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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.

Background: Despite the growing interest in the role of isolated left ventricular (LV) diastolic dysfunction in cardiac remodeling, little is known about its association with cognitive performance in midlife, prior to the onset of dementia. Hypothesis: We hypothesized that LV diastolic dysfunction and cardiac remodeling will be associated with cognitive performance in middle-aged adults. These associations might differ by sex and race. Aim: To investigate the impact of left atrial (LA) size, LV mass, volume, systolic and diastolic function on cognition in middle-aged Black and White, men and women from a rural, community-based cohort, the Bogalusa Heart Study (BHS), in Louisiana. Methods: A total of 1,107 participants from the BHS (48.1±5.4 years, 56.7% female, 34.3% black) with echocardiography and cognitive testing were included. Cognitive performance was quantified in a global cognitive score (GCS) comprised of the z standardized sum of 7 neuropsychiatric tests. Multivariate linear regression analysis was used for the association of E/e’, LA volume index (LAVi), LV end-diastolic volume (LVEDV), mass index (LVMi) as well as ejection fraction (LVEF) with GCS adjusted for age, sex, race, systolic and diastolic blood pressure, total and HDL cholesterol, history of smoking, diabetes, and hypertension as well as education. Interactions by sex and race were tested. Results: Even after adjusting for age, sex and race, larger LAVi, LVEDV, LVMi, higher E/e’ and lower e’ were associated with poorer cognitive function (all p <0.05), but not LVEF. These associations remained significant for E/e’, e’, and LVMi after adjusting for systolic and diastolic blood pressure, total and HDL cholesterol, history of smoking, diabetes, hypertension, as well as education. There was no significant race interaction. In contrast, the association of E/e’ with GCS was significantly stronger (standardized β coefficient =-0.20; p <0.01) in middle-aged women, but not in middle-aged men (standardized β coefficient =-0.04; p <0.36; p interaction=0.02). Conclusion: LV diastolic function is more closely associated with mid-life cognition than systolic function, and the association is present among middle aged women but not men.

AbstractBackgroundThe potential association of long‐term oral corticosteroid (OCS) use with adverse events (AEs) in patients with bullous pemphigoid (BP) is not well characterized in a real‐world setting.ObjectivesTo evaluate the effect of OCS use and treatment duration on the incident AEs in patients with BP.MethodsThis retrospective cohort study used medical and pharmacy claims and patient enrollment data from IQVIA PharMetrics® Plus from 2006−2021. Eligible patients had a diagnosis of BP between 1 January 2006 and 30 June 2020 (≥2 claims for BP ≥ 30 days apart). Patients in the OCS cohort also had a claim for OCS use, ≥7.5 mg daily dose of prednisone or equivalent, and no claims for a nonoral systemic corticosteroid (CS) at any time during the study period. A control cohort of patients with BP not using OCS was also selected. Relative risk ratios were estimated between the incidence of AEs in OCS users with different exposure durations (short‐term, <30 days; medium‐term, 30−90 days; long‐term, >90 days) and nonusers by Poisson regression, after adjusting for age, sex, prior drug use, and baseline Charlson Comorbidity Index score within the follow‐up period.ResultsAt the 1‐year follow‐up, long‐term OCS users had a higher incidence of infections, cataract, osteoporosis, heart failure, depression or anxiety, and diabetes compared with OCS nonusers (p < 0.05). Furthermore, compared with nonusers, long‐term users had increased 1‐year risks (risk ratio; 95% confidence interval) for heart failure (2.27; 1.50−3.44), diabetes (2.05; 1.30−3.24), osteoporosis (1.72; 1.23−2.41), and infection (1.50; 1.13−1.99). Long‐term OCS users also had increased 1‐year risks for heart failure (2.00; 1.21−3.28) and osteoporosis (1.70; 1.16−2.50) compared with short‐term OCS users.ConclusionsLong‐term OCS use (≥7.5 mg) in patients with BP was associated with an increased risk of AEs. Study findings demonstrate a need for steroid‐sparing options with an improved safety profile.

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.

ABSTRACT Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8). Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/− MPI 8 and UHRA-8 (50 μg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, P < 0.05 significant. Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], P < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], P = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], P = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], P < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], P < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all P < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, P < 0.001). Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.