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PubMed2026

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 = 40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE + 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 + CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p < 0.01). At 24 weeks, hunger decreased by -24.1 mm (95% CI: -35.8, -12.5) in the CCR group and -32.7 mm (95% CI: -44.2, -21.3) in the TRE + CCR group. Satiety also increased by 21.7 mm (95% CI: 9.46, 33.9) and 29.4 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 + CCR groups. Intensive lifestyle interventions incorporating CCR or TRE + 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.

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PubMed2026

Evaluating the Effectiveness of an Intimate Partner Violence Training Intervention on Healthcare Providers' Preparedness, Knowledge, and Experiences: A Mixed-Methods Study From Nepal.

Intimate partner violence (IPV) places a considerable burden on health systems globally due to its profound effects on women's health, and women who experience violence often seek care from healthcare providers (HCPs). However, HCPs often lack the preparedness and confidence to respond effectively, resulting in missed opportunities for support and care. This study, conducted in Nepal, evaluated the impact of structured training intervention on HCPs' perceived preparedness, knowledge, and attitudes toward managing IPV and its mental health consequences, including self-harm and suicidal tendencies. The study was nested within a larger cluster randomized trial. A convergent mixed-methods design with a comparison group was conducted among 46 female HCPs in all public hospitals (except one) and 17 primary healthcare centers in Madhesh Province, Nepal. The intervention group (n = 24) received a 10-day intensive IPV and mental health training, while the control group (n = 22) completed 3-day training. Quantitative data were collected using a validated self-administered Physician's Readiness to Manage IPV questionnaire and IPV consequences scale. Paired and independent t-tests were applied to assess changes. Insights from key informant interviews were thematically analyzed to explore participant experiences and perceived impacts. At baseline, over 80% of participants had not received IPV management training. Post-intervention, significant improvements were observed in HCPs perceived preparedness (median change 2.1; 95% confidence interval (CI): 1.1- 2.9), knowledge (median change 2.7; 95% CI: 2.0-3.1), and awareness of IPV consequences (mean difference 1.2; 95% CI: 0.5-2.0), with greater gains in the intervention group. Qualitative findings revealed enhanced confidence in identifying IPV, addressing psychological impacts, and supporting survivors through safety planning and referral. The training significantly improved HCPs' knowledge, preparedness, and confidence to manage IPV and related mental health issues, underscoring the need to scale similar programs to frontline providers, particularly in rural and underserved settings, to strengthen health system's response to IPV.

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PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

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PubMed2026

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

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PubMed2026

Effects of essential amino acid supplementation on musculotendinous recovery following eccentric plantar flexor exercise: a randomized controlled trial.

BACKGROUND: Exercise-induced muscle damage (EIMD) resulting from eccentric contractions leads to transient impairments in muscle function. Essential amino acids (EAAs) stimulate muscle protein synthesis and may support recovery following damaging exercise. However, limited research has examined the effects of EAAs on muscle function following eccentric plantar flexor exercise. The purpose of this study was to examine the effects of EAA supplementation on indirect markers of muscle and musculotendinous recovery following EIMD. METHODS: Thirty-six recreationally active males (age: 21.2 ± 2.7 years) were randomly assigned to an EAA group (10 g of EAAs), placebo (10 g of maltodextrin), or control (no supplementation). Supplements were consumed 30 minutes before and immediately after an eccentric plantar flexor protocol (4 × 50 repetitions followed by one set to failure) and during the 72 hours recovery period. Indirect markers of muscle damage were assessed pre-exercise, immediately post-exercise, and 24, 48, and 72 hours post-exercise, consisting of perceived soreness (NPRS), pain pressure threshold (PPT), calf muscle thickness and Achilles tendon thickness (ultrasound), and calf circumference. RESULTS: The eccentric protocol elicited responses consistent with EIMD, including increased soreness (p < 0.001), increased calf muscle thickness and circumference (p < 0.001), and reduced PPT (p = 0.018). EAA supplementation attenuated soreness at 24 hours compared with placebo. Calf muscle thickness increased following exercise in both groups; however, swelling returned to baseline by 72 hours in the EAA group but remained elevated in placebo (Condition × Time, p < 0.001). Achilles tendon thickness decreased immediately post-exercise (p = 0.005) but was not influenced by supplementation. CONCLUSIONS: EAA supplementation modestly reduced soreness and was associated with faster recovery of muscle swelling but did not influence tendon morphology within 72 hours.

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PubMed2026

PHACE syndrome: a systematic literature review and illustrative case report of a patient with severe cerebrovascular and neurodevelopmental sequelae.

BACKGROUND: PHACE syndrome is a rare neurocutaneous disorder defined by the association of large segmental infantile hemangiomas of the head and neck with malformations of the posterior fossa, cerebral and cervical arteries, heart, eyes, and ventral midline structures. Although facial hemangiomas are often the presenting feature, the cerebrovascular, neurodevelopmental, and airway manifestations are responsible for the greatest long-term morbidity. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Web of Science, EMBASE, and PsycINFO. After removal of duplicates and screening of 308 records, five studies meeting the inclusion criteria were retained for qualitative synthesis. We additionally present the case of a now 12-year-old girl with PHACE syndrome characterized by a left V1-distribution facial hemangioma, ocular abnormalities, multiple cerebrovascular venous and arterial malformations, neonatal intraventricular hemorrhage with hydrocephalus, and a subsequently diagnosed dural arteriovenous fistula requiring repeated embolization. RESULTS: The five included studies collectively describe epidemiology and early supportive care needs, long-term health outcomes and quality of life into adulthood, airway hemangioma prevalence and management, and the clinical spectrum of infantile hemangiomas with minimal or arrested growth (IH-MAG) as a cutaneous marker of PHACE syndrome. Across studies, cerebrovascular arteriopathy (72-91%) and facial hemangioma residua (> 90%) were the most consistent findings, while progressive arteriopathy, headaches, learning differences, and airway involvement emerged as the principal sources of long-term morbidity. The reported case illustrates an unusually severe cerebrovascular phenotype, including neonatal hemorrhagic hydrocephalus, dural venous sinus thrombosis, and a late dural arteriovenous fistula, culminating in ataxic cerebral palsy and mild intellectual disability. CONCLUSIONS: PHACE syndrome requires a multidisciplinary, lifelong follow-up strategy. The presented case underscores that cerebrovascular complications may evolve over years to decades after the initial diagnosis, reinforcing the need for long-term neuroradiological surveillance even after apparent clinical stability.

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PubMed2026

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM. A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events. Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16 Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%. SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

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PubMed2026

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

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PubMed2026

[Moxibustion combined with Jianpi Wenshen formula for cancer-related anorexia of spleen-kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of moxibustion combined with Jianpi Wenshen formula in treating cancer-related anorexia of spleen-kidney yang deficiency. METHODS: A total of 80 patients with cancer-related anorexia of spleen-kidney yang deficiency were randomized into an observation group and a control group, with 40 cases in each group.Jianpi Wenshen formula was given orally in the control group. On the basis of the treatment in the control group, moxibustion was applied at bilateral Zusanli (ST36), Neiguan (PC6) and Zhongwan (CV12), Guanyuan (CV4), Mingmen (GV4) in the observation group, once daily for the first 15 days, then once every other day. Both groups were treated for 4 weeks. The scores of appetite, Karnofsky performance status (KPS), nutritional risk screening 2002 (NRS-2002), and patient-generated subjective global assessment (PG-SGA), as well as the serum levels of interferon-γ (IFN-γ) and C-reactive protein (CRP)were observed before and after treatment, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the scores of appetite, NRS-2002, PG-SGA, and the serum levels of IFN-γ and CRP were decreased compared with those before treatment in the two groups (P<0.001, P<0.05, P<0.01), and the above indexes in the observation group were lower than those in the control group (P<0.05, P<0.001); the KPS scores were increased in the two groups compared with those before treatment (P<0.001, P<0.05), and the KPS score in the observation group was higher than that in the control group (P<0.001). The marked response rate was 57.5% (23/40) in the observation group, which was higher than 30.0% (12/40) in the control group (P<0.05). CONCLUSION: Moxibustion combined with Jianpi Wenshen formula can effectively improve appetite and overall status, and reduce the levels of IFN-γ and CRP in patients with cancer-related anorexia of spleen-kidney yang deficiency.

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PubMed2026

The prevalence of isthmic and degenerative lumbar spondylolisthesis: an analysis of 1376 patients.

INTRODUCTION: Typically, spondylolisthesis is an asymptomatic spinal condition that is often captured accidently in radiographic studies. The limited studies reviewing incidence primarily used lateral radiographs, which lack the granularity of advanced imaging. In response, computed tomography (CT) has been recommended to enhance the accuracy of spondylolisthesis diagnosis (degenerative versus isthmic). In the present study, we sought to determine the prevalence of isthmic and degenerative spondylolisthesis using CT imaging. METHODS: We conducted a retrospective study of 1,680 patients who underwent abdominal/pelvic CT scans at a single level-1 trauma center from January 1, 2017, to January 31, 2017. RESULTS: A total of 1,680 CT scans were screened, of which 1,376 patient scans met the inclusion criteria of having undergone complete imaging (axial and sagittal images). The average age of the study population was 57.1 (standard deviation, 18.7) years; 51.1% were female, and 83.2% were Caucasian. The prevalence of isthmic spondylolisthesis was 5.4% (n = 71): 3.6% of cases were at the L5-S1 level, 2.1% were at the L4-L5 level, and 0.6% were at the L3-L4 level. The female-to-male ratio was 0.73:1. The prevalence of degenerative spondylolisthesis was higher at 21.5% (n = 285), and the level most commonly affected was L4-L5 (11.8%), followed by L5-S1 (9.7%) and L3-L4 (4.6%). The female-to-male ratio was 1.3:1. There was a higher prevalence of degenerative spondylolisthesis in women at L4-L5 (51.2% vs. 35.6%; P < 0.001). CONCLUSION: We found that degenerative spondylolisthesis was more prevalent, occurring primarily in older women, between the L4-L5 vertebrae. On the other hand, isthmic spondylolisthesis more commonly occurred within male patients between the L5-S1 vertebrae. Our study is one of the first to recognize a high rate of degenerative spondylolisthesis within the L5-S1 region, highlighting the utility of CT scan to visualize spinal translation. LEVEL OF EVIDENCE: IV.

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PubMed2026

Safety and efficacy of Meridian sinew tuina (MST) for post-surgical upper limb lymphedema: a systematic review and meta-analysis.

BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z = 20.81; p < 0.0001; I2=0.0%; N = 924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (≥ 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z = 10.62; p < 0.0001; I2=0.0%; N = 1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N = 924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD = -1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD = -2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.

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PubMed2026

Transcranial Motor Evoked Potential Monitoring Using Propofol-Fentanyl Versus Desflurane-Dexmedetomidine Anesthesia During Spinal Cord Tumor Resection: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing resection of spinal cord tumours require intraoperative neuromonitoring. Transcranial electrical stimulation is used to record myogenic responses during surgery. This study aimed to compare the effect of 2 anaesthetic regimens, propofol/fentanyl versus desflurane/dexmedetomidine, on the ability to record MEPs with an amplitude of 50 µV or greater. Our secondary outcome compared intraoperative haemodynamics, recovery profile, and postoperative analgesia between the groups. METHODS: We conducted a prospective, double-blinded, open-label, single-centre, randomized controlled trial of 50 adult patients undergoing spinal cord tumour resection with TcmMEP monitoring. Patients were randomized to 2 groups: Group P (n=25) received intravenous anaesthesia with propofol and fentanyl; group D (n=25) received desflurane and dexmedetomidine. RESULTS: We recorded TcmMEP's in 80% of group P and 76% group D (95% CI: -23% to 31%, P =1.00). The time in minutes for spontaneous breathing (21.04±11.31 vs. 8.00±3.42 [8.29-,17.79, P =0.01]), extubation (31.56±17.56 vs. 10.84±3.99 [13.48-27.96; P =0.01]), emergence (33.68±18.11 vs. 10.92±4.01 [15.30-30.22, P =0.001]), discharge readiness (45.00±25.24 vs. 15.56±6.08 [19.00-39.88; P =0.001]) and requirement of first analgesia (136.6±108.04 vs. 230.8±81.33) (-148.58 to -39.82; P =0.01) was lower in group D compared with group P. Postoperative analgesia assessed using the Visual Analogue Score was lower in group D compared with group P at 12 and 24 hours. (1.68±1.18 vs. 0.64±1.31 [0.33-1.74 P =0.001]) :1.4±0.95 vs. 0.36± 0.70 (0.56-1.51; P =0.001). CONCLUSIONS: We found similar rates of successful TcMEP monitoring using desflurane-dexmedetomidine and propofol-fentanyl. Patients who received desflurane-dexmedetomidine had reduced emergence time, discharge readiness, and lower pain scores in the postoperative period.

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PubMed2026

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max. METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

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PubMed2026

Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.

BACKGROUND: We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes. METHODS: In this multicenter, randomized trial, patients with high-risk LA-NPC (T4N0-2M0 or TanyN3M0) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety. RESULTS: Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups. CONCLUSIONS: Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).

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PubMed2026

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 > 5 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 > 5 cm2 after PVI, four variables-age ≥ 75 years, left atrial diameter > 44 mm, estimated glomerular filtration rate < 60 mL/min/1.73 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 = 336), a significant treatment-by-score interaction was observed (P < 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 = 494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P = 0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5 cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

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PubMed2026

Pedagogical Efficacy of LLM-Generated Synthetic Data Versus Real-World Clinical Records: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND: Expert-reviewed clinical cases generated by large language models (LLMs) may supplement case resources in medical education, but their short-term educational performance relative to real-case-derived teaching materials remains uncertain. We compared immediate post-training test performance after teaching with the two types of case materials and assessed non-inferiority against a prespecified margin. METHODS: We conducted a prospective, parallel-group, randomized non-inferiority trial. Through the Wenjuanxing online platform, participants were randomized 1:1 to learn with either real-case-derived teaching cases compiled by clinicians and reviewed by experts or AI-generated clinical cases produced by Gemini 3.0 Pro from fully de-identified matched real cases and reviewed by three senior general surgery specialists with full-professor rank. The primary outcome was the total score on an independent 10-item immediate post-training test (0-10 points), with a prespecified non-inferiority margin of -0.5 points. Secondary outcomes included the training-phase performance score, learning efficiency index, single-item mental effort rating, case realism, and case-source judgment. RESULTS: A total of 403 participants were randomized, of whom 386 were included in the modified intention-to-treat analysis: 192 in the real-case group and 194 in the AI-generated case group. The mean post-training test score was 4.95 (SD, 3.35) in the real-case group and 4.61 (SD, 3.35) in the AI-generated case group. The mean difference (AI-generated minus real-case group) was -0.335 points (95% CI, -1.006 to 0.337). Because the lower bound of the confidence interval was below the prespecified non-inferiority margin of -0.5 points, non-inferiority was not demonstrated (one-sided P = 0.314). No significant between-group differences were observed in the training-phase performance score, learning efficiency index, or single-item mental effort rating. AI-generated cases received lower realism ratings for Level 3 cases. The proportion of participants with at least one high-confidence completely incorrect response was 1.6% in the real-case group and 2.1% in the AI-generated case group. CONCLUSIONS: In this short-term, text-based online case-learning setting, no statistically significant between-group difference was observed in immediate post-training test performance; however, non-inferiority of AI-generated clinical cases relative to real-case-derived teaching materials was not demonstrated.

Humans↗

PubMed2026

Effects of Photobiomodulation Therapy in Lateral Luxation of Anterior Permanent Teeth: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Among the traumatic dental injuries (TDIs), lateral luxation may present poor prognosis due to frequent root resorption and consequent tooth loss. Photobiomodulation therapy (PBMT) modulates cellular activities (proliferation, differentiation, growth factor secretion) and may improve outcomes. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated PBMT (660 vs. 808 nm) for post-operative pain and pulp sensitivity recovery in lateral luxation of permanent anterior teeth. METHODS: Initially, 41 patients were included, with a total of 63 teeth traumatized by lateral luxation and were allocated to G1 (n = 21): Splinting + sham PBM (placebo), G2 (n = 21): Splinting + 808 nm infrared PBM and G3 (n = 21): Splinting + 660 nm red PBM. Four weekly sessions (3 J/point, 3 points) were administered. Pain (by numeric rating scale) and pulp sensitivity (by cold test) were assessed weekly. Pain was analyzed using the Kruskal-Wallis test, followed by multiple comparisons using Dunn's method with Bonferroni correction, and pulp sensitivity by a logistic regression model (p < 0.05). RESULTS: Three participants (total of 5 teeth) were excluded due to loss to follow-up. Fifty-eight teeth were analyzed (G1 = 21, G2 = 17, G3 = 20). Pain: All groups showed a significant reduction in pain over time (p < 0.001). Both G2 and G3 demonstrated a significantly greater reduction in pain compared to G1 (p < 0.001 and p = 0.026, respectively). No significant difference in pain reduction was observed between G2 and G3. Pulp sensitivity: G2 showed a significant improvement over time (p < 0.001), despite starting from a more unfavorable baseline. In contrast, no significant change in pulp sensitivity was observed for G1 or G3 between the initial and final assessments. CONCLUSION: Within the limitations of this clinical study, all intervention groups were effective in reducing pain in lateral luxation of permanent anterior teeth, with superior results for laser groups compared to the placebo. However, only the 808 nm laser irradiation protocol demonstrated a significant improvement in pulp sensitivity, suggesting it may offer a more complete therapeutic response.

Humans↗

PubMed2026

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6 months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250 mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4 months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0 months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8 months (95% CI: 3.3-8.2), and median OS was 10.9 months (95% CI: 6.0-15.8). Grade ≥3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

Humans↗