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Importance Exposure to fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM 2.5 ) has been associated with multiple malignant neoplasms, but its relationship with sinonasal malignant neoplasm (SNM) remains poorly characterized. Objective To evaluate the association between regional PM 2.5 exposure and first observed SNM diagnosis. Design, Setting, and Participants This national case-control study used commercial outpatient claims with eligible index dates from January 2007 to December 2020. Cases were defined by the first eligible SNM diagnosis after a 1-year enrollment washout period. Controls without any SNM diagnosis throughout claims history were randomly sampled at an approximate 1:5 case to control ratio. Regional PM 2.5 exposure was derived from NASA 1-km gridded models integrating satellite, meteorologic, land-use, and atmospheric data, aggregated to each participant’s residential metropolitan statistical area and index date. Associations were evaluated using mixed-effects logistic regression with a metropolitan statistical area–level random intercept, adjusted for demographic characteristics, comorbidities, regional smoking prevalence, and socioeconomic deprivation. The analysis was conducted from March 2025 to August 2026. Exposures Mean regional PM 2.5 exposure during the 6-month, 1-year, and 5-year periods preceding the index date. Main Outcome and Measure First observed SNM diagnosis after a 1-year enrollment washout period. Results The analytic cohort included 21 295 individuals: 3600 patients with SNM (mean [SD] age, 51.5 [10.6] years; 1656 [46.0%] female and 1944 [54.0%] male participants) and 17 695 controls (41.5 [14.0] years; 9663[54.6%] female and 8032 [45.39%] male participants). Mean (SD) PM 2.5 concentrations were higher among cases than controls across the 6-month (8.57 [2.52] vs 8.36 [2.50] μg/m 3 ), 1-year (8.69 [2.45] vs 8.45 [2.43] μg/m 3 ), and 5-year (9.36 [2.67] vs 9.08 [2.67] μg/m 3 ) windows. In fully adjusted models, each SD increase in PM 2.5 was associated with higher odds of first observed SNM diagnosis (adjusted odds ratio, 1.25 [95% CI, 1.05-1.49] for 6-month average exposure, 1.31 [95% CI, 1.08-1.59] for 1-year average exposure, and 1.36 [95% CI, 1.11-1.66] for 5-year average exposure). Conclusions and Relevance In this case-control study, greater regional PM 2.5 exposure was associated with higher odds of a first observed SNM diagnosis, with larger estimates for longer averaging windows. Further epidemiologic and mechanistic investigation is warranted.

Nearly 10% of the global population has been labeled as having a penicillin allergy. Of those labeled, about 95% are not truly allergic, yet most do not receive any allergy evaluations. Patients with penicillin allergy labels are more likely to have worse clinical outcomes and incur higher health care costs, largely because they do not receive penicillin and other first-line β-lactam antibiotics for the treatment of infectious diseases. Consequently, the process of evaluating and removing inaccurate penicillin allergy labels—a process known as “delabeling”—has become increasingly supported by a growing body of evidence. Recently, penicillin allergy has garnered substantial public interest with the proposal of federal legislation to include evaluation of penicillin allergy during routine medical visits for Medicare patients. Although this moves delabeling into the generalist purview, most of the emphasis on penicillin allergies and delabeling has been on adult patients. Yet, penicillin allergy is a pressing issue for pediatrics, as most penicillin allergy labels are placed in childhood. Pediatric literature similarly demonstrates negative clinical and public health consequences of inaccurate penicillin allergy labels. Recent guidelines have strongly recommended a proactive effort to identify and delabel inaccurate penicillin allergies in children. To facilitate this process, simple delabeling procedures, such as direct oral challenge with amoxicillin, have been recommended for patients with low-risk allergy status, based on historical reaction verification, because of their safety and accuracy. These advancements are relevant to practicing pediatricians across specialties and practice locations.

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: Pulsed field ablation is now widely used for atrial fibrillation (AF) ablation, but atrial tachyarrhythmia recurrence remains common and postablation risk tools are limited. We assessed whether a validated sinus‑rhythm artificial intelligence— enabled ECG AF probability score, and its early postablation change, predicts recurrence after pulsed field ablation. METHODS: We studied consecutive patients undergoing index pulsed field ablation across 3 Mayo Clinic sites (February 2024–March 2025) with ≥1 sinus‑rhythm ECG within 180 days preprocedure. Baseline artificial intelligence—enabled ECG AF score (range 0–1) was the mean across baseline ECGs. Recovery indices (RI30/60/90), defined as mean postprocedure artificial intelligence—enabled ECG score within days 1–30/60/90 minus baseline, predicted post‑blanking recurrence using corresponding 30‑, 60‑, and 90‑day blanking windows. The primary outcome was time to first documented AF/atrial flutter/atrial tachycardia episode >30 seconds, ascertained via clinic ECGs, ambulatory monitoring, and device interrogations. Cox regression adjusted for prespecified clinical and echocardiographic covariates assessed associations; Harrell C‑statistic quantified discrimination. RESULTS: Among 1052 patients (67±10 years; 33% women), median baseline score was 0.35; 320 (30%) recurred over 188 days. Higher baseline score independently predicted recurrence (hazard ratio per 0.1 increase, 1.08 [95% CI, 1.03–1.14]). Scores rose on day 0 after ablation, then declined over subsequent weeks, with persistently higher, less‑improving trajectories among patients who recurred (time×recurrence interaction P <0.001). Day 0 score was not independently associated with recurrence after adjustment. Attenuated early recovery (higher recovery index) was independently associated with recurrence, most robustly for RI-90 (hazard ratio per 0.1 increase, 1.15 [95% CI, 1.07–1.24]), and improved discrimination beyond baseline and covariates (C‑statistic, 0.63–0.67; ΔC=0.04). Findings were consistent in a historical thermal ablation cohort. CONCLUSIONS: Baseline and early postablation dynamics of a sinus‑rhythm artificial intelligence—enabled ECG AF probability score are associated with pulsed field ablation recurrence and may aid multivariable risk stratification; prospective validation is warranted.

Abstract Background Lung transplant (LT) recipients are at high risk for severe respiratory syncytial virus (RSV) infection, but predictors of worse outcomes remain poorly defined. Methods Retrospective multicenter cohort study of adult LT recipients hospitalized with PCR-confirmed RSV infection between January 2016 and December 2019. Clinical characteristics, treatments, and outcomes within 90 days were analyzed. Logistic regression was used to identify predictors of outcomes, while Cox proportional hazards models assessed risk factors for mortality. Results 155 LT recipients were included. Median age was 61 years, RSV occurred a median of 14 months post-transplant. Risk factors for hypoxic respiratory failure were baseline oxygen use [OR 4.8, (1.29–23.93)] and lower respiratory tract symptoms [OR 3.74, (1.49–10.18)]. Older age increased the risk of mechanical ventilation [OR 1.06, (1.02–1.12)], while oral ribavirin was associated with reduced risk [OR 0.34, (0.14–0.82)]; this association was attenuated when oral and inhaled ribavirin were combined into a single exposure variable [OR 0.77, (0.22–2.66)]; oral ribavirin was not associated with reduced 90-day mortality [HR 5.27, (0.68–40.83)]. Secondary bacterial or fungal infections occurred in 33.5%, associated with prior mechanical ventilation. Lung function declined significantly post-RSV infection, with nearly half experiencing &gt;10% decrease in FEV1. Ninety-day all-cause mortality was 7.7%, with mechanical ventilation independently associated with death [HR 7.79, (2.47–24.60)]. Conclusions RSV infection in LT recipients is associated with high morbidity, graft function decline, and mortality. The association between older age and severe outcomes suggests the importance of preventive strategies in this high-risk population.

ABSTRACT Background Prior studies in the pre‐MRI era suggest that patients with NCCN Intermediate and High Risk Grade Group 1 prostate cancer (GG1 PCa) on biopsy have increased risk for adverse oncologic outcomes. However, prostate MRI has altered patient selection for biopsy and improved prostate sampling. Herein, we examined factors associated with adverse pathologic features (APF) at radical prostatectomy (RP) and biochemical recurrence (BCR) among patients with GG1 in the MRI era. Methods A prospectively maintained institutional prostate cancer registry identified patients with GG1 PCa on biopsy who underwent RP from 2000 to 2023, stratified by MRI use. Multivariable logistic regression and Cox regression identified factors associated with APF at RP (GG3‐5, ≥ pT3a, or pN1) and BCR free survival (two consecutive PSA ≥ 0.2 ng/mL), respectively. Results Among patients without MRI ( n = 6732), NCCN risk group was associated with APF, BCR, and distant metastasis. Among 302 patients with GG1 and pre‐operative MRI, NCCN risk group was associated with neither APF nor BCR. Age (OR 1.07, 95% CI 1.01–1.14, p = 0.01), PIRADS ( p = 0.01), and % core positivity (OR 1.02, 95% CI 1.00–1.03, p = 0.04) were associated with APF. Age (HR 1.07, 95% CI 1.01–1.13, p = 0.03), APF (HR 4.36, 95% CI 2.14–8.86, p < 0.001), and positive margins (HR 4.88, 95% CI 2.39–9.98, p < 0.001) were associated with BCR. Conclusions Prior to prostate MRI, NCCN risk groups offered meaningful prognostication among patients with GG1 PCa. However, the utility of NCCN risk groups for GG1 in the MRI era appears limited. Contemporary risk stratification for GG1 should focus on biopsy and MRI characteristics rather than NCCN criteria.

Advanced-stage high grade serous ovarian cancer (HGSC) initially responds to platinum-based chemotherapy; however, most HGSC tumors recur and develop chemotherapy-resistance, making recurrent ovarian cancer (OC) a fatal disease. Ovarian cancer stem cells (OCSCs), a subpopulation of cells capable of surviving treatment and repopulating tumors, contribute to disease relapse, and understanding the mechanisms(s) responsible for OCSC survival is critical for developing strategies to overcome acquired resistance and prevent tumor recurrence. However, whether platinum-induced OCSC enrichment results from the selection of pre-existing OCSCs or chemotherapy-induced cellular plasticity, and the molecular mechanisms underlying these processes, remain poorly understood. Here, we demonstrated that cisplatin treatment not only enriched for OCSCs but promoted the conversion of ALDH- cells to ALDH+ cells, revealing chemotherapy-induced plasticity as a potential mechanism for OCSC expansion. This conversion was associated with nuclear receptor signaling pathways, vitamin D receptor signaling (VDR/RXR) and retinoic acid receptor signaling (RAR/RXR). Importantly, activation of VDR/RXR signaling with vitamin D reduced stemness phenotypes and the cisplatin induced conversion to ALDH+ cells. In addition, vitamin D combined with cisplatin decreased tumor volume in vivo compared to either treatment alone. In contrast, cisplatin treatment increased RAR/RXR signaling, supporting an associative role for ligand-dependent nuclear receptor signaling in OCSC plasticity. Together, these findings reveal that platinum chemotherapy can actively promote the acquisition of stem-like properties and identifies VDR/RXR signaling as a potential regulatory mechanism of OCSC plasticity. Targeting this pathway with vitamin D may provide a therapeutic strategy to target OCSCs and improve responses to platinum-based chemotherapy.

Abstract Context. Thyroid nodule ultrasound findings are crucial in guiding management decisions for patients with thyroid nodules. However, the frequency with which ultrasound images are discussed and reviewed with patients during clinical visits is not well understood. Objective. To assess how often thyroid ultrasound images are shown and discussed with patients during consultations, and to identify predictors of image review during clinical visits. Design and setting. Secondary analysis of a multicenter pilot randomized clinical trial conducted at two academic medical centers in the United States. Participants. Adults undergoing evaluation for thyroid nodules. Intervention. Participants were randomized to receive either usual care or care enhanced with a conversation aid. Main Outcome Measures. The primary outcome was the frequency of thyroid nodule imaging review evaluated as a binary outcome. Secondary outcomes included evaluation of predictors of image discussion. Results. Eighty-five patients were evaluated. Most participants were women (80%), mean age (60 years, SD 16), and White (86%), undergoing new patient visits (84%). Thyroid nodule ultrasound images were reviewed with patients in 53% of visits (45/85), and in all cases, clinicians initiated the imaging discussion. Predictors of image review included type of consultation (new patient visit) (OR 10.6, 95% CI: 1.79, 62.3). Age, sex, study arm, thyroid nodule size or cancer risk and plan of care (e.g., completing a biopsy) were not statistically associated with review of clinical images. Conclusions. Review of thyroid ultrasound images during clinical visits is relatively common, with consultation type serving as significant predictor.

Background: Normothermic machine perfusion (NMP) may reduce preservation injury in donation-after-circulatory-death (DCD) liver transplantation, but its association with patient-centered recovery and longer-term graft survival remains uncertain. Study Design: We retrospectively analyzed 306 consecutive adult DCD liver transplant recipients at a single center from January 2019 through December 2022, comparing NMP (n=95) with static cold storage (SCS; n=211). The primary endpoint was days alive and out of hospital at 365 days (DAOH365). Quasi-Poisson regression evaluated factors associated with DAOH365, and Cox regression evaluated graft survival. Propensity-matched and calendar-year sensitivity analyses assessed measured confounding. Results: Median DAOH365 was 357.0 (352.0, 360.0) days with NMP versus 353.0 (336.0, 359.0) with SCS (p<0.001), but preservation strategy was not independently associated with DAOH365 (adjusted rate ratio 1.02; p=0.331). NMP recipients had less early allograft dysfunction (35.8% vs 59.7%; p<0.001), ischemic cholangiopathy (4.2% vs 23.7%; p<0.001), and retransplantation within 2 years (0.0% vs 6.6%; p=0.007). Two-year patient survival did not differ significantly. NMP was associated with improved twoF-year graft survival (HR 2.9, 95% CI 1.23–6.87; p=0.015), an association maintained in propensity-matched and calendar-year sensitivity analyses. Adjusted total 1-year costs did not differ (p=0.512). Conclusions: In this single-center DCD cohort, NMP was associated with superior 2-year graft survival but not independently with DAOH365. These hypothesis-generating findings support multicenter prospective evaluation of NMP using both graft survival and patient-centered recovery endpoints.

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.