esophageal carcinoma and gastric cancer (). He had no family history of malignancy. Pathology examination confirmed they were locally advanced esophageal squamous cell carcinoma and adenocarcinoma of gastric horn (). On March 21, 2019, the patient underwent laparoscopic feeding jejunostomy and postoperative radiotherapy.
On November 15 and 18, 2019, esophagogastroduodenoscopy and abdominal CT showed that esophageal and gastric cancers were under control. However, CT indicated a tumor in the right-sided colon. On November 19, 2019, colonoscopy and pathological findings confirmed it was locally advanced moderately differentiated adenocarcinoma of colon (). Immunohistochemical stains revealed proficient mismatch repair proteins and positive expression of S-100, but negative expression of D2-40 or CD34. The patients underwent laparoscopic-assisted resection of right-sided colonic cancer and lysis of abdominal adhesions on November 22, 2019. By the time of submission of this manuscript, the patient had been well and no sign of recurrence or metastasis had been detected. The timeline was shown as .
In order to seek possible personalized therapy strategies, the paraffin-embedded tissue blocks from malignant esophagus, stomach and right-sided colon, respectively, were subjected to next-generation sequencing (NGS) using a pan-cancer 599-gene panel [ChosenOne599, ChosenMed Technology (Beijing) Co. Ltd, Beijing, China] on July 20, 2020. NGS demonstrated the TMB value was 10.11 Muts/Mb, 11.37 Muts/Mb, 6.32 Muts/Mb in the tumor tissues of esophagus, stomach and colon, respectively, which ranked 29.58% (moderate), 6.45% (high) and 62.73% (low) in patients with corresponding malignancy. TP53 mutation was identified in all three tumor tissues. However, the mutation location was different from each other. In the esophagus cancer tissues, two TP53 variations were identified (NM_000546: exon6: c.580C>T: p.L194F and NM_000546: exon8: c.814G>A: p.V272M). In the gastric carcinoma tissues, there were also two TP53 alterations (NM_000546: exon4: c.375G>A: p.T125T and NM_000546: exon7: c.715A>G: p.N239D). In the right-sided colon carcinoma tissues, there was one TP53 mutation (NM_000546: exon8: c.821T>G: p.V274G) ().
At the same time, other important variations were also identified in the esophagus carcinoma tissues, including ATRX (NM_000489: exon21: c.5424T>G: p.Y1808*), CHEK1 (NM_001114121: exon7: c.676dup: p.T226fs), copy number variations (CNVs) of CCND1 and FGF3/4/19. In the gastric carcinoma tissues, the same CHEK1 variation was also detected. In the colon carcinoma tissues, there were two APC variations (NM_000038: exon16: c.4468del: p.H1490fs and NM_000038: exon16: c.2621C>G: p.S874*, ).


An 18-year-old male patient was admitted to the emergency department following a two-day history of fever, cough, shortness of breath, and malaise. On admission, there was no confirmed case of COVID-19 in his family. The patient had a history of operation due to urolithiasis which was performed 10 years ago. In the emergency clinic, his workup included a computerized chest tomography (CT) scan with a result of no finding suggesting COVID-19 infection. On admission, his body temperature was 37.5 °C. Laboratory results from the emergency department showed a normal white blood cell count (4.5 x 109/L), a hemoglobin level of 12.4 g/dl, a low platelets count (89,000 per mm3), elevated transaminases (Aspartate aminotransferase level of 133 U/L, alanine aminotransferase level of 100 U/L), and a high c-reactive protein concentration (66.54 mg/L). After an initial evaluation, he was suspected of having a COVID-19 and was hospitalized on account of his high body temperature, dry cough, and dyspnea. In the clinic, a reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) with nasopharyngeal swab culture was taken, and the drugs hydroxychloroquine (400 mg/2 times on day 1 and then 200 mg/2 times per day for 4 days) and azithromycin (500 mg/2 times on Day 1 and then 250 mg/2 times per day for 4 days) were administered as empirical treatments.
On the second day of hospitalization, his fever was measured at 39.6°C, and a blood culture was sent to the microbiology laboratory. The first swab culture RT-PCR result for COVID-19 infection was found negative, and a second swab culture was taken. The second swab culture for COVID -19 reported a negative result, as well.
On the fourth day of hospitalization, the patient complained of pain in his left knee. Paracetamol 3x500 mg was added to his treatment. After five days of hospitalization, he was discharged with advice to quarantine at home for l4 days. At the time of discharge, his temperature and other vitals were normal. His respiratory symptoms and pain in the lower extremities had improved. Two days later, after his discharge, the blood culture reported Brucella melitensis. Further, the radiologic images, including the thorax CT, was re-assessed and hepatosplenomegaly was detected in lower sections of the thorax CT (Figure ). Brucellosis was diagnosed based on clinical, laboratory, and radiological findings and the patient’s history. The patient was re-called for further clinical evaluation and treatment.


A 65-year-old woman with a history of diabetes mellitus type 2 on metformin therapy presented to the respiratory emergency department after experiencing a sudden onset of dyspnea on mild exertion. Concomitantly, she was complaining of severe nonproductive cough, fatigue, and weakness for about 4 days of duration. At admission, the patient was afebrile and eupneic in oxygen therapy (pulse oxygen saturation = 95% with simple mask flow 2–4 L/min). Blood investigation revealed a total leucocyte count of 15,000/μL (normal 4000 to 11,000/μL), hemoglobin (HB) 12 g/dL (normal 13 to 18 g/dL), platelet 444 × 103 (normal 140 × 103 to 400 × 103), partial thromboplastin time (PTT) 32 (normal 23 to 35 s), international normalized ratio (INR) 1.4 (normal 0.8 to 1.1), erythrocyte sedimentation rate (ESR) 110 mm/1 h (normal up to 14 mm/h), and C-reactive protein (CRP) 100 (normal < 10 mg/L). The result of the RT-PCR test was positive for SARS-Cov-2, and the chest computed tomography (CT) scan revealed bilateral ground-glass opacities (GGO) (Fig. ). The patient was admitted to the COVID-19 ward, and based on the local protocol, remdesivir, azithromycin, dextromethorphan (due to violent cough), and prophylactic dose of heparin (5000 every 8 h) had begun. The second day after admission, the patient presented sudden tachycardia and hypogastric pain; on abdomen physical examination, a huge lower abdominal tender mass was noticed (blood pressure 100/80 mmHg, pulse rate 100/min, and respiratory rate 19/min) and there was a 2-g/dL decrease in HB from 12 to 10 g/dL. The patient underwent an abdomen CT scan which confirmed a huge rectus sheath hematoma with no extension to other parts of the body (Fig. ). On the same day, the patient underwent angioembolization of the inferior epigastric artery. Overall, the patient received isotonic fluids and the trend of blood investigation is shown in Table . After 6 days of embolization, she recovered completely and no evidence of further expansion was seen. She was discharged, and after 2 weeks of follow-up, she did not develop any complication.


A 50-year-old woman presented to the respiratory emergency department with a chief complaint of shortness of breath on exertion. She reported severe nonproductive cough, fever, and fatigue for about 6 days ago. She has no history of trauma and the patient was otherwise in good health. On physical examination, a decreased breath sounds in the lower lobes of the lungs was heard, bilaterally. At that time, she was febrile (temperature 39 °C) and eupneic in oxygen therapy (pulse oxygen saturation = 96% with nasal oxygen 2–4 L/min). Laboratory blood investigation revealed a total leucocyte count of 14,000/μL (normal 4000 to 11,000/μL), hemoglobin (HB) 12 g/dL (normal 13 to 18 g/dL), platelet 368 × 103 (normal 140 × 103 to 400 × 103), partial thromboplastin time (PTT) 29 (normal 23 to 35 s), international normalized ratio (INR) 1.2 (normal 0.8 to 1.1), erythrocyte sedimentation rate (ESR) 154 mm/1 h (normal up to 14 mm/h), and C-reactive protein (CRP) 75 (normal < 10 mg/L). The result of the RT-PCR test was positive for SARS-Cov-2, and the chest computed tomography (CT) scan revealed bilateral ground-glass opacities (GGO) (Fig. ). The patient was admitted to the COVID-19 ward, and based on the local protocol, remdesivir, azithromycin, dextromethorphan (due to violent cough), and prophylactic dose of subcutaneous enoxaparin (40 mg every 24 h) had begun. Suddenly, 4 days after admission, the patient started complaining of tachycardia, pain, and mass in the lower abdomen. On abdomen physical examination, a huge lower abdominal tender mass was noticed (blood pressure 120/90 mmHg, pulse rate 110/min, and respiratory rate 19/min). Laboratory tests showed a fall in Hb from 12 to 8 g/dL. Coagulation factors such as PTT, INR, and platelet were in the normal range at that time (Table ). Overall, the patient was transfused 4 units of packed blood cells, which raised her Hb to 11 g/dL. The patient underwent an abdomen CT scan which confirmed a huge rectus sheath hematoma with no extension to other parts of the body (Fig. ). The next day, she underwent angioembolization of the inferior epigastric artery. The trend of blood investigation is shown in Table . After 6 days of embolization, she recovered completely and no evidence of further expansion was seen. She was discharged, and after 3 weeks of follow-up, she did not develop any complication.


A 54-year-old male with a 2-year history of hypertension presented to the ER with dyspnea, anosmia and dysgeusia. Oxygen saturation (SatO2) was 62%, blood pressure (BP) was 149/100 mmHg and temperature was 35.6°. A detailed lab analysis is shown in . Due to COVID-19 suspicion, the patient was administered with paracetamol (3 g), dexamethasone (6 mg), plus oxygen therapy via mask reservoir (15 l/min). Later, he was admitted and started on high-flow oxygen therapy (Day 2), with the addition of daily enoxaparin (60 mg), baricitnab (4 mg) and methylprednisolone (80 mg). After 7 days, the patient developed severe abdominal pain localized to the iliac fossa and was referred for a surgical consultation (Day 9). A computed tomography (CT) abdomen showed hepatic steatosis without anatomical alterations in other organs. The visible portion of the thorax demonstrated a pattern of bilateral interstitial infiltrates, which is consistent with bilateral pneumonia (). An ultrasound (US) of the biliary ducts ruled out chronic cholecystitis or acute cholelithiasis. Three days later, the patient presented hematochezia and a reduction in hemoglobin (7.1 g/dl) (Day 12). A transfusion of packed red blood cells was started. A new abdominal US showed expansion of the ascending colon with mural engrossment without effusions. COVID-19-positive polymerase chain reaction (PCR) was reported on this same day (Day 13). A colonoscopy performed on Day 14 showed multiple ulcerations covered with fibrin ( and ). The patient was prepared for surgery and started on ceftriaxone (2 g) and metronidazole (1.5 g). An exploratory laparotomy performed on Day 16 revealed necrotic tissue and perforations of the ascending colon and retroperitoneal fasciitis. A right (stapled) hemicolectomy and ileostomy were completed. Vitals taken after surgery, the readings were as follows: SatO2: 80%, BP: 107/69 and temperature: 37.0°. Immediately after surgery, retroperitoneal purulent drainage was observed, which continued during his post-surgical stay. Blood work on Day 17 revealed fibrinogen and D-dimers, indicating a hypercoagulable state and signs of septic shock and neurological deterioration. After 7 days of the surgery (Day 23), the patient suffered wound dehiscence with erythematous markings and edema localized to his right flank. Blood work taken on that same day is shown in . A pack of red blood cells and two packs of fresh frozen plasma were transfused. Antibiotic treatment was changed to IV imipenem 2 g per day. Regrettably, the preceding interventions were not met with success, and after 28 days of hospitalization, the patient expired from sepsis-related complications. A portion of the colonic tract was preserved for histopathological analysis ().


Mr. P is a 44-year-old single, unemployed, disabled, African American male, with a past psychiatric history of schizophrenia and cocaine use disorder, who presented to his local Mental Health Center (MHC) for a routine appointment, and was noted to be experiencing a sustained painful erection. Mr. P was noted to have a history of recurrent priapism related to past trazodone and cocaine use and no other significant medical problems. Note that any information that can be used to specifically identify the patient has been changed to ensure confidentiality. As Mr. P was seen in various medical settings, the following case report is split into three locations: Inpatient Medical Hospitalization, Mental Health Center/Emergency Department (ED), and Inpatient Psychiatric Hospital (see for a timeline of the clinical course).
Mr. P presented to the ED with a chief complaint of a painful erection. He denied taking any medications for erectile dysfunction. He had been given his paliperidone palmitate long-acting injectable three days prior from the MHC. Mr. P explicitly stated that he had never experienced a sustained erection after his paliperidone palmitate injection (he had been on this medication for many months). No paliperidone level was obtained. Though trazodone 150 mg as needed for insomnia was on his home medication list, his frequency of use was unclear. Urology was consulted in the ED, diagnosed priapism, and admitted the patient. He received a phenylephrine 100 mcg/mL injection into the corpora cavernosa, resulting in successful detumescence.
During this hospitalization, the patient had a normal hemoglobin electrophoresis. Reticulocyte count indicated slight elevation at 3.5% with 0.11 million reticulocytes per microliter. Partial thromboplastin time and prothrombin time were within normal limits. Mr. P was discharged from the hospital within 24 hours.
Four weeks later, Mr. P presented to his outpatient follow-up appointment with florid psychosis and recurrence of priapism. It was confirmed that Mr. P had discontinued his trazodone due to concerns that this medication had been the culprit of the previous episode of priapism. It appeared that he had not received any prescribed antipsychotics in four weeks, as he refused his last paliperidone injection. Mr. P was taken to the ED, where complete blood count (CBC) and comprehensive metabolic panel (CMP) were within normal limits; urine drug screen (UDS) was positive for cocaine. Urology again performed a phenylephrine injection that resulted in successful detumescence. Mr. P remained in the ED for forty-eight hours and was discharged upon resolution of acute psychosis. One day later, he presented again to the MHC exhibiting signs of acute psychosis. He was transferred to the ED, and his UDS was positive for cocaine; however, upon reaching the timeframe for full metabolism of cocaine, he remained psychotic. Four days later, after switching his antipsychotic to aripiprazole, he was transferred to an inpatient psychiatric hospital.
Upon arrival, Mr. P continued to experience psychosis despite treatment with aripiprazole. Records indicated during previous admissions that he responded well to loxapine 40 mg twice daily, trazodone 150 mg nightly, and lorazepam 1 mg four times daily. Mr. P was placed on the same regimen of medications, except for trazodone, given his recent episode of priapism, and aripiprazole was discontinued. One day after loxapine 40 mg twice daily per os (PO) and lorazepam 1 mg four times daily PO were started, the patient experienced another episode of priapism. The team explored possible causes of priapism, and there was strong clinical suspicion that loxapine was the culprit.
The patient was reluctant to be transferred to the ED again for another phenylephrine injection and aspiration. Given his low threshold for agitation and worsened aggression with security, noninvasive pharmacological options were considered. Upon reviewing rare case reports of M1 antagonists being used to treat MIP, trihexyphenidyl 1 mg PO was administered. This did not result in resolution of the sustained erection. After reviewing the consequences of failing to treat priapism, the patient agreed to be transferred to the ED, where he underwent another phenylephrine injection and aspiration of blood, resulting in detumescence.
Upon return to the psychiatric hospital, he was further interviewed about his pattern of loxapine use. It was discovered that his first episode of priapism occurred three months prior, shortly after discharge from the psychiatric hospitalization in which loxapine was first initiated. This raised concern at the MHC that loxapine was causing his priapism, prompting a change to paliperidone palmitate. Despite this change, Mr. P admitted to intermittently taking loxapine throughout the three-month gap between the two psychiatric hospitalizations, which appeared to correlate with his episodes of priapism. Mr. P's antipsychotic was switched to olanzapine and he continued lorazepam 1 mg four times daily. He was also started on mirtazapine 15 mg nightly for insomnia and depressive symptoms. Mr. P did not have any further episodes of priapism during this hospitalization. At the time of this writing (two years later), he has presented to the ED multiple times for psychosis, intermittently with positive sympathomimetic UDS, but no recurrence of priapism.


The case presented is that of a 45-year-old woman (height, 155 cm; weight, 56 kg; body mass index, BMI 23.0). The patient was a clerical worker who complained of working in a sitting position for a long time (6 h) a day, four times a week. The patient was informed that data from the case would be submitted for publication, and she gave her consent for publication of this report.
The patient was diagnosed with low back pain (LBP) and sciatica (lumbar disc herniation was not observed on magnetic resonance imaging). The patient experienced moderate dull pain from the right lower back to the hip and severe radiating pain in the right lower extremity of the lateral side for a week before her visit to the clinic (- day 7). In addition to the two types of pain, the patient also experienced numbness in the lower extremities. The chief complaint was radiating pain and insufficient sleep due to numbness; thus, the patient hoped that the pain would be relieved and she could sleep well. Another characteristic history was occasionally missing steps on the stairs and on uneven ground. Pregabalin was started at a dose of 150 mg/day. Except for the pain, there was no other medical history. However, it was noteworthy that the patient had experienced pain and numbness three years earlier. At the time, she did not visit any hospital because her symptoms did not worsen as she performed some self-stretching in the bath and could manage the symptoms herself. The symptoms were relieved after approximately a year. A summary of the patient’s pain course is shown in .
Sciatica symptoms (increased numbness and radiating pain in the lateral lower extremity) were prominent in orthopedic tests ( and ). Positive signs were observed when a straight leg raising (SLR) test was performed at 30° and on the Bragard test; radiating pain and numbness increased significantly with these tests. In addition, increased radiating pain was registered when Freiberg’s test [] and the piriformis test [] were performed; thus, these tests were deemed as positive. Extreme stiffness of the gluteus medius was observed, with muscle tenderness and increased radiating pain. However, muscle weakness was not observed in manual muscle testing.
For the pain assessment, the S–D dimension of pain was assessed using the numerical rating scale (NRS) [] and the sub-class score in the McGill Pain Questionnaire (MPQ). The scores of the other subclasses in the MPQ were used to assess the A–E and C–E dimensions of pain. The NRS scores for dull and radiating pain were 5 points and 9 points, respectively. Further, the NRS score for numbness was 10 points in the sitting position. The total scores (average score) of the S–D, A–E, and C–E dimensions of pain were 22 (2.2), 2 (0.4), and 3, respectively.
The Japanese version of the PCS [], which is a translation of the original scale [], was used to assess the patient’s catastrophizing beliefs involving pain. The patient’s total PCS score was 36 points, which exceeded the cut-off point (30 points) []. The total scores (average score) of the sub-class’s rumination, helplessness, and magnification were 18 (3.6), 9 (1.8), and 8 (2.7) points, respectively.
A line drawing of the patient’s lower extremity, drawn by herself, is shown in . The patient was instructed to draw her legs without looking at them and to not compare the affected side with the unaffected side. The maximum widths and areas of the lower extremity drawings were measured using a Foxit Reader (Ver. 9.3.0, Foxit Japan, Inc. Fremont, CA, USA). The maximum width was 3.84 cm for the right side and 1.81 cm for the left side; i.e., the right side was 2.12 times wider than the left side. Further, the areas were 39.95 cm2 for the right side and 21.06 cm2 for the left side. That is, the area of the right side was 1.89 times larger than that of the left side ().
Radiating pain and numbness were attributed to sciatica, as many of the assessment results (tightness of the piriformis muscle, limitation of the range of motion of external rotation, and positive piriformis and Freiberg tests) indicated sciatica caused by piriformis syndrome. In addition, the reason for the dull pain from the right lower back to the hip was considered to be spasm resulting from sciatica. Therefore, sciatica management was prioritized. To address this issue, physical therapy programs were provided based on the clinical evidence of Last et al. [], which included stretching and massage of the hamstring and piriformis muscles [] and manipulation of the lumbar spine []. These interventions were provided once per week.
In addition to these programs, the patient received education based on the clinical practice guidelines for chronic pain [] in the pre-session on day 1. First, explanations about clinical reasoning, intervention plans, and expected changes in pain after treatment were provided. Second, we advised the patient to perform self-exercise training (piriformis muscle stretching, cat and cow stretch, and bending the trunk sideways in the crawling position) daily, as much as possible. Subsequently, the patient performed these training exercises five or six times per week. Furthermore, the patient was instructed to increase physical activity as much as possible to prevent pain catastrophizing and fear-avoidance beliefs by disuse and enhancement of the descending pain inhibitory system [].
The results of all assessments are shown in . A remarkable point about the pain was that there was an incongruency between each dimension of pain. By day 15, symptoms of sciatica disappeared according to the orthopedic tests (i.e., SLR test and Bragard test), and the severity of the S–D dimension in the MPQ, and the degree of dull pain, radiating pain, and numbness, as expressed by the NRS score, were also reduced. However, there was no reduction in the C–E dimension of pain in the MPQ by day 15. After day 15, the pain catastrophizing beliefs slightly improved; however, it should be noted that the PCS score still exceeded the cut-off point of 30. No improvement in the C–E dimension was observed on the patient’s line drawing of her lower extremities. The line drawing of the affected lower extremity did not improve much in comparison with the unaffected side by day 15 but had become similar to that of the unaffected side on day 36. Likewise, there was an improvement in the symptoms of missing the steps on stairs or on uneven ground on day 36; the patient could step optimally.


We present the case of a 35-year-old female admitted to the hospital after a cesarian section who presented with acute left lower limb pain, swelling and erythema. A Doppler compression sonogram test revealed proximal DVT of the ilio-femoral and popliteal veins. Anticoagulant therapy was immediately initiated with unfractionated heparin. The treatment proved inefficient, the patient developed a massive left calf and thigh oedema and shortness of breath. Contrary to her clinical state, the troponin and BNP levels were in the normal range (troponin I—1.9 pg/mL and BNP—11.1 pg/mL). The D-dimer levels were high—13.332 ng/mL and the CT scan revealed that the deep venous thrombosis extended to the inferior vena cava and a massive thrombus was situated in the right atrium and through the tricuspid valve. presents the massive thrombus after removal. In a transthoracic echocardiography showing the presence of a massive embolus in the right atrium and through the tricuspid valve is presented. Taking into consideration the size and location of such a thrombus, the patient was referred to a cardiovascular surgeon. During the preoperative evaluation of the patient further exams revealed a before unknown inherited thrombophilia, which revealed positive results for the mutations of the EPCR G4678C gene (Homozygous), prothrombin G20210A gene (Heterozygous), Factor XIII mutation V34L (Heterozygous), MTHFR C6677T (Heterozygous) and PAI1 4G/5G (Heterozygous), the X-ray was clean, the transthoracic echocardiography showed dilated right cavities, an 8-cm long thrombus passing through the tricuspid valve, a thrombus in the inferior vena cava, dilated pulmonary artery and a PVAT (pulmonary velocity acceleration time) value of 43 ms, which corelates to a severely elevated PAP. No risk factors for venous thromboembolism, neither acquired nor congenital were confirmed during her preoperative exams, other than her inherited thrombophilia.
The patient became hemodynamically unstable and was rushed into the operating room, severely desaturated, bradycardic, without consciousness, with severe hypotension. After intubation and general anesthesia, a transesophageal echocardiography was performed and showed clear right cavities and complete obstruction of the main pulmonary artery and the right branch with a giant thrombus. A direct thrombectomy was performed through median sternotomy, cardiopulmonary bypass without aortic cross clamp, with bicaval cannulation. This approach was elected for maximum visibility given the hemodynamical instability of the patient.
Postoperatively, the patient was extubated after only 4 h, and was weaned of the vasopressor support on the first day. She was discharged after one week with persistent left calf and thigh oedema for which she was prescribed warfarin and beta-blockers. After two weeks, the patient was readmitted in the hospital for a scheduled interventional thrombaspiration of the inferior vena cava and balloon dilatation of the left common iliac vein and common femoral vein with good angiographic results. The postoperative Doppler check-up showed left superficial femoral vein compressible by 80%, with residual thrombus (0.46 cm in diameter), left common femoral vein with permeabilization flow, with residual thrombus and the left popliteal vein completely compressible. The transthoracic echocardiography revealed adequate cardiac function.


A 47-year-old man, who was a farmer, with chronic hepatitis B infection and Child-Pugh class A cirrhosis, was referred to the Department of Internal Medicine with a markedly elevated alpha-fetoprotein (AFP) level and a hypoechoic hepatic lesion with a diameter of approximately 3 cm, observed with abdominal ultrasonography. He had been treated with entecavir and adefovir for 5 years at a local clinic but had voluntarily stopped taking antiviral agents a year ago. His initial laboratory findings were as follows: aspartate aminotransferase (AST) level, 170 IU/L; alanine aminotransferase (ALT) level, 278 IU/L; total bilirubin level, 1.2 mg/dL; albumin level, 3.69 g/dL; platelet count, 103 × 103/μL; prothrombin time (PT), 14.8 s; and AFP level, 585.2 ng/mL (normal range: 0–7 ng/mL). After confirming viral breakthrough with the presence of 2.8 × 107 IU/mL hepatitis B virus (HBV) DNA, and the drug-resistant mutations L180M and M204I, we switched the antiviral treatment to tenofovir disoproxil fumarate monotherapy.
Dynamic T1-weighted MRI revealed a 3-cm-sized, lobulated mass at segment 6, demonstrating hyperintensity in the arterial phase, isointensity in the delayed phase, and hypointensity in the hepatobiliary phase, suggesting the possibility of HCC (). Due to the elevated AFP level and the peripheral location of the mass, tumor resection was performed instead of a biopsy.
Histological examination of the resected mass revealed the loss of focal hepatocytes with increased capillary-sized vessels and fibrotic tissue in the cirrhotic liver, consistent with findings of parenchymal extinction (). Some blood vessels in the lesion were partially occluded by intimal thickening. To exclude the presence of HCC, immunohistochemical staining was performed. The hepatocyte lobules in the lesion were negative for glypican-3, which is a diagnostic marker for HCC.
After approximately 1 year, the patient’s laboratory and radiological findings were normalized (). His follow-up laboratory tests were as follows: AST level, 20 IU/L; ALT level, 31 IU/L; total bilirubin level, 0.63 mg/dL; albumin level, 3.56 g/dL; platelet count, 127 × 103/μL; PT, 11.2 s; and AFP level, 5.1 ng/mL. The repeat HBV DNA was undetectable.


A 77-year-old male with a relevant past medical history of high-grade prostate cancer managed by radical prostatectomy in 1994 was referred to our tertiary medical center for evaluation of GI symptoms. The patient was evaluated by our gastrointestinal team for worsening constipation, incomplete sense of defecation, and change in the caliber of stool over a period of nine months. Computed tomography (CT) scan of the abdomen and pelvis noted significant anal and rectal wall thickening (Figure ). Subsequent diagnostic colonoscopy showed circumferential malignant appearing anal stenosis, with friable, erythematous mucosa (Figure ). Biopsies of the anal lesion were positive for invasive poorly differentiated adenocarcinoma. MLH-1/PMS-2/MSH-2/MSH-6 were positive (proteins expressed), and thus, ruling out genetic predisposition syndromes.
The patient was referred to oncology. Records of his medical care between 1994 and 2010 were reviewed and included a prostate-specific antigen (PSA) of 9 ng/ml at the time of the first diagnosis in 1994, treatment with a retropubic nerve-sparing radical prostatectomy, and prostatic lymph nodes obtained intraoperatively at the time were negative for malignancy. The patient did not receive any radiotherapy or androgen deprivation therapy. Follow-up PSA over the following 16 years did not exceed 0.06 ng/ml.
At the time of referral to oncology, PSA was 155 ng/ml. CT scan of the chest, abdomen, and pelvis was ordered as part of workup for recurrent prostate cancer. The CT showed moderate rectal wall thickening, few new sub-centimeter sclerotic foci in the bilateral ribs and right scapula concerning osseous metastatic disease, and mildly enlarged abdominal and pelvic lymph nodes. Additional urologic findings included bladder wall thickening with a new moderate left hydronephrosis and hydroureter and a new mild right hydroureter. The cause of these findings was suggested to be either result of local recurrence or sequelae of chronic outlet obstruction and postprocedural changes.
A care plan for the patient was established by a multidisciplinary team. Treatment consisted of triple therapy including bicalutamide, enzalutamide, leuprorelin as well as multiple laxatives for constipation and tenesmus. The patient received radiation therapy for further control of symptoms. The patient tolerated therapy well with satisfactory outcomes and intermittent improvement of tenesmus.


A 32-year-old Hispanic woman reported sudden vision loss in her right eye (OD), associated with a 1-week history of pain, redness, and photophobia. She had a history of ARN in the left eye (OS), which had occurred 3.5 years prior. She had received treatment with IV acyclovir for 2 weeks, followed by oral valacyclovir, which she had discontinued 1 year before the current presentation. Her left ARN had caused rhegmatogenous retinal detachment, which resulted in the loss of light perception, despite the best surgical efforts. Her past medical history and review of systems were otherwise unremarkable. She was sexually active with her husband and had no history of alcohol or illicit drug abuse.
The best-corrected visual acuity was finger counting at 5 feet in OD; she had no light perception in OS. The intraocular pressure was 10 mmHg in OD and 5 mmHg in OS. Her right pupil was round and reactive to light; the left pupil was corectopic and unreactive, and a left afferent pupillary defect was present; finally, the left eye had atrophic phthisis bulbi. A slit-lamp exam of her right eye revealed diffuse conjunctival injection, punctate epithelial erosions, Descemet folds, and granulomatous keratic precipitates in Arlt's triangle. The anterior chamber had 1+ cells and flare, and the lens had 1+ nuclear sclerosis.
A dilated fundus exam of the right eye revealed 1+ vitritis, optic nerve edema, and retinal necrosis extending from 1 to 11 o'clock in zones 2 and 3 and in zone 1, sparing a small patch of the retina temporal to the optic disk (). The left eye revealed persistent retinal traction with fibrous tissue (). A fluorescein angiogram of the right eye revealed disk hyperfluorescence, macular and perivascular leakage, and severe peripheral capillary nonperfusion. The extraocular physical exam was unremarkable; in particular, she had normal vital signs, her lungs were clear to auscultation, her abdomen was soft to palpation, and her neurological status was unremarkable.
As her clinical findings were highly suggestive of ARN, she was admitted to the ward and treated with IV acyclovir (800 mg every 8 hours), topical prednisolone acetate 1% eye drops (4 times daily), and atropine sulfate 1% eye drops (3 times daily). A vitreous tap was performed, the resulting sample was sent for PCR analysis, and ganciclovir (2 mg/0.05 cc) was injected intravitreally. Forty-eight hours after commencing therapy, the infectious disease service switched her IV therapy to ganciclovir (380 mg IV every 12 hours).
Despite treatment, her clinical course continued to deteriorate, and after 4 days of therapy, she developed an inferior retinal detachment, which caused her visual acuity to drop to “hand motion.” The patient was scheduled for a pars plana vitrectomy with a silicone oil tamponade to repair the retinal detachment, and as part of the preoperative workup, a SARS-CoV-2 PCR test was ordered. The following day, the patient's visual acuity was “light perception,” and the partial retinal detachment had progressed to a total detachment.
Twenty-four hours later, the SARS-CoV-2 PCR test was reported as positive. No surgical management was pursued because of the patient's poor visual prognosis and positive SARS-CoV-2 test result. The patient continued to receive IV ganciclovir for 14 days. She was placed in an isolation room and received prophylactic anticoagulation with enoxaparin (40 mg subcutaneous every 12 hours) and iron supplementation to avoid COVID-19-associated complications. During her hospitalization, the patient had no COVID-19-associated symptoms and did not develop any other related complications.
The vitreous PCR test result was positive for HSV-2, confirming the diagnosis of HSV-2-associated ARN. Her serology results revealed positive HSV-1 IgG, HSV-2 IgG, CMV IgG, and VZV IgG. Toxoplasma antibodies (IgG and IgM), serum rapid plasma reagin, and human immunodeficiency virus testing were all negative. The vitreous PCR was negative for HSV-1.


A 23-year-old Brazilian male with no prior history of cardiopulmonary disease was diagnosed with P. vivax and P. falciparum by peripheral blood smear (16560 parasites/µL) in the emergency care unit (UPA, Cruzeiro do Sul, Acre, Brazil). 48 days earlier he had completed treatment for mono-infection of P. vivax (peripheral blood smear, 300 parasites/µL) with primaquine 30 mg (7 days) and chloroquine 600 mg (day 1) + 450 mg (day 2 and 3). The patient now presented with headache and chills and reported onset of stabbing chest pain and shortness of breath 3 days prior to examination.
The patient was circulatory stable (blood pressure 110/62 mmHg; heart rate 109 beats/min), auscultation of heart and lungs was normal. Axillary temperature was < 37.5 °C. Laboratory results showed inflammation (C-reactive protein 96 mg/L), thrombocytopenia (platelets 99/mm3) and moderate anemia (hemoglobin 9.2 g/dL). Liver function was slightly affected (aspartate aminotransferase 47 U/L). Cardiac biomarkers were all within normal range (pro-brain natriuretic peptide 24 pg/mL; troponins < 0.001 ng/mL). The electrocardiogram (ECG) showed PR-depressions in lead I, II, aVF and V1–V6. Ultrasound revealed pericardial effusion (18 mm) and 24 B-lines by LUS (Table ; Fig. ), which was assessed as the sum of B-lines in eight thoracic zones. All other echocardiographic measurements were within normal range, including left ventricular ejection fraction (> 50 %) and right ventricular function and no pleural effusions were found. Test for coronavirus by polymerase chain reaction was negative. The patient started treatment the same day with (i) primaquine 30 mg (14 days) (ii) artemether 80 mg + lumefantrine 480 mg × 2 (3 days) and (iii) colchicine 0.5 mg × 2 + ibuprofen 600 mg (7 days).
Follow-up day 5: Chest pain and shortness of breath improved after initiation of treatment and the patient reported to be compliant with the medication. The ECG showed sinus rhythm without PR-depressions. The pericardial effusion was reduced to 9 mm and 6 B-lines were observed. Blood sample analyses showed a decrease in C-reactive protein (32 mg/L) and peripheral blood smears were negative for Plasmodium species.
Follow-up day 21: The patient reported to be free from all symptoms and peripheral blood smears were negative. Ultrasound displayed no significant pericardial effusion (< 5 mm) and 0 B-lines.


A 63-year-old female with a past medical history of SS and a diagnosis of right breast cancer presented for nipple-sparing mastectomy and tissue expander insertion.  The patient’s SS clinical manifestations included Raynaud’s phenomenon, interstitial lung disease, and GERD and an associated gastrointestinal dysmotility disorder.  Further medical history included osteoporosis and well-controlled hypertension.
The patient was diagnosed with right breast invasive lobular carcinoma arising in a small focus of pleomorphic lobular carcinoma in situ, estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 of 2+. Staging of the cancer was determined to be T1B, N0, M0 clinically and she was referred to oncology for further management.
At the time of her initial breast cancer diagnosis, she was not actively on any DMARDs or steroid medications. Previously she had been on courses of prednisone, methotrexate, and d-penicillamine to treat her symptoms, approximately 30 years prior to her breast cancer diagnosis. Her Raynaud’s digital symptoms were treated with nifedipine, along with conservative measures, such as hand warmers. Her GERD symptoms were well controlled on a proton-pump inhibitor as well. She had interstitial lung disease secondary to SS, but her diffusion capacity had not changed significantly over the previous four years, once she had established aggressive care treatment at our university. Pulmonary evaluation indicated that her pulmonary hypertension was unlikely to complicate anesthesia. Given the long course of her disease process, this indicated that her sclerotic disease was progressing slowly, which was seen as a good prognostic indicator.
Due to the patient’s long-standing SS and interstitial lung disease, mastectomy was thought to be the best option. Lumpectomy and radiation therapy were not recommended due to the possibility of exacerbating wound-healing issues and worsening pulmonary function if she were to have chest wall radiation therapy. The patient subsequently underwent right breast nipple-sparing mastectomy, sentinel lymph node biopsy, and prepectoral insertion of a tissue expander with an acellular dermal matrix wrap.
Two months after initial operation, she progressively developed a small incisional wound on her right breast, which subsequently expanded in size without infection. Upon discussion with the rheumatology, it was determined that this wound-healing problem was not consistent with a rheumatologic wound-healing problem. This wound was first managed with local topical care but ultimately required skin debridement and primary closure of the right breast wound. At the time of skin debridement, the implant pocket was examined and there was no gross evidence of infection, and cultures were negative. Her breast incision subsequently healed well without further complications.
Nine months after initial mastectomy, tissue expander placement, and subsequent expansion, the tissue expander was exchanged for a permanent implant. At that time, right breast fat grafting was performed and a left breast mastopexy was undertaken for symmetry. This surgical intervention was uneventful and she healed in a normal manner on both breasts.
Over a year after her final procedure, the patient continued to do well without any wound-healing problems (Figure ). Of note, the patient had no complications postoperatively attributed to her underlying SS. She has not had any recurrence. She was ultimately satisfied with her final reconstructive outcome.


This 38-year-old female patient, with a body mass index (BMI) of 13, had suffered from progressive lower abdominal pain and intermittent fever for 3 months. She also had lost 32 kg of her body weight within 5 years. This time, the patient complained of progressive watery diarrhea for 2 weeks, and then visited our emergency department in November 2018. Due to her history of hyperthyroidism, she was first treated for a thyroid storm, and then admitted for further investigation due to her normal thyroid function.
The patient’s history of past illness includes an episode of esophageal ulcer, 33–38 cm level from the incisor, diagnosed in December 2017, status post proton pump inhibitor treatment, complicated with stricture in March 2018, status post endoscopic dilatation in August 2018 (Fig. ). Pathologist found granulation tissue with acute and chronic inflammation with necrotic tissue. Besides, she also had hyperthyroidism under methimazole use since 2002 and history of coronary arterial disease, one vessel disease, right coronary artery, status post two bare metal stents and one drug-eluting stent insertion in January 2016 and February 2017, under aspirin use.
After admission, physical examination found lower abdominal tenderness and tympanic sound to percussion, but no peritoneal signs. Laboratory survey revealed white blood cell count of 17,600/μL, segment 86%, myelocyte 0.5%, band 1%, lymphocyte 7%, monocyte 5.5%, hemoglobin 5.1 g/dL, platelet count 79,5000/μL, alanine aminotransferase (ALT) 9 U/L, sodium (Na) 127 mEq/L, potassium (K) 3.2 mEq/L, C-Reactive protein (CRP) 122.3 mg/L, free-T4, 0.91 ng/dL and thyroid-stimulating hormone (TSH)1.159 uIU/mL. Tests for cytomegalovirus (CMV) DNA, Epstein-Barr virus (EBV)- viral capsid antigen (VCA) IgM, human immunodeficiency virus (HIV) antibodies (Ab), amebic Ab, and cultures for Salmonella, Shigella, Campylobacter and pus cells in the stool were all negative. Positive CMV IgM, CMV IgG, EBV-VCA IgG and occult blood were noted. Computed tomography (CT) revealed wall thickening over the ascending colon, cecum and terminal ileum (Fig. A), a suspicious terminal ileal perforation tract with a thick enhanced wall (Fig. B) and irregular shaped fluid and gas collection with a thick, enhanced wall, extending from the upper to the lower peritoneal cavity and cul-de-sac, which measured up to 14 cm (Fig. C, D). Antibiotic treatment with piperacillin/ tazobactam was then administered and CT guided drainage was arranged. Ganciclovir IVF was also prescribed from 2nd December 2018 to 17th January 2019 due to the CMV IgM positive, DNA negative finding. Abscess culture grew Enterococcus faecium and Candida glabrata. Antifungal treatment with anidulafungin was prescribed from the 7th December 2018 to 24th January 2019. A colonoscopy showed deep ulcers over the ileocecal valve (ICV) (Fig. A) and proximal A-colon with ICV stricture (Fig. B). The pathologist noted ulcers, and the remaining mucosa showed crypt branching, crypt shortening, and pyloric metaplasia. This was compatible with Crohn’s disease with a negative immunohistochemistry for CMV, which was performed with a monoclonal antibody directed against the CMV pp65 antigen (Novocastra™ lyophilized mouse monoclonal antibody; Leica Microsystems, Wetzlar, Germany). This led to a diagnosis of Crohn’s disease with a Montreal classification of A2L3L4B2B3, a Crohn’s disease activity index (CDAI) of 623 points and a Harvey–Bradshaw Index (HBI) of 22 points. After infection control, oral prednisolone 20 mg/D and azathioprine 25 mg/D were prescribed. We stopped the azathioprine treatment due to nausea and vomiting side effects. The patient was discharged with oral prednisolone 20 mg and oral levofloxacin in January 2019. One month later, she complained of stool-like discharge from the vagina. A fistulogram through the vagina revealed peritoneal space to rectal and vaginal fistulas (Fig. A).
The final diagnosis was Crohn’s disease, with a Montreal classification of A2L3L4B2B3, which was complicated by an esophageal ulcer with stricture and chronic terminal ileal perforation with peritoneal space to rectal and vaginal fistulas.
The patient received surgical resection of the cecum, terminal ileum and chronic perforated tract over the terminal ileum, and ileo-colostomy side to side anastomosis and an end-ileostomy on the 1st April 2019. The pathologist noted that the entire specimen measured 9.5 × 8.0 × 5.5 cm. The intestine showed ulceration, pseudopolyps, and a fistular tract surrounded by purulent exudate (Fig. A). These microscopic findings were compatible with the diagnosis of Crohn’s disease (Fig. B–D). She had no more stool like material passing out from her vagina 1 week later. The patient was prescribed vedolizumab treatment with standard induction and maintenance dose (300 mg in 0th week, 2nd week, 6th week, and then every 8 weeks) on the 24th April 2019.
In July 2019, the patient underwent colonoscopy examination, which only showed mild inflammatory activity over the blind end, and a lower gastrointestinal (LGI) series also noted no more fistula. Closure of the end-ileostomy with an end-to-side ileo-ascending-colon anastomosis was performed in August 2019. A lower gastrointestinal tract X-ray examination was arranged, which revealed no remaining fistula or obstruction (Fig. B). The patient regained 23 kg of body weight, with her BMI increasing from 13 to 22. Her CDAI dropped from 623 to 4 points and her HBI fell from 22 to 0 points.


A 52 year old female patient with a shortness of breath (New York Heart Association class III) and vertigo on exertion, gradually worsening exercise intolerance and occasionally chest pain for the last 4 months was referred to the Eastern Slovakian Institute of Cardiovascular Diseases for evaluation. Although as a child she was diagnosed with a murmur, she had not been treated and she was lost from the follow-up. At presentation she had a blood pressure of 110/95 mmHg and permanent atrial fibrillation. She exhibited a 1/6 systolic murmur and electrocardiogram showed right axis deviation and signs of right ventricular overload. On physical examination, peripheral edema was present. Serum NTpro brain natriuretic peptide was elevated, 2324 pg/ml.
Two-dimensional transthoracic echocardiography with a CW Doppler (Siemens SC 2000 Prime, Siemens Medical Solutions, Inc, Mountain View, California, USA) (2D-TTE) revealed AV septum deficiency with enlargement of the right heart chambers (right ventricle and right atrium) and hemodynamically significant left-to-right shunt (pulmonary to systemic blood flow 2:1), right and left AVV valves located at the same level, with bridging leaflet chordal attachments to the crest of the interventricular septum (IVS), typically seen in AVS, right ventricle ejection fraction slightly decreased, severe valvular regurgitation of the common AV valve, large septum primum defect (23 × 28 mm), defect in the membraneous part of the IVS and left ventricle (LV) to right atrium shunt. Moreover, left ventricular outflow tract was prolonged with a hemodynamically insignificant obstruction caused by the attachment of the bridging leaflets. Left ventricle was of normal size with normal global systolic function (Fig. A–C).
Transesophageal 2D echocardiography (TEE) with a continuous wave (CW) Doppler, confirmed TTE findings of AV septum deficiency, primum atrial septal defect with left-to-right shunt with better visualization of superior bridging leaflets attachments to the IVS and AVV regurgitation (Fig. A–C).
According to the above results of the 2D echocardiography, the diagnosis of AVSD intermediate (transitional) type was made. For precise assessment of AV septal defects and common AV valve anatomy real time three-dimensional echocardiography (RT3D) was performed.
Real time 3D transthoracic echocardiography (RT3DTTE) enabled complete 3D analysis of the right ventricle, with a calculated ejection fraction of 34% and end-diastolic volume of 161 ml. Real time 3D transesophageal echocardiography (RT3DTEE) revealed an oval in appearance atrial septal primum defect, which could not be visualized in 2D echocardiography with a more precise measurements of 31 × 23 mm. Moreover, two small inlet VSD in the membraneous part of the IVS, between the chordate attachements to the crest of IVS of bridging leaflets, with sizes of 4 × 5 and 7 × 8 mm with a left-to-right shunt were also detected. The common AV valve was found to be with one annulus and two orifices different in shape (triangle on the left side, elliptic on the right side) with malposition of the aorta. The common valve was found to have five leaflets-superior, inferior, left mural, larger right anterior or superior and smaller right inferior leaflet. The left mural leaflet was relatively small with slight restriction. Finally, no tricuspid pouch, described in 2D TTE was detected (Fig. A–D).
The main findings of the cardiac computed tomography (CCT) were, intermediate AVSD, large atrial septal defect (17 mm), smaller membraneous ventricular septal defect (6 mm), extremely dilated right heart chambers, mainly the right atrium and dilated left atrium, large communication between the atrial septal defect and the right atrium, common AV valve, with the tricuspid part attached to the free wall and the the mitral part (anterior leaflet) thickened and attached to the interventricular septum (Fig. A–C).
Right heart catheterization showed bidirectional shunt (1:1) at the level of the left atrium and right ventricle, mild pulmonary hypertension (22 mmHg), and pulmonary vascular resistance of 1.7 Wood Units. Left heart catheterization showed no coronary disease.
Initially, due to the lack of expertise by the local hospital, the patient was considered by the local heart team as highly risk (right ventricular dysfunction and dilatation) for surgical correction, and she was offered only conservative treatment. Later, the indication was re-evaluated and she was referred to the National Institute of Cardiovascular Diseases for an elective surgery. The National Institute is a tertiary hospital with an expertise in correction of congenital heart diseases and especially complex patients like the patient who is discussed in this case report.


A 62-year-old female presented with 4 weeks of right-sided watery rhinorrhea. She reported spontaneous clear, salty nasal drainage without a history of trauma. Two weeks later, she developed a frequent dry cough caused by postnasal drip and gradually worsened especially when lying down, which prevented her from falling asleep. The patient underwent nasal cavity examination and computed tomography (CT) scan of sinuses after visiting department of otolaryngology, and we found a continuous flow of clear fluid to posterior pharyngeal wall (Fig. a) and sinus CT showed the lesion tissue extending from the right middle cranial fossa into sphenoid sinus through a local bone defect in the lateral wall of the right sphenoid sinus (Fig. b). Combined with measurement of glucose level in nasal secretions (4.4 mmol/L), the patient was initially diagnosed with spontaneous sphenoid sinus meningoencephalocele accompanied by CSF rhinorrhea, and she was admitted to department of otolaryngology -head and neck surgery on June 29, 2020.
Chest computed tomography (CT) scan was performed and showed multiple flocculent ground glass density shadows in both lungs after consultation with a respiratory physician, which could not be ruled out as viral pneumonitis. The patient had no epidemiological history related to coronavirus disease 2019 (COVID-19). COVID-19 was ruled out after the results of both oropharyngeal swabs and serum IgM/IgG for COVID-19 were negative. Meanwhile, test results of TORCH (TOX, RV, CMV, HSV), EB virus nucleic acid, and nine respiratory pathogens were all negative and the possibility of the patient suffering from viral pneumonitis was excluded. Meanwhile, she underwent a pulmonary function test that showed normal pulmonary ventilation, and the serum allergen-specific IgE test showed no seasonal allergy. Therefore, we considered preliminarily that pulmonary inflammation might result from chronic aspiration of CSF. The patient underwent endoscopic resection of meningoencephalocele and repair of skull base defect on July 10, 2020. We found a 4 * 5 mm2 bone defect in the lateral wall of the right sphenoid sinus (Fig. a), and a free mucosal flap of nasal floor was used to repair the defect. The patient’s dry cough disappeared on the first day after surgery. Pathological diagnosis revealed the resected lesion was brain tissue. Nasal endoscopy showed that the repaired area of the skull base defect healed well 2 months after surgery (Fig. b). Compared to preoperative imaging (Fig. a), pneumonitis seemed to be still in progressive stage with characteristics of the consolidation lesion with a mini cavity in the right lung 1 week after surgery although parts of multiple flocculent ground glass density shadows were gone (Fig. b). The lesion disappeared completely 2 months after surgery (Fig. c). Infection-related inflammatory indexes, such as c-reactive protein (CRP), white blood cells (WBC), and neutrophils were completely improved 1 week after surgery (Fig. ).


A 44-year-old woman presented to the gynecology clinic with menorrhagia for six months. Except for the feeling of mild pressure in the lower abdomen, she had no other symptoms. Transvaginal ultrasonography showed no uterine abnormalities (A), but revealed a right adnexal mass of 8×7cm with both solid and cystic components (B). No ascites was observed. The serum CA125 level was measured, and turned out low (18 kU/L). An abdominal computed tomography (CT) scan was requested for within two weeks. Five days later, the woman presented to the gynecologic emergency unit with increased abdominal discomfort. Transvaginal ultrasonography demonstrated significantly increased size of the right adnexal mass, which now measured 12×9cm (C-D). An abdominal CT scan was made the same day, revealing a right ovarian tumor, as well as a mass in the transverse colon and multiple hypodense lesions in both the right and left lobes of the liver (A-B). A diagnosis of metastatic colon cancer was suspected, which was subsequently supported by an increased serum carcinoembryonic antigen (CEA) level of 346 µg/L. Histopathological analysis of a liver biopsy confirmed the diagnosis, revealing classical adenocarcinoma. Immunohistochemical stainings and molecular analysis (using the IdyllaTM KRAS Mutation Assay) demonstrated mismatch repair proficiency and a KRAS p.G12V mutation, respectively. Detailed examination of the patient's family history by a clinical geneticist revealed no relatives with colorectal cancer and/or colonic polyposis. Palliative chemotherapy consisting of Capecitabine, Oxaliplatin and Bevacizumab (CapOx-B) was initiated. Oxaliplatin was discontinued after three courses due to toxicity (acute neuropathy: throat discomfort and muscle cramps). CT scans after three courses of CapOx-B and three subsequent courses of Cap-B showed gradual growth of the right ovarian metastasis (C), whereas the colon tumor and liver metastases had decreased in size after three courses of CapOx-B and stabilized after three courses of Cap-B. Since the abdominal discomfort had also increased, bilateral salpingo-oophorectomy was performed. Notably, Bevacizumab was discontinued several months before surgery and resumed one month after surgery to avoid impaired wound healing. In addition to the right ovarian metastasis (D), histopathological analysis revealed a microscopic focus of metastatic adenocarcinoma in the left ovary. Next-generation sequencing demonstrated the same KRAS p.G12V mutation in the right ovarian metastasis, as well as inactivating mutations in TP53 (p.R282W) and APC (p.K1350fs). Chemotherapy was switched to Folinic acid, Fluorouracil, Irinotecan and Bevacizumab (FOLFIRI-B) five months after surgery due to radiological progression of the colon tumor and liver metastases, as well as increasing serum CEA levels (). After four courses of FOLFIRI-B, partial response was observed on abdominal CT, and serum CEA levels had significantly decreased (). After twelve courses, exploratory laparotomy was performed; however, colectomy and hepatic metastasectomy were not executed because multiple peritoneal metastases were observed. At eighteen months after diagnosis, the patient remains in good clinical condition (WHO performance score 0).


An 18-year-old boy referred to our hospital on January 14, 2020, complained about proteinuria and hematuria for 8 months. Physical examination was unremarkable with neither hearing loss nor ocular abnormalities.
Biochemistry analysis revealed serum total protein 62.5 g/L, albumin, 40.4 g/L and creatinine, 85 μmol/L (57–111 μmol/L). By urinalysis, protein excretion was 2.3 g/day and RBCs were 24/HPF. Immunological evaluation was as follows: C3, 1.18 g/L; C4, 0.254 g/L (normal range, 0.9–1.8 g/L; 0.1–0.4 g/L, respectively). Serology for antinuclear, anti-double-stranded DNA, anti-streptolysin O, antiphospholipid, anti-glomerular basement membrane (GBM), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-PLA2R antibodies, and serum immunofixation electrophoresis were all negative. There was no serological evidence of hepatitis B and C or HIV infections.
Then, kidney biopsy was performed. Sixteen glomeruli were sampled for light microscopy with two spheroidal sclerosis. Light microscopy showed glomerular mesangial mild hyperplasia, mild tubulointerstitial lesions (). Immunofluorescence revealed all negative for IgA, IgG, IgM, C3, C1q, and Fibrin. Electron microscopy demonstrated mesangial electron-dense deposits, podocyte foot process effacement, and segmental GBM with splitting appearance (). The GBM changes raised concern for Alport syndrome (AS), and additional immunofluorescence was performed for type IV collagen α1, α3, and α5 chains. However, α5 was completely absent in both glomeruli and tubules ().
Regarding the family history, his elder sister was initially presented with hematuria and proteinuria in her 9th year of age. Light microscopy of kidney biopsy showed segmental mesangial proliferative glomerulonephritis (). Electron microscopy finding revealed splitting of GBM (). Immunofluorescence was all negative including α5 chain (). However, she had discontinued periodic examination for 18 years. In September 2020, she was admitted to the outpatient department of our hospital with proteinuria and hematuria. Urine analysis detected 82 dysmorphic RBCs/HPF, 2.1 g/d proteinuria. Biochemistry analysis showed serum total protein 64.3 g/L, albumin, 39.2 g/L, and serum creatinine, 123 μmol/L. Furthermore, their father, mother, and paternal aunt all had microscopic dysmorphic hematuria with normal renal function, and without proteinuria.
Considering the unusual pathological features and family medical history, next-generation sequencing was performed for the proband. The result demonstrated CFB c.2054_2057del (p.Ser687Profs∗16) variant and X-linked COL4A5 c.2999G > T (p.Gly1000Val) variant (). Sanger sequencing analysis of the family members revealed CFB c.2054_2057del (p.Ser687Profs∗16) variant in the patient’s father and paternal aunt, X-linked COL4A5 c.2999G > T (p.Gly1000Val) variant in his mother. And his elder sister has the same genetic variants as the proband ().
In silico analysis indicated the pathogenic nature of the c.2054_2057del (p.Ser687Profs∗16) novel genetic variant in CFB gene. The frameshift mutation has been predicted by rare exome variant ensemble learner as “likely pathogenic,” which has an impact on splice site changes and protein features might be affected (). Additionally, X-linked COL4A5 c.2999G > T (p.Gly1000Val) variant has been reported in a family with hematuria without a renal biopsy ().
Furthermore, we performed immunohistochemical staining for Factor B (FB), C3c, C3d, and C4d in renal tissue to determine the complement activation pathway. The result demonstrated that FB, C3c, and C3d were all positive in the proband and his elder sister, C4d, was negative in glomeruli (). Furthermore, the plasma FB levels in the proband and his sister were 0.168 g/L and 0.3 g/L (normal range: 0.19–0.5 g/L), respectively. At this time, the proband and his sister were diagnosed as CFB c.2054_2057del (p.Ser687Profs∗16) variant associated glomerular nephropathy combined with X-linked Alport Syndrome.
The patient was treated with initial prednisone (35 mg/d, gradually reducing the dose taken by 5 mg every 8 weeks), Benazepril (10 mg/d), and Hydroxychloroquine sulfate (0.2 g, bid) for 6 months. Now, oral administration of 25 mg prednisone continued. At present, his proteinuria persisted and increased to 3.0 g/d, and serum creatinine reached 130 μmol/L with renal insufficiency.


A 46-year-old male presented to the emergency unit with a 3-month
history of progressive lower limb swelling, a persistent non-productive
cough and non-specific abdominal discomfort that had worsened
over the preceding week. Other than a previous traumatic lower
limb amputation, he reported no medical comorbidities but had a
significant smoking history. On initial assessment the patient was
afebrile, had significant pedal oedema and sub-centimeter inguinal
lymph nodes with no visible or reported skin rashes. Cardiovascular,
respiratory and neurological examinations were normal. Minimal
abdominal tenderness was elicited, and he was noted to have extensive
penile ulceration.
Initial urine dipsticks revealed significant proteinuria therefore
a cause for nephrotic syndrome was investigated. Notable
preliminary results included a urine protein creatinine ratio (U-PCR)
of 0.317 g/mmol, normal renal function (creatinine of 58 µmol/L),
a raised calcium (3.12 mmol/L) and a cholestatic liver profile (alanine
transaminase of 33 U/L, gamma-glutamyl transferase of 349 U/L,
and alkaline phosphatase of 461 U/L). His serology was negative for
HIV and hepatitis B, but positive for T. pallidum antibody (TPAb).
The TPAb antibody assay is an initial screening in our laboratory and
if positive, a rapid plasmin reagin (RPR) gets performed. The RPR
results became available 72 hours after admission, by that time the
patient had already undergone chest radiography and computed
tomography (CT).
Admission chest radiography revealed a suspicious left lower lobe
mass with multiple smaller pulmonary nodules in the lower zones
. Contrasted chest CT was performed the following day,
which showed an irregular left lower lobe mass (37 × 28 × 26 mm)
with multiple posterior lower lobe subpleural nodules, sub-centimetre
mediastinal and bilateral hilar nodes, no pleural effusions and
background paraseptal emphysematous changes in the upper lobes
.
In view of the patient history, blood results (raised calcium and liver
enzymes), U-PCR and CT findings, the provisional diagnosis was that
of metastatic lung cancer complicated by nephrotic syndrome. The
patient subsequently underwent CT-guided biopsy of the lung lesion.
In the interim, the result of RPR came back positive with a titre of
1:256 – this was thought to be an independent finding and unrelated
to the current clinical presentation.
Provisional histology of the lung mass reported no evidence of
atypia or malignancy. There was a marked plasma infiltrate with
multiple granulomas, and some showed early central necrosis.
Furthermore, scattered anthracotic pigment deposition was noted
within the stroma. There were no acid-fast bacilli identified after
Ziehl-Neelsen and modified Ziehl- Neelsen staining or fungi after
Periodic Acid-Schiff and Grocott staining. Gram stain showed no
organisms and subsequent bacterial culture was negative. In view
of these findings and positive RPR, further immunohistochemistry
was requested. AE1/3 highlighted entrapped reactive alveolar
structures and T. pallidum antibody was positive. The granulomatous
inflammation and positive TPAb supported a final diagnosis of
pulmonary syphilis with early necrotic granulomas being precursors
of gummas.
The patient went on to have a renal biopsy, which showed mild
mesangial proliferative glomerulonephritis, keeping with syphilitic
nephropathy. Renal ultrasound showed an oedematous right kidney
with moderate loss of cortico-medullary differentiation in both
kidneys. Although no formal imaging or tissue sampling of the liver
was done, the raised canalicular enzymes suggested liver involvement.
The patient was treated with two doses of benzyl-penicillin (2.4
million U) intramuscularly 2 weeks apart and received supportive
therapy in the form of an angiotensin-converting enzyme inhibitor, a
loop diuretic and paracetamol for analgesia. He responded well with
no signs of a Jarish-Herxeimer reaction. His symptoms resolved within
a few days of commencing therapy and ten days later, his U-PCR
improved from 0.317 g/mmol to 0.049 g/mmol. Chest radiography
revealed that the left lung mass had resolved at 8 weeks of follow-up
, the RPR titre decreased to 1:64, and normalisation of serum
calcium and liver function.