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Source- and Solubility-specific Choline, Gut Microbiota, and Dyslipidemia Risk: Trimethylamine N-oxide-associated and Non-trimethylamine N-oxide-Associated Patterns in a Prospective Cohort Study.

BACKGROUND: Dietary choline, a major precursor of the gut microbial metabolite trimethylamine N-oxide (TMAO), is implicated in dyslipidemia risk; however, source- and form-specific associations and interactions with gut microbiota remain unclear. OBJECTIVES: The aim of this study was to examine longitudinal associations of source- and form-specific dietary choline with plasma TMAO and dyslipidemia and to identify gut microbiota interactions. METHODS: Using data from the China Health and Nutrition Survey (2018-2023), dietary intake was assessed via 3 consecutive 24-h recalls in this prospective cohort study. Two-level generalized linear mixed-effects models were applied in 4828 adults (mean age: 55.9 ± 12.6 y, 56.6% females) to assess choline-dyslipidemia associations. Choline-TMAO and TMAO-dyslipidemia analyses were conducted in 1091 participants free of dyslipidemia at baseline. Among 7169 adults with gut microbiome data, Least Absolute Selection and Shrinkage Operator and logistic regression identified lipid-associated gut genera; TMAO relationships were examined in a subset of 693 participants. RESULTS: Higher intakes of total [Q4 compared with Q1: odds ratio (OR) = 1.261; 95% confidence interval (CI): 1.007, 1.580], red meat-derived (OR: 1.753; 95% CI: 1.196, 2.568), and lipid-soluble choline (OR: 1.304; 95% CI: 1.047, 1.624) were associated with higher risk of elevated low-density lipoprotein cholesterol (LDL cholesterol), whereas vegetable-derived choline was inversely associated. Egg-derived and lipid-soluble choline were positively associated with plasma TMAO, which was prospectively associated with 5-y incident dyslipidemia (Q4 compared with Q1-OR: 1.620; 95% CI: 1.047, 2.509), elevated LDL cholesterol (Q3 compared with Q1-OR: 2.478; 95% CI: 1.187, 5.174), and hypertriglyceridemia (Q4 compared with Q1-OR: 1.829; 95% CI: 1.028, 3.225). Three TMAO-associated genera were identified: Lachnospiraceae and Phascolarctobacterium as pro-risk taxa and Turicibacter as protective. The adverse LDLcholesterol association of egg-derived choline was observed exclusively in Phascolarctobacterium-enriched individuals. CONCLUSIONS: Dietary choline source and solubility differentially associated with dyslipidemia risk through TMAO-associated and non-TMAO-associated patterns, with gut microbiota as key modulators.

Humans

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans

Clinical accuracy and short-term outcomes of intraoral photogrammetry for complete-arch implant rehabilitation: A retrospective multicentre study on 35 patients.

OBJECTIVES: To evaluate the clinical accuracy and short-term outcomes of complete-arch implant-supported fixed dental prostheses (ISFDPs) fabricated using an intraoral photogrammetry (IPG) based digital workflow in completely edentulous patients. METHODS: This multicenter retrospective clinical study included 35 patients rehabilitated with 52 complete-arch ISFDPs (10 FP1, 18 FP2 and 24 FP3 restorations) supported by 221 implants. All definitive prostheses were designed and fabricated using a fully digital workflow initiated by IPG acquisition with the Aoralscan Elite IPG® (SHINING 3D). The primary outcome was clinical accuracy, assessed at definitive prosthesis delivery through evaluation of passive fit using the Sheffield test and radiographic verification. Secondary outcomes included biologic and prosthetic complications, as well as implant and prosthesis survival rates during the follow-up. RESULTS: Passive fit was achieved in all definitive restorations (100%). Radiographic evaluation confirmed accurate marginal adaptation at the implant-prosthesis interface in all cases. No statistically significant differences in clinical accuracy were observed according to treated arch, number of supporting implants, or prosthetic design (P > .05). During a mean follow-up period of 12.1 ± 3.5 months, biologic and prosthetic complications were limited and generally minor. Implant survival was 99.5%, and prosthesis survival was 100%. CONCLUSIONS: Within the limitations of this retrospective clinical study, the IPG based workflow demonstrated high clinical accuracy and predictable short-term outcomes for complete-arch implant rehabilitation, consistently enabling passive fit and favorable prosthetic performance. CLINICAL RELEVANCE: IPG may represent a clinically reliable and predictable approach for complete-arch digital implant impression acquisition. The high rates of passive fit, together with the low incidence of biologic and prosthetic complications observed in this multicenter clinical study, support the use of IPG based workflows for the fabrication of complete-arch ISFDPs.

Humans

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p&#xa0;<&#xa0;0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (&#x394;Neff), landscape geometry (&#x394;Evar and &#x394;Gmag), and dominant low-energy attractor organization (&#x394;Low mass and &#x394;Low area) showed significant monotonic trends (p&#xa0;<&#xa0;0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r|&#xa0;=&#xa0;0.353-0.423, p&#xa0;=&#xa0;0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r|&#xa0;=&#xa0;0.333-0.455, p&#xa0;=&#xa0;0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans

ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.

BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 after PVI, four variables-age&#xa0;&#x2265;&#xa0;75&#xa0;years, left atrial diameter&#xa0;>&#xa0;44&#xa0;mm, estimated glomerular filtration rate&#xa0;<&#xa0;60&#xa0;mL/min/1.73&#xa0;m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n&#xa0;=&#xa0;336), a significant treatment-by-score interaction was observed (P&#xa0;<&#xa0;0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n&#xa0;=&#xa0;494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P&#xa0;=&#xa0;0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5&#xa0;cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans

Estimated prevalence and distribution of causes of immune-mediated hypertrophic pachymeningitis in S&#xe3;o Paulo, Brazil.

BACKGROUND: The prevalence of hypertrophic pachymeningitis (HP) remains poorly defined worldwide. In Japan, the estimated prevalence is 0.949 cases per 100,000 inhabitants, with most cases related to ANCA-associated vasculitis or IgG4-related disease. In contrast, epidemiological data from other regions, including Latin America, are scarce. METHODS: This study was conducted at a tertiary referral center in the city of S&#xe3;o Paulo, Brazil. The prevalence of HP was estimated by comparison with the known prevalence of multiple sclerosis (MS), based on the number of patients with each condition followed at our institution. The etiological distribution of HP was also analyzed. In addition, HP prevalence was compared with that of tuberculous meningoencephalitis, a compulsory notifiable disease and a well-established cause of chronic meningitis in Brazil, using data from the national surveillance system (SINAN). RESULTS: We identified 55 patients with HP: 36 (65%) idiopathic, 10 (18%) IgG4-related disease, 4 (7%) ANCA-associated pachymeningitis, 4 (7%) probable or definite neurosarcoidosis, and 1 (2%) secondary to rheumatoid arthritis. Among 968 registered MS patients and assuming an MS prevalence of 15 per 100,000 inhabitants in S&#xe3;o Paulo, the estimated HP prevalence was 0.85 per 100,000 inhabitants. This estimate was comparable to the prevalence of tuberculous meningoencephalitis in the same region. CONCLUSION: The estimated prevalence of HP in S&#xe3;o Paulo (0.85 per 100,000) is consistent with reports from other regions and is comparable to that of tuberculous meningeal disease, although with a distinct etiological profile. IgG4-related disease was the most frequent systemic association, differing from previous reports. ANCA-associated HP appears to be less frequent than in other geographic regions, possibly reflecting differences in disease phenotype. Key Points &#x2022; The estimated prevalence of HP in S&#xe3;o Paulo was 0.85 per 100,000 inhabitants. &#x2022; IgG4-related disease was the most common systemic disease identified among patients with HP. &#x2022; ANCA-associated HP was less common than reported in Asian and European cohorts. &#x2022; The prevalence of HP was comparable to that of tuberculous meningoencephalitis in S&#xe3;o Paulo.

Humans

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence,&#xa0;opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n&#x2009;=&#x2009;60, sham n&#x2009;=&#x2009;59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24&#x2009;mg single dose; MAD: 12&#x2009;mg once daily (QD) for 7&#x2009;days in healthy subjects) and phase IIa studies (0.75 to 6&#x2009;mg once or twice daily for 4&#x2009;weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24&#x2009;h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5&#x2009;h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12&#x2009;h post-administration, with FEV1 peaking at approximately 2&#x2009;h post-dose and returning to baseline levels by 12&#x2009;h, which supports a twice-daily dosing regimen for the future, and peak FEV&#x2081; improvements ranging from 186 to 272&#x2009;ml across dose groups after 4&#x2009;weeks of treatment. Moreover, twice-daily 3 and 6&#x2009;mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult

Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study.

PURPOSE: To evaluate the efficacy and safety of the cluster of differentiation 47-targeted antibody magrolimab plus azacitidine (Magro/Aza) versus azacitidine alone in treatment-na&#xef;ve patients with higher-risk myelodysplastic syndromes (MDS) in the phase III ENHANCE study (ClinicalTrials.gov identifier: NCT04313881). METHODS: Based on the Revised International Prognostic Scoring System, patients with intermediate- to very-high-risk MDS were randomly assigned to receive Magro (1 mg/kg on days [D]1 and 4; 15 mg/kg on D8; 30 mg/kg on D11 and D15, and then once per week for five doses, followed by 30 mg/kg maintenance doses once every 2 weeks)/Aza (75 mg/m2 daily on D1-7 or on D1-5 and 8-9 in 28-day cycles) or matched placebo plus azacitidine (Placebo/Aza). Dual primary end points were complete remission (CR) rate (per 2006 International Working Group criteria) and overall survival (OS). RESULTS: At final analysis, 539 patients were randomly assigned to Magro/Aza (n = 268) or Placebo/Aza (n = 271) arms. Baseline characteristics were generally well balanced between treatment arms. In the Magro/Aza versus Placebo/Aza arms, the CR rate was 21.3% versus 23.6% (odds ratio, 0.876 [95% CI, 0.585 to 1.312]; P = .5218), and median OS was 15.9 versus 18.6 months (hazard ratio, 1.203 [95% CI, 0.947 to 1.528]; P = .1299). Magro/Aza had a higher incidence of grade &#x2265;3 adverse events (AEs; 92.8% v 79.2%), AE-associated study drug discontinuations (24.0% v 12.1%), serious AEs (71.9% v 51.5%), and fatal AEs (15.2% v 9.8%) versus Placebo/Aza. CONCLUSION: ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm.

Humans

Sensor-based measures of knee brace adherence have low agreement with self-report methods: A multi-measure study among knee osteoarthritis patients.

OBJECTIVE: To explore agreement between self-report and objectively measured adherence to brace wearing by patients with knee osteoarthritis. METHOD: A single-arm observational analysis nested within the PROP OA randomised controlled trial (ISRCTN28555470). Of 237 adults with symptomatic knee osteoarthritis randomised to brace treatment, 60 were included in this sub-study investigating three different methods of assessing knee brace wear time over 26 weeks: 1. Self-report questionnaires (SRQ) at 12 weeks and 26 weeks; 2. Short message service (SMS) questions (days worn in past week, typical hours per day when worn) administered from week 1 to week 24; 3. A skin temperature sensor embedded in the brace, sampling every 10&#x202f;min for 26 weeks. The presence and reason for the sensor were concealed from participants. The estimated proportion of participants meeting "minimum brace use", defined a priori as &#x2265;1&#x202f;h on &#x2265;2 days in past week, was described for each measurement method, overall and by brace type (unloader, neutral). For temperature sensor measurements, time spent above 24&#xb0;C and time spent above 25&#xb0;C were used. Agreement between the measures was summarised by percentage agreement and kappa (&#x138;). RESULTS: The estimated proportions of participants meeting "minimum brace use" at 12 weeks were 83% (SRQ), 83% (SMS), 60% and 58% (temperature sensor, 24&#xb0;C and 25&#xb0;C thresholds, respectively). At 26 weeks, the corresponding estimates reduced to 72%, 71% (SMS at 24 weeks), 43% and 37%. Sensor data suggested the sharpest decline in brace use occurred within the first 12 weeks. Agreement between self-report measures was higher than between self-report measures and sensor (SRQ vs SMS at 12 weeks: 92% agreement, &#x138;=0.67 (95%CI: 0.34, 1.00); SRQ vs Sensor at 12 weeks: 74%, 0.35 (0.10, 0.60); SMS vs Sens at 12 weeks: 76%, 0.36 (0.05, 0.66). Agreement between all measurement methods reduced at 26 weeks. CONCLUSIONS: This novel use of a temperature sensor to monitor brace adherence in knee osteoarthritis indicates that self-report adherence substantially overestimates knee brace wearing time, with implications for clinical trials and practice.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Implementing a novel digital health platform for self-management of postmenopausal osteoporosis: A qualitative study of user experiences, perspectives and implementation outcomes.

BACKGROUND: Osteoporosis self-management requires scalable support, and digital health platforms may meet this need. This study aimed to characterise the experiences and perspectives of postmenopausal women who participated in a 12-month randomised controlled trial (RCT) of a digital voice assistant (DVA) delivered osteoporosis self-management intervention, and to assess key implementation outcomes. METHODS: This was a qualitative analysis of interviews with postmenopausal women from the intervention arm (DVA group) of the RCT. The DVA program broadcast education videos, medication reminders, home-based exercise, nutrition advice and monthly quizzes through a DVA device. Semi-structured interviews were recorded, transcribed and managed in NVivo through reflexive thematic analysis, guided by the Practical Planning for Implementation and Scale-Up and Proctor's implementation outcome taxonomy frameworks. Evidence weighting summarised participant coverage and code density. RESULTS: Twenty-two of 25 (88%) DVA group participants completed semi-structured interviews. Thematic analysis identified seven themes mapped to Proctor's implementation outcomes. Evidence weighting indicated strong support for the intervention's appropriateness and acceptability, moderate support for its adoption, fidelity, feasibility and sustainability, and limited support for costs. Participants valued clear audiovisual guidance, conversation-based interactions with natural language, and flexible home-based access to self-management. CONCLUSION: Digital health platforms for osteoporosis self-management appear feasible, acceptable and sustainable among postmenopausal women. Findings indicate that these platforms are approaching readiness for evaluation in implementation-focused settings, contingent on streamlined content, reliable delivery modalities, accessible user support, clear privacy regulations and pragmatic pricing models.

Humans

Analgesia for Awake Internal Jugular Vein Cannulation in Trauma Emergency Bay: A Randomized Comparison of Ultrasound-Guided Superficial Cervical Plexus Block With Local Infiltration.

BACKGROUND: Internal jugular vein (IJV) cannulation is a critical component of trauma resuscitation but is often associated with significant pain during vessel dilation and suturing when performed under local anesthetic (LA) infiltration. OBJECTIVES: We hypothesized that an ultrasound (USG)-guided superficial cervical plexus block (SCPB) would provide superior analgesia and improve procedural efficiency in awake trauma patients compared to standard LA infiltration. METHODS: This was a prospective, randomized study of conscious, adult trauma patients requiring IJV cannulation. Participants were randomized to receive either 10 mL of 1% lignocaine via ultrasound-guided SCPB (Group S) or LA infiltration (Group L). The primary outcome was procedural pain measured by Numeric Rating Scale (NRS 0-10) during skin puncture, vessel dilation, catheter insertion, and suturing. Secondary outcomes included total procedure time, Verbal Numeric Rating Discomfort Scale (0-10), and complications. RESULTS: We enrolled 60 patients, with 30 patients assigned to each study group. Median NRS pain scores were significantly lower in Group S compared to Group L at all procedural time points (p < 0.01). The total procedure time was reduced by approximately 50% in Group S (7.5 min [interquartile range (IQR) 6.0-9.3]) compared to Group L (15.5 min [IQR 9.5-16.5]; p < 0.01). Patient discomfort scores were also significantly lower in Group S (p < 0.01). No periprocedural complications were reported in either group. CONCLUSION: Ultrasound-guided SCPB may be a useful alternative to local infiltration for IJV cannulation in selected awake trauma patients, when performed by clinicians experienced in ultrasound-guided regional anesthesia. By providing comprehensive sensory coverage, the technique significantly reduces procedural time and enhances patient cooperation without need for systemic sedation.

Humans

Pembrolizumab-Chemotherapy Versus Pembrolizumab in Head and Neck Squamous Cell Carcinoma: A PD-L1 CPS-Stratified Analysis of Updated KEYNOTE-048 Data.

Based on KEYNOTE-048, pembrolizumab monotherapy and pembrolizumab-chemotherapy are established category 1 first-line treatments for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with programmed death ligand-1 (PD-L1) combined positive score (CPS) &#x2265;&#x2009;1. We compared their efficacy using updated trial data. We analyzed 4-year progression-free survival on next-line therapy (PFS2) and 5-year overall survival (OS) data from KEYNOTE-048 by reconstructing time-to-event data using KMSubtraction. Efficacy was compared in CPS 1-19 and CPS &#x2265;&#x2009;20 subgroups using Kaplan-Meier estimates, Cox models, restricted mean survival time (RMST), and landmark analyses. Among 499 patients with CPS &#x2265;&#x2009;1, 240 (48.1%) had CPS 1-19 and 259 (51.9%) had CPS &#x2265;&#x2009;20. In the CPS 1-19 subgroup, pembrolizumab-chemotherapy showed numerically longer median PFS2 (10.1 vs. 8.0&#x2009;months; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.62-1.06) and OS (12.8 vs. 10.8&#x2009;months; HR: 0.87; 95% CI: 0.67-1.15) versus monotherapy, without statistical significance. For CPS &#x2265;&#x2009;20 patients, efficacy was comparable between regimens, with similar median PFS2 (11.3 vs. 11.7&#x2009;months; HR: 0.95) and OS (14.7 vs. 14.9&#x2009;months; HR: 0.96). RMST and landmark analyses showed an early PFS2 benefit and a trend toward OS benefit with pembrolizumab-chemotherapy in CPS 1-19, with comparable outcomes in CPS &#x2265;&#x2009;20. Pembrolizumab-chemotherapy showed a trend toward improved outcomes in the CPS 1-19 subgroup, with comparable efficacy in the CPS &#x2265;&#x2009;20 subgroup, supporting a refined first-line strategy: monotherapy for CPS &#x2265;&#x2009;20 to minimize toxicity, and combination therapy for CPS 1-19 to potentially enhance disease control.

Humans

No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.

INTRODUCTION: Hip osteoarthritis (OA) is estimated to affect 62.6 million individuals by 2050. A probable link exists between alcohol use and hip OA. However, the results are inconsistent, and the relationship between alcohol and hip OA remains speculative. To address these gaps, this study aimed to utilize the diverse, nationally representative All of Us Research Program dataset to explore the association between alcohol consumption and hip OA. METHODS: This retrospective case-control study utilized data from the All of Us Research Program Controlled Tier Dataset v8. 17,517 hip OA cases and 70,068 controls were identified. A 1:4 case-to-control matching ratio was applied based on age and sex. Alcohol use frequency was categorized into five levels: Never, Monthly or Less, Two to Four Times per Month, Two to Three Times per Week, and Four or More Times per Week. Multivariable logistic regression models evaluated the association between alcohol use frequency and hip OA after adjusting for demographic and clinical variables. RESULTS: Multivariable analysis found that alcohol use frequency was not significantly associated with hip OA. Compared to never users, participants with low (OR 0.98, 95% CI 0.93-1.04, P&#x2009;=&#x2009;0.583), moderate (OR 0.99-1.01, all P&#x2009;>&#x2009;0.05), and high (OR 1.02, 95% CI 0.95-1.09, P&#x2009;=&#x2009;0.599) levels of alcohol consumption had no statistically significant differences in odds of hip OA. Female sex, Asian race, diabetes,&#xa0;hypertension, hyperlipidemia, and nicotine dependence increased the odds of hip OA. CONCLUSION: Any level of alcohol consumption was not significantly associated with the odds of hip OA. This study adds valuable insight to the current body of conflicting evidence. Further prospective studies appear warranted to shed light on the long-term effects of different alcoholic beverages on different joints. Key Points &#x2022; This study found no significant association between any degree of alcohol consumption and the odds of developing hip osteoarthritis. &#x2022; Utilizing data from 87,585 adults in the NIH "All of Us" Research Program, this is the first study to analyze this relationship in a large, nationally representative population. &#x2022; The research provides clarity to previously conflicting literature by demonstrating that alcohol lacks a clear harmful or protective effect on the clinical course of the disease. &#x2022; The analysis highlights that independent risk factors such as Asian race, nicotine dependence, and components of metabolic syndrome increase the odds of hip osteoarthritis.

Humans

Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n&#xa0;=&#xa0;40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE&#xa0;+&#xa0;CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE&#xa0;+&#xa0;CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p&#xa0;<&#xa0;0.01). At 24 weeks, hunger decreased by -24.1&#x202f;mm (95% CI: -35.8, -12.5) in the CCR group and -32.7&#x202f;mm (95% CI: -44.2, -21.3) in the TRE&#xa0;+&#xa0;CCR group. Satiety also increased by 21.7&#x202f;mm (95% CI: 9.46, 33.9) and 29.4&#x202f;mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE&#xa0;+&#xa0;CCR groups. Intensive lifestyle interventions incorporating CCR or TRE&#xa0;+&#xa0;CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans
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Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study.2026-07-13PMID 42441929pubmed
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Use of wearable technologies for physical activity promotion in older adults: A systematic review.2026-07-13PMID 42442508pubmed
Implementing a novel digital health platform for self-management of postmenopausal osteoporosis: A qualitative study of user experiences, perspectives and implementation outcomes.2026-07-13PMID 42442524pubmed
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Pembrolizumab-Chemotherapy Versus Pembrolizumab in Head and Neck Squamous Cell Carcinoma: A PD-L1 CPS-Stratified Analysis of Updated KEYNOTE-048 Data.2026-07-11PMID 42433120pubmed
No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.2026-07-11PMID 42435290pubmed
Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.2026-07-10PMID 42431239pubmed

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