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Background Secondary lymphedema frequently occurs following surgery, malignancy, trauma, or radiation and is characterized by limb swelling, discomfort, and recurrent infections. Two advanced supermicrosurgical techniques—lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT)—have recently gained popularity as treatment options. However, long-term outcome data for these procedures remain limited. This systematic review and meta-analysis aim to evaluate the long-term efficacy of LVA and VLNT in patients with secondary lymphedema followed for more than 2 years postoperatively, focusing on outcomes such as cellulitis rates and limb circumference. Methods This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed studies involving adult patients with secondary lymphedema treated with LVA or VLNT and with at least 24 months of follow-up. The primary outcomes were annual cellulitis incidence and limb circumference change, analyzed separately for upper and lower extremities. Meta-analysis was conducted using R version 4.3.1. Pooled effect sizes were estimated using random-effects models. Subgroup and sensitivity analyses were also performed. Results A total of 23 studies met the inclusion criteria, covering 648 limbs treated with either LVA (n = 216) or VLNT (n = 432). The weighted average patient age was 56.3 years, and the cohort was predominantly female (99.9%). For LVA, the pooled mean reduction in annual cellulitis events was −1.13 (95% confidence interval [CI], −1.70 to −0.57) for upper extremities and −1.32 (95% CI, −2.08 to −0.55) for lower extremities. VLNT yielded greater reductions in cellulitis, with pooled mean differences of −2.43 (95% CI, −3.36 to −1.50) and −1.38 (95% CI, −2.11 to −0.65) for upper and lower limbs, respectively. Additionally, VLNT reduced limb circumference by 42.7% (95% CI, 36.7–49.7) in upper extremities and 21.98% (95% CI, 19.8–24.4) in lower extremities. Conclusion LVA and VLNT both result in durable, long-term improvements in cellulitis rates, and VLNT was shown to reduce limb circumference. Given the significant impact on patient quality of life, these interventions should remain integral to the treatment algorithm for secondary lymphedema.

Metastatic castration-resistant prostate cancer (mCRPC) progresses aggressively and resists existing therapies. Although poly(ADP-ribose) polymerase inhibitors (PARPis) benefit a subset of patients with mCRPC and BRCA1/2 deficiencies, therapeutic options remain limited for those without such mutations. Here, we uncover a critical role for the ATM-TRMT10A-BRCA1 signaling axis in regulating homologous recombination (HR) repair and PARPi sensitivity. We demonstrate that ATM phosphorylates TRMT10A at serine-28 after DNA damage, promoting BRCA1 recruitment and efficient HR repair. TRMT10A deletion disrupts HR repair, sensitizing cells to PARPis. Moreover, TRMT10A is up-regulated in mCRPC through stabilization by USP10. Targeting USP10 with spautin-1 induces TRMT10A degradation and enhances tumor sensitivity to PARPis in cell-derived xenografts and patient-derived xenograft models. These findings identify TRMT10A as a therapeutic vulnerability in mCRPC and demonstrate that combined inhibition of PARP and USP10 offers a promising synthetic lethal strategy for a broader group of patients lacking classical BRCA mutations.

Key Points We studied the link between brachial-ankle pulse wave velocity (baPWV) and CKD risk in adults undergoing cardiovascular disease screening. A higher baseline baPWV was predictive of an increased annualized rate of creatinine-based eGFR (eGFR Cr ) decline. Compared with normal baPWV, higher baseline baPWV was associated with increased risk of developing CKD and lower CKD-free survival time. Background CKD affects 35 million adults in the United States and is associated with high morbidity and mortality. We investigated whether brachial-ankle pulse wave velocity (baPWV), a noninvasive measure of arterial stiffness, was associated with kidney function decline in adults undergoing cardiovascular disease (CVD) screening. Methods In 1862 patients referred for an exercise electrocardiogram test between 2007 and 2009, baPWV was measured using an Omron Colin oscillometric device. Creatinine-based GFR was estimated (eGFR Cr ) for participants with available baseline and follow-up creatinine values using the CKD Epidemiology Collaboration formula. We performed multivariable linear regression analyses to assess whether baseline baPWV was associated with annualized change in eGFR Cr , after adjustment for age, sex, body mass index, baseline eGFR Cr , and traditional CVD risk factors, including mean arterial pressure, diabetes and hypertension diagnoses, nephroprotective medication use, smoking status, and total cholesterol. To determine risk of developing CKD and CKD-free survival time by arterial stiffness subgroups, we performed covariable-adjusted Cox proportional hazards modeling and a Kaplan-Meier survival analysis, respectively. Results After exclusion of participants with missing covariable data and adjustment for covariables, one SD increase in baPWV was associated with a 0.18 ml/min per 1.73 m 2 BSA greater yearly decrease in eGFR Cr ( P = 0.023) over a median follow-up time of 13.2 years. Participants with higher baseline baPWV had increased risk of CKD (hazard ratio [95% confidence interval], P value; elevated baPWV: 2.4 [1.1 to 5.4], P = 0.037; borderline-elevated baPWV: 1.8 [1.1 to 3.1], P = 0.028) and had a shorter CKD-free survival time (median CKD-free survival time [years]; normal baPWV: 16.2; borderline-elevated baPWV: 16.0; elevated baPWV: 15.6 [ P < 0.001]). Conclusions Elevated baPWV, a noninvasive measure of arterial stiffness that can be obtained in the office setting, was associated with decline in kidney function, risk of CKD development, and CKD-free survival in individuals undergoing CVD screening.

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.

ABSTRACT Background Patients with cancer undergoing cardiac implantable electronic device (CIED) implantation face unique challenges. This study evaluates the outcomes and implications of CIED implantation in this population. Methods Using data from the National Readmission Database (NRD) from 2016 to 2019, we analyzed CIED implantations in patients aged ≥18 years, categorized by cancer status: no cancer, historical cancer, and active cancer. Multivariable logistic and linear regression models assessed associations with in‐hospital, 30‐day, and 90‐day outcomes, adjusting for various patient characteristics. Results A total of 748,957 CIED procedures were analyzed among which 13.3% were in patients with historical cancer and 3.8% with active cancer. Active cancer was linked to higher odds of pacemaker implantation but lower odds for ICD and CRT devices. Patients with active cancer experienced higher index hospitalization mortality (aOR 1.68; 1.50–1.89; p < 0.001), major adverse cardiovascular events (aOR 1.07; 1.02–1.14; p = 0.01), bleeding (aOR 1.36; 1.27–1.46; p < 0.01), and sepsis‐related (aOR 1.31; 1.19–1.44; p < 0.01) complications, with increased readmission rates at 30 (aOR 1.37; 1.30–1.44; p < 0.01) and 90 days (aOR 1.37; 1.31–1.44; p < 0.01) compared to those without cancer. Historical cancer was associated with better outcomes. Key predictors of adverse outcomes included chronic heart failure, kidney disease, cerebrovascular disease, and protein‐calorie malnutrition. Conclusions Patients with active cancer undergoing CIED implantation have an increased risk of in‐hospital complications and readmissions as compared to those without cancer.

Abstract Background Although periodontitis and oral microbiota are linked to cardiometabolic diseases (CMD), it is unclear if they similarly predict CMD mortality. We compared the predictive ability of salivary microbiota and periodontal disease measures for CMD mortality in the National Health and Nutrition Examination Survey (NHANES). Methods We included 5,037 adults aged ≥30 years (mean age [± standard deviation (SD)]: 48[± 14]; 50% male) from the 2009–2010 and 2011–2012 NHANES cycles. We used 16S rRNA sequencing data from saliva to operationalize microbial composition and diversity. We calculated the relative abundance log‐ratio of Treponema (linked with periodontal disease) to Corynebacterium (linked with periodontal health) to compute the Microbial Indicator of Periodontitis (MIP). Interproximal periodontal probing depth and clinical attachment loss were measured from periodontal examinations. Mortality was ascertained through 2019. Survey‐weighted Cox models regressed mortality rates on MIP, microbial diversity, and periodontal measures to estimate hazard ratios and 95% confidence intervals (HR [95% CI]). Results Over 8.8 median follow‐up years, there were 81 CMD and 267 all‐cause deaths. After multivariable adjustment, MIP was associated with increased CMD mortality risk (HR per 1‐SD: 2.10 [1.30–3.38]). Neither microbial diversity nor periodontitis measures were associated with CMD mortality. MIP was associated with periodontitis in multivariable modeling (risk ratio per 1‐SD: 1.29 [1.22–1.39]). Conclusions In a nationally representative cohort, greater baseline salivary Treponema to Corynebacterium ratio predicted increased CMD mortality risk, while microbial diversity metrics and periodontal parameters were not significantly associated with CMD mortality. Longitudinal studies that further contextualize the oral microbiota are warranted. Plain Language Summary Bacteria in the mouth that cause gum disease are linked to cardiometabolic diseases (e.g., diabetes, cardiovascular disease, kidney disease). However, it is not well understood if bacteria of the mouth can predict the risk of death due to cardiometabolic diseases. We used data from a nationwide survey of US adults to explore whether bacteria from saliva, collected from a single time point, are associated with the future risk of cardiometabolic disease death. We found that people with higher levels of gum disease bacteria were more likely to die from cardiometabolic diseases. Future studies are needed to better understand the role of gum disease bacteria in the development of cardiometabolic diseases and the risk of death.

Lipid nanoparticles/liposomes (LNPs) represent a highly adaptable nanocarrier system that has gained significant traction in oncology for both therapeutic and diagnostic (theranostic) purposes. Their structural flexibility, biocompatibility, and capacity to encapsulate diverse therapeutic agents ranging from chemotherapeutics to nucleic acids and imaging tracers have enabled targeted cancer treatment with improved efficacy and reduced systemic toxicity. This review critically examines liposome-based platforms across a broad spectrum of cancers, including melanoma, lung, colorectal, liver, breast, ovarian, pancreatic, brain tumors, sarcoma, neuroblastoma, and leukemia. It outlines recent advances in ligand-mediated targeting, pH- and temperature-responsive release systems, and multifunctional LNPs capable of delivering combined therapeutic and imaging payloads. Moreover, the review discusses preclinical outcomes, current clinical trial status, and the challenges hindering clinical translation. By integrating recent innovations and emphasizing translational potential, this work highlights the pivotal role of LNPs in advancing precision cancer therapeutics and diagnostics.