Citations

Abstract Background Artificial intelligence enhanced electrocardiograms (AI-ECG) have matured over the past 10 years. More recently, the AI-ECG estimate of biological sex has shown potential as a novel tool for cardiovascular risk stratification among women. Cardiovascular disease is a leading cause of pregnancy-related mortality; however, there have been limited approaches for estimating the physiological demands of pregnancy and its impact of maternal cardiovascular outcomes. Purpose To estimate pregnancy-related changes on AI-ECG-based sex and age estimation in a prospective cohort of otherwise healthy, complication free pregnant women. Methods This secondary analysis of the SPEC-AI Nigeria Clinical Trial identified pregnant women without any pregnancy-related complications (at baseline or during follow-up) who had at least two 12 lead ECGs recorded during the study. The ECGs were analyzed with previously-developed algorithms to predict age and biological sex. To address bias in the AI-ECG age estimate, a reference cohort of 25,144 healthy patients was analyzed using quantile regression to estimate the 75th percentile of the reference distribution as a function of age. The estimate of biological sex was used to determine a sex discordance score with a discordance of 0.2 considered clinically relevant. To simplify the trends in the data, the ECGs were categorized as during pregnancy (<=28 days prior to birth), peripartum (+/- 28 days of birth), and postpartum (28+ days after birth), and mixed effects models with a random intercept were used for analysis. Results A total of 207 females with a median age of 31 years (IQR 28 to 36 years) and normal blood pressures (systolic: 110 (IQR 10 to 120); diastolic: 70 (IQR 60-77); mmHg) were included from 5 clinical sites in Nigeria. The majority (73%, 150/207) of participants were in their second trimester at time of enrollment and the median number of ECGs per participant was 3 (max 7). The sex discordance score was elevated in 38% of the women at baseline and this percentage fell to 23% postpartum; which resulted in a decrease in the mean discordance score of 0.03 (95% CI: -0.06 to 0.0; p=0.028). Conversely, the percentage of patients with elevated age prediction increased from 35% to 41% over the course of pregnancy. This resulted in an increase in the bias-corrected AI-ECG age of 3.0 years (95% CI: 1.5 to 4.6 years; p<0.001). Conclusion This study demonstrates the preliminary utility of serial AI-ECG based assessment as a marker for the biological effects of pregnancy. The increase in sex discordance score during pregnancy may be related to changes in cardiac structure, such as increased ventricular mass and chamber dilation which often reverses postpartum. However, the impact on age estimation appeared to persist in the early postpartum period. Further study is warranted to associate any changes observed with long term maternal or fetal outcomes.Figure

Carbohydrate availability and caffeine ingestion have been shown to elicit improvements in performance independently of one another. The purpose of the study was to examine the effect of a carbohydrate + caffeine beverage on performance and perceived effort in soccer players. Forty-three collegiate women’s soccer athletes were recruited to participate during a single day of simulated match play, in which each team played once. Athletes consumed either a carbohydrate + caffeine (Experimental) beverage or a control (Control) beverage (flavored water) during half-time in a double-blind, placebo-controlled, randomized control trial design. Prior to and after each game, Ratings of Perceived Exertion (RPE) and blood glucose levels were assessed. Heart rate, training impulse (TRIMP), total distance covered, high-speed distance, and velocity were recorded. Blood glucose levels after the match simulation were positively associated with total distance (r = 0.434; p = 0.01), distance per minute (r = 0.439; p < 0.01), average velocity (r = 0.438; p = 0.01), and TRIMP (r = 0.404; p = 0.018) during the second half. There was a significant main effect for half regarding blood glucose (p < 0.001), total distance (p < 0.001), high-speed distance (p < 0.001), and TRIMP (p = 0.046). There was a significant half × condition effect for blood glucose (p = 0.05). Pairwise comparisons indicated the Experimental beverage condition resulted in a +27 mg/dL (95% CI: −3.6, 58.8) difference compared to the Control beverage following the 2nd Half. In the current study, consumption of the carbohydrate + caffeine beverage during half-time resulted in higher blood glucose levels post-game compared to placebo; however, the experimental beverage did not influence the total distance covered, average velocities, average heart rate, or TRIMP values during the second half of simulated match play.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem , but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer’s disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ 40 , Aβ 42 , tTau, and pTau (pTau 181 , pTau 217 , pTau 231 ) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE -ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ 40 ( p = 0.039) and Aβ 42 ( p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ 40 ( p = 0.0041) and Aβ 42 ( p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ 40 ( p = 0.011) and Aβ 42 (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.

PURPOSE Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer. PATIENTS AND METHODS Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms. RESULTS Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 ( P = .02), and 6.89 ( P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 ( P = .07), and 13.95 ( P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg ( P = .042) and 5 mg ( P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo. CONCLUSION Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.

Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Introduction: Gastroesophageal reflux disease (GERD) plays an important role in lung transplant (LT) outcomes. This study aims to evaluate the impact of a novel sleep positioning device (SPD) on lung function in LT recipients with GERD. Methods: In this single-center cohort study, LT recipients (2014 to 2019) with GERD who were prescribed an SPD within 2 years of LT were included. A historical control group of LT recipients with GERD on PPI only (2011 to 2013) was selected to compare forced expiratory volume in 1 second (FEV1) as a marker of lung function. Results: Twenty LT recipients using SPD (cases) and 54 patients in the historical control group with proven GERD were included. Mean (SD) interval between LT and SPD prescription was 8.6 (5.7) months. Mean % predicted FEV1 was higher in SPD users than controls post-LT at 6 months (80% vs. 69%) and 1 year (80% vs. 71%), respectively. Among SPD users, post-SPD FEV1 was higher than pre-SPD FEV1 (82% vs. 70%). Conclusion: Use of a novel SPD can stabilize or improve pulmonary function in patients with GERD after LT. SPD may be a safe and cost-effective adjunctive therapy for the management of GERD after LT.

Abstract Neuroendocrine prostate cancer (NEPC) is an increasingly prevalent manifestation of acquired resistance to next generation AR signaling inhibitors (ARSI), that arises via transformation from advanced prostate adenocarcinoma (PRAD) through a mechanism called lineage plasticity. Through characterization of isogenic PRAD and NEPC mouse tumoroid models generated using human-relevant driver mutations (Pten-/-;Rb1-/-;Trp53-/-), we revealed an extensive epigenetic reprogramming in NEPC versus PRAD, particular at enhancers. CRISPR screens focused on TFs and coactivators revealed a NEPC lineage TF survival network comprised of ASCL1, NFIB, SOX1/11, FOXA1/2 and MYCL with exquisite dependency on the TIP60 acetyltransferase complex. During the PRAD-to-NEPC transition, FOXA1, NFIB and TIP60 chromatin binding redistributes to NEPC specific enhancers, resulting in expression of NEPC target genes in a coordinate fashion with ASCL1 functioning as master regulator, culminating in activation of MYCL. MYCL then directly recruits the TIP60 complex to target sites, where it acts as a requisite MYCL coactivator for target gene activation for NEPC growth/survival. The acetyltransferase activity of TIP60 and acetylation of its substrate H2A.Z are both required for NEPC survival, as well as two chromatin reader subunits of the TIP60 complex, BRD8 and YEATS4. Targeted chemical degradation of TIP60 revealed &gt;500-fold dependency in NEPC relative to normal prostate, credentialing the TIP60 complex as a potential therapeutic target in NEPC. Citation Format: Zhen Sun, Jimmy L. Zhao, Wazim M. Ismail, Zahra F. Khan, Teng Han, Subhiksha Nandakumar, Serina Young, Matthew Lange, Richard Koche, Alexandre Gaspar-Maia, Charles L. Sawyers. The TIP60 acetyltransferase complex is a critical dependency in neuroendocrine prostate cancer through its role as a critical coactivator of MYCL downstream of ASCL1 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr PR036.

Abstract Introduction Cardiac CT is increasingly used to screen for cardioembolism in stroke patients. We assessed the frequency and management of non-cardiac incidental findings on prospective ECG-gated cardiac CT in patients with a suspected stroke. Patients and methods This was a post-hoc analysis of the Mind the Heart study, a prospective single-centre cohort study including consecutive adult patients with acute ischaemic stroke (AIS), transient ischaemic attack (TIA), or a stroke mimic who underwent cardiac CT as part of an acute stroke imaging protocol. Endpoints were pre-defined non-cardiac incidental findings that were detected on cardiac CT: pulmonary embolism (PE), potential malignant lesions, pulmonary consolidations or ground-glass densities, bone fractures, lymphadenopathy, focal liver lesions, and ascending aortic or pulmonary artery dilatation. Change of management was defined as additional treatment or follow-up. Results We included 654 patients (57% men, median age 71 [IQR 59–80] years) of whom 451 (69%) had AIS, 48 had TIA (7%), and 155 had a stroke mimic (24%). Overall, 58 non-cardiac incidental findings were found in 55 (8%; 95%CI, 6–11) patients. The most frequent incidental findings were consolidations or ground-glass densities (n = 17, 3%), liver cysts or non-specific hypodensities (n = 14, 2%), pulmonary nodules or masses (n = 9, 1%), and PEs (n = 8, 1%). Incidental findings led to a change of management in 17/55 (31%) patients of whom 13/55 (24%) had additional follow-up and 9/55 (16%) received treatment (anticoagulation n = 8, chemotherapy n = 1). Discussion & Conclusion Non-cardiac incidental findings were observed on cardiac CT in 8% of patients with a suspected stroke. These findings changed management in 31% of these patients.

Abstract Introduction Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. Patients and methods This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). Results 268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts (p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p &gt; 0.05). Conclusions Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.