Citations

Introduction: Frontotemporal lobar degeneration (FTLD) is a devastating disease that commonly results in early onset dementia, yet its rarity and heterogeneity limit large-scale research and clinical trials. Remote monitoring via low-burden digital health tools may overcome these barriers. We evaluated clinical utility of passive smartphone monitoring in FTLD using a multi-domain mobile assessment platform. Methods: Participants were 567 adults (53% clinically normal, 21% prodromal FTLD, 26% symptomatic FTLD) who completed an in-person study visit and downloaded the ALLFTD Mobile App on their personal smartphones. The app delivered unsupervised cognitive tests and passively collected continuous data on battery percentage (proxy for smartphone use) and step count. Longitudinal follow-up included smartphone monitoring and annual in-person study visits. Primary analyses examined associations between passive smartphone features and markers of disease severity at baseline and longitudinally, and tested whether passive features added incremental value beyond app-based cognitive testing. Results: Passive smartphone features were feasible to collect and showed excellent reliability with <2 weeks of monitoring (ICCs>0.9). Features capturing smartphone use and movement demonstrated sensitivity to gold-standard clinical measures of disease severity both at baseline and longitudinally. A classification model combining passive features, the app-based cognitive composite score, and demographics detected longitudinal functional decline (AUC=0.89); passive features alone (AUC=0.84) performed comparably to a cognitive screener (AUC=0.85). Discussion: Passive smartphone monitoring is a valid, zero-burden measure of disease severity and progression in FTLD that adds modest incremental value beyond app-based cognitive testing. Findings support its use as a scalable digital endpoint in longitudinal FTLD research.

Summary: Bone defects are among the most challenging problems treated by limb reconstruction surgeons and orthopaedic traumatologists. Bone transport is a biological reconstruction technique which harnesses distraction osteogenesis to create new bone in critical bone defect. This technique has been successfully performed with a variety of internal and external solutions. This work introduces a newly available technology which provides a fully implantable, all-internal solution (eg, without the need for external fixation) for bone transport with the option to simultaneously address residual limb length discrepancy.

Follicular occlusion disorders (FOD) represent a tetrad of chronic, recurrent inflammatory conditions united by a common pathophysiologic mechanism: follicular hyperkeratosis leading to occlusion, rupture, and subsequent abscess or sinus tract formation. First conceptualized as a triad in the 1950s and later expanded to a tetrad in the 1970s, this grouping includes hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal sinus (PS). Despite their shared pathogenesis, each condition carries distinct clinical features, epidemiological profiles, and management considerations. This article aims to provide a comprehensive review of FOD, with a primary emphasis on HS (the most prevalent of the disorders). Hidradenitis suppurativa is a debilitating disease affecting ∼1% of the global population, predominantly in females, and the diagnosis is often delayed by 7 or more years. Multiple genes are linked to FOD patients with a positive familial history in 35% to 40%, along with lifestyle factors (smoking, alcohol consumption, and obesity). Key inflammatory mediators, including TNF-α, IL-1β, and IL-17, drive the chronic tissue destruction characteristic of FOD, frequently resulting in scarring, lymphedema, and significant psychosocial impairment. Wound care is critical and often underemphasized in disease management. This article outlines evidence-informed wound care strategies for both nonsurgical and postsurgical presentations, including dressing selection, exudate and odor management, pain and itch control, infection management, and the emerging role of intravenous ertapenem as rescue therapy. An interprofessional approach, integrating dermatology, surgery, wound care nursing, and psychosocial support, is emphasized throughout as essential to improving patient outcomes and quality of life. GENERAL PURPOSE: To increase clinicians’ understanding of follicular occlusion disorders including the associated risk factors, clinical manifestations, and evidence-based approaches for management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will: Assess clinical characteristics of each follicular occlusion disorder Evaluate the basic disease mechanisms for follicular occlusion disorders Describe principal disease burdens that require wound care attention Identify the unique wound care strategies and follicular occlusion disorder challenges JOURNAL/aswca/04.03/00129334-202610000-00004/figure1/v/2026-09-18T181327Z/r/image-jpeg

Importance The incidence of human papillomavirus type 16 (HPV16–positive) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rising. Approved therapies offer a durable response to a minority of patients. Objective To determine the efficacy and safety of a therapeutic HPV16-targeted immunotherapy, PDS0101, in combination with pembrolizumab in participants with HPV16-positive R/M HNSCC, with separate evaluation of immune checkpoint inhibitor (ICI)–naive and ICI-resistant cohorts. Design, Setting, and Participants VERSATILE-002 was a phase 2, open-label, multicenter nonrandomized clinical trial conducted at 26 oncology centers from March 29, 2021, to May 15, 2025, across the US, UK, and Ireland using the Simon 2-stage optimal design. Efficacy analyses were performed on modified intent-to-treat (mITT) population; safety analyses included all participants who received 1 or more doses. Eighty-eight participants with histologically confirmed R/M HPV16-positive HNSCC were enrolled, of whom 87 (98.9%) received treatment and composed the safety population. Seventy five (85.2%) were in the mITT population used for efficacy analyses, of whom 53 (70.7%) were ICI-naive with a programmed cell death ligand 1 combined positive score of 1 or greater and 22 (29.3%) were ICI-resistant. Exposures Pembrolizumab (200 mg, intravenously, every 3 weeks for up to 35 cycles) plus subcutaneous PDS0101 (5 scheduled doses per protocol). Main Outcomes and Measures The primary end point was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors , version 1.1, by a masked independent central reviewer. Secondary end points included progression-free survival (PFS), median overall survival (mOS), and safety, with exploratory end points of duration of response, disease control rate, and response rates by programmed cell death ligand 1 status. Results Of the 75 patients in the mITT population, the mean (SD) age was 64.0 (8.3) years; 4 individuals (5%) were female and 71 (95%) were male; and 2 individuals (3%) were Asian, 1 (1%) was Black, 5 (7%) were Hispanic, and 71 (95%) were White. Among 53 ICI-naive participants in the mITT cohort, ORR by the central reviewer was 34.0%, median PFS was 5.3 months (95% CI, 2.10-9.00), and mOS was 39.3 months (95% CI, 23.90 to not evaluable). Among 22 ICI-resistant patients in the mITT cohort, no objective responses were observed and the primary end point (ORR by central reviewer) was not met, but mOS was 14.8 months (95% CI, 8.50-26.00). The treatment was well tolerated, with 13.8% experiencing grade 3 or higher treatment-related adverse events. Conclusions and Relevance The results of this nonrandomized clinical trial suggest that PDS0101 plus pembrolizumab showed antitumor activity in ICI-naive HPV16-positive R/M HNSCC, with favorable safety, response rates, and survival outcomes. The findings support further evaluation in a first-line setting. Trial Registration ClinicalTrials.gov Identifier: NCT04260126

Abstract Stroke thrombi are heterogeneous; their composition influences their mechanical properties, including stiffness, elasticity, and adhesiveness, which in turn affect their response to therapy. Systemic characterization of the thrombi components could help select therapeutic techniques and anticipate outcomes. We conducted a systematic review and meta-analysis to evaluate associations between thrombi composition and angiographic and functional outcomes in acute ischemic stroke (AIS). Up to May 2025, relevant studies were sourced from four databases: PubMed, Web of Science, Scopus, and Embase. We included cohort studies whose populations are patients with AIS in relation to thrombi composition. Thirty-six studies involving 5,462 patients matched our eligibility criteria. Angiographic success (Thrombolysis in Cerebral Infarction ≥ 2b/3) did not differ significantly between red blood cell (RBC)-rich and fibrin-rich thrombi (risk ratio [RR] 1.02, 95% confidence interval [CI] 0.85–1.22; p = 0.84; I 2 = 63.8%; very low certainty). However, thrombi from patients with good angiographic outcomes had a significantly higher RBC content compared to patients with poor outcomes (mean difference = 7.22%, 95% CI 3.31–11.13; p < 0.001; low certainty). No significant difference was observed between RBC-rich and fibrin-rich thrombi regarding functional independence at 90 days (modified Rankin Scale 0–2) (RR = 1.22, 95% CI 0.73–2.05; p = 0.31; low certainty). While RBC-rich thrombi are associated with more favorable angiographic performance, thrombus composition alone does not predict functional outcomes. Stroke outcomes remain multifactorial, dominated by time to reperfusion, collateral circulation, and baseline severity. Preinterventional assessment of clot composition via imaging or biomarkers may support individualized therapy but should complement, not replace, other prognostic determinants.

Abstract Introduction Remote cognitive assessments offer an accessible, scalable way to support clinical characterization and longitudinal monitoring of cognition. This study evaluates the feasibility of implementing Mayo Test Drive (MTD), a remote, self-administered digital cognitive assessment, within a specialized clinic focused on eligibility assessments for anti-amyloid therapies for Alzheimer’s disease (AD). Method Two-hundred and nine ( N =209) patients (M age =71.2, 53% female) were evaluated through the Mayo Clinic Rochester Alzheimer’s Disease Treatment Clinic (ADTC) and had the opportunity to complete MTD, either as a remote, patient-initiated session through a patient-facing healthcare portal or during an in-clinic neuropsychological evaluation. Results Clinical diagnoses included 55.2% mild cognitive impairment (MCI), 31.0% mild dementia, and 11.6% moderate dementia, in addition to 2.2% cognitively unimpaired (CU), as determined by neurology consensus at a multidisciplinary case conference. Among those who initiated MTD ( n =197/209), 97.5% completed a session (70.6% remotely, 26.9% in clinic). Completion rates were high across diagnostic groups and did not significantly differ by clinical severity ( p =.12): CU (100%), MCI (99.1%), mild dementia (97.0%), and moderate dementia (89.5%). Remote completion rates overall were high (97.9%). Among completers, administration setting (remote vs. in-clinic) did not significantly differ by clinical stage, χ²(3)=2.37, p =.49. Reasons for non-initiation included not receiving or opening portal messages and other/unknown factors. Discussion Remote digital cognitive assessment is feasible within the context of clinic eligibility evaluations for AD therapies. The high completion rates of MTD across clinical impairment levels in this setting support development of paths for broader use in cognitive characterization in AD care.

Abstract BCMA-directed CAR T-cell and T-cell engager (TCE) therapies produce high response rates in relapsed multiple myeloma, yet most patients progress. Prior work identified TNFRSF17 alterations mediating antigen escape in up to 43% of TCE progressions. To evaluate the generalizability of these findings and examine antigen-loss-independent resistance, we performed whole-exome sequencing on 32 paired pre- and post-treatment progression bone marrow samples from 15 patients (5 CAR T, 10 TCE); two patients received both agents. TNFRSF17 alterations were infrequent and restricted to TCE recipients (one concurrent frameshift and missense mutation; two heterozygous copy-number losses); no biallelic loss or CAR T-associated events were observed. In contrast, deleterious/loss-of-function variants in NF-κB, PI3K-AKT-mTOR, and MAPK/ERK pathways were universal in pre-treatment samples and acquired or clonally enriched in 80% of patients at progression. Acquired events included loss-of-function alterations in CYLD , activating mutations in KRAS , NRAS and BRAF , and acquired TP53 mutations. In this series, antigen escape via TNFRSF17 /BCMA alteration was uncommon. Instead, pre-existing, acquired and clonally enriched pathogenic variants in NF-κB, PI3K-AKT-mTOR and MAPK cascades, together with TP53 mutation, emerged as a frequent finding. These alterations suggest that deregulation of BCMA-downstream survival signaling, enhanced proliferative fitness, and elevation of apoptotic threshold constitute antigen-loss-independent mechanisms of resistance.