Citations

BACKGROUND: The impact of life-course blood pressure (BP) trajectories on later-life focal left ventricular (LV) fibrosis by late gadolinium enhancement (LGE) remains elusive. METHODS: MyoFit46 prospectively recruited ≈500 participants from a 1946 birth cohort for a cardiovascular magnetic resonance scan at 77 years, assessing LV LGE calculated using the 3-SD method or 5-SD method. Systolic BP (SBP) and diastolic BP were recorded at 36, 43, 53, 63, 69, and 77 years. For each participant, annual rates of BP change (steepness) and area under the BP trajectory (cumulative burden) for each age interval were calculated using mixed-effects models. Associations between life-course BPs and LGE were tested using generalized linear models, adjusted for antihypertensives, demographics, lifestyle, and comorbidities. Time-to-event associations between LGE and incident major adverse cardiovascular event (hospitalizations for coronary artery disease, stroke, heart failure, and atrial/ventricular arrhythmias; n=29) were also evaluated. RESULTS: Among 472 participants (54% male), each 10 mm Hg greater individual SBPs at 36 to 69 years were associated with 6% to 11% greater LV LGE calculated using the 3-SD method (all P ≤0.033), whereas each 10 mm Hg sustained greater SBPs on any age interval from 36 to 69 associated with 16% to 24% greater LGE calculated using the 3-SD method at 77(all P ≤0.005), independent of SBP at 77 years. Each 1 mm Hg/y steeper SBP rise during age intervals 36 to 43, 43 to 53, and 53 to 63 was associated with 6% to 12% greater LGE calculated using the 3-SD method at 77 years. LGE presence was associated with greater major adverse cardiovascular event rates (hazard ratio, 2.5 [95% CI, 1.2–5.2]). CONCLUSIONS: Higher life-course BPs, cumulative burden, and steeper increases were associated with greater older-age LV LGE, which was linked to incident major adverse cardiovascular events. BP trajectories, beyond single-point BP measurements, warrant further investigation as tools to guide BP management strategies.

Background: Monitored anesthesia care (MAC) combined with regional anesthetic techniques is commonly used for open reduction and internal fixation (ORIF) of unstable ankle fractures. When compared to general anesthesia (GA), MAC with regional anesthesia has been associated with reduced systemic adverse effects and shorter recovery times, although regional anesthesia carries additional costs and potential complications of its own. A new technique involving the infiltration of high-volume, low-concentration (VL) local anesthetic was therefore developed. When used in conjunction with MAC, we refer to this technique as MAC-VL. This study evaluates outcomes and recovery metrics following outpatient ankle ORIF performed under GA vs MAC-VL without regional anesthesia. Methods: An IRB-approved retrospective cohort study was conducted including 159 adults who underwent outpatient ankle ORIF between February 1, 2023, and January 31, 2026. Patients were identified using standardized diagnostic and procedural codes and grouped according to anesthesia type. All patients received a standardized injection of local anesthetic around the proposed operative sites before the procedure; anesthesia type was MAC (n = 48) or GA (n = 111). The primary outcome was time to discharge, defined as the interval from incision closed to hospital discharge. Secondary outcomes were considered exploratory and included tourniquet, operative, anesthesia time, time in room, Post Anesthesia Care Unit length of stay, conversion from MAC to GA, reported postoperative nausea and vomiting, admissions, and postoperative emergency department visits. Results: Among 160 procedures for which no significant difference in case mix could be detected with the numbers available, MAC-VL was associated with a significantly shorter time to discharge—reducing discharge time by 55.2 minutes ( P < .001) following adjustment for demographic, clinical, and operative covariates—and shortened total anesthesia and operating room time compared with GA. With the numbers available, no significant difference was detected for the remaining secondary outcomes. Conclusion: The MAC-VL protocol was associated with shorter operating room and recovery times and may improve health care resource use. Level of Evidence: Level III, retrospective cohort study.

The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.

Abstract Pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer, is a deadly disease with a complex tumor microenvironment (TME). Cytotoxic combination chemotherapy treatments are the mainstay of PDAC therapy, but patients rapidly develop chemoresistance, highlighting the need to elucidate how chemotherapy alters the TME and whether these changes drive chemoresistance. Here, we examined matched pre- and post-treatment tissue specimens using single-cell RNA-sequencing and found near-universal enrichment after treatment of axonal guidance genes in cancer-associated fibroblasts (CAFs). These neural CAFs were enriched near sites of perineural invasion, coinciding with regions of increased tumor cell proliferation, and were enriched in tumor areas distant from nerves after chemotherapy. Metastatic recurrent lesions had the highest prevalence of neural CAFs versus primary tumors and untreated metastases. Neural CAFs showed elevated non-canonical WNT mediators and axonal guidance genes, which complemented matching cognate binding partners in tumor epithelial cells, suggesting a role in tumor-stroma crosstalk. Additionally, in vitro studies revealed enrichment of axonal guidance genes in patient-derived CAF lines upon exposure to chemotherapy or tumor cells. Altogether, these findings implicate fibroblast-derived axonal-guidance genes in promoting PDAC invasion and point to a promising therapeutic target for this disease.

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

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 The 6th Edition of the World Health Organization Classification of Digestive System Tumours has introduced two new categories of gastric neuroendocrine tumors, reflecting recent data on subtypes that do not conform to the three established subtypes: type 1 (associated with autoimmune gastritis), type 2 (associated with Zollinger-Ellison Syndrome) and type 3 (sporadic). The new type 4 category is exceptionally rare and is caused by endogenous dysfunction of parietal cell proton pumps, potentially secondary to mutation of ATP4A. Type 5 gastric NETs are caused by chronic pharmacologic inhibition of the parietal cell proton pump, typically due to proton pump inhibitor use, and are increasingly common. Given the relatively low malignant potential of the new subtypes compared to sporadic (type 3) gastric NETs, it is important that clinicians and pathologists recognize these entities, limiting radical surgical resections when unnecessary.

Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies.