SEARCH · Search PubMed

Results for “Graft vs Host Disease”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,117 records · Page 20Linked to original sources

PubMed2026

Granger connectivity and graph-theoretical analysis of scalp EEG across the preictal to ictal transition for presurgical evaluation.

OBJECTIVE: To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. METHODS: Adults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. RESULTS: Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. CONCLUSIONS: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. SIGNIFICANCE: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Humans↗

PubMed2026

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41 ± 0.24 vs. 2.35 ± 0.06, P < 0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans↗

PubMed2026

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2 with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p < 0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43 months, p < 0.0001; 9.46 vs. 14.44 months, p = 0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans↗

PubMed2026

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n = 45) or a control group receiving conventional anatomy training (n = 45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34 ± 2.89 vs. 87.20 ± 3.29; p < 0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p < 0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p < 0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p < 0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans↗

PubMed2026

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged ≥18 years) with type 2 diabetes (HbA1c ≥8·0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3·9-5·0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9·57% for IcoSema and 9·50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3·32 vs -2·44 percentage points; estimated treatment difference [ETD] -0·88 percentage points [95% CI -1·12 to -0·63]), confirming superiority of IcoSema (p<0·001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0·79 vs 3·81 kg; ETD -4·61 kg [95% CI -5·46 to -3·75]), confirming superiority of IcoSema (p<0·001). Rate of combined clinically significant (blood glucose <3·0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0·29 vs 0·59 episodes per person-year of exposure; estimated rate ratio 0·56 [95% CI 0·32 to 0·97]; p=0·04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans↗

PubMed2026

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had ≤US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans↗

PubMed2026

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans↗

PubMed2026

Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

Humans↗

PubMed2025

Effect of transcutaneous vagus nerve stimulation in hemodialysis patients: A randomized controlled trial.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (tVNS) has shown potential in neurological, autoimmune, and cardiovascular disorders, but its effects on HD patients remain unclear. This study aimed to evaluate the efficacy and safety of tVNS in HD patients. METHODS: We conducted a randomized controlled clinical trial on patients receiving HD ≥6 months. The tVNS group received stimulation for 1 h during the first 2 h of HD sessions, three times weekly for 8 weeks, while the control group received standard care. The primary outcomes were dialysis efficiency (Single-pool Kt/V, Sp Kt/V) and dialysis-related symptoms (Dialysis Symptom Index, DSI), assessed every 4 weeks. Secondary outcomes included pain and fatigue scores, physical performance, Hemodialysis Comfort Scale, hemoglobin levels, Mini-Mental State Examination, and anxiety and depression scores, measured at baseline and 8 weeks after intervention. RESULTS: A total of 63 patients were enrolled in the study, with 32 patients assigned to the tVNS group and 31 patients to the control group. At 8 weeks, the tVNS group showed significant improvements in Sp Kt/V (1.31 ± 0.11 vs. 1.25 ± 0.10, p = 0.02), and DSI (12.09 ± 5.84 vs. 16.26 ± 5.27, p = 0.004), as well as reductions in pain and fatigue, and increases in physical function, comfort, and hemoglobin. However, there were no statistically significant changes observed in cognitive function, anxiety, or depression. CONCLUSIONS: tVNS could improve dialysis efficiency, symptoms, and physical function in HD patients, indicating it may have a role as a complementary therapy.

Humans↗

PubMed2026

Effect of ketofol versus Fentanyl-Midazolam sedation on neurological recovery in traumatic brain Injury: A randomised study.

Neurological recovery after traumatic brain injury (TBI) is multifactorial, and sedation is a cornerstone of neurocritical care because of its neuroprotective role. Although ketofol is widely used for anaesthesia, its effectiveness as a sedative regimen in the intensive care unit (ICU) has not been well studied. This preliminary exploratory double-blind, randomised study compared ketofol (KP) with fentanyl-midazolam (FM) sedation in adults with moderate-to-severe TBI. Sedation was administered for 72 h and titrated to a Richmond Agitation-Sedation Scale (RASS) score ≤  - 3. The primary outcome was the Extended Glasgow Outcome Scale (GOSE) at 30 days. Secondary outcomes included GOSE at 90 days, incidence of propofol infusion syndrome (PRIS), duration of mechanical ventilation, haemodynamic stability, and ICU and hospital length of stay. Of 120 enrolled patients, 111 were included in the final analysis (57 FM, 54 KP). Baseline characteristics, including injury severity and Marshall CT scores, were comparable. At 30 days, good neurological recovery (GOSE 7-8) was more frequent in the KP group than the FM group (26% vs. 10.5%, p = 0.03). At 90 days, recovery remained higher with KP (44.4% vs. 33.3%), though the difference was not statistically significant (p = 0.16). Multivariate analysis confirmed ketofol as an independent predictor of good recovery at 30 days (adjusted OR 3.63, 95% CI 1.11-11.85, p = 0.033). No PRIS occurred, and secondary outcomes were similar. Ketofol-based sedation was safe and may be associated with improved early neurological recovery compared with fentanyl-midazolam, with a favourable trend toward improved long-term neurological recovery.

Humans↗

PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

Humans↗

PubMed2026

USleep: efficacy of app-based audio interventions to improve sleep disturbance in working adults, a multi-arm randomized controlled trial.

STUDY OBJECTIVES: To evaluate the efficacy of three categories of standalone, audio-based sleep interventions (Bedtime Stories, Sleep Sounds, Sleep Skills) delivered via mental health application (MHapp) in improving sleep among working adults with sleep disturbance. METHODS: A multi-arm, parallel randomized controlled trial was conducted. Adults with self-reported sleep disturbances were recruited online and randomly allocated to Bedtime Stories, Sleep Sounds, Sleep Skills, or digital control. Participants completed self-report questionnaires on sleep disturbance and other related outcomes at baseline (t0) and after the 4-week intervention (t1). The primary analysis followed an intention-to-treat approach using mixed-effects models. RESULTS: A total of 495 working adults (mean age = 32.7 years; 55.8% female) were randomized. For sleep disturbance (primary outcome), the between-group Hedges' g effect sizes were very small and not statistically significant (Bedtimes stories vs. control: g = 0.12, 95% CI -0.13 to 0.37, Sleep Sounds vs. control: g = 0.14, 95% CI -0.11 to 0.39, Sleep Skills 0.07, 95% CI -0.07 to 0.29), with slightly greater reductions in sleep disturbance for the intervention groups than control. The same pattern was observed for sleep-related impairment, mental health, well-being, and pre-sleep arousal. CONCLUSION: Audio-based sleep interventions delivered via a MHapp did not demonstrate superior efficacy over a digital control condition in reducing self-reported sleep disturbance among working adults. Although safe and well-tolerated, their use as standalone treatments for sleep disturbance is not supported by these findings. Future research should explore effectiveness in real-world settings, including user content choice across categories, and use objective sleep measures. CLINICAL TRIAL REGISTRATION: Registered at https://www.isrctn.com/ under "Evaluating the efficacy of audio-based digital tools to improve sleep on the Unmind workplace well-being platform"; https://www.isrctn.com/ISRCTN13426045; registration number: 13426045.

Humans↗

PubMed2026

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult↗

PubMed2026

Obinutuzumab or Tacrolimus in Primary Membranous Nephropathy.

BACKGROUND: Studies of obinutuzumab, a type II anti-CD20 antibody, have shown efficacy in the treatment of hematologic cancers and autoimmune diseases. An evaluation of the efficacy and safety of obinutuzumab in patients with primary membranous nephropathy is needed. METHODS: In a phase 3 trial, we randomly assigned adults with primary membranous nephropathy in a 1:1 ratio to receive intravenous obinutuzumab or oral tacrolimus. The primary end point was complete remission (defined as a urinary protein-to-creatinine ratio of 0.3 or lower and a stable estimated glomerular filtration rate [eGFR]) at week 104. Key secondary end points were complete or partial remission at week 104, complete remission at week 76, a sustained reduction in the eGFR of at least 30%, duration of complete remission, and change in the Patient-Reported Outcomes Measurement Information System Fatigue T score from baseline to week 104. Fixed-sequence hierarchical testing was performed. Safety was assessed. RESULTS: A total of 142 patients underwent randomization. At week 104, complete remission was observed in 26 of 71 patients in the obinutuzumab group and in 4 of 70 patients in the tacrolimus group (37% vs. 6% with multiple imputation for missing data; adjusted difference, 31 percentage points; 95% CI, 18 to 44; P<0.001). The analyses of complete or partial remission at week 104 and complete remission at week 76 also showed a significant treatment effect. The analysis of a sustained eGFR reduction did not show a significant treatment effect; thus, subsequent end points in the hierarchy were not formally tested for significance. Adverse events of grade 3 or higher were reported in 16 patients (22%) in the obinutuzumab group and in 13 patients (19%) in the tacrolimus group; serious adverse events occurred in 12 (17%) and 10 (14%), respectively. There were 61 and 57 infections per 100 patient-years in the obinutuzumab and tacrolimus groups, respectively; 3 and 4 serious infections per 100 patient-years; and 11 and 14 serious adverse events per 100 patient-years. Adverse drug reactions with obinutuzumab included infusion-related reactions, respiratory tract infections, and neutropenia. One patient in each group died during escape therapy. CONCLUSIONS: Obinutuzumab was superior to tacrolimus in inducing complete remission in patients with primary membranous nephropathy. (Funded by F. Hoffmann-La Roche; MAJESTY ClinicalTrials.gov number, NCT04629248.).

Adult↗

PubMed2026

Impact of oliceridine versus sufentanil on postoperative nausea and vomiting in patients undergoing thyroid surgery: a prospective, double-blind, randomized controlled trial.

PURPOSE: Postoperative nausea and vomiting (PONV) is a common complication following thyroid surgery, often exacerbated by opioid use. Oliceridine, a novel G protein-biased μ-opioid receptor agonist, may reduce opioid-related adverse events. This study aimed to compare the impact of oliceridine versus sufentanil on the incidence and severity of PONV in patients undergoing thyroid surgery. PATIENTS AND METHODS: In this prospective, double-blind, randomised controlled trial conducted between May 2025 and February 2026, 232 patients scheduled for thyroid surgery were randomly assigned to receive either oliceridine or sufentanil for intraoperative analgesia. The primary outcome was the incidence of PONV during the first 48 h postoperatively. Secondary outcomes included PONV severity, need for rescue anti-emetics, postoperative pain scores, recovery quality, and other adverse events. RESULTS: The incidence of PONV within 48 h postoperatively was significantly lower in the oliceridine group [13/107 (12%)] compared with the sufentanil group [31/110 (28%)] (OR = 0.35, 95% CI: 0.17-0.72, p = 0.006). Postoperative pain scores, rescue analgesia requirements, and Quality of Recovery-15 scores were comparable between the two groups (p > 0.05). Besides, exploratory unadjusted analyses revealed fewer rescue anti-emetics: O group 8/107 (8%) vs S group 25/110 (23%) (OR = 0.27, 95% CI: 0.12-0.64, p = 0.002); and less abdominal distension: O group 4/107 (4%) vs S group 19/110 (17%) (OR = 0.19, 95% CI: 0.06-0.57, p = 0.001). CONCLUSION: For young ASA I-II patients undergoing thyroid surgery, oliceridine yields adequate postoperative analgesia and lower PONV rates versus sufentanil. Additional trials involving high-intensity surgical procedures are needed to confirm consistent equivalence.

Humans↗

PubMed2026

Understanding and Usefulness of Effect Size and Certainty of Evidence: A Cross-Sectional Survey of Evidence-Based Practice Competencies Among US Registered Dietitians.

INTRODUCTION: Understanding of absolute and relative effect estimates, and determining effect size and certainty of evidence corresponding to effect estimates, represent fundamental evidence-based practice competencies that promote informed clinical decision-making. While research has been conducted in the medical profession, based on our literature review there is no published research on these competencies in the nutrition and dietetics profession. METHODS: Among registered dietitians, our main objectives were to assess (1) their understanding and perceived usefulness of three absolute and two relative effect estimate approaches to determine effect size, (2) their perceived usefulness of certainty of evidence, and (3) factors influencing their understanding and perceived usefulness. We conducted a web-based, cross-sectional survey by recruiting dietitians from the Academy of Nutrition and Dietetics (United States). Participants received effect estimates based on hypothetical dietary interventions vs. usual diet for reducing myocardial infarction risk. RESULTS: Of the 11,050 dietitians who received the survey link, 210 participated, and only completers (n = 114) were included in our analysis. Participants demonstrated a similar understanding of the relative (27.6%) and absolute (27.5%) effect estimates, with Risk Difference being the best understood approach and Number Needed to Treat being the least (30.7% vs. 24.6% correct responses). While perceived usefulness scores were similar between five approaches, they were highest when data was presented as Relative Risk [mean (SD): 4.82 (1.50)]. Dietitians rated the usefulness of certainty of evidence favorably [mean (SD): 5.07 (1.83), on a 7-point scale], and no factors were associated with correct understanding. CONCLUSION: Dietitians may have limited understanding of effect size thresholds presented in our survey, a finding mostly consistent with surveys of other health professionals. To optimize informed decision-making between dietitians and clients, dietetic programs and continuing education platforms should consider additional training on effect estimate approaches (relative and absolute), and determining effect sizes and certainty of evidence for effect estimates.

Clinical nutrition↗

PubMed2026

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans↗

PubMed2026

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen™) and AID (MiniMed™ 780G) for 6 months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81 % vs 66 %; +15 %, 95 % CI 10-19; P < 0.001) and lower HbA1c (6.9 % [52 mmol/mol] vs 7.3 % [56 mmol/mol]; -0.4 %, 95 % CI - 0.6 to - 0.3; P < 0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46 %). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult↗