Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Rare Case of Immune-Mediated Necrotizing Myopathy With Isolated Dysphagia as Presenting Symptom

Introduction: Immune mediated necrotizing myopathy (IMNM) is a rare, but progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in 20-30% of IMNM patients. It often follows proximal muscle weakness and ensues in the later stages of the disease. We report a rare case of IMNM, presenting with dysphagia as the initial symptom, followed by proximal muscle weakness. Case Description/Methods: A 74-year-old male with a past medical history of coronary artery disease, hypertension, and hyperlipidemia presented to the ED with 2-3 weeks of intractable nausea, vomiting, and dysphagia for solids and liquids. Vital signs were stable, and initial labs displayed an AST of 188 U/L and ALT of 64 U/L with a normal bilirubin. Computed tomogram of the chest, abdomen, and pelvis were negative. An esophagram showed moderate to severe tertiary contraction, no mass or stricture, and a 13 mm barium tablet passed without difficulty. Esophagogastroduodenoscopy exhibited a spastic lower esophageal sphincter. Botox injections provided no significant relief. He then developed symmetrical proximal motor weakness and repeat labs demonstrated an elevated creatine kinase (CK) level of 6,357 U/L and aldolase of 43.4 U/L. Serology revealed positive PL-7 autoxantibodies, but negative JO-1, PL-12, KU, MI-2, EJ, SRP, anti-smooth muscle, and anti-mitochondrial antibodies. Muscle biopsy did not unveil endomysial inflammation or MHC-1 sarcolemmal upregulation. The diagnosis of IMNM was suspected. A percutaneous endoscopic gastrostomy feeding tube was placed as a mean of an alternative route of nutrition. He was started on steroids and recommended to follow up with outpatient rheumatology. He expired a month later after complications from an unrelated COVID-19 infection. Discussion(s): The typical presentation of IMNM includes painful proximal muscle weakness, elevated CK, presence of myositis-associated autoantibodies, and necrotic muscle fibers without mononuclear cell infiltrates on histology. Dysphagia occurs due to immune-mediated inflammation occurring in the skeletal muscle of the esophagus, resulting in incoordination of swallowing. Immunotherapy and intravenous immunoglobulin are often the mainstay of treatment. Our patient was unique in presentation with dysphagia as an initial presenting symptom of IMNM, as well as elevated enzymes from muscle breakdown. It is critical as clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and refractoriness to treatment.

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

Syphilis: "The Great Imitator" Presenting as Acute Hepatitis

Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).

Myocardin Reverses Hypoxia-Inducible Factor-1α Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride.

PURPOSE: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro. MATERIALS AND METHODS: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF-1α and Myocd was evaluated. RESULTS: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 µM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression. CONCLUSIONS: Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.

Clinical, Histological and Serological Features of Autoimmune-Like Acute Liver Injury after Sars-Cov-2 Vaccination

Introduction and Objectives: Acute autoimmune-like liver injury has been increasingly reported after vaccination against SARS-CoV-2. Pathogenesis, steroid requirement and long-term prognosis are unknown. This study aimed to evaluate clinical, serological and histological features, response to treatment and prognosis in patients with post-vaccination acute hepatitis. Material(s) and Method(s): We included patients without known pre-existing liver diseases with transaminase levels >= 2.5 upper limits of normal within 90 days after the SARS-CoV-2 vaccine with an available liver biopsy. Clinical data and outcomes after a six months follow-up were collected. Result(s): 17 patients were included,12 females, median age 60 (51,5/66) exposed to vectorial (Sputnik V n=7, AstraZeneca n=6), inactivated (Sinopharm n=3) or ARNm Vaccines (Moderna=1). In 8 patients, liver injury developed after the first dose and in 7 after the second dose and in 2 after the third dose. The median time to the development of injury was 33(23,50/53,50) days. Eight patients had a history of extrahepatic autoimmune disease and five patients had metabolic syndrome and used statins. Immune serology showed anti-antinuclear antibody in 10 (58,8%), anti-smooth muscle antibody in 5(29,4%). 14/17 patients presented with elevated IgG levels. Liver histology showed lobular hepatitis in 13/17, portal hepatitis in 17/17 with plasmocytic lymphocytic infiltrate and 4/17 had eosinophils, 6/17 with severe interface hepatitis, and one patient had fibrosis Ishak stage >=3. 12/17 (70,5%) were treated with steroids. Transaminases improved in 17 cases and normalized in 6/12 by month 6. Only 1/17 developed liver function deterioration, yet no patient required liver transplantation. Most patients tolerated the tapering of steroids and in 6 azathioprine was started before month 3. Conclusion(s): Long-term follow-up might help to differentiate between induced classical autoimmune hepatitis, autoinflammatory self-limited events, or drug-induced liver injury in these patients.Copyright © 2023

Involvement of the chemerin-ChemR23 system in severe COVID-19 patients

Background: ChemR23 knock-out mice displays aggravated viral pneumonia, with similar features as observed in severe COVID-19 patients. Aims and objectives: We evaluated the involvement of the chemerin-ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic role. Method(s): Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC). Result(s): 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. The concentration of chemerin in plasma was significantly higher in ICU patients vs HC at any time-point (p<.0001) and also when comparing deceased patients vs survivors (p=.02). In line with that, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein, interleukin-6 and tumour necrosis factor alpha. Plasmacytoid dendritic cells and natural killers (NK) cells were strongly decreased in hospitalized and ICU COVID 19 patients. On NK cells of all COVID 19 patients, the expression of ChemR23 was reduced regardless its severity. Moreover, IHC analysis showed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts during the organizing phase of acute respiratory distress syndrome (ARDS). Conclusion(s): Chemerin is an early marker of severity in COVID-19 patients and could be involved in lung fibrosis post-ARDS.

Case Report: Induced Lactation in an Adoptive Parent

Letters

Emergency Management of Priapism

Pathophysiology To have an erection, the smooth muscle of the cavernosal arteries and tissue must be relaxed, resulting in increased non-ischemic inflow and decreased venous outflow. The sickling of red blood cells can decrease venous outflow in the corpora cavernosa during an erection leading to low-flow priapism in men with sickle cell disease. Doppler ultrasound can be utilized to observe if blood flow is low or absent, but corporal aspiration is the gold standard. Adjunctive laboratory evaluation should be performed based on the clinical concern for blood dyscrasia or other conditions affecting clinical decision-making.

An Unexpected Enzyme in Vascular Smooth Muscle Cells: Angiotensin II Upregulates Cholesterol-25-Hydroxylase Gene Expression.

Angiotensin II (AngII) is a vasoactive peptide hormone, which, under pathological conditions, contributes to the development of cardiovascular diseases. Oxysterols, including 25-hydroxycholesterol (25-HC), the product of cholesterol-25-hydroxylase (CH25H), also have detrimental effects on vascular health by affecting vascular smooth muscle cells (VSMCs). We investigated AngII-induced gene expression changes in VSMCs to explore whether AngII stimulus and 25-HC production have a connection in the vasculature. RNA-sequencing revealed that Ch25h is significantly upregulated in response to AngII stimulus. The Ch25h mRNA levels were elevated robustly (~50-fold) 1 h after AngII (100 nM) stimulation compared to baseline levels. Using inhibitors, we specified that the AngII-induced Ch25h upregulation is type 1 angiotensin II receptor- and Gq/11 activity-dependent. Furthermore, p38 MAPK has a crucial role in the upregulation of Ch25h. We performed LC-MS/MS to identify 25-HC in the supernatant of AngII-stimulated VSMCs. In the supernatants, 25-HC concentration peaked 4 h after AngII stimulation. Our findings provide insight into the pathways mediating AngII-induced Ch25h upregulation. Our study elucidates a connection between AngII stimulus and 25-HC production in primary rat VSMCs. These results potentially lead to the identification and understanding of new mechanisms in the pathogenesis of vascular impairments.

Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.

BACKGROUND: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise. METHODS AND RESULTS: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8-71.7]; picrosirius red 68.6% [95% CI: 64.4-72.8]} vs. controls [MT 64.9% (95% CI: 59.4-70.3) (P = 0.028); picrosirius red 60.1% (95% CI: 55.4-64.8), (P = 0.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9-49.3) vs. controls (10.0%; 95% CI: 4.4-15.6) (P < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated. CONCLUSION: Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.

Uptake of severe acute respiratory syndrome coronavirus 2 spike protein mediated by angiotensin converting enzyme 2 and ganglioside in human cerebrovascular cells.

Introduction: There is clinical evidence of neurological manifestations in coronavirus disease-19 (COVID-19). However, it is unclear whether differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/spike protein (SP) uptake by cells of the cerebrovasculature contribute to significant viral uptake to cause these symptoms. Methods: Since the initial step in viral invasion is binding/uptake, we used fluorescently labeled wild type and mutant SARS-CoV-2/SP to study this process. Three cerebrovascular cell types were used (endothelial cells, pericytes, and vascular smooth muscle cells), in vitro. Results: There was differential SARS-CoV-2/SP uptake by these cell types. Endothelial cells had the least uptake, which may limit SARS-CoV-2 uptake into brain from blood. Uptake was time and concentration dependent, and mediated by angiotensin converting enzyme 2 receptor (ACE2), and ganglioside (mono-sialotetrahexasylganglioside, GM1) that is predominantly expressed in the central nervous system and the cerebrovasculature. SARS-CoV-2/SPs with mutation sites, N501Y, E484K, and D614G, as seen in variants of interest, were also differentially taken up by these cell types. There was greater uptake compared to that of the wild type SARS-CoV-2/SP, but neutralization with anti-ACE2 or anti-GM1 antibodies was less effective. Conclusion: The data suggested that in addition to ACE2, gangliosides are also an important entry point of SARS-CoV-2/SP into these cells. Since SARS-CoV-2/SP binding/uptake is the initial step in the viral penetration into cells, a longer exposure and higher titer are required for significant uptake into the normal brain. Gangliosides, including GM1, could be an additional potential SARS-CoV-2 and therapeutic target at the cerebrovasculature.

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)

CircRNAs: Key molecules in the prevention and treatment of ischemic stroke.

Ischemic stroke is a prevalent disease that seriously threatens human health. It is characterized by high morbidity, mortality, disability, and recurrence rates, causing a significant economic burden on individuals and society. Circular RNA, a novel non-coding RNA, not only serves as the sponge for microRNAs and proteins but also promotes transcription of their parental genes and translates into peptides. In recent years, circRNAs have emerged as key regulators in ischemic stroke. This article aims to provide new ideas about the pathogenesis and progression of ischemic stroke by reviewing the roles of circRNAs in cerebral ischemic injury and summarizing the association between circRNAs and risk factors for ischemic stroke.

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs.

Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. COVID-19 patients with cardiovascular disorder (CVD) develop a more severe disease course with a significantly higher mortality rate than non-CVD patients. A common denominator of CVD is the dysfunction of endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in COVID-19 patients suffering from CVD are caused by SARS-CoV-2 infection of ECs through the angiotensin-converting enzyme 2 (ACE2) receptor and the cellular transmembrane protease serine 2 (TMPRSS2) and the consequent dysfunction of the infected vascular cells. Meanwhile, other factors associated with SARS-CoV-2 entry into the host cells have been described, including disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), the C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss the current data about the putative entry of SARS-CoV-2 into endothelial and smooth muscle cells. Furthermore, we highlight the potential role of long non-coding RNAs (lncRNAs) affecting vascular permeability in CVD, a process that might exacerbate disease in COVID-19 patients.

Severe progression of autoimmune hepatitis in a young COVID-19 adult patient: A case report

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

MALIGNANT GLOMUS TUMOR WITH UNSTABLE HEMORRHAGE

SESSION TITLE: Critical Complications of Cancer Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Glomus tumors are rare, benign neoplasms made up of cells resembling modified smooth muscle cells of glomus bodies. Glomus bodies are a type of arteriovenous anastomosis located primarily in dermal soft tissue and responsible for thermoregulation (1). Glomus tumors are suspected when presenting with a classic triad of severe pain, pinpoint tenderness, and hypersensitivity to cold (2). A vast majority of glomus tumors are benign with less than 1% demonstrating malignant pathology. Extradigital glomus tumors can occur, but often lack the typical presentation, making them difficult to diagnose. Treatment is surgical excision. CASE PRESENTATION: We report a case of a 35 year old female with past medical history of diabetes mellitus and morbid obesity who presented with a large 4cmX5cm fungating mass of the left posterior thigh (Figure 1 and 2). The patient was admitted to the ICU for concurrent acute hypoxemic respiratory failure secondary to COVID-19 pneumonia. The patient never received full dose anticoagulation. Due to the patient's instability, surgical evaluation was initially deferred until the patient began experiencing significant hemorrhage from the fungating mass (Figure 3), which correlated with a precipitous drop in hemoglobin requiring multiple transfusions. The mass was surgically excised (Figure 4), but continued bleeding, necessitating blood transfusions. Further evaluation of the mass by pathology established the mass as "Malignant glomus tumor showing chiefly spindle cell morphology, arising from a pre existing benign glomus tumor… showing some stromal oncocytic change as well as degenerative-appearing nuclear atypia and calcification.” The patient remained under ICU care through the remainder of her hospital stay for COVID-19 and sequela. Despite treatment, her clinical status worsened, the patient decompensated secondary to COVID-19, and the decision was made by the family to proceed with comfort measures. DISCUSSION: This patient presented with an abnormal fungating mass without symptoms typically consistent with glomus tumor. The mass displayed a malignant transformation, making it particularly unique. The case was further distinguished by hemorrhage and hemorrhagic shock directly related to the mass. Although this patient experienced a complicated course due to the hemorrhage requiring multiple postoperative transfusions, the patient was eventually stabilized and hemostasis was obtained. While it remains unclear if her malignant glomus tumor conferred increased risk of mortality from COVID-19, it is the author's belief that more research should be done to identify if a relationship between all type cancer and COVID-19 mortality exists. CONCLUSIONS: This case represents a unique case of malignant glomus tumor with previously undescribed presenting symptoms. Reference #1: 1. Gombos, Z., & Zhang, P. J. (2008). Glomus tumor. Archives of Pathology & Laboratory Medicine, 132(9), 1448–1452. https://doi.org/10.5858/2008-132-1448-gt Reference #2: 2. Sbai, M. A., Benzarti, S., Gharbi, W., Khoffi, W., & Maalla, R. (2018). Glomus tumor of the leg: A case report. Pan African Medical Journal, 31. https://doi.org/10.11604/pamj.2018.31.186.9706 Reference #3: 3. Aiba, M., Hirayama, A., & Kuramochi, S. (1988). Glomangiosarcoma in a glomus tumor. An immunohistochemical and ultrastructural study. Cancer, 61(7), 1467–1471. https://doi.org/10.1002/1097-0142(19880401)61:7<1467::aid-cncr2820610733>3.0.co;2-3 DISCLOSURES: No relevant relationships by Syed Akbarullah No relevant relationships by Devin Bradshaw No relevant relationships by LLOYD Del Mundo No relevant relationships by Gerard DiChiara No relevant relationships by Dushawn Harley No relevant relationships by Jerome Hruska No relevant relationships by Ian Ogurek No relevant relationships by Xenia Schneider No relevant relationships by Paul Stewart No relevant relationships by Joseph Telliard No elevant relationships by Ilya Yegudkin

THE MONSTROSITY OF MAGNESIUM CITRATE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Magnesium citrate is an osmotic laxative which is occasionally used in the intensive care unit (ICU) for refractory constipation. We present a patient in whom a bowel regimen containing magnesium citrate resulted in severe hypermagnesemia with paralytic ileus, requiring renal replacement therapy. CASE PRESENTATION: 70-year-old male was admitted to the ICU for COVID-19 associated acute hypoxic respiratory failure and suffered multi-day, refractory constipation, treated with one dose of 17 grams of magnesium citrate. Vital signs were remarkable for bradycardia and hypotension. On examination, patient was lethargic and the abdomen was soft and non-distended, but there were decreased bowel sounds throughout. Subsequently, laboratory findings were notable for a magnesium level of 8.8 mg/dL and serum creatinine of 2.3 mg/dL (estimated glomerular filtration rate 28mL/min/1.73m2), all of which were previously normal at admission. Computerized Tomography of the abdomen was performed showing dilated cecum, ascending and transverse colon and moderate to large amount of intraluminal rectal stool and air. Patient was started on intravenous fluids, loop diuretics, and calcium gluconate, however, the patient required renal replacement therapy for magnesium clearance. Patient clinically improved with normalization of kidney function and magnesium levels as well as resolution of ileus. DISCUSSION: Magnesium homeostasis is regulated by gastrointestinal absorption and renal excretion, for which the kidney maintains magnesium equilibrium until creatinine clearance falls below 20 ml/min [1]. Elevated magnesium levels can decrease bowel motility by blocking myenteric neurons and interfere with excitation - contraction coupling of smooth muscle cells as well as serve as a reservoir for continuous magnesium absorption [2]. Our patient suffered acute kidney injury, likely from COVID-19 pneumonia and acute tubular necrosis from shock, placing him at increased risk for hypermagnesemia. One retrospective study identified that patients with COVID-19 are more prone to the development of hypermagnesemia, which is associated with renal failure and increased risk of mortality [3]. The magnesium load from magnesium citrate in our patient created for a seemingly out of proportion effect of hypermagnesemia-induced paralytic ileus and presumably a magnesium reservoir, refractory to conservative measures. CONCLUSIONS: The use of magnesium containing bowel regimens should be considered with caution due to the possibility of hypermagnesemia in at-risk patients, which may result in paralytic ileus and other sequelae. Hypermagnesemia reduces colonic peristalsis and interferes with magnesium equilibrium, prolonging its effects. There are rare case reports in the literature discussing this phenomenon, but should be further evaluated for specific patient susceptibility and effects on morbidity and mortality. Reference #1: Cascella, M. (2022, February 5). Hypermagnesemia. StatPearls [Internet]. Retrieved March 16, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK549811/ Reference #2: Bokhari, S., Siriki, R., Teran, F., & Batuman, V. (2018, September 8). Fatal Hypermagnesemia due to laxative use. The American Journal of the Medical Sciences. Retrieved March 16, 2022, from https://www.amjmedsci.org/article/S0002-9629(17)30467-6/fulltext Reference #3: Stevens, J. S., Moses, A. A., Nickolas, T. L., Husain, S. A., & Mohan, S. (2021, July 29). Increased mortality associated with hypermagnesemia in severe covid-19 illness. American Society of Nephrology. Retrieved March 16, 2022, from https://kidney360.asnjournals.org/content/2/7/1087 DISCLOSURES: No relevant relationships by Adnan Abbasi No relevant relationships by Sarah Upson