Citations

ABSTRACT Tissue‐resident memory T cells (TRMs) are a distinct memory T‐cell subset that permanently reside in tissues such as the skin. In chronic immune‐mediated dermatoses, including psoriasis, atopic dermatitis, and vitiligo, TRMs are implicated in site‐specific “disease memory,” contributing to persistence and relapse at previously affected sites. This review synthesizes emerging concepts on TRMs in chronic inflammatory skin diseases and discusses clinical and translational implications, including TRM‐targeted therapies. Original human, animal, or in vitro studies evaluating TRMs in the pathogenesis or persistence of dermatologic diseases were included. In psoriasis, CD8 + TRMs (CD69 + CD103 + ) persisted in clinically healed skin. For atopic dermatitis, both CD4 + and CD8 + TRMs are implicated in maintaining Th2/Th22 inflammation. In vitiligo, autoreactive CD8 + TRMs at lesional margins mediate melanocyte destruction. Across dermatological diseases, TRMs share three core features: persistence in previously affected skin after clinical resolution, rapid reactivation by diverse triggers (stress, autoantigens, allergens, or cytokines) leading to site‐specific recurrence, and relative resistance to conventional therapies. Together, these properties provide a unifying framework linking tissue immune memory to the chronic, relapsing nature of inflammatory skin diseases. However, the dominant TRM pathways vary by disease, reflecting differences in immune polarization and antigen specificity. Targeting TRMs represents a promising strategy for disease control and serves as a biomarker of residual disease or flare. image

Abstract Objectives Medical nutrition therapy significantly impacts cardiovascular risk and overall health, but effects on muscle diseases remain unclear. This systematic review evaluates the safety and efficacy of dietary interventions and supplements on muscle disease outcomes. Methods A multidisciplinary team conducted a PRISMA-guided systematic review registered on PROSPERO. Searches were conducted across multiple databases and screened against pre-specified inclusion criteria. Results Of 107 full-text articles screened, 51 met inclusion criteria. Most identified interventions used dietary supplements rather than whole dietary approaches. In inflammatory myopathies, creatine (loading dose 20 g/day, maintenance 3 g/day) combined with exercise improved high-intensity functional performance in PM and DM over 6 months. In Duchenne muscular dystrophy, creatine (2–10 g/day for 8–16 weeks) improved maximal voluntary contraction and fatigue resistance. Carbohydrate-rich diets (65% CHO) reduced exercise-related symptoms in McArdle disease, while high-dose creatine (150 mg/kg/day) paradoxically worsened symptoms. Four trials of aceneuramic acid (6 g/day for 48 weeks) in GNE myopathy demonstrated dose-dependent strength improvements, leading to regulatory approval in Japan. High-protein supplementation showed positive trends for muscle preservation in critical illness myopathy. Quality assessment revealed 31% at low risk of bias, 49% with some concerns and 20% at high risk. Conclusion Evidence for nutritional interventions in muscle diseases remains limited, especially for inflammatory myopathies. The strongest support emerged for mechanistically targeted approaches: creatine with exercise, carbohydrate-rich and ketogenic diets in McArdle disease and sialic acid in GNE myopathy. Future research requires adequately powered multicentre trials with standardized outcomes, with focus on inflammatory myopathies.

Abstract Background Presacral tumours are rare, heterogeneous lesions. Historical classification systems for presacral tumours have provided a valuable framework, but were based on limited available data. This study aimed to develop a contemporary classification aligned with current tumour entities and clinical practice. Methods A prospectively registered systematic review of surgically managed presacral tumours published from 1975 to 2025 was combined with a retrospective multisite institutional surgical pathology review from 1986 to 2025. Pathological descriptors were extracted, cross-referenced, harmonized to current terminology, and organized through multidisciplinary expert review to obtain a new classification. Results The systematic review identified 5997 records, of which 203 studies met the inclusion criteria and contributed 181 pathological terms after generic and unclassifiable diagnoses were removed. Review of 3606 pathology reports identified 19 additional terms, bringing the total to 200 pathological terms. After harmonization to current terminology and exclusion of non-neoplastic processes, a contemporary classification was developed using biological descriptors: developmental versus acquired origin; tissue lineage (neurogenic, osseous/haematopoietic, soft tissue, or miscellaneous); and tumour behaviour (benign, locally recurrent without metastatic potential, locally recurrent with low metastatic potential, malignant non-sarcoma, or malignant sarcoma). Conclusion The Mayo Clinic classification of presacral tumours updates historical systems by reflecting the broader, more modern spectrum of neoplasms and distinguishing lesions by lineage and biological behaviour. It may improve diagnostic clarity, communication, and selection of appropriate observation, multidisciplinary assessment, and treatment pathways.

Abstract Physical activity (PA) is a modifiable lifestyle behaviour associated with lower dementia risk; however, molecular pathways bridging PA-related dementia prevention are poorly understood. We leveraged large-scale plasma proteomics to identify biological signatures of objectively monitored PA and cognitive ageing in functionally intact older adults, cross-validated these signatures in independent exercise cohorts and tested associations with both symptomatic and presymptomatic stages of neurodegeneration across multiple Alzheimer’s disease and related dementias (ADRD) cohorts. We analysed large-scale plasma proteomics data (SomaScan 7k) across three cohorts including naturalistic, objective PA monitoring (University of California, San Francisco Brain Aging Network for Cognitive Health cohort, n = 65), self-reported PA (Atherosclerosis Risk In Communities study, n = 10 644) and PA intervention (Health Risk Factors, Exercise Training and Genetics study, n = 654). Differential regression models examined individual protein correlates of PA, adjusting for age and sex. Weighted gene co-expression network analysis assembled proteins into unbiased modules of protein co-expression, which were annotated for gene ontology and cell-type enrichment. To test clinical relevance to ADRD, we examined PA-related protein levels across-cohorts of symptomatic Alzheimer’s disease and Parkinson’s disease (Stanford Alzheimer’s Disease Research Center), as well as frontotemporal dementia-spectrum disorders (ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium). PA-related plasma proteins were also tested as predictors of antemortem cognitive change and post-mortem brain tissue mass spectrometry proteomic signatures in brain donors from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) cohort. Differential regression and network analyses identified PA plasma proteomic signatures linked to cell adhesion/extracellular matrix (ECM), immune response and lipid metabolism. Protein co-expression module M12 ECM/neurodevelopment harboured growth factor, cell adhesion and vascular remodelling proteins that (i) were positively associated with PA across exercise cohorts, (ii) positively associated with cognitive function and (iii) negatively associated with Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia. Furthermore, M12 was enriched for proteins from Alzheimer’s disease risk genes and antemortem plasma abundance of anthrax toxin receptor cell adhesion molecule 2 (ANTXR2), an M12 ‘hub’ protein and top PA hit across-cohorts, forecasted longitudinal global cognitive decline and post-mortem brain tissue signatures of synaptic function and proteolysis in ROSMAP. Collectively, our integrated systems biology analysis of six independent plasma proteomic datasets facilitated discovery and validation of blood-detectable molecular signatures of PA and neurodegenerative disease, including PA-related proteins with clinical and biological relevance to early stages of disease. Circulating levels of PA-related proteins reflecting ECM biology (e.g. ANTXR2) may represent key molecular targets for dementia prevention.

BACKGROUND: Randomized trials comparing radial and femoral access report access site crossover rates of 3% to 9% for radial access and 1% to 3% for femoral access. However, contemporary real-world crossover rates are not well characterized. The aim was to evaluate contemporary trends and predictors of vascular access site crossover during percutaneous coronary intervention (PCI). METHODS: We analyzed index PCI procedures recorded in the National Cardiovascular Data Registry CathPCI Registry from 2018 to 2024. Access site crossover was identified using documented access data, with radial-to-femoral crossover inferred when the final successful access site was femoral. Temporal trends and clinical predictors of crossover were examined. Operator experience was assessed using cumulative total and radial PCI volumes from 2011 to 2024 as captured in CathPCI Registry versions 4 and 5. RESULTS: Among 3 861 790 index PCIs, 192 902 (5.0%) involved access site crossover, with a modest increase over time. Radial-to-femoral crossover accounted for 81.2% of crossover events. Factors independently associated with crossover included older age, female sex, higher body mass index, and peripheral vascular disease. Operators with the lowest total PCI volume and the lowest radial PCI volume experienced the highest crossover rates. Notably, operators with low radial PCI volume demonstrated a substantial decline in radial-to-femoral crossover over the study period. CONCLUSIONS: In contemporary clinical practice, access site crossover rates are consistent with those reported in randomized trials. Although crossover occurs more frequently among lower-volume operators, rates decline with increasing operator experience, supporting the presence of a radial access learning curve and improvement in procedural performance over time.

Background/Objectives: Fixed-dose triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) at high risk of exacerbations; however, direct comparative effectiveness data between available triple therapy regimens remain limited. We compared real-world clinical outcomes among adults with COPD receiving fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR). Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network. Adults with a spirometrically confirmed diagnosis of COPD who received fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) between July 2020 and August 2024 were included in the analysis. A 365-day landmark period was applied to establish maintenance therapy, with outcome follow-up beginning 1 year after treatment initiation. Patients were followed for outcomes through August 2025, the date of database analysis. After 1:1 propensity score matching, treatment groups were compared for COPD exacerbations, acute respiratory failure (ARF), hospitalization, and all-cause mortality using RR and Cox proportional hazards analyses. Results: In matched cohorts, FF/VI/UMEC was associated with a significantly higher risk of COPD exacerbations (5.6% vs. 3.9%; RR 1.44; 95% CI 1.30–1.59; p < 0.001) and ARF (2.5% vs. 1.9%; RR 1.28; 95% CI 1.11–1.46; p < 0.001) compared with BUD/GLY/FOR. Time-to-event analyses demonstrated lower event-free probability for exacerbations (HR 1.35; (95% CI 1.21–1.50) and ARF (HR 1.15; (95% CI 1.00–1.32))). All-cause mortality was numerically higher in the FF/VI/UMEC cohort (5.2% vs. 4.7%; RR 1.09; 95% CI 1.00–1.19; p = 0.050); however, time-to-event analysis did not demonstrate a statistically significant difference. Hospitalization rates were similar between groups. Conclusions: In this large propensity score-matched real-world cohort study, patients receiving BUD/GLY/FOR experienced lower rates of COPD exacerbations and acute respiratory failure than those receiving FF/VI/UMEC. Because of the retrospective observational nature of the analysis, these findings should be considered hypothesis-generating and require confirmation in prospective comparative effectiveness studies.

Background Subjective cognitive decline (SCD) is a preclinical condition associated with an increased risk of dementia and Alzheimer’s disease, with no consensus regarding effective therapeutic interventions to date. As the global burden of aging-related neurodegenerative diseases continues to rise, early intervention has become increasingly critical. Cognitive training has been proposed as a promising behavioral intervention; however, few studies have integrated multimodal assessments to elucidate its underlying neurobiological and psychological mechanisms, particularly within the educational system that shapes cognitive reserve and learning strategies across the lifespan. This pilot study aims to estimate effect sizes for future definitive trials, assess the feasibility and acceptability of the intervention and multimodal evaluations, and generate hypotheses regarding the relationship between recitation practice and clinical biomarkers. Methods A total of 60 individuals with subjective cognitive decline will be enrolled in a randomized, assessor-blinded, controlled pilot study. Participants will be randomly assigned to either an intervention group or a non-active control group prior to baseline assessment. The intervention group will undergo a six-month structured recitation training program. Both groups will undergo short-term follow-up after the intervention, and long-term follow-up annually post-intervention. Multimodal assessments will include neuropsychological testing, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), blood biomarker profiling, gut microbiota analysis, and fecal metabolomics. Discussion This study protocol outlines a randomized, assessor-blinded, controlled pilot study designed to advance understanding of the feasibility of Chinese Classics recitation training on both physiological and psychological outcomes in individuals with subjective cognitive decline. The findings are expected to provide mechanistic insights into non-pharmacological interventions and to address the current underrepresentation of Asian populations in neuroscience research. Clinical trial registration We registered this randomized controlled trial on ClinicalTrials.gov on March 11, 2026, under the identifier NCT07463391.

Background/Objectives: Appointment volume is a primary measure of provider workload and a key contributor to provider burnout in primary care settings. It is highly driven by the size and patient mix of patient panels assigned to providers. To ensure that workload is balanced among providers, an effective patient panel assignment strategy is essential. Methods: A patient panel assignment framework was developed and demonstrated using a year of data from a large family medicine practice to assign patients evenly among providers with the following steps: 1. Predicting patient appointment needs using patient characteristics and Adjusted Clinical Group (ACG) scores; 2. Placing patients in appointment groups based on predictive appointment needs; 3. Determining the patient cap of each appointment group for each provider group; 4. Allocating patients from each appointment group to each provider group without exceeding the patient cap. Results: The results were demonstrated across 100 simulated reassignments to a retrospective dataset. The variations in the number of appointments among providers within a provider group were compared between current practice and the proposed framework. For the largest provider group with 14 providers, the proposed framework with appointment prediction using all features reduced the standard deviation and range by 85% and 84%, respectively. While the proposed framework improved appointment workload balance among providers, 11.7% of patients required reassignment. Conclusions: The proposed framework demonstrates its utility in supporting workload balance. Future work is needed to minimize patient reassignments while accounting for patient care continuity and to incorporate other contributing factors into the framework.