Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease marked by TDP-43 proteinopathy, affecting approximately one-third of individuals aged 80 and above. LATE neuropathological change (LATE-NC) is characterized by the accumulation of phosphorylated TDP-43 preferentially in the limbic system, with potential extension to the neocortex and other brain regions. Notably, the anatomic pattern of LATE-NC differs from that seen in frontotemporal lobar degeneration with TDP-43-immunoreactive inclusions (FTLD-TDP). LATE-NC can occur in a “pure” form but more commonly exists alongside other dementia-related comorbidities, including both degenerative and vascular pathologies. When those “mixed” pathologies are factored in, LATE contributes significantly to cognitive decline in human populations. However, LATE currently lacks a molecular-specific diagnostic method for definitive diagnosis in living people. There are new consensus-based guidelines for predicting the presence of either pure LATE-NC or LATE-NC combined with Alzheimer’s disease neuropathologic change (ADNC). Aimed at developing more specific diagnostic methods, recent research efforts have been directed toward identifying unique features on neuroimaging and molecular signatures in biological fluids such as blood and cerebrospinal fluid to facilitate clinical diagnosis for LATE. This review discusses current progress in molecular understanding of LATE-NC, the search for biomarkers for LATE, and highlights key gaps that need to be addressed to advance early detection and improve patient management and clinical trial stratification.
Coma represents a critical failure of brain systems regulating arousal and awareness, posing significant diagnostic challenges when its origin is unknown. Accurate and timely diagnosis is essential to identify reversible causes and guide treatment. Here, we propose a comprehensive stepwise diagnostic algorithm integrating clinical examination, electroencephalography, neuroimaging, and laboratory investigations, emphasizing iterative reassessment to inform early decision-making. This approach, grounded in the pathophysiology of coma and current consciousness frameworks, facilitates localization of brain dysfunction and prioritizes detection of treatable etiologies. Emerging neurotechnologies, including advanced MRI and multimodal AI, hold promise for enhancing diagnosis and personalized management. Our framework aims to improve clinical outcomes by promoting systematic, physiology-based evaluation of coma of unknown origin in acute-care settings.
Background:. Wound complications following primary closure after abdominoperineal resection reach rates of up to 66%. The de-epithelialized V-Y flap has emerged as a common closure technique, particularly in irradiated patients. This study evaluates the 10-year experience of the modified V-Y flap at our institution. Methods:. A retrospective review of patients who underwent de-epithelialized V-Y flap reconstruction for abdominoperineal resection defects between 2013 and 2024 was performed. An analysis of wound complications (eg, infections, dehiscence) and surgical outcomes (eg, reoperations, readmissions) was performed. Multivariate logistic regression assessed the effects of comorbidities and operative factors on wound complications, 30-day reoperations, 30-day readmissions, interventional radiology drainage, and length of stay. Results:. Eighty-three patients were included, with a wound complication rate of 30.1%. The most common complication was pelvic fluid collections (22.9%), followed by dehiscence (21.7%). Within 30 days, 6 (7.2%) patients required reoperation, and 13 (15.7%) patients were readmitted. Patients with chronic obstructive pulmonary disease (P = 0.046) or atrial fibrillation (P = 0.048) were more likely to have wound complications. Mesh use (n = 6) was associated with higher wound complications (P = 0.02), reoperations (P = 0.03), readmissions (P < 0.001), and interventional radiology drainage (P = 0.01). Conclusions:. The modified V-Y flap demonstrated improved wound complication with more robust data compared with our prior study. Patients with chronic obstructive pulmonary disease or atrial fibrillation may face higher risks of wound complications. Mesh use was associated with an increased rate of complications and interventions.
Aortic stenosis (AS) and hypertension (HTN) frequently co-exist in older adults, worsening disease progression and increasing mortality risk compared to either condition alone. To examine mortality trends and demographic-geographic disparities from comorbid AS and HTN in the U.S. from 1999–2020. Data were extracted from the CDC WONDER Multiple Cause of Death database. Crude and age-adjusted mortality rates (CMRs, AAMRs) per 100,000 were calculated. Joinpoint regression estimated annual (APC) and average annual percent change (AAPC). Trends were projected to 2030 using an autoregressive integrated moving average (ARIMA) model. Between 1999 and 2020, 100,507 deaths were attributed to comorbid AS and HTN. The overall AAMR significantly increased (AAPC: 5.01
This study aims to determine the potential association of postmastectomy radiotherapy and survival in patients with clinically node-positive axillary breast cancer who achieved ypN0 after neoadjuvant chemotherapy. We conducted a retrospective cohort study using the National Cancer Database. Eligible patients were women aged 18–80 with cT1-2, cN+ invasive breast cancer and achieving ypN0 status. Inverse probability weighting (IPW)-based analyses were used to assess the differences in overall survival (OS) between the radiotherapy and no radiotherapy groups. Absolute 5-year OS rates between the two groups were analyzed by nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) analysis. Sensitivity analyses were conducted using multivariable Cox regressions. We identified 3,351 patients who met eligibility criteria, of whom 57.0
