Citations

Stereotactic radiosurgery was associated with a higher obliteration rate compared with embolization in patients with eloquent brain arteriovenous malformations, whereas there was no evidence of a difference in functional outcomes or complications after adjustment.

Background Mitral valve prolapse (MVP) can be associated with ventricular arrhythmias (VA), but little is known about the relationship between VA and exercise in these patients. The aim of this study was to assess the occurrence and severity of VA during exercise tests in patients with MVP, and to explore the association between VA during exercise and the occurrence of arrhythmic events during follow-up. Methods In this multicentre study, 375 patients with MVP (58 (48–69) years, 53% male) who underwent a clinically indicated exercise test were included. Severity of VA during exercise was defined as: (1) no VA, (2) minor VA (premature ventricular contractions ≥5% or non-sustained ventricular tachycardia (nsVT) <120 beats per minute) and (3) major VA (nsVTs ≥120 beats per minute). Results During exercise test, 242 (65%) patients showed no VA, 88 (24%) minor VA and 45 (12%) major VA. Patients with minor and major VAs showed more often bileaflet prolapse and mitral annular disjunction (MAD) than patients with no VA (p<0.001). Over a median follow-up of 101 months (IQR 58–138 months), 35 patients (9%) developed a severe arrhythmic event, defined as sustained VA or ventricular fibrillation, implantation of an implantable cardioverter-defibrillator and VA ablation. At the Kaplan-Meier curve analysis, patients with major VA showed the worst arrhythmic event-free survival (log-rank p<0.001). On multivariable analysis, left ventricular end-systolic diameter, MAD and VA severity during exercise were independently associated with this outcome. Conclusions In patients with MVP, the occurrence of VA during exercise is associated with more advanced mitral valve abnormalities, including MAD, and with higher rates of severe arrhythmic events during follow-up. Performing an exercise test, combined with the clinical and echocardiographic assessments, may therefore offer important complementary information useful for patient management.

Abstract Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical–pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease‐modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences. Highlights We celebrate 40 years of NIA‐funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD. Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies. Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease‐modifying therapies. Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics. Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.

ABSTRACT Background Atrial fibrillation (AF) is a prevalent arrhythmia that frequently coexists with cardiomyopathy, leading to deteriorated cardiovascular outcomes. Analyzing the trends associated with these conditions is essential for improving prevention strategies and management practices. Methods CDC WONDER (1999–2023) data were analyzed to assess AF with cardiomyopathy‐related mortality in patients aged ≥ 25. Using Joinpoint regression analysis, we calculated age‐adjusted mortality rates (AAMRs) per 100,000 patients and average annual percentage changes (AAPCs) to analyze mortality trends. Results AF with cardiomyopathy is responsible for 126,377 deaths among adults aged 25 and older. Alarmingly, AAMRs have surged from 1.8 per 100,000 in 1999 to 3.0 in 2023 (AAPC: 2.11, p < 0.001). The upward trend remains pronounced, particularly between 2016 and 2021, with an annual percentage change of 6.17 ( p = 0.02). Disparities in mortality rates are striking. Men face a higher AAMR than women (3.1 vs. 1.5), and Black individuals bear the heaviest burden at 2.4, closely followed by Whites at 2.3. Regionally, Vermont stands out with the highest AAMR at 3.6, while New York reports the lowest at 1.3. Both rural and urban areas maintain equal AAMRs of 2.1, yet the increase in rural regions is particularly concerning, reflecting an AAPC of 2.44 compared to 1.78 in urban settings. Conclusion The rising mortality rates from AF with cardiomyopathy in patients, particularly among men, Black individuals, and rural residents, demand urgent action. These concerning trends underscore a public health crisis that must be addressed.

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.

Background: Housing instability and HIV are both associated with early onset of aging-related health conditions, including frailty. However, little is known about the relationship between housing and frailty among people with HIV. Methods: We analyzed data on adults in HIV care collected during routine clinical visits at 6 sites within the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between 2019 and 2024. We measured frailty using a previously validated approach, defined as having at least three of four components (fatigue, weight loss, immobility, inactivity) vs. less than three components. Housing status was based on self-perceived living situation in the past month (“Stable,” “Unstable,” “Homeless,” or “Don’t know”). We estimated the association between most recent housing status and frailty with prevalence ratios from relative risk regression adjusted for sociobehavioral and clinical characteristics. Results: Among 6961 people with HIV (84% men, 16% women) with a median age of 52 years (IQR: 40–60), 11% ( n = 760) were frail and 9% ( n = 625) were unstably housed (5% unstable, 3% homeless, 1% do not know). Compared to individuals with stable housing, the prevalence of frailty more than doubled among those experiencing unstable housing [prevalence ratio = 2.41, 95% confidence interval (95% CI): 1.95–2.97] or homelessness (prevalence ratio = 2.05, 95% CI: 1.56–2.69). Stratified analyses indicated stronger associations among younger vs. older individuals and among those virally suppressed vs. unsuppressed. Conclusion: Housing instability and frailty were both prevalent and strongly associated among adults in HIV care, including within younger and virally suppressed subgroups. These findings highlight the importance of social determinants of health for clinical outcomes among all people with HIV.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.