Mogensenblair7022

Chronic lung allograft dysfunction (CLAD), is a major hurdle for long-term lung allograft survival after lung transplant and roughly 50% of lung transplant recipients (LTxRs) develop CLAD within 5 years. The mechanisms of CLAD development remain unknown. Donor-specific immune responses to human leukocyte antigen (HLA) and lung self-antigens (SAgs) are vital to the pathogenesis of CLAD. Reduction in Club cell secretory protein (CCSP) has been reported in bronchoalveolar lavage (BAL) fluid samples from LTxRs with bronchiolitis obliterans syndrome (BOS).

CCSP levels in BAL fluid and development of antibodies to lung SAgs in plasma were determined by ELISA. Cytokines in BAL fluid were analyzed by 30-plex Luminex panel. Exosomes from BAL fluid or plasma were analyzed for SAgs, natural killer cells markers, and cytotoxic molecules.

We demonstrate that LTxRs with BOS have lower CCSP levels up to 9 months before BOS diagnosis. Cinchocaine order LTxRs with antibodies to SAgs 1 year posttransplant also developed DSA (43%) and had in CLAD development.

Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in USA. HCC recurrence is the main complication affecting short- and medium-term outcome after LT.

A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age 57.8 ± 8.5 years; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and since 2014, AFP score to be listed. Patients with HCC recurrence were classified into early (≤ 2years) and late recurrence (> 2years) and were retrospectively reviewed.

Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and UCSF criteria, high AFP score and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5 and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence respectively 64.0% and 27.1% (p<0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months respectively in the two groups (p<0.001). Multivariable cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (HR=3.074; p=0.007), bi-lobar tumor at time of LT (HR=2.001; p=0.037), and a tumor size (>50mm) in the explant (HR=1.277; p=0.045) as independent predictors of early recurrence.

Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence improve long-term survival.

Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence improve long-term survival.

Chronic renal allograft dysfunction (CRAD) is a major condition that impedes the long-term survival of renal allografts. However, the mechanism of CRAD is obscure, and effective strategies for controlling the progression of CRAD are lacking. The present study used a CRAD rat model to assess the effect of glycogen synthase kinase 3β (GSK-3β) inhibition on the development of CRAD.

A classical F334-to-LEW orthotopic renal transplantation was performed on the CRAD group. The treatment group was treated with the GSK-3β inhibitor TDZD-8 for 12 consecutive weeks following renal transplantation. The study included uninephrectomized F344 and Lewis rats as control subjects. Twelve weeks post-surgery, the rats were retrieved for analysis of renal function, urine protein levels, histological, immunohistochemical, and molecular biological parameters.

Administration of TDZD-8 inactivated GSK-3β and thereby improved renal function, attenuated proteinuria, and reduced renal tissue damage in CRAD rats. Besides, inactivation of GSK-3β inhibited NF-κB activation, macrophage infiltration, and expression of multiple proinflammatory cytokines/chemokines. Inhibition of GSK-3β also decreased the levels of MDA, increased SOD levels, upregulated the expression of HO-1 and NQO-1, and enhanced nuclear translocation of Nrf2 in the kidneys of CRAD rats.

Inhibition of GSK-3β attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3β inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD.

Inhibition of GSK-3β attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3β inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with hematological diseases but associated with high mortality and morbidity. Cytomegalovirus (CMV) infection is common in HSCT patients and modulates vitamin D metabolism in vitro. We aimed at validating CMV-associated vitamin D metabolism in vivo in HSCT.

Patients treated for significant CMV viremia after HSCT were evaluated for CMV load before, during and after antiviral treatment. RNA was isolated from whole blood samples to test for regulation of key components of the vitamin D receptor (VDR) pathway during different phases of CMV viremia.

CMV viremia developed a mean time of 102 (±34) days post HSCT. Maximum levels of CMV-DNA reached a mean of 5668 (±7257) copies/ml. VDR expression was downregulated to a mean of 64.3% (±42.5%) relative to the VDR expression pre-CMV viremia (p=0.035) and lagged in recovery following antiviral treatment. TLR2 mRNA was upregulated to 225.4% during CMV-viremia relative to the expression pre-CMV viremia (p=0.012), but not TLR6/7/8 and the TLR-adaptor protein MyD88. Levels of 25-OH vitamin D were reduced in all viremic patients (48.0 ± 4.8 vs. 25.1 ± 3.7 ng/ml) and were even lower after periods of CMV viremia compared to the control group (48.3 ± 3.5 vs. 17.8 ± 1.8 ng/ml; p=0.008).

CMV viremia is associated with significant dysregulation of vitamin D metabolism in HSCT patients.

CMV viremia is associated with significant dysregulation of vitamin D metabolism in HSCT patients.