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ABSTRACT BACKGROUND Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) testing has the potential to expedite decision-making and reduce emergency department (ED) length of stay for patients presenting with possible myocardial infarction (MI) by ensuring that results are consistently available when looked for by clinicians. We assessed the real-life effectiveness and safety of implementing POC hs-cTn testing in the ED. METHODS We conducted a pragmatic, stepped-wedge cluster randomized trial. The control arm was usual care with an accelerated diagnostic pathway utilizing a single-sample rule-out step with a central laboratory hs-cTn assay. The intervention arm used the same pathway with a POC hs-cTnI. The primary effectiveness outcome was ED length of stay assessed using a generalized linear mixed model, and the safety outcome was 30-day MI or cardiac death. RESULTS Six sites participated with 59,980 ED presentations (44,747 individuals, 61±19 years, 49.5% female) from February 2023 to January 2025, in which 31,392 presentations were during the intervention arm. After adjustment for co-variates associated with length of stay, the intervention reduced length of stay by 13% (95% confidence intervals [CI], 9 to 16%. P<0.001), corresponding to a reduction of 47 minutes (95%CI, 33 to 61 minutes) from a mean length of stay in the control arm of 376 minutes. The 30-day MI or cardiac death rate was similar in the control and intervention arms (0.39% and 0.39% respectively, P=0.54). CONCLUSIONS Implementation of whole-blood hs-cTnI testing at the POC into an accelerated diagnostic pathway was safe and reduced length of stay in the ED compared with laboratory testing. (Australia New Zealand Clinical Trials Registry ACTRN12619001189112) Clinical Perspective What is new? Point-of-care troponin assays with good precision have become available and received regulatory approval as high-sensitivity assays. A pragmatic stepped-wedge cluster randomized trial implementing the validated Siemens VTLi high-sensitivity point-of-care assay into 6 emergency departments investigating ∼60,000 patients, was conducted to ascertain if the rapid turnaround time reduced lengths of stay. Introduction of the VTLi high-sensitivity point-of-care assay into clinical pathways reduced emergency department lengths of stay by an average 13% (47 minutes) without compromising safety. What are the clinical implications? Early decision-making using a point-of-care high-sensitivity troponin assay within a structured clinical pathway was safe. Faster turnaround means troponin results are consistently available when clinicians first seek them. This can facilitate earlier decisions and reduce patient length of stay.

Importance Standard treatment for human papillomavirus (HPV)–associated oropharyngeal carcinoma (OPC) often includes 7 weeks of intensive chemoradiotherapy with substantial toxic effects. Lowering the radiation dose to gross disease may maintain cancer control with fewer toxic effects. Objective To evaluate long-term oncologic outcomes among patients with HPV-associated OPC treated with definitive deintensified (chemo)radiotherapy. Design, Setting, and Participants This cohort study evaluated consecutive patients treated with (chemo)radiotherapy between September 2014 and August 2022 at multiple institutions under one academic hospital system. Eligible patients had p16-positive OPC with a clinical stage from T0 to T3 and N0 to N2c (according to the American Joint Committee on Cancer [AJCC] Staging Manual, seventh edition ) and favorable smoking history. Data were analyzed between August 2023 and October 2025. Interventions Treatment was 60-Gy intensity-modulated radiotherapy with first-choice concurrent chemotherapy of weekly cisplatin, 30 mg/m 2 , or weekly cisplatin, 40 mg/m 2 . Patients with OPC with a clinical stage from T0 to T2 and N0 to N1 (according to AJCC, seventh edition ) were recommended 60-Gy radiotherapy alone. Main Outcomes and Measures Evaluation of locoregional recurrence was the primary outcome. Distant recurrence, progression-free survival (PFS), and overall survival (OS) were secondary outcomes. Results A total of 240 patients received definitive deintensified (chemo)radiotherapy (207 receiving prospective protocol-adherent treatment and 33 receiving non–protocol-adherent treatment). Mean (SD) patient age was 60.3 (9.9) years (range, 33.0-84.0 years); 206 (85.8%) were male, and 34 (14.2%) were female. The cohort included 139 never smokers (57.9%) and 101 former smokers (42.1%) (median smoking history, 9.0 pack-years [range, 0.25-50.0 pack-years]). Concurrent chemotherapy was prescribed for 205 patients (85.4%), with 185 (77.1%) receiving cisplatin, and 165 (68.8%) receiving weekly cisplatin, 30 mg/m 2 . Median follow-up for surviving patients was 6.5 years (range, 0.44-11.0 years; 208 of 210 [99.0%] with minimum 2-year follow-up). Outcomes were as follows: 2-year OS was 97.9% (95% CI, 96.1%-99.7%), and 5-year OS, 92.4% (95% CI, 89.0%-96.0%); 2-year PFS, 94.1% (95% CI, 91.2%-97.2%), and 5-year PFS, 86.5% (95% CI, 82.1%-91.0%); 2-year locoregional recurrence, 1.3% (95% CI, −0.2% to 2.7%), and 5-year locoregional recurrence, 3.4% (95% CI, 1.1%-5.8%); 2-year distant recurrence, 4.6% (95% CI, 1.9%-7.3%), and 5-year distant recurrence, 7.3% (95% CI, 3.9%-10.7%). The median time to progression events was 1.9 years (range, 0.3-5.1 years); 12 of 26 recurrences (46.2%) occurred after 2 years. Thirty-three patients with low-risk disease (clinical stage T0-T2, N0-N1, according to AJCC, seventh edition ) received radiotherapy alone, which resulted in a 5-year PFS of 93.8%, with no patients experiencing a locoregional recurrence. Conclusions and Relevance In this cohort study, modest dose deintensification of 60-Gy radiotherapy in patients with HPV-associated OPC shows favorable rates of locoregional control. These findings provide support for ongoing investigations of deintensified radiotherapy.

ABSTRACT Background Retrospective evaluations of multidisciplinary team (MDT) review of pancreatic cystic lesions (PCL) demonstrate improved PCL management. Endoscopic ultrasound (EUS) evaluates PCL for worrisome features; however, its influence on MDT is unclear and may be attenuated by anchoring/confirmation bias. We aimed to evaluate the impact of EUS and the overall performance of MDT evaluation of PCL. Methods Four mock MDT sessions at two institutions were presented imaging from 40 consecutive PCL cases (20 “high‐risk” with advanced neoplasia, 20 “low‐risk” with pathologic low‐grade dysplasia or ≥ 3 years of non‐progression on surveillance), with and without upfront EUS/FNA (cytology, CEA, Amylase), in a randomized, crossover design. Group 1 adjudicated without EUS, Group 2 adjudicated with EUS, and Group 3 adjudicated with EUS after initially adjudicating without it. Results The cohort included branch‐duct ( n = 20), mixed type ( n = 6), and main duct ( n = 4) IPMN, MCN ( n = 5), and non‐mucinous PCL ( n = 5). Group 2 (EUS) correctly identified mucinous PCL with 97% sensitivity and 70% specificity, significantly higher than Group 1 (No EUS) (Sensitivity 91%, Specificity 20%; p = 0.04). Group 3 (Unblinded to EUS) performed significantly worse in mucinous PCL identification compared with Group 2, indicating cognitive bias (Sensitivity 97%, Specificity 10% ( p = 0.0003)). Group 2 correctly identified high‐risk PCL that required surgical intervention with 85% sensitivity and 85% specificity, significantly higher than Group 1 (Sensitivity 60%, Specificity 75%; p = 0.0016) and Group 3 (Sensitivity 73%, Specificity 80%, p = 0.0485). Conclusion While susceptible to cognitive bias, EUS significantly improves MDT assessment of PCL. MDT establishes a high bar for iterative additions of biomarkers to PCL analysis.

Abstract Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( CLPTM1L , rs383009:T>C, T Allele Frequency=0.51, OR:1.45, P value=1.24×10 -8 ), a locus previously associated with PDAC. Known loci at 5p15.33, 7q32.3, 8q24.21 and 7q25.1 also replicated (P value <0.01). Multi-ancestral fine-mapping identified two potential causal SNPs (rs3830069 and rs2735940) at 5p15.33. Collectively these findings identified novel PDAC risk loci and expanded our understanding of this deadly cancer in underrepresented populations, emphasizing the multifactorial nature of PDAC risk including inherited genetic and non-genetic factors. Statement of Significance To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.

Common sex chromosome aneuploidies (SCAs) often present with cognitive and cardiovascular dysfunction in humans. To address SCA effects on gene expression and DNA methylation in relevant cell types, we differentiated neural precursor cells (NPCs) and cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) with different numbers of sex chromosomes, including isogenic and independent lines. As expected, the expression of genes that escape X inactivation (escapees) mostly increases with the number of inactive X chromosomes (Xi). However, allelic analysis shows dampening of escapees specifically on the Xi in XXY compared to XX in both NPCs and CMs, revealing a novel type of dosage compensation in SCA. In contrast, Y-linked gene expression is higher in XXY versus XY NPCs, but the opposite is observed in CMs. This may explain the greater number of differentially expressed autosomal genes in NPCs versus CMs with an added Y chromosome, while effects of added X chromosomes are similar between cell types. Concordantly, changes in autosomal DNA methylation are mainly driven by the presence of a Y chromosome. These findings highlight the cell-type specificity of sex-linked and autosomal gene regulation in SCA conditions.

BACKGROUND AND OBJECTIVES: Perioperative protocols facilitate earlier discharge without compromising safety in nonfunctioning pituitary adenomas, but no large multicenter studies in the United States have investigated protocols regarding Cushing disease (CD). We sought to characterize perioperative protocols and how their implementation influences clinical outcomes in patients with CD. METHODS: A retrospective analysis was conducted using data from the Registry of Adenomas of the Pituitary and Related Disorders consortium comprising 13 US academic pituitary centers. Institutions were surveyed regarding perioperative procedures for patients undergoing transsphenoidal tumor resection for CD. The impacts of institutional procedures and approaches to implementation on length of stay (LOS) and unplanned 90-day readmission were evaluated. RESULTS: Thirteen institutions contributed survey responses and clinical data for a total of 832 patients meeting inclusion criteria. Ten (76.9%) institutions reported having a postoperative protocol, 9 (69.2%) used a formal document to outline their protocol, and 3 (23.1%) had protocols implemented into hospital policy. Mean LOS was significantly reduced in centers with an established protocol (3.14 vs 3.42 days, P = .032), and more so with a formal document (3.10 vs 3.48 days, P = .001) or hospital policy (2.72 vs 3.36 days, P < .001). Patients treated after protocol implementation experienced shorter LOS ( P < .001). Other factors associated with reduced LOS were presence of a separate CD pathway, intraoperative checklist specific to pituitary surgery, non-narcotic pain regimen, Foley removal order, dedicated outpatient advanced practice provider follow-up, and target discharge date ≤2 days. Intraoperative checklist ( P = .045), non-narcotic pain regimen ( P = .048), nasal packing ( P = .005), and 1-day target discharge date ( P = .032) were important factors against readmission. Compared with microscopic surgery, endoscopic surgery was associated with shorter LOS but increased readmission odds. CONCLUSION: This is the first multicenter study to illustrate that implementation of perioperative protocols is associated with a reduction in LOS and readmission risk in patients with CD.

Importance Brain imaging biomarkers may (1) identify underlying mechanisms of intervention effects and (2) define brain characteristics of those most likely to benefit cognitively from the intervention. Objective To test whether (1) a lifestyle intervention is related to brain changes, (2) brain changes are correlated with intervention-specific cognition changes, and (3) brain imaging biomarkers provide information about who is likely to benefit from a lifestyle intervention. Design, Setting, and Participants In this randomized clinical trial, the POINTER Imaging study was an ancillary study of the 2-year, single-blind multicenter US POINTER clinical trial in which neuroimaging data were collected on eligible enrolled participants. The study was conducted from May 2019 to March 2023 (final follow-up, May 14, 2025). Participants were enrolled into the POINTER Imaging study following a standard procedure at 5 clinical sites in the US. Participant eligibility criteria included an age of 60 to 79 years, sedentary lifestyle, and suboptimal diet, plus at least 2 additional risk criteria for cognitive decline and no contraindications for neuroimaging. Interventions Participants were randomly assigned to receive the structured or self-guided intervention. Both interventions emphasized increased physical and cognitive activity, healthy nutrition, social engagement, and cardiovascular health monitoring, but they differed in intensity and accountability. Main Outcomes and Measures There were 4 primary imaging outcomes: global β-amyloid (Aβ) burden, tau burden in the entorhinal cortex (ERC), hippocampal (HC) volume, and white matter hyperintensity volume. The primary cognitive measure was a global cognitive composite. Results Among 1943 parent trial participants who were assessed for eligibility, 983 underwent at least 1 magnetic resonance imaging or positron emission tomography scanning session. The mean (SD) age was 68.4 (5.2) years; 605 participants (61.5%) were female and 378 male (38.5%). Five hundred sixteen participants received the structured intervention and 467 the self-guided intervention. There were no intervention group differences in longitudinal cognitive or imaging outcomes. Intervention group differences were not associated with or moderated by Aβ status or accumulation. There was a negative association between change in ERC tau and change in global cognition in the self-guided group that was attenuated in the structured group (difference in association: 0.289; 95% CI, 0.029 to 0.550; interaction P = .03). Lower baseline HC volume was associated with greater cognitive benefit for participants in the structured group vs the self-guided group (lower HC: 0.077 SD; 95% CI, 0.022 to 0.132; higher HC: 0.002 SD; 95% CI, −0.037 to 0.041; interaction P = .03). Conclusion and Relevance This study found that a high-intensity multidomain lifestyle intervention did not affect brain biomarker trajectories and was not associated with Aβ pathology, but older adults with specific at-risk brain characteristics, including lower baseline HC volume, showed a greater cognitive benefit of the structured intervention. Trial Registration ClinicalTrials.gov Identifier: NCT03688126

Purpose To evaluate the clinical, radiographic, and functional outcomes of arthroscopic treatment of scaphoid nonunion in adolescents, using cancellous bone grafting combined with headless compression screw fixation. Methods This retrospective study included adolescent patients treated between 2015 and 2022 with arthroscopically assisted bone grafting and headless compression screw fixation for scaphoid nonunion. Inclusion criteria were nonunion ≥6 months after injury and minimum 12‐month follow‐up; exclusion criteria included degenerative wrist changes. Collected variables included demographic data, injury‐to‐surgery interval, radiographic parameters (including scapholunate angle), time to union, pain scores (visual analog scale), functional outcomes (QuickDASH), and range of motion. Statistical analysis showed significant improvements in visual analog scale and QuickDASH scores ( P < .05). Results Fifteen patients (14 males; mean age 16 years, range 13‐19) met inclusion criteria. The mean follow‐up was 29.2 months. All patients achieved bone union, with an average healing time of 5.7 weeks. Pain (visual analog scale) improved from 2.6 to 0.8, and QuickDASH scores improved from 26.5 to 7.9. The scapholunate angle improved from 60.6° to 46.6°, with stable range of motion postoperatively. No major complications or reoperations occurred. Minimal clinically important difference analysis confirmed meaningful clinical improvement in 93% of patients for pain and 87% for QuickDASH. Conclusions Arthroscopic treatment of scaphoid nonunion in adolescents shows high union rates, improved function, and low morbidity. Level of Evidence Level IV, therapeutic retrospective case series.

Introduction Sleep is routinely assessed in the management of mental health conditions. Wearable technologies like smartwatches offer a non-intrusive method to quantitatively measure sleep. However, there are limited empirical benchmarks for sleep duration and sleep quality measured by wearables against user reports. This study aims to evaluate the concordance between user-reported and smartwatch-measured hours of sleep and sleep quality. Methods Participants were recruited from two decentralized digital health well-being studies and completed a 7-day sleep diary while simultaneously wearing their smartwatch to sleep (November 7, 2023 - June 30, 2024). Participants self-reported sleep timestamps and perceived sleep quality using the Sleep Quality Scale. Sleep timestamps and quality were also derived from their smartwatches (Garmin Vívoactive 4 2019, Garmin Venu 2 Plus 2022, and Garmin Venu 3/3S 2023). Statistical analyses included paired t-tests, equipercentile linking, and chi-square tests to assess agreement between smartwatch and self-reported sleep parameters. Exploratory analyses established the difference between reported and recorded sleep duration in healthcare shift workers. Results From 841 sleep instances reported by 130 participants wearing three different generation smartwatches, the mean difference in sleep duration between smartwatch-recorded and participant-reported was 21.22 (Garmin Vívoactive), 11.67 (Garmin Venu 2 Plus), and 6.58 (Garmin Venu 3/3S) minutes, respectively. There were statistically significant between-group differences in mean sleep durations assessed by participant self-report vs. Vívoactive 4 smartwatches, but not self-report vs. Venu 2 Plus or Venu 3/3S smartwatches. Equipercentile linking revealed concordance between smartwatch sleep scores and self-reported sleep quality using the Sleep Quality Scale (SQS) between 4 and 7, with disagreements observed at the SQS ranges from 0–4 and 7-10. Conclusions These results suggest that wearables can reliably measure sleep duration, and future research warrants improvements in algorithms that estimate sleep quality with validations across different wearable vendors.