Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma.

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management.

FUT2 gene as a genetic susceptible marker of infectious diseases: A Review

Some blood group antigens are reported as a susceptibility marker for some diseases. For instance, HBGA (Histo-blood group antigen) which is controlled by gene FUT2 also considered as a susceptible marker. The FUT2 gene which exhibits the expression of alpha-1, 2-L-fucosyltransferase enzyme also leads to HBGA expression for the gut, and it provides a composition of the phenotypical profile that exists in some populations with unique histories of evolution and it can be considered as a marker of the genetic population. It is found to have an association with many diseases which is discussed in this review. Polymorphic mutations are known to inhibit and reduce its function which are population specific. Detailed understanding and deeper knowledge of its role in the pathogenesis and prevention of many diseases is required. FUT2 may also have a potential role in the case of COVID-19 as a susceptible marker due to its association with respiratory diseases and the ABO blood group. There is an utmost need for this kind of review knowing its importance and owing to limited collective information.

Study to estimate the role of blood groups in the development of cardiovascular complications among SARS Cov 2 patients – A cross-sectional study

Background: SARS Cov 2 virus infection has led to the development of morbidities and mortalities throughout the world in the form of a pandemic. Aim: To find out the role of blood group antigens in the development of cardiovascular complications among those infected with SARS Cov 2 infection. Materials and methods: Details of 134 patients were collected who were infected with SARS Cov 2 and admitted to Chettinad Hospital and Research Institute. Results: There was no significant role of blood groups in the severity of Covid infection or in the development of cardiovascular risks among Covid patients.

ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients.

BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.

Predictors of New-onset Diabetes After Kidney Transplantation During 2019-nCoV Pandemic: A Unison of Frequentist Inference and Narrow AI

BACKGROUND: New-onset diabetes after kidney transplant (NODAT) is a severe metabolic complication that frequently occurs in recipients following transplantation. AIM: The study aims to verify NODAT, compare cases and non-cases of this entity, and explore potential predictors in recipients within 1 year following kidney transplantation. METHODS: The research is a retrospective study of 90 renal transplant recipients (n = 90). Demographic factors and clinical aspects were analyzed using non-Bayesian statistics and machine learning (ML). The clinical aspects included the glycated hemoglobin (HbA1c) level, associated viral infections (hepatitis B virus [HBV], hepatitis C virus [HCV], and cytomegalovirus [CMV]), prior kidney transplant, hemodialysis status, body mass index (BMI) at transplant time, and 3 months later, primary causes of renal failure, and post-transplant therapeutics. All individuals were on cyclosporine and prednisolone treatment. RESULTS: The mean age was 39 (±1.5) years;recipients included 27 females (30%) and 63 males (70%). Donor type was live related (16, 17.8%) or live unrelated (74, 82.2%);27 recipients (30%) had O+ blood group, while 70% belonged to other groups. Thirteen recipients (14.4%) were not on dialysis. Only 32 individuals (35.6%) developed NODAT. Concerning virology, confirmed by real-time polymerase chain reaction before transplantation, 19 recipients (21.1%) were CMV positive, 9 (10%) were HCV positive, and 2 (2.2%) had HBV. CONCLUSIONS: In reconciliation with frequentist statistics, the dual ML model validated several predictors that either negatively (protective) or positively (harmful) influenced HbA1c level, the majority of which were significant at 95% confidence interval. Individuals who are HCV and CMV positive are predicted to develop NODAT. Further, older individuals, with blood group O+ve, prior history of hemodialysis, a relatively high BMI before the transplant, and receiving higher doses of prednisolone following the transplant are more likely to develop NODAT. The current study represents the first research from Iraq to explore NODAT predictors among kidney transplant recipients using frequentist statistics and artificial intelligence models.

Dynamics of the COVID-19 Clinical Findings and the Serologic Response.

The factors affecting the dynamics of lengthening of symptoms and serologic responses are not well known. In order to see how the serologic responses change in relation to the clinical features, we selected a group of 472 adults with a positive IgM/IgG antibody test result from a baseline study of the anti-SARS-CoV-2 seropositivity, assessed their COVID-19 and past medical histories, and followed them up in about 3 months. Nearly one-fourth of the subjects were asymptomatic at the baseline; 12.8% subjects became symptomatic at the follow-up (FU) when 39.8% of the subjects had some persisting symptoms. At the baseline, 6.1% showed anti-SARS-CoV-2 IgM positive, 59.3% only for IgG, and 34.5% for both. At the FU, these figures declined to 0.6, 54.0, and 4.4%, respectively, with the mean IgM and IgG levels declining about 6.3 and 2.5 folds. Blood group A was consistently linked to both sustaining and flipping of the gastrointestinal (GI) and respiratory symptoms. The baseline IgM level was associated with GI symptoms and pre-existing cirrhosis in multivariate models. Both of the baseline and FU IgG levels were strongly associated with age, male, and lung involvement seen in chest computed tomography (CT)-scan. Finally, as compared with antibody decayers, IgM sustainers were found to be more anosmic [mean difference (MD): 11.5%; P = 0.047] with lower body mass index (BMI) (MD: 1.30 kg/m2; P = 0.002), while IgG sustainers were more commonly females (MD: 19.2%; P = 0.042) with shorter diarrhea duration in the FU (MD: 2.8 days; P = 0.027). Our findings indicate how the anti-SARS-CoV-2 serologic response and COVID-19 clinical presentations change in relation to each other and basic characteristics.

Glycosylation is a key in SARS-CoV-2 infection.

SARS-CoV-2 causes the respiratory syndrome COVID-19 and is responsible for the current pandemic. The S protein of SARS-CoV-2-mediating virus binding to target cells and subsequent viral uptake is extensively glycosylated. Here we focus on how glycosylation of both SARS-CoV-2 and target cells crucially impacts SARS-CoV-2 infection at different levels: (1) virus binding and entry to host cells, with glycosaminoglycans of host cells acting as a necessary co-factor for SARS-CoV-2 infection by interacting with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, (2) innate and adaptive immune response where glycosylation plays both a protective role and contributes to immune evasion by masking of viral polypeptide epitopes and may add to the cytokine cascade via non-fucosylated IgG, and (3) therapy and vaccination where a monoclonal antibody-neutralizing SARS-CoV-2 was shown to interact also with a distinct glycan epitope on the SARS-CoV-2 spike protein. These evidences highlight the importance of ensuring that glycans are considered when tackling this disease, particularly in the development of vaccines, therapeutic strategies and serological testing.