Citations

Background: Measles is a highly transmissible virus. A single case can result in significant exposures within a healthcare facility and prompt action is needed to prevent secondary cases. In October 2025, Infection Prevention and Control (IPAC) was notified of a patient being admitted to our facility with recent international travel and symptoms consistent with measles. The patient was unvaccinated and had five healthcare facility visits prior to measles being suspected and subsequently confirmed. Objective: To describe our facility’s effective identification, prioritization, and prophylaxis of individuals exposed to measles. Methods: IPAC leveraged the electronic medical record to identify potentially exposed patients. Patients were quickly assessed for age and immune status, then prioritized and assigned to primary care teams. These teams promptly contacted patients and coordinated PEP administration. Results: Across five encounters, the index patient exposed 539 other patients. Due to delayed notification, our teams had less than four days to administer PEP for those exposed and still within PEP window. PEP administration began within hours of the index case’s positive test and patients received PEP within three days (Table 1). No secondary measles cases occurred within our facility. Conclusion: Timely and coordinated multidisciplinary effort enabled us to rapidly respond to our first measles case and control secondary transmission. Although the index case resulted in a large exposure, patients that were exposed and eligible for PEP were quickly prioritized to prevent secondary transmission.

Background: Advanced planning and adaptable response strategies are essential for preventing measles transmission in healthcare facilities. Objective: To describe a measles management plan and subsequent modifications in response to a cluster of measles cases. Methods: Drawing on previously published work (doi:10.1017/ice.2025.49), the Infection Prevention and Control (IPAC) team initiated a multi-disciplinary team and developed a measles preparedness plan with the following domains: Guidance and education; early detection and testing; isolation and patient movement; contact tracing and exposure management (Table 1). In October 2025, a patient was admitted during their fifth healthcare encounter and was diagnosed with measles. Two family members were later hospitalized with measles. Delayed recognition of the first case prompted enhancements to our preparedness framework (Table 1). Results: The first case resulted in 539 exposed patients. The second resulted in 87 exposures, and the third resulted in no exposure. Despite the extensive exposure, zero secondary measles were reported. Conclusion: Proactive planning enabled rapid response to our first case and controlled secondary transmission. Despite extensive planning, delayed identification of the first case caused significant exposures. As the cluster unfolded, we refined our plan, resulting in zero exposures from the last patient and zero secondary cases, despite over 850 exposures. These efforts may guide other healthcare facilities in improving their measles preparedness and response.

Background: Carbapenemase-producing organisms (CPO) are a serious public health threat. The Centers for Disease Control and Prevention (CDC) guidelines for combating CPO includes a recommendation to screen selected high risk patients. We describe a program to identify and screen patients at risk for CPO. Setting: An academic, tertiary care center with 2,059 licensed beds and 74,359 admissions a year. Methods: A report was created in the electronic medical record (EMR) to identify adult patients admitted in the previous 24 hours who were from countries and states with known CPO transmission based on address and zip code. A nursing protocol was subsequently developed in the EMR to facilitate CPO screening for eligible patients at admission. After the CPO order is placed, an electronic communication is sent via the EMR alerting the patient care team of the order, the rationale for screening, details on swab collection, and links to a toolkit with resources to help answer patient questions. A single perirectal swab is obtained by the patient’s primary nurse and is tested for Klebsiella pneumoniae Carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), oxacillinase-48 (OXA-48), and Verona integron-encoded metallo-β-lactamase (VIM) by polymerase chain reaction (PCR). Patients may refuse testing. Results: From May 2018 through November 2025, 6,039 patients were identified for CPO screening using case-finding report. Of these patients, 2,424 had CPO swabs completed. Eighteen patients with CPO were identified with an overall yield of 0.75% on admission screening. There was one patient who tested positive for KPC, 10 patients who tested positive for NDM, and 5 patients who tested positive for OXA-48. Two patients were identified to have both NDM and OXA-48. Conclusions: The EMR can be leveraged for early identification and screening of patients with epidemiologically significant pathogens. Use of the nursing protocol has enabled IPAC to complete timely CPO surveillance and prevent transmission to other patients. Protocols within the EMR can be effectively replicated for a timely response to emerging infections.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Abstract Polygenic risk scores (PRSs), which quantify inherited susceptibility to complex traits and diseases, have emerged as valuable tools for risk stratification and precision medicine. Despite their promise, PRS developed on European cohorts often demonstrate substantially reduced predictive accuracy in non-European populations, due to differences in genetic architecture. The disproportionate representation of European ancestry cohorts in genome-wide association studies (GWAS) leads to inequitable deployment of PRS technologies across diverse populations. Here, we introduce PRANA (Polygenic Risk Adaptation via Neural-network Architecture), a deep learning framework that adapts an existing PRS developed on one population to other ancestries. Unlike methods that require large-scale GWAS in the target population, PRANA leverages pre-trained PRS models derived from European cohorts and adapts them using modestly sized cohorts from the target population. We evaluated PRANA on seven complex traits in South Asian, East Asian and Ashkenazi Jewish populations, as well as in selected smaller East Asian subpopulations where the scarcity of training data poses a particular challenge. PRANA mostly improved predictive performance of the baseline PRS models by 5%-20% in terms of effect size (β) and Nagelkerke’s R², and, in most cases, outperformed existing cross-ancestry multi-PRS approaches. These results highlight PRANA as a scalable and practical strategy to reduce disparities in genomic risk prediction and advance the equitable application of PRS in diverse populations.

Background: Alzheimer’s disease (AD) and cerebrovascular pathology are the two most common causes of dementia, frequently co-occurring in older people. Community-based neuropathology studies indicate that vascular disease accounts for approximately one-third of the population-attributable risk of dementia, controlling for other pathologies (including AD). The proportion with vascular disease as co-pathology is likely to be higher (50–70%). The most common vascular substrate is cerebral small vessel disease, which includes small artery fibrosis (arteriolosclerosis), vascular amyloid deposits (cerebral amyloid angiopathy), and monogenic forms of small vessel disease, the commonest being Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Post-stroke cognitive impairment following both ischemic stroke and intracerebral hemorrhage also contributes. Aims and Methods: In this World Stroke Organization (WSO) scientific statement, we assembled a multi-disciplinary international group of experts to review the vascular contribution to dementia, encompassing both vascular and neurodegenerative dementia. This statement has been reviewed and approved by the WSO executive. Results: We summarize the epidemiology, neuropathology, cognitive profile, clinical impact and management of vascular disease in dementia and discuss the recent VasCog-2-WSO diagnostic criteria. We consider the substantial overlap with clinical stroke and with AD dementia. We catalog transcriptomic and proteomic studies that have revealed novel candidate molecules ( COL4A1/4A2, HTRA1, TRIM47, FOXF2 ) as possible treatment targets. We appraise imaging-based biomarkers relevant to vascular disease and potential biochemical markers (vascular endothelial growth factor-A, placental growth factor, interleukin-6, matrix metalloproteinase-9, cathepsin-B). We highlight the potential for vascular interventions to treat not only vascular dementia but also the vascular component of neurodegenerative dementia. We review recent clinical trials targeting multiple pathways, including nitric oxide signaling, high blood pressure, the GABAergic system, angiogenic activity, microglial inhibition, PDE3 and PDE5 inhibition, as well as dietary supplementation with omega-3 fatty acids, s-equol and vitamin E. Finally, we consider upcoming opportunities and challenges relevant to vascular disease in dementia. Conclusion: The vascular contribution to dementia is i) substantial, ii) increasingly understood at molecular and mechanistic levels, iii) a source of potential treatment opportunities. Data Access Statement: no original data are presented in this document.

Background: Older adults with advanced heart failure experience significant morbidity and mortality and face higher complication rates from advanced therapies. Ensuring these therapies match patients’ values is essential for patient-centered care, and palliative care can be instrumental in clarifying patients’ goals. Aim: To examine the relationship between advanced heart failure patients’ expressed goals of care and their subsequent clinical outcomes and circumstances of death. Design: In this retrospective cohort study, electronic medical records were reviewed for demographic information, advanced therapy evaluation outcomes, and quality-of-death metrics. Goals of care were identified from palliative consult notes and compared with outcomes to assess goal-concordance. Setting/Participants: This single-center study included adults who were referred to both advanced heart failure and palliative care specialists from 2012 to 2022. Results: Of 212 patients, 91 (42.9%) underwent evaluation for advanced therapies, though few received a heart transplant (16, 7.5%) or left ventricular assist device (32, 15.1%). Most (148, 69.8%) had only one palliative physician visit. One hundred thirty-nine (65.6%) died, often in the hospital (55, 40%) and with life-sustaining therapy in the last 24 h (73, 52.5%). Most (167, 78.8%) received goal-concordant care, with the main reasons for discordance being the desire for advanced therapy (33, 15.6%) and complications post-implantation affecting quality of life (9, 4.2%). Conclusions: Few older adults received advanced therapies, and palliative care was underutilized, with many patients seeing palliative care only once. Most received goal-concordant care, but decisions were often made late, highlighting the need for earlier, longitudinal palliative care for these vulnerable patients.

Most patients with chest pain do not have acute myocardial infarction (AMI), yet post-AMI rule-out disposition remains variable. Detectable but sub-99th percentile high-sensitivity cardiac troponin I (hs-cTnI) provides additional prognostic information. We evaluated the economic value of hs-cTnI-guided hospitalizations among non-AMI patients. We analyzed 1481 non-AMI chest pain visits with detectable baseline hs-cTnI across 29 U.S. emergency departments (2014–2016) in the prospective HIGH-US trial using the Atellica IM TnIH assay(Siemens Healthcare Diagnostics, Tarrytown, NY, US). We compared observed standard-of-care admissions with modeled pathways incorporating hs-cTnI thresholds and risk scores, assessing admission rates, costs, and diagnostic accuracy for 30-day death/MI. Overall, 1.0% (n = 15/1481) experienced 30-day death/MI. Standard-of-care admitted 59% of patients with 93% sensitivity and 41% specificity. The modeled pathway using hs-cTnI ≥ 5 ng/L plus non-low risk scores was associated with reduced projected admission of 41%, higher specificity of 60%, and the same 93% sensitivity. Estimated per-patient diagnostic costs were lower under Scenario 1 (noninvasive diagnostic testing only; $1025 vs. $1139) and under Scenario 2 (including inpatient/invasive procedures; $2672 vs. $3536). In subgroups, higher hs-cTnI thresholds conferred further economic benefit without compromising sensitivity. Incorporating sub-99th percentile hs-cTnI thresholds alongside risk scores may support more efficient resource use while maintaining safety, although findings require prospective validation.

Importance In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. Objective To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. Design, Setting, and Participants This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. Exposures RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. Main Outcomes and Measures Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ–positron emission tomography (PET; 18 F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET ( 18 F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. Results Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET–positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217–negative and Aβ-PET–positive; 7 participants were p-tau217–positive and Aβ-PET–negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. Conclusions and Relevance The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.

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