The Role of CXCLs and CXCR3 mRNA Expression Levels in Viral Hepatitis-Infected Liver Transplant Recipients

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The Role of CXCLs and CXCR3 mRNA Expression Levels in Viral Hepatitis-Infected Liver Transplant Recipients

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Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.
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CXCR4 and SDF-1 Production Are Stimulated by Hepatocyte Growth Factor and Promote Glioma Cell Invasion
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Background: Hepatocyte growth factor (HGF) and its receptor play an important role in the formation and progression of glioma and can promote tumor proliferation. In this study, we investigated the ability of HGF to promote the proliferation and invasion of U251n cells; we also tested the effects of HGF on stromal cell-derived factor 1 (SDF1) and CXCR4 mRNA expression. Methods: We measured the effect of HGF on the proliferation of U251n cells using enzyme-linked immunosorbent assays (ELISAs) to detect incorporated bromodeoxyuridine (BrdU) as a marker of DNA synthesis. The effects of HGF and SDF-1 on U251n cell invasion and proliferation were measured using the inhibitors K252a to c-Met and AMD3100 to CXCR4. SDF-1 and CXCR4 mRNA and protein expression were measured using quantitative polymerase chain reaction (PCR) and fluorescence-activated cell sorter (FACS) analysis. Small interfering (si)RNAs were also used to down-regulate HGF and c-Met expression in U251n cells. Results: HGF significantly increased U251n cell proliferation and invasion in a dose-dependent manner; K252a blocked this. AMD3100 blocked invasion but not proliferation. CXCR4 and SDF-1 mRNAs were up-regulated when cells were treated with HGF. CXCR4 and SDF-1 mRNA levels and HGF and c-Met protein levels were down-regulated after cells were transfected with siRNAs. Conclusions: HGF has a direct effect on glioma cell proliferation and invasion. HGF up-regulates SDF-1 and CXCR4 mRNA expression and contributes to cell invasion.

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Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality.
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The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings. To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States. We conducted a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients. A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001]. The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.

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Epstein-Barr virus (EBV) DNAemia poses a significant risk to transplant recipients, leading to Post-transplant lymphoproliferative disorder (PTLD). This study aims to determine the occurrence of EBV DNAemia among liver transplant (LT) recipients and analyze its association with various clinical parameters. Retrospective data search on 801 patients who underwent LT from January 2015 to December 2024 was performed. Of these, 257 recipients with available EBV DNA test records post-transplant were included and divided into EBV DNAemia and non-EBV DNAemia group. Various pre-transplant (age, MELD/PELD score, transplant type, EBV/CMV serostatus), transplant (cold/warm ischemia time, blood transfused), and post-transplant factors (EBV DNAemia, CMV infection, rejection, and immunosuppressant) were compared in both groups using univariate and multivariate analysis. Out of 257 cases, 138 (53.7%) were adults with a median age of 29 (IQR: 4.5-47) years. EBV DNAemia group included 50 (19.5%) cases with median age 2 (IQR: 1-5) years, majority (56%) classified as high-risk. The median time of EBV DNAemia detection since LT was 319 (IQR: 190-732) days with median viral load of 3.33 (IQR: 2.85-3.80) log10 copies/mL. PTLD developed in three cases (both high/intermediate risk). Non-EBV DNAemia group included 207 (80.5%) cases, with median age of 36 (IQR: 11-49) years, primarily belonging to intermediate risk. Age and pre-transplant EBV serostatus were found to be associated with EBV DNAemia on multivariate analysis. Routine monitoring of EBV DNAemia in both adult and pediatric LT recipients, regardless of pre-transplant serostatus, is crucial for early detection and management of EBV DNAemia/associated complications.IMPORTANCEThere is a significant lack of comprehensive studies on the prevalence and clinical impact of EBV DNAemia among liver transplant (LT) recipients in India. The absence of standardized monitoring and management protocols across Indian transplant centers further adds to inconsistencies in clinical practices, leading to challenges in early detection and intervention. Existing research primarily focuses on the high-risk pediatric renal transplant recipients with limited data available for adult LT recipients. This study aims to address these gaps by providing crucial insights into EBV DNAemia among Indian LT recipients and its association with various clinical parameters.

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