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Abstract Background Up to 50% of cases of Shiga-toxin-producing Escherichia coli hemolytic uremic syndrome occur in adults, and the clinical presentation is variable. Microbiological analyses must be performed in all patients with thrombotic microangiopathy to identify Shiga-toxin-producing Escherichia coli, even in the absence of diarrhea. Case presentation A 79-year-old Caucasian woman was admitted to hospital because of severe proctitis. In the following days, the patient’s level of consciousness declined, and she developed acute kidney injury, thrombocytopenia, and hemolytic anemia. Shiga-toxin-producing Escherichia coli was found in fecal cultures, suggesting the diagnosis of hemolytic uremic syndrome. In the following days, her clinical conditions improved, but thrombocytopenia worsened, and the patient developed posterior tibial vein thrombosis. The discordant evolution of thrombocytopenia compared with other clinical and laboratory parameters prompted a new evaluation of its causes. Diagnosis of heparin-induced thrombocytopenia was confirmed by heparin-induced platelet aggregation assay and positive antibodies to platelet factor 4. Conclusions A discordant evolution of platelet count in patients with thrombotic microangiopathy requires a systematic reevaluation of the thrombocytopenia.

Abstract Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy. Here, using single-cell RNA-sequencing, we find that senescent tumor cells rely on the anti-apoptotic gene Mcl-1 for their survival. Mcl-1 is upregulated in senescent tumor cells, including cells expressing low levels of Bcl-2, an established target for senolytic therapy. While treatment with the Bcl-2 inhibitor Navitoclax results in the reduction of metastases in tumor bearing mice, treatment with the Mcl-1 inhibitor S63845 leads to complete elimination of senescent tumor cells and metastases. These findings provide insights on the mechanism by which senescent tumor cells survive and reveal a vulnerability that can be exploited for cancer therapy.

Aim. Noninvasive identification of haemodialysis patients at high risk of cardiovascular events and death might improve their outcome. Growth differentiation factor 15 is a prognostic biomarker in multiple disease entities, including cardiovascular disease. The aim of this study was to assess the association between plasma GDF-15 and mortality in a cohort of haemodialysis patients. Methods. Circulating GDF-15 was measured in 30 patients after a regular haemodialysis session, followed by a clinical follow-up for all-cause death. Measurements were performed using the Proseek Multiplex Cardiovascular disease panels (Olink Proteomics AB) and validated using the Elecsys GDF-15 electrochemiluminescence immunoassay on a Cobas E801 analyzer (Roche Diagnostics). Results. During a median of 38 months, 9 patients (30%) died. Seven deaths occurred in the group of patients with a circulating GDF-15 above the median and two in the group with lower GDF-15. Mortality was significantly higher in patients with circulating GDF-15 levels above the median, log-rankP = 0.044. The performance of circulating GDF-15 to predict long-term mortality has an area under the ROC curve of 0.76, P = 0.028. Prevalence of most relevant comorbidities and the Charlson comorbidity index were similar across the two groups. A high agreement with a correlation among both diagnostic methods was observed (Spearman’s rho = 0.83, P

Abstract Background Restless legs syndrome (RLS) is a common sleep-related movement disorder characterized by an urge to move the legs during inactivity, especially at evening-night. RLS is highly prevalent in patients with kidney failure and have an impact on quality of life, mood, sleep quality and overall on compliance to the dialysis. Alport syndrome (AS) is a rare inherited disease, predominantly X-linked, secondary to mutations in genes encoding α3, α4 or α5 chains of type IV collagen, and characterized by hematuria, chronic kidney disease, neurosensory deafness, and lenticonus. Case presentation Here we describe a family with a combination of X-linked AS and severe RLS accompanied by periodic limb movements during sleep (PLMS). In the first patient we identified, RLS was complicated by a paradoxical response to dopamine agonists named “augmentation”, leading to sleep disruption, hallucinations and five peritoneal perforations during the peritoneal dialysis due to the difficulty to rest still. Therapeutic adjustments and renal transplantation improved RLS and PLMS. In two brothers, severe RLS prevented a compliance with hemodialysis. Female family members carrying the mutation were also affected by RLS, while those without the mutations were RLS-free. Conclusions RLS has not been reported earlier in association with AS, but the peculiar combinations observed in this family will stimulate further clinical studies and motivate nephrologists to seek for RLS symptoms and sleep disturbances in AS patients.

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.