Citations

ABSTRACT Background Uremic toxins are a growing area of research in nephrology, with significant implications in the progression and treatment of chronic kidney disease (CKD) and the management of end‐stage kidney disease (ESKD). This bibliometric analysis aims to evaluate the global research trends, key contributors, and the impact of publications in the field of uremic toxins from 1991 to 2024. Methods The data were retrieved from the Science Citation Index Expanded (SCI‐EXPANDED) database. The study analyzed 2210 articles using various bibliometric indicators, including total publications ( TP ), average number of citations per publication ( CPP 2024 ), and the Y ‐index for author contributions. Publication trends were examined across countries, institutions, and authors. The analysis included document types, languages, Web of Science categories, and journals. Results The study revealed a steady increase in uremic toxin research publications. Japan, the USA, and China remained the most productive countries, with Japan maintaining the highest output, while Belgium achieved the highest citation impact. Citations of uremic toxin‐related research peaked 2 years following publication and plateaued after approximately 6 years. The research foci evolved, with CKD, ESKD, indoxyl sulfate, protein‐bound solutes, and gut microbiota gaining prominence. Studies on oxidative stress, inflammation, metabolomics, and advanced adsorption‐based toxin removal strategies increased markedly. International collaboration and interdisciplinary integration across nephrology, microbiology, and biochemistry correlated with higher citation performance and research visibility. Conclusion This bibliometric study provides an in‐depth analysis of uremic toxin research trends, identifies major contributors, and suggests future research priorities. The findings can inform future research directions, guide funding allocation, and strengthen global collaborative efforts towards improved management of toxin‐related kidney disease.

Importance The effect of cornea donor diabetes on endothelial cell density (ECD) and morphometry after Descemet membrane endothelial keratoplasty (DMEK) is not known. Objective To determine whether endothelial cell loss (ECL) and morphometric changes 1 year after successful DMEK are related to cornea donor’s diabetes status. Design, Setting, and Participants This was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2024 at 28 US clinical sites (46 surgeons) and 13 eye banks. Included in the trial were the eyes of recipients (some of whom received tissue from donors without diabetes and others who received tissue from donors with diabetes) who underwent successful DMEK, primarily for Fuchs endothelial corneal dystrophy, and had at least 1 analyzable postoperative endothelial image. Intervention DMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure to achieve an approximate 2:1 distribution. Main Outcomes and Measures ECD, ECL, coefficient of variation in cell area (CV), and percentage of hexagonal cells (HEX) at 1 year from eye bank and postoperative specular central endothelial images. Results A total 1274 eyes of 982 recipients (mean [SD] age, 70 [8] years; 569 female [57.9%]; 816 [64.1%] with tissue from donors without diabetes and 458 [35.9%] with tissue from donors with diabetes) were included in the study. Preoperatively, mean (SD) central ECD in tissue from donors without diabetes and with diabetes were 2676 (290) cells/mm 2 and 2671 (286) cells/mm 2 , respectively. At 1 year, mean (SD) ECL was 28.3% (16.1%) and 28.0% (17.0%), in the donor groups without and with diabetes, respectively (adjusted mean difference = −0.4%; 95% CI, −2.3% to 1.4%), resulting in a mean (SD) 1-year ECD of 1927 (498) cells/mm 2 and 1920 (496) cells/mm 2 , respectively (adjusted mean difference = 10 cells/mm 2 ; 95% CI, −36 to 56; P = .95). No difference in ECD at 1 year associated with diabetes severity was noted ( P = .97). Mean (SD) CV did not differ at 1 year between the 2 groups of eyes (31.5% [4.1%] vs 31.4% [4.1%]; adjusted mean difference = −0.4%; 95% CI, −0.9% to 0.1%; P = .51), and mean (SD) HEX did not differ at 1 year between the 2 groups of eyes (57.7% [5.8%] vs 57.2% [5.8%]; adjusted mean difference = 0.1%, 95% CI, −0.8% to 0.9%; P = .33). Conclusions and Relevance This randomized clinical trial found that ECL and morphometry 1 year after DMEK were not affected by cornea donor diabetes status. With comparable 1-year graft success with tissue from donors with and without diabetes demonstrated in this trial, these findings support the use of corneas from donors with diabetes for endothelial keratoplasty procedures. Trial Registration ClinicalTrials.gov Identifier: NCT05134480

Importance If the success of Descemet membrane endothelial keratoplasty (DMEK) is not affected by whether the donor has diabetes, then the donor pool should expand. Objective To determine whether the 1-year DMEK success rate is affected by the presence of diabetes in the donor. Design, Setting, and Participants This was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2025 at 28 clinical sites (46 surgeons), with donor corneas provided by 13 eye banks in the US. Included in the study were individuals undergoing low to moderate risk DMEK (95% for Fuchs endothelial corneal dystrophy). Study data were analyzed from April to September 2025. Intervention DMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure (comparable with randomization) to achieve an approximate 2:1 distribution, respectively. Main Outcomes and Measures Graft success at 1 year Results A total of 1097 individuals (1421 study eyes; median [IQR] age, 71 [66-76] years; 631 female [57.5%]) were included in the study. The 1-year cumulative probability of graft success was 96.3% (95% CI, 95.0%-97.5%) among 912 study eyes (64.2%) receiving tissue from donors without diabetes and 97.1% (95% CI, 95.5%-98.4%) among 509 study eyes (35.8%) receiving tissue from donors with diabetes (difference between groups = 0.7 percentage points; 95% CI, −1.2 to 2.6; P = .63). The 1-year cumulative probability of graft success was 96.5% (95% CI, 93.6%-98.9%) in the mild donor diabetes severity subgroup (n = 173) and 97.3% (95% CI, 95.4%-98.8%) in the moderate to severe donor diabetes severity subgroup (n = 336), using a diabetes severity rating scale based on medical history. The rates of primary donor failure, early failure related to surgical complications, and subsequent failure were as follows: 2.5% (23 of 912), 0.7% (6 of 912), and 0.3% (3 of 912), respectively, in recipients of tissue from a donor without diabetes, and 2.6% (13 of 509), 0.4% (2 of 509), and 0%, respectively, among recipients of tissue from a donor with diabetes. There were no failures due to graft rejection. Conclusions and Relevance The 1-year success rate in eyes undergoing DMEK with successfully prepared tissue was very high regardless of donor diabetes status. These results, supported by the separately reported finding that endothelial cell loss and cornea morphometry after 1 year were not affected by donor diabetes status, provide strong support for having no restrictions on the use of tissue from donors with diabetes for DMEK. Trial Registration ClinicalTrials.gov Identifier: NCT05134480

Heart failure with reduced ejection fraction is a major cause of morbidity and mortality. Cardiac resynchronization therapy (CRT) improves outcomes but faces challenges such as unsuccessful lead placement and suboptimal responses. The Wireless Stimulation Endocardially for CRT (WiSE-CRT) system, a novel leadless left ventricular (LV) pacing technology, uses ultrasonic energy to deliver electrical stimulation directly to the LV endocardium, potentially improving the response rates. A comprehensive literature search was performed across multiple databases from inception until August 2024. The outcomes of interest included the New York Heart Association (NYHA) functional score, LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and QRS duration. Statistical analysis involved pooling the mean differences (MDs) and their corresponding 95% confidence intervals (CIs) from each study using the inverse-variance random-effects model in RevMan version 5.4.1 software. Seven studies, including 468 patients with heart failure treated with the WiSE-CRT system, were included. The pooled analysis showed significant improvements in NYHA functional score (MD: −0.44; 95% CI: −0.67 to −0.21; P = 0.0002; I 2 = 77%), LVEF (MD: 5.71; 95% CI: 4.54 to 6.87; P < 0.001), LVEDV (MD: −24.49; 95% CI: −33.24 to −15.73; P < 0.001), and LVESV (MD: −24.47; 95% CI: −32.80 to −16.14; P < 0.001). The QRS duration also decreased significantly (MD: −38.62; 95% CI: −46.76 to −30.49; P < 0.001; I 2 = 60%). The WiSE-CRT system significantly improved NYHA functional score, LVEF, QRS duration, LVEDV, and LVESV in patients with heart failure. This leadless pacing technology offers a promising alternative for ineligible candidates or for those who do not respond to conventional CRT.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Low-dose colchicine is a novel and nonstandard management approach for patients with CVDs who are at an increased risk of adverse events. However, few studies have reported the risk of stroke with colchicine, with controversial results. This meta-analysis aimed to compare the efficacy of colchicine and placebo for stroke prevention in patients with CVD. Major electronic databases were screened for randomized controlled trials (RCTs) comparing colchicine and placebo in patients with CVDs from inception to June 2024. Pooled estimates were calculated as risk ratios (RRs) with 95% confidence intervals (CIs) using an inverse-variance random-effects model. Statistical significance was set at P < 0.05. A total of 15 RCTs encompassing 25,116 patients with CVDs were included (12,568: colchicine and 12,548: placebo). The pooled analysis demonstrated a significant reduction in stroke [RR, 0.80 (95% CI, 0.64–0.99); P = 0.04] with colchicine compared with placebo. The risk of all-cause mortality [RR, 1.00 (95% CI, 0.77–1.28)] was comparable between the 2 groups. On subgroup analysis, low-dose colchicine (0.5 mg/day) demonstrated a significantly lower risk of stroke compared with high-dose (>0.5 mg/day) colchicine, which failed to achieve statistical significance. Based on this meta-analysis, colchicine significantly reduced stroke in patients with CVDs compared with placebo. This effect was most significant with low-dose colchicine at 0.5 mg/day. However, no differences were observed in all-cause mortality. Further long-term RCTs are warranted to investigate stroke prevention using colchicine in this population.

Abstract Metastasis accounts for the overwhelming majority of cancer deaths. In prostate cancer and many other solid tumors, progression to metastasis is associated with drastically reduced survival outcomes, yet the mechanisms behind this progression remain largely unknown. ATPase family AAA domain containing 2 (ATAD2) is an epigenetic reader of acetylated histones that is overexpressed in multiple cancer types and usually associated with poor patient outcomes. However, the functional role of ATAD2 in cancer progression and metastasis has been relatively understudied. Here, we employ genetically engineered mouse models of prostate cancer bone metastasis, as well as multiple independent human cohorts, to show that ATAD2 is highly enriched in bone metastasis compared with primary tumors and significantly associated with the development of metastasis. We show that ATAD2 expression is associated with MYC pathway activation in patient datasets and that, at least in a subset of tumors, MYC and ATAD2 can regulate each other’s expression. Using functional studies on mouse bone metastatic cell lines and innovative organ-on-a-chip bone invasion assays, we establish a functional role for ATAD2 inhibition in reducing prostate cancer metastasis and growth in bone. Implications: Our study highlights ATAD2 as a driver of prostate cancer progression and metastasis and suggests it may constitute a promising novel therapeutic target.

Introduction: Thoracic aortic aneurysms (TAA) are a significant health concern, with the true prevalence likely underestimated due to undiagnosed cases. Outcomes in TAA are influenced by factors like age, sex, and comorbidities such as hypertension. This study examines mortality trends and disparities associated with TAA in US adults. Methodology: This study analyzed death certificates from 1999 to 2020 using the CDC WONDER Database to identify TAA-related deaths in individuals aged 25 and older using ICD-10 codes I71.1 and I71.2. Age-adjusted mortality rates (AAMRs) per 1 000 000 and annual percent changes (APCs) were calculated and stratified by year, sex, age group, race/ethnicity, region, and urbanization status. Results: Between 1999 and 2020, 47 136 TAA-related deaths were reported among US adults. The AAMR decreased from 16.2 to 8.2 per 1 000 000, with a significant decline from 1999 to 2013 (APC: −5.00; 95% CI: −5.54 to −4.54; P<0.001). Older adults had the highest AAMRs at 44.6 per 1 000 000. Men had higher AAMRs than women (11.2 vs. 9). AAMRs were highest among non-Hispanic (NH) Black (11), followed by NH White (10.3), NH Asian or Pacific Islander (9.5), NH American Indian or Alaska Native (7.8), and Hispanic (5.2) populations. Nonmetropolitan areas had higher AAMRs than metropolitan areas (11 vs. 9.8). Conclusions: The analysis showed a significant decline in TAA mortality since 1999, with recent stabilization. However, disparities persist, with higher AAMRs among men, older adults, NH Black adults, and nonmetropolitan residents, highlighting the need for targeted and equitable interventions.

Background: Acute Kidney Injury (AKI) is a multifactorial complication following repair of Stanford Type A aortic dissection (TAAD) with an alarmingly high incidence, varying from 20 to 77%. Postoperative AKI following life-threatening disease tends to be much more complex. However, the exact role of postprocedural AKI in the prognosis of patients undergoing TAAD repair has not been elucidated. Aims: This meta-analysis aimed to evaluate the prognostic significance of postprocedural AKI in patients undergoing TAAD repair. Methods: A literature search was conducted using PubMed, EMBASE, and SCOPUS databases. The primary endpoint was 30-day mortality with several secondary endpoints. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled using Review Manager software. Statistical significance was set at p <0.05. Random-effects meta-analyses were performed for all outcomes. Results: Our analysis included 21 studies comprising 10396 patients. Patients with AKI exhibited a significantly higher risk of 30-day mortality (RR=3.98; 95% CI: 3.04-5.22; p<0.00001; I 2 =57%), stroke (RR= 2.05; 95% CI: 1.68-2.50; p<0.00001; I 2 =32%), dialysis requirement (RR= 32.9; 95% CI: 10.39-104.24; p<0.00001; I 2 =90%) (Figure 1), cardiovascular complications (RR= 2.85; 95% CI: 1.65-4.92; p<0.0002; I 2 =85%), sepsis (RR= 4.92; 95% CI: 2.62-9.24; p<0.00001; I 2 =64%), and re-exploration for bleeding (RR=2.46; 95%CI: 1.79-3.39; p<0.00001; I 2 =58%) compared to those without AKI (Figure 2). Conclusion: Patients with AKI demonstrated a significantly increased risk of mortality, stroke, need for dialysis, sepsis, postoperative cardiovascular complications, and re-exploration for bleeding. Further prospective studies are required to better understand the prevention strategies and long-term effects on prognosis of AKI post-repair for TAAD.