Hepatitis E Virus (HEV) Infection in Hemodialysis Patients: A Multicenter Epidemiological Cohort Study in North-Eastern Greece.

Hepatitis E virus (HEV), a common cause of viral hepatitis in developing countries, is mainly transmitted via the fecal-oral route, but also may be a prevalent hospital-transmitted agent among patients on regular hemodialysis due to parenteral transmission. Previous epidemiological studies among hemodialysis patients in Greece, using different diagnostic techniques, gave conflicting results. Τhe present study aimed to measure the exposure rate of hemodialysis patients of north-eastern Greece to HEV by estimating the overall seroprevalence, and to identify potential risk factors. Serum samples from all patients attending the hemodialysis centers of north-eastern Greece (n = 6) were tested for the presence of anti-HEV IgG antibodies using a modern and sensitive ELISA (Enzyme-linked Immunosorbent Assay) technique (Wantai). In total, 42 out of 405 hemodialysis patients were positive for anti-HEV IgG (10.4%), while all samples were negative for HEV RNA when tested using nested RT-PCR. HEV seropositivity among hemodialysis patients was significantly associated with area of residence and contact with specific animals (pork, deer). No association was found with religion, gender distribution and hemodialysis duration. This study showed an increased seroprevalence of HEV among hemodialysis patients in Greece. Agricultural or livestock occupation and place of residence seem to be independent factors that increase the risk of HEV infection. In conclusion, HEV infection calls for the regular screening of hemodialysis patients regardless of the hemodialysis duration or clinical symptoms.

Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure.

Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11). COMBI was significantly associated with lower in-hospital mortality and intubation rate, shorter duration of hospitalization, and prolonged overall survival after a median follow-up of 110 days. In vitro, COVID-19 plasma induced tissue factor/thrombin pathway in primary lung fibroblasts. This effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results support the conduct of randomized trials using combined immunomodulation in COVID-19 to target multiple interconnected pathways of immunothrombosis.

Risk Factors of the Development of Diabetes Mellitus After Kidney Transplantation.

BACKGROUND: The occurrence of diabetes mellitus is common after kidney transplantation (posttransplant diabetes mellitus [PTDM]) and enhances the cardiovascular risk and risk for kidney graft loss. The incidence of PTDM is about 5% to 40%. This study aimed to examine the potential risk factors that determine the occurrence of PTDM. METHODS: This study retrospectively included 298 patients from transplantation unit of Evangelismos who underwent kidney transplantation during a 10-year period (January 1, 2009, to January 1, 2019). Kidney transplant recipients with diabetes mellitus prior to transplantation or those with follow-up of <6 months were rejected from the study. In total, the study included 274 recipients with a mean age of 50 ± 18 years. The mean time of monitoring was 63 ± 18 months. The PTDM diagnosis was based on the 2018 criteria of the American Diabetes Association. RESULTS: Of 274 kidney transplant recipients, PTDM developed in 38 (13.8%) patients over a period of 11 ± 9 months after transplantation. Given that immunosuppressive therapy was identical in most patients, statistical analysis did not correlate the incidence of diabetes with treatment. However, there was a correlation for the occurrence of PTDM between the presence of hypomagnesemia and increased uric acid levels. Finally, there was a negative correlation between the age of the recipient and the time of PTDM onset. CONCLUSION: Hypomagnesemia and hyperuricemia increased the risk of PTDM in these patients. Given the association between hypomagnesemia and the development of diabetes mellitus after kidney transplantation, prospective studies are needed to identify the causes of PTDM and to develop prevention strategies.