45-year-old female with no significant history presented with shortness of breath and cough. She was febrile and hypoxic on admission with SpO2 of 80% requiring 15 l oxygen via nasal cannula (SF ratio 133). Lymphopenia and elevated inflammatory markers were noted on initial blood work. Her COVID-19 PCR swab was positive. She underwent a CT scan of the chest which demonstrated extensive bilateral consolidative and ground glass opacities. Her oxygen requirements soon increased up to 50LPM and 100% FiO2 via HFNC. She was intubated and initial ventilator settings were RR 18 bpm, TV 450 ml, FiO2 100% and PEEP of 10 cm H2O with a resulting PF ratio of 148. Post-intubation CXR revealed right mainstem bronchial intubation and an atelectasis of the left lung. The ETT was then retracted to a proper position and a repeat imaging revealed a small left-sided apical pneumothorax. A chest tube was placed using a thoracostomy approach that resulted in resolution of the pneumothorax. The following day, no further air leak was observed. She was treated with corticosteroids, antibiotics, convalescent plasma and off label Tocilizumab. The chest tube was removed on day 14 after the patient’s recovery and extubation. The patient was eventually weaned off oxygen. She is currently undergoing rehabilitation in the hospital.


47-year-old woman with a history of meningioma, diabetes, hypothyroidism and obesity (BMI 33.6) presented with a 2-weeks history of dry cough, fevers and fatigue. Upon presentation she was febrile, tachypneic and hypoxic requiring oxygen via HFNC (SF ratio 92). Her blood work was concerning for lymphopenia and elevated inflammatory markers. A CT angiogram of the chest showed a saddle pulmonary embolism, bilateral consolidations and ground glass opacities. She was started on broad-spectrum antibiotics, corticosteroids, anticoagulation with intravenous continuous Heparin and later received off label Tocilizumab. Three days later, the patient was noted to be more hypoxic with increased work of breathing requiring mechanical ventilation. The ventilator settings were RR 18 bpm, TV 400, FiO2 60% and PEEP 10 cm H2O. Her PIP and plateau pressure were 27 and 23 cm H2O respectively. Twelve days into her hospitalization, the patient was noted to be more hypoxic requiring increasing FiO2 on the ventilator. Her CXR revealed bilateral pneumothoraces, with the right being larger than the left. A right sided chest tube was placed using a surgical approach. Her pneumothorax resolved within 2 days. Her hospital course was complicated by disseminated intravascular coagulation (DIC), renal failure and ventilator associated pneumonia. She later developed multiorgan failure. She died as a result of cardiac arrest due to worsening acute respiratory distress syndrome and septic shock.


76-year-old female with a history of pulmonary sarcoidosis, obesity (BMI 43.15) and hypertension who initially presented progressive muscle weakness concerning for sensorimotor polyneuropathy and myopathy. Due to worsening hypercapnia and somnolence in the settings of muscle weakness, she required mechanical ventilation followed by tracheostomy tube placement. While in the hospital she became persistently febrile and hypoxic (SF ratio 155 and PF ratio 143). Her chest imaging showed bilateral consolidations, more pronounced at the bases, in addition to atelectatic changes on the left. She tested positive for COVID-19. Her hospital course was complicated by bilateral lower extremity deep venous thrombosis, ventilator associated pneumonia with pseudomonas, bacteremia, fungemia and septic shock. After a long hospital course, and despite remaining on the same ventilator settings RR 14 bpm, TV 450 ml, FiO2 100%, PEEP of 12.5 cm H2O with observed PIP 20 and plateau pressure 16 cm H2O, she developed a large right sided pneumothorax and a chest tube was placed via surgical approach that resulted in lung expansion. Unfortunately, the following day she had a cardiac arrest. She died despite providing resuscitative measures.


An 82-year-old man presented with an out-of-hospital VF arrest. He reportedly felt very unwell whilst in a supermarket, before suffering from angina and collapsing. He was promptly attended by an ambulance crew who found he was initially in fast AF whilst conscious, before descending into VF, requiring cardiac pulmonary resuscitation (CPR) and subsequent DC cardioversion (DCCV). ROSC was achieved after 10 minutes, where he was found to be in fast AF with anterior ST elevation on ECG, resulting in a HEMS (Helicopter Emergency Medicine Service) transfer for possible primary percutaneous coronary intervention. His cardiovascular risk factors included hypertension, possible previously untreated MI, type 2 diabetes mellitus, previous smoker, and poor compliance with all medication whilst also suffering longstanding chronic obstructive pulmonary disease (COPD). On angiography, he was found to have nonflow limiting moderate plaque disease in the left anterior descending artery (LAD), with no significant atheroma in the other coronary arteries. He was thus returned to the ward, clinically stable and without any coronary intervention. Furthermore, his troponin T results suggested he had not suffered a myocardial infarction, rising from an initial 44 to just 48 units (3 and 6 hours, normal < 14 units), which could be explained by fast AF, CPR, or DCCV—in combination or alone. His resting ECG (electrocardiogram) showed T wave inversion in the anterior leads suggesting previous myocardial insult. His electrolytes were all within range, with a potassium of 4.1 mmol/l, sodium of 137 mmol/l, and magnesium of 0.9 mmol/l. His Creatinine was 100 μmol/l and glucose was 7.1 mmol/l. A cardiac MRI was carried out, which identified a left ventricle scar that can be a plausible explanation for his initial VF arrest, with MI unlikely due to a lack of surrounding oedema and reasonable LV contractility. During his stay in the ward, he had further chest pain and ST elevation () in the anterior leads which self-resolved. On subsequent review of his angiographic images, the consensus was he should have a further coronary angiogram with a pressure wire study to the LAD. During the angiogram, the LAD went into coronary spasm () which was associated with further chest pain and ST elevation, which resolved once IV nitrates were administrated through the coronary catheter (). He was clinically stable throughout the procedure and returned to the ward for a provisional plan to implant an ICD. He suffered three further VF arrests that same night, which made clear the diagnosis. Each episode of VF was preceded by both chest pain and significant ST elevation in anterior leads before descending into VF (), which was terminated by prompt DCCV. The following morning, an ICD was inserted with concomitant vasodilator therapy started. He received a combination of diltiazem and bisoprolol, which he tolerated well and remained stable on. He was discharged soon after, with no shocks delivered by his ICD and no further episodes of chest pain in the ward.


A 38-year-old white male patient started experiencing daily pain of high intensity and mechanical characteristics on the medial plantar surface at the base of the left hallux in October 2018. Associated with this, he had self-limiting episodes of slight local swelling without related inflammatory signs. The patient was an athlete who participated in daily physical activity (soccer and tennis) and who needed to stop due to substantial limitation because of pain. He did not have chronic comorbidities and did not take medications. He drank alcohol in small/moderate amounts on weekends, was not a smoker, and had a positive family history of gout (father). On general physical examination, there were no alterations, except for limited dorsiflexion of the left hallux and discrete local swelling. As a result of the above, he was submitted to preliminary laboratory tests and imaging examinations. The laboratory tests showed the following results: hemoglobin, 14.4 g/dL; leukocytes, 5570 cells/mm3; platelets, 208,000 cells/mm3; uric acid, 5.6 mg/dL; erythrocyte sedimentation rate, 11 mm; CRP, negative; antinuclear factor, negative; rheumatoid factor, 5.3 U/mL; creatinine, 0.8 mg/dL; urea, 48 mg/dL; fasting glucose, 82 mg/dL; A1C, 5.2%; sodium, 139 mEq/L; potassium, 4.0 mEq/L; AST, 16 IU/L; ALT, 20 IU/L; triglycerides, 99 mg/dL; total cholesterol, 171 mg/dL; LDL cholesterol, 109 mg/dL; HDL cholesterol, 43 mg/dL; urinalysis, normal; and 24-hour urinary uric acid, 639 mg. Complementary investigation with foot X-ray showed only bilateral bipartite medial sesamoid (), while magnetic resonance imaging (MRI) of the left foot demonstrated bipartite medial sesamoid with suspected stress fracture, diffuse marrow edema of the medial sesamoid, periarticular soft tissue edema, and small joint effusion ().
It was concluded that it was a case of stress-related sesamoiditis with possible associated fracture in the bipartite medial sesamoid, and we decided on clinical treatment with the use of an orthopedic boot for local immobilization, anti-inflammatory drugs (nonsteroid anti-inflammatory drug and intramuscular betamethasone) and a nonnarcotic analgesic (dipyrone). There was partial improvement and subsequent recurrence. After 4 months, he was showing the same picture in the contralateral foot, which prompted us to deepen our investigation of systemic disease that causes joint involvement, with an emphasis on gout. Thus, due to the impossibility of joint puncture due to the absence of significant effusion, dual-energy computed tomography (CT) was performed, which identified deposits of sodium monourate crystals in several structures of the feet (), which led to the diagnosis of gout. Colchicine treatment was started, which led to the resolution of symptoms in one week, and later, chronic therapy with allopurinol was introduced. After 2 months, the patient was asymptomatic and resumed all his sports activities at the same intensity as before.


A 59-year-old male patient came to department of surgery dentistry at the Institute of Dentistry (Sechenov University) complaining about partial teeth absence, difficulty in chewing, and dissatisfaction in teeth aesthetics. According to the patient, he loses his teeth gradually over 20 years due to caries and its complications (). Prosthetic constructions were made about 10 years ago.


The patient was a 68-year-old male nursing home resident, with a past medical history of diabetes mellitus, hypertension, and stage IV chronic kidney disease. He denied any history of tobacco, alcohol, or substance use. After an outbreak of COVID-19 at his residence, a routine polymerase chain reaction (PCR) test was done, which confirmed COVID-19 infection two days prior to presenting to the emergency department (ED). The patient complained of loss of appetite and nausea for one week while denying any respiratory symptoms. In the ED, he was afebrile and saturating 97% on room air. On examination, he appeared dehydrated and lethargic, while his lung sounds were clear and his abdomen was soft and non-tender. Laboratory workup on admission revealed white blood cell (WBC) 8900 ug/L without lymphopenia, sodium 136 mmol/L, blood urea nitrogen (BUN) 77 mg/dl, creatinine 6.6 mg/dl, glucose 46 mg/dl, procalcitonin 6.04 ng/ml, C-reactive protein (CRP) 158 mg/L, aspartate aminotransferase (AST) 27 U/L, alanine aminotransferase (ALT) 20 U/L, alkaline phosphatase (ALP) 123 U/L and total bilirubin of 0.5 mg/dl. The chest radiograph showed a faint patchy opacity in the left perihilar region (Figure ). He was admitted for acute on chronic kidney injury and hypoglycemia due to poor oral intake. He was also empirically covered with antibiotics for possible superimposed bacterial pneumonia.
Over the next few days, the patient's kidney function improved with hydration. He had persistent nausea, vomiting, and anorexia, but no abdominal pain. A non-contrast abdominal computed tomography (CT) scan revealed peripancreatic fat stranding, greatest around the tail, with mild duodenal wall thickening and adjacent fat stranding, likely from pancreatitis. The gallbladder appeared normal, without wall thickening or surrounding inflammatory changes, and the common bile duct was not dilated (Figure ). Amylase and lipase levels were elevated at 1030 U/L and 2035 U/L, respectively, but the triglyceride and calcium levels were normal. The patient was kept on bowel rest, and given continuous intravenous fluids and antiemetics. Throughout the admission, he did not have any respiratory signs or symptoms, nor did he require oxygen supplementation. Repeat chest radiograph did not show any focal consolidations. The patient's appetite eventually improved, and his diet was advanced. He was discharged seven days later back to his nursing home with a follow-up appointment.


56 years old male, obese, smoker since 20 years, without occupation, admitted in our structure for epigastric and right hypochondrium pain progressing since one week with a 5 days of sub occlusive syndrome. The initial clinical examination showed epigastric and right hypochondrium sensibility associated with a fever reaching 38.5°.
Biology revealed hyperleukocytosis at 13,000 elements/mm3 associated with a raised C reactive protein at 57 mg/l.
An emergency abdominal ultrasound examination was performed and revealed a left supra-umbilical pseudo-mass, containing multiple partitions with significant fat and infiltration all around ().
The patient had an abdominal CT scan with contrast injection, which showed a rounded formation at the expense of the large supra-umbilical omentum slightly lateralized on the left, under the transverse colon, which had a low-density, with thin septas inside, a regular wall and peripheral contrast enhancement. It is associated with a significant local infiltration. The appendix had a normal morphology: there was no intestinal occlusion ().
The surgeons indicated an exploration by midline laparotomy, and not radiological drainage, considering the clinical peritonitis and also the suspicion of ulcer perforation due to the patient's smoking history, even without pneumoperitoneum, its revealed an inflammatory epiploic mass, associated with a single microbial abscess, without any abnormalities of the gastrointestinal wall, so surgical excision of the mass was performed, and then the surgical piece was sent for anatomo-pathological study. The post-operative status was normal without immediate or late complications; the patient received antibiotic therapy with good clinical evolution.
One week after his hospitalization, the biological results improved with a hemoglobin level from 10.3 to 12 g/dl, leukocytes from 13,000 elements/mm3 to 11,000 elements/mm3 without significant variation in other parameters.
The microbiological results of the collection revealed that it was a sterile abscess, with no isolated germ.
The anatomopathological study of the pseudo-mass showed a macroscopic appearance of a fibrinoleukocyte layer (). The microscopic study showed altered fibrin and polynuclear tissue around the fat ().


The patient was a 37-year-old man with HBV infection. He was admitted to a local hospital with hepatalgia and discomfort in December 2017. The computed tomography (CT) showed multiple intrahepatic masses, indicating primary liver cancer with multiple intrahepatic metastases, stage IV. Later, CT showed an enlarged mass during reexamination on January 12, 2018, which suggested potential adrenal metastasis. On January 23, 2018, transarterial chemoembolization (TACE) was started and repeated on March 26, 2018, with documentation of progressive disease (PD) and aggravated hepatalgia according to RECIST 1.1 (Fig. A). For further treatment, the patient was referred to our hospital and started lenvatinib (10 mg, po, qd) treatment on May 13, 2018. The levels of glutamic-pyruvic transaminase (123 U/L) and glutamic oxalacetic transaminase (GOT, 230 U/L) increased significantly after 7 days of treatment. Lenvatinib was discontinued and liver protection treatment began. The glutamic-pyruvic transaminase (87 U/L) and GOT (165 U/L) levels decreased and the patient restarted lenvatinib (10 mg, po, qd) treatment on May 25, 2018. From May 23 to September 27, the patient received 7 cycles of immunotherapy with pembrolizumab (100 mg, Q21d). After the second cycle of treatment, the liver lesions were significantly reduced and the hepatalgia basically improved. At the same time, the patient was treated with high-intensity focused ultrasound 43 times from May 26 to September 30. In June and August, CT examination (Fig. B, C) showed that the liver lesions reduced and partially disappeared, suggesting partial response evaluated using RECIST 1.1. Due to hepatalgia at the end of September, lenvatinib was withdrawn on September 28. On October 9, CT scanning (Fig. D) showed enlarged liver lesions, which indicated PD according to RECIST 1.1. Histopathology of liver biopsy showed unclear structure of the portal area, a different and atypical liver cell nucleus, which indicated liver cancer. The patient received chemotherapy with oxaliplatin (150 mg, d1) plus capecitabine (1000 mg, d1–14) for 2 cycles on October 24, and November 15, respectively. Subsequently, the hepatalgia appeared and the patient turned to nivolumab (140 mg, Q21d) therapy from October 29, 2018. On November 28, CT scanning (Fig. E) showed PD according to RECIST 1.1, and chemotherapy was withdrawn.
The tissue biopsy was prepared for next-generation sequencing on October 10, 2018. Mutations of PIK3CA E545Q, JAK1 S703I, KMT2D W91∗ and SETD2 E639∗, and AXIN1 rearrangement, as well as a BRCA2 L2510P germline mutation were identified. On November 30, 2018, the patient started poly (ADP-ribose) polymerase-(PARP) inhibitor olaparib (300 mg, bid) plus nivolumab (140 mg, Q21d) therapy. During a reexamination on March 2, 2019, the hepatalgia basically improved and CT scan showed SD according to RECIST 1.1 (Fig. F). No obvious adverse reactions occurred during olaparib plus nivolumab treatment. Unfortunately, during a reexamination on March 29, 2019, CT scan showed PD according to RECIST 1.1. Soon after, the patient stopped olaparib plus nivolumab treatment and taken oral lenvatinib by himself. Subsequently, the patient did not come to the hospital for follow-up treatment. The patient died in home in January, 2020. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanjing Medical University. Informed consent for publication of data and images was obtained from the patient included in the study.


A 69-year-old male with a past medical history of hypertension, atrial fibrillation, antineutrophil cytoplasmic antibody (ANCA) vasculitis, chronic kidney disease, gastroesophageal reflux disease, and hiatal hernia presented to the ED with chief complaint of abdominal pain. He described a one-day history of gradual-onset, constant, dull, moderate severity, non-radiating epigastric discomfort with associated abdominal distention, nausea, and decreased appetite. He reported two episodes of vomiting prior to arrival. He denied fevers, chills, diarrhea, constipation, dark or bloody stools, flank pain, back pain, urinary complaints, chest pain, shortness of breath, palpitations, or syncope. Initial vital signs were temperature 36.8°C, blood pressure 157/106 mmHg, heart rate 83 beats per minute, respiratory rate 14 breaths per minute, and oxygen saturation of 95% on room air. Physical examination revealed an elderly male in moderate distress secondary to pain. Significant tenderness to palpation in the epigastrium and left upper quadrant was elicited on abdominal examination without rebound, guarding, or peritoneal signs. The remainder of the physical examination was unremarkable. Electrocardiogram (ECG) revealed normal sinus rhythm without acute ischemic changes.
The clinical presentation was concerning for an acute intra-abdominal emergency. CT of the abdomen and pelvis, laboratory studies, pain medications, antiemetics, and intravenous (IV) fluids were ordered. Emergency medicine resident physicians and an ultrasound fellowship-trained attending EP then performed an abdominal POCUS examination. POCUS was notable for a large, dilated, fluid-filled stomach highly concerning for an obstructive process (Figures , ; Videos , ).
CT imaging was subsequently expedited based upon the POCUS findings. CT of the abdomen/pelvis revealed a moderate to large hiatal hernia and a distended edematous stomach with partial obstruction due to GV (Figures -). General surgery was consulted emergently and evaluated the patient at bedside in the ED. Multiple prolonged attempts at nasogastric tube (NGT) insertion were initially unsuccessful. NGT placement was ultimately successful yielding ~2,000 mL of non-bilious stomach contents, and repeat POCUS confirmed gastric decompression (Figure ). Laboratory analysis was unremarkable for acute clinically significant abnormalities.
The patient was admitted for further management of GV. Gastroenterology was consulted for emergent esophagogastroduodenoscopy (EGD) that confirmed the presence of a partial organoaxial volvulus without evidence of gastric ischemia. EGD did not reveal any underlying pathology in the upper gastrointestinal tract with the exception of large hiatal hernia and mild gastritis. General surgery then performed laparoscopic reduction of GV, hiatal hernia repair with mesh, and Nissen fundoplication. The patient was soon tolerating a full liquid diet and closely managed post-operatively by general surgery and gastroenterology. The patient was discharged home in stable condition on hospital day 6 with instructions for outpatient surgery follow-up.


Patient 1 has been first described in 2007 [] and is now a 16-year-old girl. She was born from healthy parents at 40 weeks of gestation by cesarean section due to loss of fetal wellbeing (pedigree in Fig. ). The main features of her disease included early-onset severe cutaneous and eye inflammation and recurrent respiratory infections (Table ).
Skin lesions appeared as early as the first day of life as numerous papulo-vesicular lesions, which became generalized during the following days requiring admission into pediatric intensive care unit. These lesions have been nearly continuously present, with exacerbations, occasionally hemorrhagic and complicated with infections, ulcerated lesions, and ulcerative granulomata (Fig. ). In recent years, large areas of cutis laxa and hyperpigmentation were detected (Fig. ). At 2.5 years of age, bilateral conjunctivitis, corneal erosions, and nodules appeared (Fig. ).
The absence of circulating immunoglobulins was detected during the first year of life (Table ). Intravenous immunoglobulin (IVIG) replacement therapy (IVIGs; 400 mg/kg q3w) was then started and has been maintained until present. Despite this treatment, multiple infections were detected (cutaneous infections, acute gastroenteritis, periodontitis, herpetic stomatitis, bronchitis, and pneumonia). At 4 years of age, multiple central bronchiectases were detected on a CT scan (Fig. ), which subsequently progressed and provoked recurrent episodes of acute hemoptysis that required urgent embolization. As consequence of these lesions, the medium right lung lobe was surgically excised at the age of 13 years.
The patient received multiple treatments including antibiotics, retinoids, corticosteroids, etanercept (25 mg q1w for 5 years), and anakinra (100 mg q1d for 1.5 years). With the use of etanercept and anakinra, a partial control of skin inflammation was detected, with no improvement of ocular manifestations or immune defects. By contrast, a marked decrease of plasma C-reactive protein (CRP) was detected with etanercept (mean 6.86 mg/L; range 0.08–21-8) and anakinra (mean 0.10 mg/L; range 0.05–0.16) compared with periods in which these treatments were not administered (mean 13.32 mg/L; range 1.3–31.63).


Patient 2 is a 9-year-old boy born from healthy parents (pedigree in Fig. ). Skin manifestations started during the first week of life as multiple erythematous macules, papules, and large plaques, mainly located at arms, abdomen, and thighs (Table ). These lesions recurred with no periodicity, sometimes presenting as urticaria-like, vesicular or pustular lesions (Fig. ) or ulcerated or exudative plaques. Infections, minor traumas, vaccinations, and heat were identified as triggering or worsening factors. They were successfully treated with oral or topical corticosteroids (1 mg/kg q1d), and partially with dapsone (1 mg/kg q1d), and they healed leaving focal, wrinkled-appearing patches of cutis laxa and residual hyperpigmentation (Fig. ). Ocular inflammatory manifestations have recently appeared as bilateral red eye, corneal limbitis, and episcleritis (Fig. ).
Infections started at the age of 2 months as recurrent, mild viral bronchitis. Since the age of 4 years, recurrent bacterial infections were detected, mainly at ear (> 10 episodes) and lung (4 pneumonias), leading to mild bronchiectasis (Fig. ). All infections were successfully treated with oral antibiotics, without hospitalization. IVIG replacement therapy (500 mg/kg q3w) was started in January 2016, which resulted in a decrease of the frequency of respiratory infections and in a marked improvement of patient’s health status.


A 57-year-old Latina woman with a past medical history of HIV on anti-retroviral therapy (ART) presented with complaints of a 2 month history of cough productive of yellow sputum with associated streaks of blood, 12 pound weight loss, bilateral hand swelling, finger clubbing and knee pain. Chest CT revealed a prominent, slightly rounded consolidation of the inferior right upper lobe with adjacent ground glass and interstitial opacities likely representing pneumonia (). The patient was admitted and initially treated for community acquired pneumonia. However, an interval chest radiograph done one month later revealed a persistent and enlarging right upper lobe infiltrate ( &). The patient subsequently underwent bronchoscopy, which revealed a protruding endobronchial lesion almost completely obstructing the right upper lobe bronchus limiting any further visualization of the RUL segments. Initial pathologic analysis of specimens biopsied during bronchoscopy revealed non-small cell lung carcinoma (NSCLC). Subsequently, a positron emission tomography (PET) scan was performed and showed a hypermetabolic RUL pulmonary mass with obstruction of RUL bronchus compatible with malignancy in addition to low level uptakes in the adrenal and thyroid glands. A MRI of the abdomen was done to better examine the adrenal gland, however, no masses were observed, only mild thickening. It was determined by the tumor board that the patient would best benefit from tumor excision and adjuvant chemotherapy. Subsequently, a definitive diagnosis was established by way of a RUL lobectomy. The resected specimen consisted of multiple fragments of tan/black soft tissue measuring 0.3 × 0.3 × 0.2 cm in aggregate. Pathologic analysis of the resected specimen showed sarcomatoid giant cell carcinoma, tumor size 9.5 cm with invasion of the visceral pleura and 1/13 hilar lymph node involvement. The pathological stage was pT3N1Mx based on the tumor node metastasis (TNM) staging system. By immunohistochemistry, the tumor cells were diffusely positive for CK7 while negative for CK20, TTF-1 and p40. The patient was started on adjuvant chemotherapy (do you know the chemo meds?) and followed as an outpatient.
This case reveals a possible paraneoplastic syndrome associated with pulmonary SC, the impact of HIV HAART on carcinogenesis and the prognosis of HIV patients with SC. Paraneoplastic syndromes are a group of clinical disorders that are associated with malignant diseases and are not directly related to the physical effects of the primary or metastatic tumors. [] Hypertrophic osteoarthropathy is a paraneoplastic syndrome consisting of a triad of symptoms including clubbed fingers, symmetric polyarthritis, and periostitis of the long tubular bones. [,] The above patient presented with signs and symptoms suggestive of this paraneoplastic syndrome which has not yet been reported to be associated with this type of cancer in the literature.
SC is a rare malignancy accounting for less than 1% of all lung cancers. [,] It is characterized by components of sarcoma or sarcoma like structures (spindle cell or giant cells) and it includes five histological variants.9 Immunohistochemical studies play an important role in determining the histological type of non-small lung carcinoma. In general, CK5/6 and p63 are markers of squamous cell carcinoma. SP-A and TTF-1 are markers of adenocarcinoma. CK7 and CK20 are important in discriminating primary lung carcinoma and metastatic lung carcinoma []. In our patient, the immunohistochemistry was positive for CK7, but negative for TTF-1, p40 and CK20. The CD7/CK20 pattern suggested a primary lung carcinoma.
Due to the heterogeneity in histopathology, surgical biopsy is required for definitive diagnosis. Treatment principle is the same as NSCLC, however, compared to NSCLC, patients with SC have a worse prognosis, higher recurrence after tumor resection and a lower survival rate. [,] The prognosis of these patients depend on tumor size and presence or absence of metastases. [] Fishback et al. in 1994 concluded that tumor size > 5 cm, a clinical stage > stage I, and lymph node involvement was associated with a significantly shorter patient survival. The median survival of patients with sarcomatoid carcinoma is 10 months, which is significantly lower when compared to that of more common lung carcinomas (20 months for adenocarcinoma, 18.5 months for squamous cell carcinoma, and 12.6 months for large cell carcinoma). []
Although uncertain, the effects of factors such as a history of HIV may alter the prognostic variables of SC in the present case. A substantive number of patients have died despite non-detectable HIV viral loads and well preserved immunity measured by CD4 cell counts. It is also unclear if HIV directly increases the risk of this malignancy in this patient population. However, HIV/AIDS is well known to increase the risk of certain malignancies including Kaposi sarcoma and non-Hodgkin’s lymphoma, both of which are classified as AIDS-defining cancers (ADC). In the post - HAART era, the non-ADCs including anal cancer, lung cancer, liver cancer and head/neck cancer constitute an increasing proportion of documented malignancies in HIV patients. Therefore the role of HAART therapy and its carcinogenic properties in relation to the increased incidence of non - ADC needs to be explored as there has been only one reported case of giant cell carcinoma of the lung not associated with HAART therapy. For example, azidothymidine approved for HAART therapy of HIV-1 integrates into DNA, resulting in mutations of the hypoxanthine-guanine phosphoribosyl-transferase and thymidine kinase genes and other genotoxic effects in cultured cells. [] Such mutations may contribute to cellular carcinogenesis.
There are currently no standard effective chemotherapeuthic regimens for pulmonary sarcomatoid giant cell carcinoma. However, traditionally platinum-based chemotherapy is used if the patient is not a surgical candidate or if adjuvant chemotherapy is indicated. Adjuvant chemotherapy is indicated for nodal or chest wall involvement because they are associated with worse prognosis. [,] SC are more resistant to first line platinum based chemotherapy in comparison of other subtypes of NSCLC. [] The role of targeted treatment like EGFR inhibitors is still not completely understood in SC as compared to NSCLC. Our patient continues to follow up at the oncology clinic and completed 4 cycles of combination cisplatin and docetaxel therapy with supplemental G-CSF four months after surgery.


A 32-year-old married man presented in December 2017 with slow-growing multiple nodules on the scrotum of 5-year duration.
He self-reported because of cosmesis and occasional mild itch. He indicated he had been applying talcum powder to the scrotum for many years aiming to reduce sweating in the area. There was no history of trauma or infection of the scrotum. He also had no systemic or metabolic disease.
On examination, the scrotum had multiple, nontender, hypopigmented, firm nodules of different sizes that were intradermal. The largest was about 25 mm in size. It was bilateral but much larger nodules on the right hemiscrotum. The testes were normal, and there was no inguinal lymphadenopathy ().
His serum calcium, phosphate, and parathyroid hormone levels were normal.
An important differential considered was multiple epidermal cysts of the scrotum.
The patient consented for an excision biopsy of the scrotal nodules.
The procedure was done under spinal anaesthesia using 2.5 mls of 0.5% hyperbaric bupivacaine through the L4-L5 interspace with a gauge 26 Whitacre needle.
The patient was positioned supine, and the site was cleaned with povidone-iodine and draped. The scrotum was inspected, and all nodules were noted considering each hemiscrotum as a unit. On careful inspection, the skin over the median raphe was noted not having any nodules. A decision was made to preserve it.
A wide local excision of the involved scrotal skin was made removing the nodules en block while taking each hemiscrotum as a unit. This required a semielliptical incision on the lateral aspects and a vertical paramedian raphe incision on the medial aspects. Dissecting was just below the dermis so as not to disrupt the dartoic muscle layer which was spared.
The wound was then closed with vicryl 2-0 using an interrupted technique ().
The histology of the excised specimen showed dense fibrosis of the dermis with foci of calcifications surrounded by multinucleated giant cells of the foreign body type. The overlying epidermis was normal confirming the diagnosis of scrotal calcinosis (Figures –).
Thirty months post excision at follow-up, the natural laxity and configuration of the scrotum had returned and the patient was satisfied with the outcome. A recurrence of a single nodule (5 mm) on the right hemiscrotum was however observed, but it was of no bother to the patient and he therefore declined excision (Figures and ).


A 70-year-old edentulous man with a history of cocaine abuse, alcoholism, and homelessness presented with altered mental status, facial pain, and swelling after an assault. Physical examination revealed periorbital ecchymosis, intra-oral ecchymosis, and trismus. The patient was intubated in the trauma bay for airway protection, given his altered mentation. Laboratory findings were significant for moderate anemia with hemoglobin of 11.7 g/dL (reference range: 14-18 g/dL), a creatinine of 1.2 mg/dL (0.84-1.21 mg/dL) suggestive of mild dehydration, transaminitis with aspartate transferase of 82 u/L (7-55 u/L) and alanine transferase 48 u/L (8-48 u/L) consistent with history of alcohol abuse, and rhabdomyolysis with a creatine kinase level of 3229 u/L (55-170 u/L). Urine toxicology screen was positive for cocaine metabolites. Computed tomographic imaging of the brain and facial bones revealed panfacial fractures, including a horizontal unfavorable left mandibular fracture extending through the left mental foramen, a left condylar neck fracture with anterior subluxation of the temporal mandibular joint, a vertically unfavorable right mandibular angle fracture, a left lateral pterygoid plate fracture, comminuted impacted fractures of the left maxillary sinus involving the anterior lateral and superior walls, a displaced left zygomatic arch fracture, and a left greater wing of sphenoid fracture (Figure ). Further imaging of the spine, chest, abdomen, and pelvis were negative for other acute traumatic pathology. The patient was extubated on post-injury day two and cleared for surgery.
On post-injury day three, the patient went to the operating room for open reduction and internal fixation with 2.3 mm miniplates using the Stryker Universal Mandible plating system (Stryker, Kalamazoo, USA). After nasotracheal intubation, the left parasymphaseal fracture was approached via an intra-oral incision with care to identify and protect the inferior alveolar nerve. The fracture was reduced with reduction clamp and then plated superiorly and inferiorly with two miniplates, bent so as to protect the inferior alveolar nerve from impingement, and fixated with mono-cortical screws (Figure ). Thereafter the right mandibular body fracture was approached via an intra-oral incision and reduced with a reduction clamp. A miniplate was used superiorly to address the vertical buttress. Then using a transbuccal trocar, a three-dimensional miniplate was used to secure the horizontal buttress (Figure ). Finally, the left lateral orbital wall fracture and left maxillary sinus fractures were reduced and plated in that order using a left intra-oral maxillary incision.
The patient was successfully extubated postoperatively and started on a clear liquid diet overnight. Meticulous oral hygiene with chlorhexidine rinses and sinus precautions was initiated. On postoperative day one, he was advanced to a full liquid diet, and imaging was performed to confirm fixation. Imaging is notable for the miniplates that were shaped around the left mental foramen so as to not impinge on the inferior alveolar nerve (Figure ). In addition, the three-dimensional miniplate spanning the right mandibular angle down to the inferior border allowed increased dispersion of masticatory forces to provide increased stability to the repair (Figure ). The postoperative course was complicated by delirium tremens and substance withdrawal, successfully treated with benzodiazepines and dexometomidine drip in the intensive care unit. He was then transferred to the intermediate care unit on postoperative day three, at which time he was able to cooperate with a detailed cranial nerve exam and was found to have intact sensation in the distribution of the inferior alveolar nerve. He was discharged from the hospital on postoperative day five.


A 53-year-old female presented to the ED following a fall while walking, complaining of increasing difficulty weight-bearing due to groin pain and a dramatic reduction in her range of movement of her left hip. Her pain had been present for approximately six weeks but was gradually worsening, particularly with weight-bearing. She described a sensation of grinding in her left hip with intermittent audible ‘squeaking’. She had a left total hip arthroplasty (THA) performed two years ago and described intermittent left groin pain prior to this event for three months. Her primary THA was for hip osteoarthritis and the components used were an uncemented Trilock femoral stem (Warsaw, IN), a Pinnacle 52mm (Warsaw, IN) multihole hemispherical acetabular shell and a 52/32mm highly cross-linked polyethylene Marathon liner (Warsaw, IN).
The ED physician referred the patient to the orthopaedic service on call as a posteriorly dislocated left total hip replacement. An isolated antero-posterior (AP) pelvic X-ray was obtained on referral which showed mild eccentric placement of the femoral head within the acetabular shell (Figure ). The tangential lateral x-ray requested by the orthopaedic team confirmed joint enlocation; however, with the femoral head situated eccentrically within the acetabular cup (Figure ).
Clinical examination of the patient revealed limited flexion, internal and external rotation and abduction of 40, 20, 20,20 degrees, respectively. Significant groin discomfort was present with passive hip movements. There was audible grinding with passive movement of the hip. The attitude of the hip was not adducted or internally rotated. No significant limb length discrepancy was noted. She had no medical co-morbidities and was a low demand patient with normal body mass index. Differential diagnosis was that of a fracture of the ceramic head, catastrophic liner wear, deep infection or liner dissociation.
An arthrogram of her left hip was performed the following day in theatre under local anaesthesia. A 20-gauge spinal needle was inserted into the left hip joint under x-ray guidance. Joint fluid was aspirated to outrule infection and 4 mls of iodinated contrast was injected into the joint. This confirmed needle placement within the joint and femoral head enlocation within the acetabular cup. It delineated integrity but inferior dissociation of the polyethylene liner from the Pinnacle acetabular cup component (Figures , ).
Live screening of the left hip also confirmed joint enlocation with liner dissociation. In addition, no radiolucencies were detected around the acetabular or femoral components.
The patient subsequently underwent a planned revision two days later following confirmation that the joint fluid culture was negative for infection. The femoral head and liner were exchanged through the previous incision via an anterolateral approach to the hip. The acetabular cup component had no evidence of loosening, nor did the implanted femoral stem. They were not revised as component integrity, stability and positioning were acceptable. The taperlock mechanism within the shell was also grossly unaltered.
Intra-operatively the liner was found to be dissociated from the acetabular cup and displaced inferiorly. The explanted ceramic size 32mm head demonstrated dramatic evidence of stripe wear due to edge loading on the implanted acetabular cup and liner rim (Figure ).
The Pinnacle shell design incorporates both a taperlock mechanism to secure the liner within it, in addition to multiple anti-rotation device crescentic concavities that accept the liner tines, increasing the overall stability of the liner within the shell. Our patient’s explanted polyethylene liner had evidence of shearing of all but two peripheral anti-rotational locking tines in addition to gross plastic deformation of the rim predominantly at the 1-4 o’ clock position (Figure ).
A new polyethylene liner was successfully seated in the acetabular cup, and a ceramic head was press fit onto the trunnion of the retained femoral component. The revision components were stable on testing with excellent impingement free range of motion preserved. Post-operatively, the patient had immediate relief of the pre-operative groin pain and underwent an uncomplicated post-operative recovery. She was discharged home on the fourth post-operative day. Her post-operative radiograph is seen in Figure and Figure .


A 28-year-old male presented complaining of intermittent diplopia. He had a slight head tilt left AHP. The cover test revealed an intermittently controlled left hypophoria at near and at distance, with worse control in the distance. Binocular single vision (BSV) was present at near, but convergence was reduced. Ocular movements and prism cover test (PCT) measurements are shown in Figure (all PCT measurements are alternate PCT, in free space, at 6m fixation). No restriction in elevation in adduction was recorded. A qualitative judgement of positive Bielschowsky head tilt test (BHTT), tilting to the right, was recorded though no measurement was recorded. Potential diagnoses were right inferior rectus (IR) palsy, right SO palsy and left IO palsy. Fresnel prisms (4Δ base up left lens) to help control the primary position deviation were prescribed, as well as prism fusion range and convergence exercises. Later prisms (4Δ base up left lens) were incorporated into glasses.
Despite prism incorporation the patient returned one year later with gradually worsening diplopia symptoms keen to discuss surgical options. All clinical findings were similar and no AHP was observed. The patient declined surgery.
The patient returned once again seeking a surgical opinion as the deviation was constantly manifest on right gaze with diplopia. Although no consistent AHP was adopted, he occasionally used a head tilt left AHP to aid control of his diplopia. The incorporated prisms were no longer helpful, so had been abandoned. Investigation of thyroid function and acetylcholine receptor antibodies gave normal results. A –3 underaction and limitation of the left eye elevating in adduction and a down drift of the left eye on dextroversion was recorded (Figure ). No click or underaction of the right IR or right SO was detected. The patient was diagnosed with a decompensating left Brown syndrome. The patient was re-measured following four hours of monocular occlusion, the deviation doubled in size as shown in Figure compared to Figure . Once again the patient declined surgery.
The patient returned complaining of worsening intermittent diplopia and using a larger AHP, 15° left head tilt (qualitative judgement), to maintain BSV. The deviation was unchanged in primary position compared to five years ago, yet had increased on right gaze (Figure ). The differential diagnosis was a left IO palsy or a left atypical Brown syndrome. No torsion was measured in primary position, upgaze or downgaze (double Maddox rod) and no limitation of the LE was detected. The patient again declined surgery.
The patient was again struggling to maintain BSV when tired despite the AHP (head tilt left) and increasingly complaining of blur. The cover test showed a moderate left hypotropia with diplopia, which was controlled to a hypophoria with the AHP. Ocular motility and negative BHTT findings are shown in Figure . Fundus examination revealed slight left incyclotropia. The patient decided to proceed with surgery to try and improve diplopia symptoms and reduce the AHP.
The ocular movements and PCT measurements are shown in Figure . Left incyclotorsion of 10° was measured in primary position at 1/3 m (double Maddox rod).
Intraoperative FDT demonstrated a –2 restriction of the left eye elevating in adduction only, confirming the diagnosis of left Brown syndrome. A 7 mm tendon spacer was inserted into the left SO tendon and a 3 mm recession of the right superior rectus (SR) was performed. FDT was normalised following spacer insertion.
The patient reported blur in the right eye, but no diplopia. Cover test revealed a minimal left hypotropia without diplopia, which was controlled to a phoria with a slight head tilt left AHP. Full extremes of gaze could not be tested, yet there was reversal of the vertical deviation on right and left gaze, with no diplopia.
No AHP was evident and the patient’s diplopia symptoms were vastly improved. Cover test revealed a minimal left hypophoria with good recovery and BSV in primary position. Ocular movements and PCT measurements are shown in Figure . Diplopia was only reported on extremes of gaze, and the patient was happy with the postoperative results.
A very slight tilt left AHP was evident and the patient reported occasional diplopia in elevation and depression. Cover test with AHP revealed a minimal left hypophoria at near with delayed recovery and minimal left hypophoria at distance with good recovery. Ocular movements and PCT measurements are shown in Figure . Without AHP the patient’s deviation and control were recorded as slightly worse. The patient still reports surgery has improved his diplopia and AHP.


A 62-year-old woman was admitted to our hospital because of mental abnormality and hypomnesia for 3 months. The main mental symptoms were gibberish, irrational talk, impaired mental attention, without apparent hallucinations and delusions. The patient did not present with fluctuating consciousness, lack of consciousness, or loss of consciousness. The family of the patient reported that she had a history of fever before she experienced the mental symptoms. Her highest body temperature was 38.6 °C. Her axillary temperature became normal after she received antibiotic therapy for 4 days. However, she gradually developed symptoms of mental abnormality. She also intermittently complained of abdominal pain, vomiting, constipation, and urinary incontinence for 1 month. She did not experience other discomforts, such as headaches, dizziness, and convulsion. She visited a local hospital in October 2018, and the routine blood test showed that the white blood cell counts were normal, and the percentage of lymphocytes was high. The blood potassium was 1.91 mmol/l (normal 3.5-5.3 mmol/l), and the prolactin level was 90.55 μg/l (normal 2.74–26.72 μg/l). The free thyroxine was slightly high, the thyroglobulin antibody was 12.32 IU/ml (normal 0–115 IU/ml), and the thyroid peroxidase antibody was 10.42 IU/ml (normal 0–34 IU/ml). The testing results of antinuclear antibody, anti-neutrophil cytoplasmic antibody, anti-Jo-1 antibody, anti-dsDNA antibody, anti-Scl-70 antibody, anti-SSA antibody, and anti-SSB antibody were yielded negative, and the tests for hepatitis, HIV, and syphilis virus were also negative. The local hospital suspected intracranial infection, endocrine disease, and electrolyte disorders and gave her symptomatic treatment. Nevertheless, her symptoms showed no noticeable improvement. It was difficult to diagnose the disease, so the patient was admitted to our hospital. The patient had a history of diabetes, hypertension, erosive gastritis, and cataract surgery, but she had no family history of neurological diseases.
The physical examination revealed that her body temperature was 36.8 °C, and there was tenderness below the xiphoid. The neurological examination showed impaired mental attention and reaction capacity, slow speech, normal manifestations of the brain nerve, normal muscle strength, and muscle tone, negative meningeal irritation sign and pathological reflex, normal tendon reflex. The patient could not cooperate with the sensory system examination. The mini-mental state examination (MMSE) score was only 6/30.
Encephalitis was initially suspected, and lumbar puncture was performed. The CSF examination showed that the CSF pressure was 110 mmH2O, and the white blood cell count was normal, but she had an increased total protein level of 0.57 g/l (normal 0.15–0.45 g/l) and a glucose level of 5.10 mmol/l (normal 2.2–3.9 mmol/l). The coxsackie B virus, enterovirus, and cytomegalovirus test levels were normal. Bacterial culture and Cryptococcus neoformans tests were negative. A contrast-enhanced MRI of the brain was normal. The diagnosis of encephalitis was excluded in general. However, leukoencephalopathy was evident on the T2 fluid-attenuated inversion recovery (FLAIR) images. A high-signal intensity in the white matter of the cerebral hemisphere, especially at the subcortex of the frontotemporal and corona radiata, was found on the T2 FLAIR images (Fig. a-c). The MRI imaging of the left basal ganglia and bilateral corona radiata showed lacunar infarction. Magnetic resonance angiography indicated that the blood vessels were normal. The DWI results revealed a symmetrically distributed strip-shaped high-intensity signal of the corticomedullary junction in the bilateral frontal, parietal, and temporal lobes (Fig. d-f).
Skin biopsy samples were obtained at 10 cm above the patient’s ankle. A light microscope was used to examine the samples, which showed hyperkeratosis of the epidermis. A few lymphocytes and tissue cells infiltrated through the superficial vessels of the dermis (Fig. a). Electron microscopy showed round-shaped intranuclear inclusions in the nucleus of the fibrocytes. The intranuclear inclusions had clear borders and were composed of fibrous substances without a membrane structure (Fig. b and c).
The fasting blood glucose was 9.48 mmol/l, and glycosylated hemoglobin was 6.6%. The routine urine test showed normal results. The patient presented with mental abnormality for 3 months. We did not consider the diagnoses of hypoglycemia, diabetic ketoacidosis, or hyperosmolar hyperglycemic syndrome. Furthermore, the patient did not present with depression, anxiety, consciousness disorders, hallucinations, and neurasthenia, which were common mental symptoms in patients with diabetes. The results of the electrolyte showed hypokalemia (2.6 mmol/L), hyponatremia (127.3 mmol/L), and hypochloremia (86.5 mmol/L). The renin-angiotensin-aldosterone system and cortisol hormone tests showed normal results. The MRI of the hypophysis showed no abnormal areas. The electroencephalography showed low-and moderate-amplitude desynchronized-mixed waves when she fell asleep.
Brain protection and symptomatic therapy were given when the patient was hospitalized, and the symptoms were relieved. However, she still complained of recurrent vomiting and urinary incontinence. The patient was alive, and the condition of the patient did not worsen or improve for 6 months after she was discharged.


The patient was a 68-year-old gentleman who had underlying co-morbidities of gouty arthritis on allopurinol, hypertension and diabetes mellitus. His medication compliance was not optimum, and he had been experiencing episodes of gout exacerbation. He presented with chronic low back pain for a year. He developed progressive worsening of lower limb weakness six months prior to his presentation. His cauda equina symptoms with intermittent loss of urinary and bowel controls developed gradually over recent six weeks. At presentation, his lower limbs power was grade two and he had saddle anaesthesia with laxed anal tone. Magnetic resonance imaging (MRI) showed end plates destruction of L5/S1, partial vertebral bodies destruction, cystic fluid collection, anterior longitudinal ligament (ALL) subligamentous spread and central spinal canal stenosis as shown in (T1 weighted image) and (T2 weighted image). C-reactive protein (CRP) was 2.37 mg/dL (slightly elevated), erythrocyte sedimentation rate (ESR) 64 mm/hour, total white blood cell (WBC) 10.2 x109/L, uric acid 371 μmol/L (normal) and alkaline phosphatase (ALP) 167 U/L (slightly elevated but other liver enzymes were within normal ranges). Infective spondylodisciitis of L5/S1 was suspected.
A two-stage operation was done. The first stage was the anterior approach for L5/S1 vertebrae partial corpectomy, and lumbar interbody titanium mesh cage was inserted. The second stage involved a posterior approach for lumbo-pelvic instrumentation and fusion. Iliac screws were inserted instead of S1 in view of the osteoporotic quality of S1 vertebrae. Demineralised bone matrix (DBM) bone allograft was used for fusion purposes. A whitish lump of tissue from the vertebrae was sent for histological examination, of which the report was consistent with gouty tophi with adjacent thick fibrocollagenous connective tissue. The crystals within the tophus were confirmed with polarised light microscope and displayed negative double refraction. No granuloma nor malignancy was found in the histology. Tuberculosis and fungal cultures did not grow any organisms. The diagnosis was then changed to spinal gouty arthritis.
His urinary and bowel controls returned to full function after three months. His lower limbs power improved to grade four after six months. He did not report of any instability spinal symptoms and lumbo-sacral radiographs did not show subsidence. However, a longer follow-up with repeated MRI and CT might be necessary to assess recurrence and fusion quality.


Our patient was a 68-year-old female with progressive stage III endometrial carcinosarcoma who was admitted for T-cell therapy. The patient had a previous history of asthma, alpha galactose intolerance, bilateral mastectomy in 2005 with breast reconstruction in 2006 due to left breast cancer, and total laparoscopic hysterectomy with bilateral salpingo-oophorectomy in 2019. She had no known history of cardiac disease. The patient was admitted for T-cell therapy in May 2020 at our tertiary care hospital. She started having clinical manifestations of CRS within 12 hours of initial dosing. She complained of chest pain and became hypotensive, tachycardia, and hypoxic. A code blue was called and resuscitative efforts began. The patient failed resuscitation and died. A restricted autopsy was performed to rule out cardiac toxicity secondary to T-cell therapy. The heart revealed hypertrophic changes in myocytes of both ventricles along with lipofuscin pigmentation around some nuclei. The right ventricle revealed interstitial edema, scattered mast cells throughout the myocardium, and patchy lymphocytic infiltrate along with focal myocyte necrosis and perivascular fibrosis. The left ventricle had similar findings but to a lesser extent than the right ventricle. Additionally, sections of the lung revealed scattered small bone marrow emboli in the pulmonary vasculature, probably secondary to prolonged chest compression/resuscitation. The overall findings of the autopsy were consistent with immune therapy-mediated myocarditis.
Microscopic sections
Myocardial sections showed focal interstitial inflammatory cell infiltration consisting of macrophages, neutrophils, and scattered lymphocytes accompanied by single-cell necrosis. Other areas showed inflammatory cells within capillaries and extracapillary also associated with contraction band necrosis, likely a terminal event secondary to catecholamine-induced necrosis. The changes within the heart sections were consistent with single-cell necrosis with inflammation, which was mostly composed of macrophages, neutrophils, and some lymphocytes (Figure ).
By immunostaining, cluster of differentiation (CD) 3 cells were observed scattered within the myocardium in sections from the right ventricle but no clusters of T cells were observed (Figure ).
The changes observed in the heart were consistent with a vasopressor (catecholamine)-induced single-cell necrosis, which was most prominent in the right ventricle and less in the left ventricle sections.
Lung sections showed multiple foci of platelet thrombi without any organization and early changes of intimal thickening in some muscular arteries. Right upper lobe sections showed hemorrhage and necrosis with scattered acute inflammatory cells (small infarct) (Figure ).


In June 2016, a 19-year-old Syrian man with a 6-month history of throat irritation was admitted to a Danish hospital. He came to Denmark as a refugee in 2015. He had no history of severe illness or excess infections, although a scar on his arm was suggestive of previous cutaneous leishmaniasis. His family history included a mother and a sister who were healthy, and a deceased father who had also been healthy. Several days before hospital admission, the symptoms had progressed to severe throat pain and fever. Laryngoscopy revealed massive edema of the mucosa of both the pharynx and larynx. The epiglottis and uvula were swollen and red with papilloma-like lesions. A biopsy of the uvula revealed histiocytic inflammation and Donovan bodies, thus granting the diagnosis of leishmaniasis. The species L. tropica was identified by polymerase chain reaction. Additional paraclinical examinations included a negative HIV test, normal levels of immunoglobulin (Ig) A and IgM and low IgG (309 mg/dL). An ultrasound scan of the abdomen revealed slight splenomegaly (14 cm) and no hepatomegaly. Treatment with a standard regimen of liposomal amphotericin B (LAB) (3 mg/kg on days 1–5, 14, and 21) was initiated and led to complete resolution of the symptoms.
However, 4 months later, the symptoms recurred. Treatment was reinitiated with LAB, but in immunodeficiency dosages (4 mg/kg on days 1–5, 10, 17, 24, 31, and 38). The IgG levels continually remained low, and immunoglobulin substitution with intravenous immunoglobulin (IVIG) was initiated. The patient showed a good clinical response, but despite ongoing immunoglobulin substitution, he was re-hospitalized in March 2017 with a second relapse. At that point, massive edema of the epiglottis threatened the airways, and tracheotomy was necessary. Miltefosine (50 mg three times daily for 28 days) was initiated, and the patient recovered completely. The patient was subsequently lost to follow-up, until he was re-admitted with a third relapse in February 2018. The uvula was completely eroded (), and tracheotomy was again necessary because of edema. At that point, the levels of IgA and IgG were both low (57 and 220 mg/dL, respectively). The patient had responded well to all treatment regimens, and the relapses were considered likely a consequence of his immune deficiency and lack of ability to clear the intracellular parasites, rather than drug resistance. He was treated with LAB in immunodeficiency dosages, and immunoglobulin substitution was reinitiated.
After completion of the treatment for the third relapse, secondary Leishmania prophylaxis with Miltefosine was initiated. The initially dose was 50 mg per day, which was reduced to 50 mg three times per week, and finally to the current dose of 50 mg once weekly. The patient continues to receive immunoglobulin substitution, currently subcutaneous immunoglobulin (SCIG). As of June 2020, 2 years after the third relapse, no further relapses or other infectious episodes had occurred.


A 68-year-old man presented with acute swelling of his right scrotum with obvious pain. His body temperature was 38.4°C. After physical and radiological examinations, the patient was diagnosed with right epididymitis with an abscess. He was admitted to the urological surgery department for antibacterial therapy for two weeks. Subsequently, he underwent a resection of the right epididymis and abscess. However, 24 hours after surgery, he experienced septic shock and was transferred to the intensive care unit for further treatment. A blood culture suggested a Klebsiella pneumoniae infection (KPI). The patient was treated with cefepime, imipenem, piperacillin-tazobactam, and tigecycline, but his symptoms did not improve. Subsequently, he was confirmed to have multidrug-resistant KPI. Polymyxin B (500,000 units, intravenous, q 12 hours) was administered with meropenem (2 g, intravenous, q 8 hours) and tigecycline (100 mg, intravenous, q 12 hours), and his symptoms improved. On the 8th day of polymyxin B therapy, the patient developed a red, scattered, dotted, pruritic rash on his trunk and limbs. On the 14th day of polymyxin B therapy, the rash subsided and the pruritus slightly improved; however, the patient's face and neck changed from a normal yellow color to a slightly black color. Despite this adverse event, polymyxin B therapy was continued for a total of 17 days due to its effectiveness against the multidrug-resistant KPI. Seven days after the withdrawal of polymyxin B, the color of the patient's face and neck was completely black (). The patient's scalp and feet underwent desquamation, which lasted for 10 days. Cod liver oil ointment was administered three times a day to lubricate and protect the newly grown epidermis. The patient was advised to let the skin layer fall off naturally and not to peel it in order to prevent a skin infection.
One nurse was assigned to care for the patient and record the changes in hyperpigmentation daily. The patient and his family were counseled regarding the psychological effects of the hyperpigmentation. Twenty-four days after the withdrawal of polymyxin B, the skin around the patient's eyes and nose began to fade significantly, followed gradually by the whole face and neck. The desquamation of the patient's feet improved. Sixty days after the withdrawal of polymyxin B, the hyperpigmentation of the patient's face and neck skin was almost entirely resolved ().


A 70-year-old woman (height 145 cm, weight 65 kg, body mass index 31 kg/m2) was transferred to our hospital with fever, abdominal pain, and elevated liver enzymes. Computed tomography (CT) revealed calculous cholecystitis and paralytic ileus. Therefore, an emergent laparotomic cholecystectomy was planned. She had tachypnea but no wheeze or cough. Arterial blood gas analysis showed pH of 7.47, PaO2 of 65 mmHg, and PaCO2 of 36 mmHg under nasal tube oxygen at 1 L/min. Chest radiography revealed an elevation of the right hemidiaphragm and right-sided pleural effusion (Fig. a). Her medical history included schizophrenia, dementia, atrial fibrillation, diabetes mellitus, and untreated asthma. She had no previous history of abdominal or thoracic surgery.
General anesthesia was induced with fentanyl 75 μg, propofol 60 mg, and rocuronium bromide 50 mg under standard monitoring. After endotracheal intubation, anesthesia was maintained with sevoflurane, fentanyl, and rocuronium bromide. Volume-controlled mechanical ventilation was started consisting of 8 mL/kg predicted body weight (respiratory rate 10 breaths per minute with an inspiratory to expiratory ratio of 1:2) without positive end-expiratory pressure (PEEP). Forty-five minutes after induction of anesthesia, we noticed a high peak inspiratory pressure (PIP) of 30 cmH2O, bilateral expiratory wheeze, and a shark-fin waveform on capnography without a decrease in percutaneous arterial blood oxygen saturation. There was minimal secretion in the trachea and no kinks in the endotracheal tube. Given the patient’s history of untreated asthma, we assumed she was having an asthma attack and administered 40 μg of procaterol via the endotracheal tube. However, the abnormal waveform and high airway pressure persisted. Although we re-administered procaterol and increased the concentration of inhalational sevoflurane from 1.5 to 2.0%, airway pressure increased further, fluctuating between 27 cmH2O and 35 cmH2O with each ventilation. Fortunately, she did not develop hypoxia or hypercapnia. Bronchoscopy revealed the collapsed trachea and main bronchi during expiration, indicating expiratory central airway collapse. The addition of PEEP (5 cmH2O) and extension of the exhalation time improved her condition promptly. Although the shark fin waveform remained on capnography, the highest PIP decreased from 35 cmH2O to 27 cmH2O. The surgeons then changed the procedure from cholecystectomy to gallbladder drainage because it was difficult to dissect the gallbladder from the liver bed. Despite lessening of the severity of her condition, peak airway pressure remained high and she was admitted to the postsurgical care unit after surgery without extubation. Operating time was 1 h 26 min and anesthesia time was 2 h 45 min.
After the surgery, we noticed that preoperative non-dynamic CT had captured bulging of the posterior membranes of the trachea and main bronchi into the airway lumen without collapse of the cartilage (Fig. ). We therefore diagnosed EDAC.
The patient was mechanically ventilated using volume-controlled synchronized intermittent mandatory ventilation with PEEP of 5 cmH2O postoperatively. Neither bronchodilators nor corticosteroids were administrated. The airway pressure started to decrease gradually on postoperative day (POD) 5. The patient was extubated after the ventilation mode was changed to continuous positive airway pressure of 5 cmH2O on POD 11 (Fig. b). The patient did not need further mechanical respiratory support.


A 38-year-old male with no significant past medical history who took no medications and had allergies to penicillin, cefepime, and cantaloupe, fell backward from the bed of a moving truck onto his head. He sustained a significant blunt head trauma, with bilateral subdural hematomas, temporal bone fracture, nasal and orbital bone fractures, effacement of cisterns, cerebral compression, and possible diffuse axonal injury. He was intubated and placed on mechanical ventilation for airway protection due to his severe traumatic brain injury and coma, and placed in the surgical intensive care unit. His hospital course was relatively uncomplicated, though he did remain on the ventilator for 12 days and required tracheostomy placement due to prolonged decreased mental status. After tracheostomy placement on hospital day 8, he was being weaned fairly aggressively from the ventilator and was showing signs of improvement from a mental status perspective.
On hospital day 9, the patient had an arterial blood gas that revealed a pH of 7.53, a pCO2 of 38, a pO2 of 67, a bicarbonate level of 28 with a base excess of +4. In an effort to help his primarily metabolic alkalosis, a single dose of ACZ was given, 500mg intravenously. He had received the same 500mg intravenous dose of ACZ on hospital day 3 for a similar indication, a week prior to this dose. At this point, he had an indwelling foley catheter, a normal creatinine, and was producing over 2 L a day of clear urine.
On hospital day 11, the patient was successfully on tracheostomy collar and was more lucid and able to communicate relatively clearly. He began complaining of severe bilateral flank pain with dysuria and had a significantly decreased urine output of only 275mL of cloudy, sediment containing urine. A urinalysis revealed red cells, no white cells, no nitrates, and no bacteria. He had some mucoid-like discharge from the indwelling foley catheter with irrigation. A computed tomography of the abdomen and pelvis with renal stone protocol was obtained to evaluate for kidney stones. The images revealed no evidence of obstructive uropathy, a decompressed bladder, and several small, nonobstructing renal calculi in bilateral kidney lower poles. The urinary catheter was exchanged and the bladder was irrigated. Only the irrigation and some blood-stained mucous was evacuated. Urinary analgesia was given to the patient and aggressive fluid therapy was started. His creatinine, which had been 0.48 on the morning laboratory panel, increased to 2.0 on an evening laboratory panel with a blood urea nitrogen (BUN):creatinine ratio of 19.5:1, which can be interpreted as normal or can also indicate post-renal disease.
Due to the fact that the patient remained afebrile, had been on aztreonam for suspected pneumonia, and had no findings on urinalysis to indicate a urinary tract infection, a thorough medication review for nephrotoxic medications was conducted. The patient had received a 24-hour course of vancomycin on hospital day 4-5, as part of empiric therapy for a fever and leukocytosis workup. It had been stopped on hospital day 5, with appropriate monitoring and clearing of troughs. No other nephrotoxic medications had been administered during the patient’s hospital course.
A literature search revealed the case reports on hemorrhagic anuria and AKI with ACZ administration, as documented in the discussion, so fluid therapy was initiated. The following day, hospital day 10, the patient had near complete resolution of his renal colic and dysuria symptoms, had returned to a normal urine output of 1000mL in 12 hours and was producing clear urine again. His creatinine had decreased to 1.64. Over the next 48 hours, his creatinine returned to normal and his urine output also returned to normal. See Figure for a representation of urine output and creatinine over the duration of his brief course of AKI.


A 75-year-old Japanese woman was admitted to hospital with the chief complaints of progressive dyspnea and back pain after eating, for 2 months prior. She had surgical histories of open appendectomy and laparotomy for bowel obstruction due to adhesions at 17 and 69 years old, respectively, but no histories of upper abdominal surgery or trauma. Upon physical examination, she measured 155.2 cm in height, weighed 53.0 kg, and had a BMI of 22.0 kg/m2. Her abdominal examination showed a lower abdominal median incision for bowel obstruction surgery and a right lower abdominal incision for appendectomy. The results of the laboratory tests were normal, but chest X-ray revealed an abnormal gas-filled bowel loops in the left thoracic cavity (Fig. a). Computed tomography (CT) revealed that the stomach, small intestine, colon, pancreas, and spleen had prolapsed into the left thoracic cavity, above the diaphragm, causing significant displacement of the left lung, which led to the diagnosis of a diaphragmatic hernia, such as para-esophageal hiatal hernia or BH (Fig. b, c). Liver was found on the normal right side. Laparoscopic hernia repair was performed under general anesthesia with endotracheal intubation by two-lung ventilation. Trocars were placed at the umbilicus (12-mm camera port), in the right upper abdomen (5-mm), at the right lower abdomen (12-mm port), left upper abdomen (12-mm port), and at the left lower abdomen (5-mm) (Fig. a). Pneumoperitoneum was established at 10 mmHg. When we examined the intra-abdominal cavity, we observed a large posterolateral defect of the left diaphragm. It was clear that part of the stomach, small intestine, transverse colon, spleen, and pancreas had prolapsed into the thoracic cavity, and there was no hernial sac (Fig. b). These hernia contents were reduced back into the abdominal cavity from the left thoracic cavity with the use of atraumatic forceps, and no ischemic change was identified in any of the organs. However, the spleen was entirely contained within the thoracic cavity. The reduction of the spleen into the abdominal cavity was difficult, because the gastrosplenic ligament had adhered to the parietal pleura (Fig. c). The adhesions were exfoliated using an ultrasonic coagulator. Thereafter, the spleen was carefully placed back into the abdominal cavity. Upon examination of the thoracic cavity, no pulmonary adhesions were observed, and a left posterolateral diaphragmatic defect measured approximately 10 × 8 cm in diameter (Fig. d). The diaphragmatic defect was closed using a single layer primary closure method with nonabsorbable 2-0 Ethibond interrupted sutures (Fig. e). Because the diaphragm around the hernial orifice was somewhat fragile, a Ventralight™ ST mesh, coated with a chemically modified substance (Bard/Davol, Warwick, USA), was placed over the defect (Fig. f). The mesh was fixed to the diaphragm with an absorbable tacker. We did not leave a drain in the left chest cavity. The collapsed lung could be re-expanded by positive pressure ventilation without developing acute lung edema. The surgery lasted 266 min, and the blood loss volume was 215 ml. The postoperative course was uneventful and the patient was discharged in good condition on postoperative day 7. There was no recurrence in the 27 months after the surgery.


A 36-year-old woman underwent a laparoscopic partial hepatectomy for HCC (20 mm in diameter) in liver segment 5 two and a half years ago during follow-up after having been identified as a hepatitis B virus carrier. She has been treated for hepatitis B with nucleoside analogue before the hepatectomy. A pathological diagnosis of moderately differentiated HCC was subsequently established. We followed up at interval of 2–3 months after the hepatectomy. During post-surgery follow-up, abdominal ultrasonography detected a 36-mm hypoechoic tumor in segment 7 of the liver. Abdominal contrast-enhanced computed tomography revealed a 40-mm tumor adjacent to the inferior vena cava (IVC) and right hepatic vein (RHV). The tumor was well enhanced in the arterial phase and washed out in the portal venous and delayed phases, suggesting HCC recurrence (Fig. ). No nodule suggesting HCC was identified elsewhere in the liver. Neither lymph-node swelling nor metastasis to other organs was detected. The following laboratory data were obtained: white blood cell count (3000/µL), hemoglobin (10.1 g/dL), platelet count (16.5 × 104/µL), C-reactive protein (2.98 mg/dL), urea nitrogen (9.2 mg/dL), creatinine (0.51 mg/dL), total protein (6.3 g/dL), albumin (3.1 g/dL), total bilirubin (0.4 mg/dL), aspartate aminotransferase (28 IU/L), alanine aminotransferase (30 IU/L), glutamyltransferase (16 IU/L), lactate dehydrogenase (179 U/L), alkaliphosphatase (192 U/L), prothrombin time (115.3%), and indocyanine green retention rate at 15 min (7.0%). α-Fetoprotein (AFP) (12,371.5 ng/mL; normal range < 10 ng/mL) and PIVKA-II (208 mAU/mL; normal range; < 40 mAU/mL) were both significantly elevated. Considering that the patient was still 20 weeks pregnant, delivery was not viable. However, surgery could not be delayed any longer given the rapid tumor growth, which could likely be associated with pregnancy. After discussion with at a cancer board consisting of experts from the departments of gastroenterology, obstetrics and gynecology, and surgery, as well as obtaining appropriate informed consent from the patient and her family, we decided to perform hepatic resection after abortion. Subsequently, abortion surgery was performed at 21 weeks and 2 days of pregnancy, followed by subsegmentectomy of liver segment 7 under general and epidural anesthesia 6 days later. Mental care for the patient was provided by obstetricians, surgeons, and nurses before and after abortion. After mobilizing the right lobe of the liver, we identified the Glissonian pedicle (G) 7 and injected indigo carmine under US guidance to mark the perfusion area. Thereafter, hepatic resection was initiated using an ultrasonic dissector under the Pringle’s maneuver. After identifying the G7, a clamp test was performed to reconfirming the ischemic area before ligating and cutting it. We continued hepatic resection along the RHV, exfoliated a tumor within the vicinity of a root of the RHV, and subsequently completed subsegmentectomy of liver segment 7 (Fig. ). The surgery lasted 274 min, with an estimated blood loss of 940 mL. Macroscopically, the whitish tumor with a maximum diameter of 4.0 cm was simple nodular type and showed expansive growth (Fig. ). A pathological diagnosis of moderately differentiated HCC, grade II, eg, fc (−), sf (+), s0, vp0, vv0, b0, im0, and sm (−) was thereafter established. Tumor cells showed a moderate degree of atypia, as well as a cord-like or pseudoglandular arrangement associated with abundant eosinophilic vesicles and a rich nucleoplasm. Given the good postoperative course, without particular complications, the patient was discharged 10 days after surgery. Approximately 2 years after surgery, the patient remains alive without recurrence, while both AFP and PIVKA-II were within normal limits.


A 66-year-old man with esophageal obstruction was admitted to a different hospital. He was referred to our institution following diagnosis of BEAC. Endoscopy revealed a squamocolumnar junction 24 cm from the incisor teeth and a type-3 circumferential tumor on the lower esophagus (Fig. ). Mucosal biopsy revealed adenocarcinoma.
Computed tomography detected an enlarged lymph node but no other distant metastatic sites. Following diagnosis of cT3N1M0, subtotal esophagectomy with lymph node dissection was performed after three courses of S-1 + oxaliplatin therapy.
The postoperative pathological diagnosis was of poorly differentiated adenocarcinoma (T3 70 × 45 mm) with lymph node metastasis (N3) (pT3 pN3 pM0 pStage III; Fig. ). Two years after the operation, the patient showed recurrence in the region of the celiac artery and is currently undergoing chemotherapy.


An 83-year-old woman who had undergone upper gastrointestinal endoscopy for detailed examination of anemia was referred to our hospital with a diagnosis of BEAC.
Endoscopy revealed a squamocolumnar junction 15 cm from the incisor teeth and a type-2 semicircular tumor on the upper esophagus (Fig. ). Mucosal biopsy showed adenocarcinoma.
Computed tomography detected enlarged cervical paraesophageal lymph nodes (#101) with no other distant metastatic sites. Following diagnosis of cT3N1M0, subtotal esophagectomy with lymph node and neck dissection were performed. The postoperative pathological diagnosis was of well-differentiated adenocarcinoma (60 × 52 mm) with supraclavicular lymph node metastasis (pT3 pN3 pM1 pStage IV; Fig. ). Two months after the operation, the patient was diagnosed with recurrence in the neck lymph nodes, for which she underwent chemotherapy; however, she died.


A 66-year-old man diagnosed with BEAC in a periodic medical check-up was referred to our institution.
Endoscopy revealed a squamocolumnar junction 20 cm from the incisor teeth and a type 0-IIb + IIc tumor with indistinct boundaries 30 cm from the incisor teeth (Fig. ). Mucosal biopsy revealed adenocarcinoma.
Computed tomography detected no enlarged lymph nodes and no other distant metastatic sites. Following diagnosis of cT1aN0M0 based on the Union for International Cancer Control TNM Classification 8th edition, subtotal esophagectomy was performed with lymph node and neck dissection. The postoperative pathological diagnosis was of well-differentiated adenocarcinoma (143 × 56 mm) with no lymph node metastasis (pT1a pN0 pM0 pStage 0 based on the Union for International Cancer Control TNM Classification 8th edition; Fig. ). The patient was found to be alive and recurrence-free 3 months after the operation.


Patient 1 was a 58-year-old man who presented to the ED with a 2-week history of worsening dyspnea on exertion accompanied by bilateral lower extremity edema. He had a history of regular cocaine use and a diagnosis of heart failure with reduced ejection fraction (HFrEF) with the last EF being 15% 1 month prior to his ED visit. He described a diet that was high in salt intake and alcohol use. Physical exam was notable for tachycardia, but had otherwise normal vitals. He had audible pulmonary crackles and an S3 gallop on auscultation. He also had 3+ pitting edema extending up to the knees and jugular venous pressure of 12 mm Hg. Laboratory results were notable for an N-terminal pro b-type natriuretic peptide (NT-pro BNP) of 5279 pg/mL. His troponin, electrolytes and creatinine were normal.


Patient 2 was a 53-year-old man with a history of HFrEF due to ischemic cardiomyopathy from a recent coronary angiogram, presenting with a 3-day history of dyspnea (at rest and exertion) and orthopnea. He reported no improvement after taking his home dose of oral furosemide. He had an EF of 15% four months prior to his ED visit. Physical exam was notable for stable vitals. He appeared to be mildly dyspneic and had bilateral crackles on auscultation. His JVP was 14 mmHg. Laboratory results revealed an NT-pro BNP of 1209 pg/mL. His troponin and electrolytes were normal. His chest X-ray showed cardiomegaly with pulmonary vascular congestion.
Please see Table and Fig. for the 3DE measurements.


A 43-year-old female shiatsu therapist with 20 years of experience complained of sudden snapping of the MCPj of the left ring finger (her nondominant hand) and pain in the dorsum of the MCPj. The patient did not have any conditions that would predispose her to sagittal band laxity including prior trauma to the hand. Two weeks later, the snapping and pain occurred in the right ring finger. On physical examination, the extensor tendons at the dorsum of the MCPjs of both ring fingers dislocated with a specific hand posture (). On actively extending the MCPjs of the ring fingers, the extensor tendons reduced with snapping. However, the ring finger extensor tendon did not dislocate if both the middle and ring finger MCPjs were flexed together. Radiography revealed no MCPj deformity. The patient did not comply with nonoperative treatment such as MCPj extension bracing because she could not continue work with bracing.
Four weeks after the first visit, we performed reconstruction of the extensor tendons of the both ring fingers with wrist blocks. Surgical exploration through a longitudinal curved skin incision at the dorsum of the MCPj of the ring finger revealed a markedly attenuated radial sagittal band and ulnarly dislocated extensor tendons bilaterally (). We plicated the juncturae tendinum of the extensor digitorum communis between the middle and ring fingers and released the ulnar sagittal band partially to centralise the extensor tendon excursion without dislocation, through the full range of motion of the MCPj intraoperatively. We also tested the range of motion of the active finger.
Postoperatively, we applied a bulky hand dressing with a forearm-based volar plaster splint to the MCPj in the extended position in order to prevent inadvertent passive flexion of the MCPj. Active flexion and extension exercises were performed from 1 to 6 weeks postoperatively. Six weeks postoperatively, we removed the splint and allowed all MCPj movements. Six months postoperatively, the patient resumed work as a shiatsu therapist without extensor tendon dislocation and snapping at the MCPjs. All finger movements were performed with no limitations in either hand. Twenty-six months postoperatively, the patient remained pain-free during work without extensor tendon dislocation or snapping in either hand.


Case 4 (Fig. ). This was a 55-year-old male patient with an IL-10 level of 16,107 pg/mL and an IL-10/IL-6 ratio of 29.04 at baseline. He presented with severe retinal infiltration and we decided to monitor his cytokine levels monthly. Positron emission tomography-computed tomography and magnetic resonance imaging did not show any brain involvement. After initiation of intravitreal MTX treatment, the IL-10 and IL-6 levels dramatically decreased from 16,107 pg/mL and 554.7 pg/mL to 8.6 pg/mL and 3.5 pg/mL, respectively. The IL-10/IL-6 ratio also decreased from 29.04 to 2.46 and was lower than 1 after 3 months. Five months after therapy start, the IL-10 level increased to 917.2 pg/mL and the IL-10/IL-6 ratio also increased to 344.46. The patient was re-evaluated and was diagnosed with large B-cell lymphoma in the nasal cavity and cervical lymph nodes. Retreatment with systemic and intravitreal chemotherapy was administered. A linear decrease in the aqueous IL-10 level was observed during the treatment, with the level becoming undetectable after 1 month of treatment, as is maintained to present (12 months later).


Case 10 (Fig. ). This was a 72-year-old male patient in whom PVRL was confirmed by diagnostic vitrectomy and who had CNS involvement. The initial mean intraocular IL-10 level was 361.7 pg/mL; it decreased to 170.1 pg/mL at 24 h and 70.6 pg/mL at 72 h after MTX injection, and became undetectable at 1 month after treatment onset. The initial IL-10/IL-6 ratio was 1.39, and a similar decrease was observed until it reached 0.01 over time. The patient was followed up for 4 months and had received 12 MTX injections when his IL-10 level increased to 267.5 ng/L and the IL-10/IL-6 ratio increased to 1.51. At the same time, recurrence was detected clinically with reappearance of vitritis. The patient received a new intravitreal MTX injection that improved the vitritis and normalized the IL-10 level by the 1-month visit. He has been under observation for 8 months.


A 41-year-old woman presented to our department with cyanosis, dyspnea and plethora. The patient suffered from chronic kidney disease (CKD) and ToF, for which she was treated palliatively in the past. On admission, her oxygen saturations were 66.6% on room air. Blood tests revealed a red blood cell count of 7.54 × 1012/L, hemoglobin 21.8 g/dL and hematocrit as high as 71%. Ferritin level was 73 ng/mL. Liver function tests revealed bilirubin levels to be 0.9 mg/dL, aspartate aminotransferase 50 U/L and alanine aminotransferase 43 U/L. A creatinine level of 3.5 mg/dL and urea 171 mL/dL indicated ESRD. A total calcium amount of 8.2 mg/dL, inorganic phosphates 6.5 mg/dL and parathyroid hormone level of 748.7 pg/mL were suggestive of secondary hyperparathyroidism. Metabolic acidosis was recognized with a pH of 7.196 and bicarbonates at 13.6 mmol/L. An ultrasound scan showed horseshoe kidney and liver with increased echogenicity.
Dysmorphic facial features were also observed, which included a prominent forehead, deep set eyes, pointed and small chin and hypertelorism (Fig. ). These characteristics, combined with horseshoe kidney, were highly suggestive of an undefined genetic syndrome, prompting further clinical investigation and genetic testing. Imaging revealed thoracic scoliosis and a deformed thoracic cage with decreased anterioposterior diameter. Skeletal anomalies typical of ALGS, such as butterfly vertebrae, were not observed. Ophthalmologic examination showed grade 3 hypertensive retinopathy and dry eye syndrome. It is worth mentioning that the patient had no family history of any genetic disease.
The patient’s physical development was impaired and, as a consequence, intellectual abilities were also diminished. A complex medical history resulting in social isolation, together with low socioeconomic status, likely impeded the patient’s learning and development potential.
Before admission to our department, the patient had already had an extensive past medical history. Some of her first symptoms, including cyanosis, were present at birth, however, neonatal jaundice was not reported. The diagnosis of ToF was made at the age of 12. Due to severe hypoplasia of the pulmonary vascular bed, a Blalock-Taussig shunt (a shunt between the right subclavian artery and right pulmonary artery) was performed on the right side. After a short period of observation, the shunt became occluded, and thus at the age of 14, a Blalock-Taussig shunt was applied on the left. When the patient was 33, she underwent multiple venesections due to grossly elevated hemoglobin levels (25.0 g/dL) and a hematocrit of 73.5%. However, phlebotomies had little effect on these parameters and were soon discontinued. Five years later, due to narrowing of the left shunt to 3 mm, stent implantation was performed. The intervention resulted in shunt flow with a maximal gradient of 124 mmHg. SaO2 increased from 68 to 82%. In contrast, the decreases in hemoglobin and hematocrit were deemed insignificant. Computed tomography (CT) of the heart performed at that time revealed ventricular septal defect of 10 mm in the membranous part of the septum, an overriding aorta with tricuspid aortal valve, very pronounced hyperplasia of the right ventricle, pulmonary stenosis, hypoplasia of the pulmonary trunk and extrapulmonary parts of the pulmonary arteries and an enlarged right atrium. When the patient was 41 years old, restenosis of the left shunt began to occur, likely due to pronounced polycythemia. In the following years, balloon angioplasty was performed twice. However, neither shunt flow nor the patient’s clinical condition improved significantly. The hemoglobin and hematocrit levels did not decrease and remained stable at 22 g/dL and 70%, respectively. Minimal flow through the left shunt was preserved. Lastly, echocardiography that the patient had at the age of 44 confirmed hyperplasia of the right ventricle (thickness of 12 mm) with preserved, good contractility (TAPSE of 23 mm). Very slight tricuspid regurgitation was visible together with signs of pulmonary hypertension (S’tr 8 cm/s).
Due to central cyanosis, the patient was suffering from repeated episodes of loss of consciousness and vertigo. She also had hypothyroidism. Moreover, the patient had suffered from hypertension since her late twenties. At the beginning, a combination of an ACE inhibitor, beta blocker and diuretic was used, but shortly after the initiation of treatment, the ACE inhibitor and diuretic were discontinued due to hyperkalemia. Her medication was limited to the beta blocker. This was sufficient until the age of 36, when the patient’s renal function started deteriorating. The patient and her mother claimed that values of blood pressure at home would fall below 140/90, but measurements at our department varied between 130/65 and 180/73 mmHg. They were performed on the patient’s leg due to the patient’s slim arms. At that time, treatment was limited to furosemide, bisoprolol and clonidine. Hepatitis and HIV screens were negative, although the patient had a record of HCV infection in the past.
With respect to the liver, bilirubin levels always remained within normal range during the 4 years of treatment at our department. Aspartate and alanine aminotransferase, though slightly elevated on admission, also remained within normal range most of the time. However, on several occasions, alkaline phosphatase was elevated, reaching values as high as 754 U/L during episodes of peritonitis.
Over time, progression to ESRD was observed. Proteinuria was not very pronounced with levels ranging between 100 and 500 mg/dL, while residual diuresis was 500 mL. Renal biopsy was never performed because the patient did not consent to it. When the patient was admitted to our department at the age of 41, renal replacement therapy was introduced. Continuous ambulatory peritoneal dialysis (CAPD) was chosen. After the introduction of CAPD, diuresis decreased to 200 mL. The mother was taught to successfully assist with CAPD. Acidosis was not compensated despite CAPD. The patient had regular appointments at the dialysis station. At the age of 44, two episodes of peritoneal dialysis-related peritonitis occurred, with the second episode being complicated by an ischemic stroke of the left hemisphere. Although it was successfully managed with conservative treatment, in the next 2 months, the overall condition of the patient gradually deteriorated. Both the patient and her family refused further hospitalizations. She died at the age of 45 and an autopsy was not performed.


A 4-month-old male, with no significant medical history, upon birth presented papular, erythematous lesions on approximately 90% of the body surface, later turned into crusty, painful lesions, some bleeding, which disappeared with finger pressure. Initially, he consulted a medical center where they took a skin biopsy with findings suggestive of histiocytosis (Figure ).
Physical examination revealed crusted hyperemic lesions on the soft and hard palates, no masses or hepatosplenomegaly were palpable in the abdomen, there were widespread scattered lesions of the skin of varying size, erythematous, some dry with crusts, others with little bleeding suggestive of cell histiocytosis from Langerhans. Rest of the physical examination without relevant findings. The admission exams showed a hemoglobin of 9.8 mg/dl, platelets 32 × 109/L, fibrinogen 57 gr/dl, prothrombin time (PT) 22.1 seconds (control 13 seconds), partial thromboplastin time (PTT) 34.7 seconds (control 31.2 seconds), preserved kidney and liver function, normal electrolytes, negative serology results for hepatitis B and C, human immunodeficiency virus (HIV), Epstein Barr virus (EBV) and human cytomegalovirus (HCMV).
Extension studies were performed, an ultrasound of the abdomen showed splenomegaly (Figure ). In the bone series, no bone or soft tissue lesions were detected, the chest radiograph was normal, echocardiogram without alterations, the peripheral blood smear showed slight anisocytosis with macrocytes and microcytes. The myelogram was hypocellular with mainly granulocytic and erythroid hematopoiesis (Figure ).
Skin biopsy revealed some attenuation by exocytosis of inflammatory cells with erosion and inflammatory scab on the epidermis, strong reactivity of the positive cells for CD68, protein S100, CD1a, and langerin, a low and reactive CD3 T lymphoid population and negative CD20. Cytokeratin 5/6 highlighted attenuation and erosion of the epidermis in some areas by the massive infiltration of positive cells. Compromise by histiocytosis of LC was considered (Figure ).
The bone marrow aspirate sample was cytogenetically performed, the conventional karyotype was normal, and the BRAF V600E mutation was detected.
With the diagnosis of LCH with a multisystem and risk organ compromise, it was decided to start chemotherapeutic management with a prednisone and vinblastine scheme.
The evaluation at the end of the first chemotherapy cycle showed anemia (hemoglobin 9 mg/dl), the chest radiograph was normal, and hepatosplenomegaly was documented in the total abdomen ultrasound, the bone marrow biopsy without histiocytosis.
It was considered that it was a refractory histiocytosis, so it was decided to administer a second line of treatment, with a regimen based on cladribine and cytarabine. Studies after two cycles of this regimen showed persistent anemia, normal liver and kidney function, total abdominal ultrasound with a slight parenchymal liver disease without hepatomegaly or splenomegaly, and bone marrow biopsy with infiltration by LCH (Figure ).
Given the partial response to the second line of chemotherapy, the administration of a third cycle was indicated.


A 30-year-old woman was referred for genetic counseling and prenatal diagnosis at 19 weeks of gestation in the Center for Reproductive Medicine and Center for Prenatal Diagnosis of First Hospital of Jilin University. Nineteen weeks sonography findings indicated that increased nuchal translucency was detected in prenatal ultrasound. And the woman had a history of spontaneous abortion. There was no teratogenic exposure or infectious diseases during mother pregnancy. She and her husband claimed that they were nonconsanguineous and healthy, and no family histories of diabetes mellitus or congenital malformations were found. The study protocol was approved by the Ethics Committee of the First Hospital of Jilin University (No.2019–283), and the informed written consents were obtained from this couple for publication of this case report and accompanying images.


A 62-year-old Malay lady with no known comorbid presented to the ophthalmology department with left eye central scotoma for a month duration. Otherwise, there was no other significant associated symptom. The visual acuity was 6/24 in the left eye and 6/9 in the right eye with intraocular pressure of 16 mmHg bilaterally. There was no relative afferent pupillary defect. Anterior segment revealed unremarkable findings with immature cataract bilaterally. Posterior segment examination showed both eyes ODD with “lumpy-bumpy” appearance and indistinct irregular disc margin. In addition, the left eye ODD was associated with an orange nodule temporal to optic disc with minimal subretinal hemorrhage (Figure ) (Abstract of unpublished E-poster: Krishnan S, Ali H, Ling KP, and Teh WM. Is Optic Disc Drusen Associated with Idiopathic Polypoidal Choroidal Vasculopathy? 11th Asia-Pacific Vitreo-Retina Society Congress (APVRS) 2017, Kuala Lumpur Convention Center, Malysia; December 8-10, 2017).
Ultrasound B-scan showed moderately high reflectivity over the elevated optic disc consistent with surface ODD (Figure ). Red-free photography revealed autofluorescence of the drusen bilaterally without fluorescein administration. Optical coherence tomography (OCT) macula of the left eye showed peripapillary pigment epithelial detachment at the region corresponding to the nodule, with subretinal fluid approaching the fovea level (Figure ). The peripapillary pigment epithelial detachment was associated with a double-layer sign suggestive of PCV. Indocyanine green angiographies (ICGA) of the left eye revealed the presence of peripapillary polyps with branching vascular network that further confirmed the diagnosis of PCV and excluded CNV secondary to ODD (Figure ) (Abstract of unpublished E-poster: Krishnan S, 2017).
Thus, her left eye was treated with combination therapy, including a photodynamic therapy (PDT) session, followed by three monthly intravitreal anti-vascular endothelial growth factors (VEGF) injection. After three months of injection, OCT showed completely resolved subretinal fluid and her left eye vision was improved to 6/9. During 12-month follow-up period, no recurrence was noted and visual acuity remained stable (Abstract of unpublished E-poster: Krishnan S, 2017).