Citations

BACKGROUND: Improved cleaning in the anesthesia workspace is important for surgical site infection prevention. We sought to identify high-priority cleaning targets to guide post-induction surface disinfection and use of a triangular ultraviolet-C (UV-C) configuration involving placement of one emitter at the head and one on each side of the surgical bed. METHODS: The 20 sites most frequently touched by anesthesia practitioners, previously identified via video-based workflow analysis, were filtered to remove disposable (eg, stopcocks) and transient (eg, the patient bed) sites, leaving durable cleaning targets amenable to repeated surface disinfection and UV-C irradiation within and/or between cases. Inequality in the distribution of cleaning target touches was quantified using the Gini coefficient, and uncertainty was estimated using bootstrap resampling (10,000 iterations). We then assessed residual contamination after standard terminal cleaning across three operating rooms and 171 sites to evaluate the difficulty of cleaning high-touch surfaces and the efficacy of UV-C disinfection. Simulations using medical devices composed of materials representative of cleaning targets contaminated with high-level Clostridium difficile were conducted to evaluate generalizability to more resistant pathogens. RESULTS: There were 13 of 20 frequently touched sites that were considered durable cleaning targets. Touches were relatively equal among the 13 cleaning targets (Gini coefficient 0.16, 95% confidence interval [CI], 0.12–0.20). Cleaning targets included components of the anesthesia cart (first and second drawer handles); anesthesia machine (reservoir bag, circuit ventilator control, oxygen dial, vaporizer dial, adjustable pressure-limiting valve), monitoring equipment (screen buttons/knob, electrocardiogram leads); and room infrastructure (intravenous pole, operating room table and chair). Residual contamination after cleaning was identified at 4% (7/171) of sites, mostly (6/7) within the anesthesia workspace, involving the anesthesia cart (N = 2), machine (N = 3), and monitor (N = 1). Only one site outside of the anesthesia workspace, the circulating nurse’s mouse, had residual contamination. Triangular UV-C reduced mean (standard deviation [SD]) colony-forming units (CFU) from 60.47 (542.22) to 0.12 (1.08), achieving a 2.7-log reduction. Simulation with high-level C. difficile contamination demonstrated ≥3-log reductions on surfaces representative of high-touch sites, confirming applicability to resistant pathogens. CONCLUSIONS: Thirteen durable cleaning targets in the anesthesia workspace are largely equivalent in terms of risk of touch. They are amenable to UV-C augmentation of surface disinfection in the real-world clinical environment. These findings can guide targeted post-induction cleaning and use of triangular UV-C, particularly for surfaces with substantial contamination or resistant pathogens.

Objective Vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome (VEXAS) syndrome is characterized by a complex spectrum of inflammatory and hematologic manifestations. Clinical research to identify effective therapies is urgently needed but is hindered by the lack of validated outcome measures. A VEXAS‐specific disease activity index (DAI) is an essential tool for reliably capturing changes in disease activity over time, thereby supporting clinical research and informing patient care in this emerging disease. This study aimed to develop a comprehensive DAI to assess disease‐related inflammation across affected organ systems in patients with VEXAS syndrome. Methods Inflammatory manifestations of VEXAS were previously identified through a systematic literature review and expert input. A multinational expert advisory committee developed the VEXAS‐DAI using modified Delphi methodology until consensus (defined as ≥75% concurrence) was reached. Item grading was adapted from the Common Terminology Criteria for Adverse Events. Scoring criteria were developed based on 158 test cases using the Physician Global Assessment of Inflammation. Results Consensus on the VEXAS‐DAI was achieved after four Delphi rounds. The index assesses inflammatory activity at the time of evaluation across 12 domains: inflammatory rash, chondritis, periorbital, ophthalmologic, joint, pulmonary, cardiovascular, genitourinary, neurologic, oral and gastrointestinal, renal, and constitutional symptoms. The total score ranges from 0 to 40. Conclusion The VEXAS‐DAI is a novel instrument designed to quantify active inflammation over time in patients with VEXAS. Prospective validation within a clinical trial setting is ongoing. image

Abstract Targeting oxidative phosphorylation (OXPHOS) represents an attractive therapeutic strategy in acute myeloid leukemia, which exhibits exceptional dependence on mitochondrial respiration compared to normal hematopoietic cells. However, clinical attempts to exploit this vulnerability have been limited by on-target toxicity to healthy tissue. Here, we comprehensively compare the cellular consequences of inhibiting distinct nodes of the electron transport chain in AML. We demonstrate that selective inhibition of the F 1 subunit of ATP synthase with EB2023 (ammocidin A) delivers an energetic stress to AML cells without the profound redox stress that characterizes complex I inhibition, preventing NAD⁺/NADH imbalance and allowing continued TCA cycling. Further, the duration of OXPHOS inhibition is transient in nature in vivo , a finding revealed through pharmacokinetic and serial pharmacodynamic monitoring of AMPK phosphorylation accompanied by OPA1-mediated mitochondrial structural remodeling that primes AML cells for BCL2 inhibitor synergy. EB2023 in combination with venetoclax demonstrates potent anti-AML activity across cell lines and patient-derived xenograft models at doses that spare normal hematopoietic progenitors and avoid the neuropathy and sustained detrimental systemic metabolic rewiring in healthy tissues associated with prior efforts to target OXPHOS. These findings establish F 1 -selective ATP synthase inhibition as a clinically actionable therapeutic strategy in AML and establish the duration of OXPHOS inhibition as a critical and previously underappreciated determinant of therapeutic index.

Abstract Rural and low-socioeconomic status women face social determinants of health barriers leading to disproportionately low rates of breast cancer screening and markedly reduced participation in clinical trials. To address this gap, we developed the WeCARE (Women’s Engagement for Cancer Awareness, Resources, and Education) intervention using a community-engaged approach. This paper describes how Community Advisory Board feedback informed the development of Mayo Clinic Health System’s WeCARE intervention components. Their input was systematically analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0) to identify determinants of acceptability, appropriateness, and feasibility and to guide actionable refinements to intervention content and delivery.

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital anomaly affecting around 0.4–0.8% of the population, but limited mortality data exist. We characterized trends and disparities in AAOCA-related mortality in the United States from 1999 to 2023. We queried the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research multiple-cause-of-death database for AAOCA-related deaths among all age groups. Age-adjusted mortality rates (AAMR) per 1,000,000 population with 95% confidence interval, stratified by year, sex, race, regions, and urbanization status, were abstracted. Annual percent changes were computed by Joinpoint regression. From 1999 to 2023, there were 6665 AAOCA-related deaths. Overall AAMR fell insignificantly from 1.1 in 1999 to 0.9 by 2001, rose to 1.1 in 2008, declined significantly to 0.5 by 2020, and then increased to 0.8 by 2023. Male AAMRs exceeded females (1999: 1.3 vs 0.9; 2023: 1.2 vs 0.4). Racially, from 1999–2020 to 2021–2023, non-Hispanic (NH) Blacks exhibited the highest AAMR (1.8 vs 1.5), trailed by NH Whites (0.8 vs 0.6) and Hispanics (0.5 vs 0.6). Regionally, AAMRs from 1999 to 2020 were 0.9 in the Northeast, Midwest, and South, and 0.8 in the West. Moreover, both urban and rural AAMRs were 0.9. Among age groups, <44 years mortality declined, with the steepest drop in 15–44 years, while mortality for >45 years plateaued. Although AAOCA mortality declined overall, especially in children and young adults, it remains high among men, NH Blacks, and Midwest residents. Its recent rebound underscores the need for early detection, risk stratification, and surveillance for timely interventions.

Abstract Since its introduction in 2002, left atrial appendage closure (LAAC) has rapidly expanded as an alternative to anticoagulation in patients with atrial fibrillation at high risk of stroke. Harmonized processes for data collection, analysis, and reporting in LAAC trials are essential to enhance research quality and improve clinical practice. The Left Atrial Appendage Academic Research Consortium (LAARC) initiative is an independent collaboration of academic research organizations, cardiology and neurology experts, clinical trialists, and regulatory authorities from the USA, Europe, and Asia. The consortium engaged clinical experts, regulators—including the US Food and Drug Administration (FDA), European Notified Bodies, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA)—and industry leaders to define standardized study elements and endpoints for LAAC trials. Key considerations included alignment with prior Academic Research Consortium initiatives, procedural and mechanistic insights, and clinical relevance. Consensus definitions were proposed for mortality, stroke, bleeding, and device performance, along with composite endpoints for safety and effectiveness. The proposed LAARC consensus definitions aim to standardize endpoint reporting, improve comparability across studies, and support regulatory and clinical trial applications for this evolving therapy through broad dissemination in the peer-reviewed literature.

Abstract Background Deep brain stimulation (DBS) is a widely used therapy for neurologic and psychiatric disorders. Conventional DBS delivers highly regular stimulation patterns that suppress pathological activity but can induce stimulation-related side effects, limiting the therapeutic window. Introducing controlled temporal variability through stochastic pulse timing may represent an alternative programming dimension to improve tolerability while preserving clinical benefit. Methods An adult in their 60’s with bilateral Vim DBS underwent evaluation of tonic, pink-noise, and white-noise stimulation patterns delivered through his chronically implanted Boston Scientific Genus system using the Chronos research platform. We assessed tremor and stimulation-induced side effects using accelerometry, spiral drawing tasks, standardized speech recordings, and patient-reported paresthesias. Results Pink noise stimulation preserved meaningful tremor suppression while improving tolerability compared with conventional tonic 130 Hz stimulation. Under tonic stimulation, dysarthria and paresthesias were prominent at 2.0 mA, narrowing the usable therapeutic window. In contrast, pink noise maintained tremor control across the same amplitude range with reduced side-effect burden. White noise stimulation demonstrated intermediate effects, providing improved tolerability relative to tonic stimulation but less tremor suppression than pink noise. Findings were consistent across accelerometry and functional drawing tasks. Conclusion This study provides first-in-human evidence that temporally structured stochastic pulse timing can preserve therapeutic benefit while expanding the tolerable stimulation range relative to tonic DBS. These findings suggest that temporal structure represents a clinically meaningful programming dimension that may broaden the DBS therapeutic window using software based updates to existing hardware. Further evaluation in larger cohorts is warranted.