Qamar, Usama

Stem cell-derived kidney organoids enable human genetic disease modeling to identify the parathyroid hormone 1 receptor as a potential new therapeutic target for developmental polycystic kidney disease.

Kidney organoids are an increasingly established model of polycystic kidney disease (PKD). Derived from human pluripotent stem cells (hPSCs), organoids may be generated from induced pluripotent stem cells (iPSCs) of patients that bear naturally occurring mutations or from CRISPR mutant hPSCs by virtue of their genetic tractability. PKD is the leading inheritable cause of kidney failure (KF), accounting for ∼5%–10% of the kidney transplant and dialysis needs worldwide. PKD is a disorder of considerable genetic heterogeneity, composed of typical adult-onset autosomal dominant (ADPKD) and fetal-onset autosomal recessive (ARPKD) forms, which share pathomechanisms. Despite advances in our understanding of the genetic and molecular underpinnings of PKD, the limited clinical treatment options have raised concerns regarding the faithfulness of preclinical models. Kidney organoids have emerged as a promising platform to study PKD by mimicking human-specific responses, enabling personalized medicine, and supporting high-throughput screens. Yet, valid criticisms have related to the relative immaturity of kidney organoids for modeling adult-onset forms of PKD, the faithfulness of organoids in modeling the cystic distribution of afflicted patients, and their batch-to-batch variability limiting experimental reproducibility. Here, we summarize a decade of kidney organoid models of PKD, emphasizing their role in advancing translational and therapeutic applications while addressing their limitations and future potential.

Managing persistent atrial fibrillation (AF) remains challenging due to its complex arrhythmic substrate, and pulmonary vein isolation through catheter ablation remains the primary treatment. This meta-analysis aims to compare the efficacy and safety outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in patients with persistent AF to provide evidence-based insights for clinical decision-making. A systematic search of PubMed, Embase, and Cochrane Central was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) comparing CBA and RFA in persistent AF were included. Data on efficacy, safety, and procedural outcomes were pooled in the form of odds ratios (ORs) or mean differences (MDs) with corresponding 95% confidence intervals (CIs) using the random effects model in the Review Manager (RevMan) software. Four RCTs comprising 899 patients were included in our analysis. There were no significant differences between CBA and RFA in terms of AF recurrence, atrial tachycardia/flutter recurrence, or any arrhythmia recurrence during a mean follow-up period of 18 months after ablation. Procedure time was significantly shorter with CBA (MD: −44.85 minutes, 95% CI: −56.46 to −32.24, P < 0.01), while fluoroscopy time was comparable between the 2 groups (MD: 4.31 minutes, 95% CI: −1.79 to 10.40, P = 0.17). Safety outcomes, including overall complications, phrenic nerve palsy, access-site complications, and pericardial effusion, showed no significant differences between the 2 groups. CBA and RFA show similar rates of atrial arrhythmia recurrence and periprocedural complications in the treatment of persistent AF, while CBA offers the advantage of a shorter procedure time.

Pyogenic arthritis (PA) related mortality trends have not been studied well across various demographics in the United States (US). This cross-sectional study aimed to evaluate these trends among the US population aged ≥ 25 years from 1999–2020 using data from the CDC WONDER database. We identified all the deaths where PA was listed as the underlying or contributing cause of death, using the ICD-10 code M00. Age-adjusted mortality rates (AAMRs) were calculated per 1 million US population and the Joinpoint regression model was used to assess the annual mortality trends by calculating the annual percent change (APC) in AAMRs. Between 1999 and 2020, 13,965 total deaths occurred among US adults aged ≥ 25 years with an AAMR of 2.94. The overall AAMR of PA increased significantly from 1999 to 2020 with an APC of 2.01 (p < 0.01). Males and older adults had consistently higher AAMRs than their respective counterparts. Non-Hispanic (NH) American Indians/Alaska Natives and NH Blacks/African Americans had higher mortality rates compared with other racial groups. The Midwest had the highest overall AAMR, followed by the West, Northeast, and South regions. In conclusion, PA mortality has been on the rise and targeted interventions are warranted to reduce disproportionate mortality rates among vulnerable populations.

Abstract Aims We aimed to perform a retrospective cohort study using the Centers for Disease Control and Prevention’s (CDC’s) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyse the trends in cardiovascular disease (CVD)–related mortality in patients with myeloproliferative neoplasms (MPNs) from 1999 to 2020. Methods and results We analysed the death certificate data from the CDC WONDER database from 1999 to 2020 for CVD with co-morbid myeloproliferative disorders in the US population. Age-adjusted mortality rates (AAMRs) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual national mortality trends, we employed the Joinpoint regression model, calculating the annual per cent change in AAMR and corresponding 95% CIs. A total of 15 269 deaths related to CVD occurred in patients with co-morbid MPNs from 1999 to 2020. Overall, there was a decreasing trend in CVD-related AAMRs throughout these years. Males contributed to 51% of total deaths, and their AAMR was persistently higher than women throughout the study. Non-Hispanic (NH) Whites had the highest overall AAMR, followed by NH Blacks, NH American Indians or Alaska Natives, Hispanics or Latinos, and NH Asian or Pacific Islanders. Conclusion Our findings indicate a significant decline with notable gender, racial/ethnic, and regional differences in CVD-related mortality among patients with MPN over the past two decades. We emphasize the importance of a collaborative approach between oncologists and cardiologists in managing these patients, highlighting the potential benefits of integrating cardio-oncology services to enhance patient outcomes.