Citations

Background: Cirrhosis and end-stage kidney disease (ESKD) are significant global health concerns, contributing to high mortality and morbidity. Haemodialysis (HD) is frequently used to treat ESKD in patients with cirrhosis. However, it often presents challenges such as haemodynamic instability during dialysis sessions, leading to less than optimal outcomes. Peritoneal dialysis (PD), while less commonly used in cirrhotic patients, raises concerns about the risks of peritonitis and mortality. Our systematic review and meta-analysis aimed to assess outcomes in PD patients with cirrhosis. Methods: We executed a comprehensive search in Ovid MEDLINE, EMBASE and Cochrane databases up to 25 September 2023. The search focused on identifying studies examining mortality and other clinical outcomes in ESKD patients with cirrhosis receiving PD or HD. In addition, we sought studies comparing PD outcomes in cirrhosis patients to those without cirrhosis. Data from each study were aggregated using a random-effects model and the inverse-variance method. Results: Our meta-analysis included a total of 13 studies with 15,089 patients. Seven studies compared ESKD patients on PD with liver cirrhosis (2753 patients) against non-cirrhosis patients (9579 patients). The other six studies provided data on PD (824 patients) versus HD (1943 patients) in patients with cirrhosis and ESKD. The analysis revealed no significant difference in mortality between PD and HD in ESKD patients with cirrhosis (pooled odds ratio (OR) of 0.77; 95% confidence interval (CI), 0.53–1.14). In PD patients with cirrhosis, the pooled OR for peritonitis compared to non-cirrhosis patients was 1.10 (95% CI: 1.03–1.18). The pooled ORs for hernia and chronic hypotension in cirrhosis patients compared to non-cirrhosis controls were 2.48 (95% CI: 0.08–73.04) and 17.50 (95% CI: 1.90–161.11), respectively. The pooled OR for transitioning from PD to HD among cirrhotic patients was 1.71 (95% CI: 0.76–3.85). Mortality in cirrhosis patients on PD was comparable to non-cirrhosis controls, with a pooled OR of 1.05 (95% CI: 0.53–2.10). Conclusions: Our meta-analysis demonstrates that PD provides comparable mortality outcomes to HD in ESKD patients with cirrhosis. In addition, the presence of cirrhosis does not significantly elevate the risk of mortality among patients undergoing PD. While there is a higher incidence of chronic hypotension and a slightly increased risk of peritonitis in cirrhosis patients on PD compared to those without cirrhosis, the risks of hernia and the need to transition from PD to HD are comparable between both groups. These findings suggest PD as a viable and effective treatment option for ESKD patients with cirrhosis.

Abstract Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse–enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type– and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.