Introduction: Acute lung injury is associated with dysfunctional immune response to SARS-CoV-2. This leads to CRS, which require immunomodulatory treatments aiming to limit the excessive production of cytokines. The literature so far indicates the effectiveness of tocilizumab in patients with COVID-19-associated pneumonia, but there is no clear evidence of its effectiveness in patients with at least 50% lung involvement; therefore, we aimed to bridge this gap in knowledge. Materials and methods: Longitudinal data for 4287 patients with confirmed COVID-19 infection were collected between 1st March 2020 and 16th of January 2022. In total, 182 cases with lung involvement >50% and biochemical indicators of cytokine release storm (Il-6 >100 pg/mL) were selected and analyzed using non-parametric statistics and multivariate Cox models. Results: Among the 182 included patients, 100 (55%) were treated with TCZ, while 82 (45%) did not receive TCZ. The groups were balanced regarding demographics, lung involvement and biochemical markers. Overall mortality in the group was 63.1%. Mortality in the TCZ group was 58.0% compared to 69.5% (n = 57) in the non-TCZ group (p = 0.023). In multivariate Cox proportional hazards models, intravenous administration of tocilizumab was associated with lower probability of ICU admission (HR: 0333 (CI: 0.159–0.700, p = 0.004)) and lower mortality (HR: 0.57306 (CI: 0.354–0.927, p = 0.023)). Conclusions: Tocilizumab is effective as a treatment in the most severely ill patients, in whom the level of lung involvement by the inflammatory process can exceed 50% with coexisting biochemical indices of cytokine storm (Il-6 > 100 pg/mL).
Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) downregulates the immune system. Lymphoid tyrosine phosphatase (Lyp)--PTPN22 protein--is suggested to be negative regulator of T-cell reaction. There are several polymorphisms in the CTLA4 and PTPN22 genes, which can influence the immune response and allograft function after kidney transplantation. The aim of this study was to examine the impact of CTLA4 and PTPN22 genes polymorphisms on the long-term renal transplant function and recipients' outcomes during a 5-year follow-up observation. The study enrolled 268 Caucasian renal transplant recipients. Genotyping of the rs231775 (+49AG) CTLA4 gene polymorphism was performed using real-time PCR and rs2476601 (C1858T) PTPN22 gene polymorphism using PCR-RFLP method. The 5-year graft survival rate was 81.7%. Dialysis was necessary in 22 (8%) patients, 7 (2.6%) patients died and 20 (7.4%) switched to another transplantation center. We found no association between studied polymorphisms and graft loss/dialysis. Comparison of the distribution of the +49AG CTLA4 and C1858T PTPN22 genes polymorphisms genotypes among dead and living patients showed no statistically significant differences. Above results suggest that the rs231775 (+49AG) CTLA4 and rs2476601 (C1858T) PTPN22 genes polymorphisms are not associated with long-term allograft failure, graft loss and mortality after transplantation.
The association of thrombotic thrombocytopenic purpura and severe proteinuria is uncommon. The majority of such patients had already been diagnosed with systemic lupus erythematosus (SLE) and present overlapping symptoms of these two diseases. We report a case of thrombotic thrombocytopenic purpura (TTP) accompanied by severe proteinuria developed simultaneously during pregnancy. Clinical and serological data for SLE were negative. Kidney biopsy revealed features of chronic thrombotic microangiopathy and membranous glomerulonephritis.
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