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PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

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

Feasibility and efficacy of left bundle branch area pacing guided by modified chest lead 1.

BACKGROUND: Left bundle branch area pacing (LBBAP) typically requires 12‑lead electrocardiogram (ECG) measurements using an electrophysiology (EP) recording system. However, a simplified approach using modified chest lead 1 (MCL1) is potentially feasible. This study aimed to compare the success rate and pacing outcomes of LBBAP guided by MCL1 with those guided by the 12‑lead ECG using an EP recording system. METHODS: This retrospective, single-center study included patients with preserved left ventricular ejection fraction who underwent LBBAP for bradyarrhythmia. LBBAP was either guided by 12‑lead ECG using an EP recording system or by MCL1. In the MCL1 group, a follow-up examination with a 12‑lead ECG using an EP recording system was conducted within one week postoperatively. RESULTS: A total of 65 patients underwent LBBAP (EP recording system group: n = 35; MCL1 group: n = 30). The overall success rate of LBBAP was 84.6%, with no significant difference between groups (88.5% vs. 80.0%, p = 0.49). No significant differences were observed in the paced QRS duration (140.4 ± 8.0 vs. 141.9 ± 13.1 ms, p = 0.54), V6-V1 interpeak interval (39.7 ± 16.5 vs. 38.3 ± 15.6 ms, p = 0.79), or V6 R-wave peak time (69.8 ± 12.3 vs. 71.5 ± 12.1 ms, p = 0.68). CONCLUSIONS: MCL1-guided LBBAP was feasible and achieved a high success rate, with outcomes comparable to those of conventional EP recording system-guided implantation. This simplified approach may reduce procedural complexity and may allow LBBAP implantation without the routine use of an EP recording system.

Humans↗

PubMed2026

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130 g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n = 3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans↗

PubMed2026

Cryostick pre-cooling reduces pain during intra-articular knee injections: a randomized, contralateral-controlled trial.

BACKGROUND: Intra-articular knee injections are essential for osteoarthritis management but often limited by "needle phobia" and procedural pain. The cryostick, a high-thermal-conductivity device, is a potential analgesic; however, evidence regarding its efficacy in reducing pain and bleeding is limited. The purpose of the study was to evaluate whether cryostick application reduces procedural pain, reduces bleeding, and improves patient satisfaction during intra-articular knee injections. METHODS: This randomized, contralateral-controlled trial included 50 patients (100 knees) with bilateral knee osteoarthritis. One knee received a 20-s cryostick protocol (-20°C) immediately before injection; the contralateral knee received a standard injection. Primary outcome was pain intensity (100-mm VAS) during needle penetration and at 5-min post-injection. Secondary outcomes included bleeding area (mm2) and satisfaction (1-5 Likert scale). RESULTS: Cryostick application significantly reduced pain during needle penetration (Mean Difference [MD] -24.8 mm; 95% CI -29.9 to -19.7; P < 0.001) and at 5-min post-injection (MD -20.8 mm; 95% CI -26.8 to -14.8; P < 0.001). The Number Needed to Treat (NNT) to achieve the Minimal Clinically Important Difference (13 mm) was 1.28 (95% CI 1.15-1.54) during penetration and 1.79 (95% CI 1.45-2.36) at 5-min post-injection. The bleeding area was significantly smaller with cryostick (MD -4.82 mm2; P = 0.014). Patients reported significantly higher satisfaction scores with the cryostick (4.10 vs 2.96; P < 0.001). CONCLUSIONS: A 20-s cryostick application is a safe, well-tolerated, and effective adjunct for attenuating pain and bleeding during knee injections. This technically simple approach requires minimal complexity, offering an efficient, non-pharmacological tool to enhance patient comfort.

Humans↗

PubMed2026

Effect of self-activating phthalocyanine gel on palatal donor site healing, inflammatory biomarkers, somatosensory and patient-centered outcomes: a randomized split-mouth clinical trial.

OBJECTIVES: To evaluate effects of self-activating phthalocyanine (PHY) gel on palatal donor site after subepithelial connective tissue graft (SCTG) harvesting, considering clinical outcomes, inflammatory biomarkers, patient-centered outcomes, and quantitative somatosensory changes. MATERIALS AND METHODS: Twenty participants were included in this randomized, crossover, split-mouth clinical trial. Donor sites received topical PHY gel (PHY group-PHYG) and placebo gel (control group-CG). Clinical parameters (residual wound area-RWA, wound epithelialization-WE, residual remodeling area-RRA and tissue thickness-TM) were assessed at baseline, 7, 14, 30, and 60 days. Patient-centered outcomes were recorded during 14 postoperative days and inflammatory biomarkers at 3 and 7 days postoperatively. Mechanical detection threshold (MDT) and mechanical pain threshold (MPT) were evaluated at baseline, 2 months, and 6 months. RESULTS: PHYG and CG exhibited similar clinical outcomes, but PHYG demonstrated superior performance in reducing RRA. Both groups presented positive postoperative progression of patient-centered outcomes. IL-10 levels showed a significant increase in PHYG, suggesting a more favorable anti-inflammatory response. MDT remained stable but, donor sites exhibited transient hypersensitivity (MPT) at 2 months. CONCLUSIONS: PHYG and CG protocols promoted satisfactory healing of palatal donor sites. Most clinical parameters and patient-centered outcomes were similar between groups. The PHYG presented reduced RRA and increased IL-10 levels. Donor sites exhibited transient hypersensitivity, which tended to resolve over time. CLINICAL RELEVANCE: Both postoperative protocols resulted in favorable healing of palatal donor sites following SCTG harvesting, with comparable clinical and patient-centered outcomes. Quantitative sensory testing indicates that hypersensitivity may occur during healing, but sensory function tends to recover progressively.

Humans↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2026

Pre-clinical evaluation of the anticaries effect of an experimental Malva sylvestris extract mouthwash using a cariogenic model in situ.

OBJECTIVE: The aim of this study was to evaluate the antimicrobial and anticariogenic potential of Malva sylvestris extract on enamel and dentin in situ. METHODS: A double-blind crossover in situ study was conducted with 12 participants wearing palatal appliances containing two bovine enamel and two dentin specimens per 3 phases, a total of 72 enamel and dentin specimens. Biofilm formation and daily sucrose exposure were allowed. Treatments were applied twice daily in three phases: Malva sylvestris (2.5%, MS); fluoride (225 ppm, F); and placebo (P). After seven days, biofilm was collected from the bovine specimens for analysis of Lactobacillus spp. and mutans streptococci by Colony Forming Unit counts (CFU log₁₀/mL). Dental demineralization of the bovine specimens was assessed by transverse microradiography (TMR). RESULTS: MS did not reduce Lactobacillus spp. counts (CFU log₁₀/mL: enamel 6.63±0.81; dentin 6.68±0.92) compared to P (6.63±0.70; 6.62±0.51). F also did not differ (6.29±0.75; 6.32±0.41; ANOVA/Tukey, p>0.38). Mutans streptococci data were inconclusive. In enamel, both MS (2320.8±768.2 %vol·µm; 101.6±27.0 µm) and F (1777.3±733.3 %vol·µm; 95.8±23.5 µm) significantly reduced integrated mineral loss and lesion depth compared to P (3517.2±1119.9 %vol·µm; 138.6±19.5 µm; ANOVA/Tukey, p≤0.0003). In dentin, MS significantly reduced integrated mineral loss (322.5 [250-580] %vol·µm) and lesion depth (30.1 [15-42.2] µm) compared to P (880 [580-1705]; 58.3 [32.2-88.6] µm; Kruskal-Wallis/Dunn, p≤0.001), while F (587.5 [305-720]; 25.2 [16.5-38.8] µm) did not differ significantly (p>0.05). CONCLUSIONS: Malva sylvestris extract had no antimicrobial effect on Lactobacillus spp. counts, but significantly reduced enamel and dentin demineralization, showing anticaries effect comparable to fluoride. CLINICAL RELEVANCE: Malva sylvestris has demonstrated promising biological activity. This study investigates the antimicrobial efficacy of Malva sylvestris against cariogenic microorganisms in situ. Our findings provide relevant evidence that M. sylvestris exert significant anticaries effects using an in situ model.

Biofilms↗

PubMed2026

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.

AIMS: To evaluate the long-term efficacy and safety of imeglimin added to dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes, focusing on glycemic durability and safety in elderly patients over 104 weeks. MATERIALS AND METHODS: This multicenter, randomized, placebo-controlled trial comprised a 24-week double-blind phase (imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label extension in which all patients received imeglimin. Eligible patients had inadequate glycemic control despite DPP-4 inhibitor monotherapy. The main assessment measured HbA1c changes from baseline to week 104. Secondary assessments included meal tolerance tests (MTT) for evaluating physiological changes in β-cell function and insulin resistance and safety monitoring. RESULTS: Of 117 randomized patients, 81 completed 104 weeks. In the early-start group that received imeglimin from week 0, the significant HbA1c reduction observed at week 24 (-0.65%) was maintained through week 104 (-0.55%; p < 0.001 vs. baseline). The delayed-start group that switched to imeglimin at week 24 achieved similar glycemic control thereafter. Elderly patients (≥ 65 years) in the early-start group maintained stable HbA1c reduction (-0.58%) without hypoglycemic events over 2 years. MTT analysis in the early-start group showed sustained improvements in glucose AUC and insulin sensitivity without unnecessary insulin secretion over time. CONCLUSIONS: Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104 weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity. TRIAL REGISTRATION: jRCTs061210082.

Humans↗

PubMed2026

Effectiveness of high-power laser use in the removal of esthetic restorations: a systematic review.

This systematic review aimed to evaluate the effectiveness of high-power lasers in the removal of esthetic restorations compared with conventional methods. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (registration number: CRD420251055736). A comprehensive electronic search was performed in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. Study selection, data extraction, and methodological quality assessment were independently performed by four reviewers using QUIN tool for in vitro studies. A total of 2.384 records were identified, of which 19 in vitro studies conducted on extracted human permanent teeth met the eligibility criteria and were included in the qualitative synthesis. The included studies evaluated different high-power laser systems, predominantly Er: YAG and Er, Cr: YSGG lasers, as well as CO₂ lasers. Five studies were classified as high quality, whereas the remaining fourteen studies were classified as moderate quality. Available laboratory evidence suggests that laser-assisted techniques may represent a potential alternative approach for removing esthetic restorations, with advantages including conservative tissue removal, reduced damage to underlying tooth structures, and intrapulpal temperature increases within acceptable limits. The Er: YAG laser was the most frequently investigated system, with power settings ranging from 1.5 to 5.9 W, showing particularly favorable laboratorial performance in the removal of lithium disilicate restorations, especially in thinner substrates. Within the limitations of the available evidence, high-power lasers appear to be a promising and minimally invasive alternative to conventional methods for the removal of esthetic restorations. However, the predominance of in vitro studies highlights the need for well-designed clinical trials to confirm these findings and support their clinical application.

Humans↗

PubMed2026

Intravenous Tranexamic Acid Reduces Perioperative Blood Loss in Reduction Mammoplasty With Immediate Implant-Based Reconstruction: A Randomized, Triple-Blinded, Placebo-Controlled Trial.

BACKGROUND: Postoperative hematoma and oozing can compromise outcomes after reduction mammoplasty with immediate reconstruction. Intravenous (IV) tranexamic acid (TXA) is antifibrinolytic, but prospective evidence in this setting is limited. OBJECTIVES: The aim of this study was to determine whether a single pre-incision dose of IV TXA reduces perioperative blood loss and fibrinolytic activation vs placebo. METHODS: In this randomized, triple-blinded, placebo-controlled trial, 60 women (American Society of Anesthesiologists I/II, 18-75 years) undergoing bilateral reduction mammoplasty with immediate implant-based reconstruction received TXA 10 mg/kg in 100 mL saline or placebo 10 min before incision. The primary outcome was total blood loss within 24 h (intraoperative suction + swab plus drain output). Secondary outcomes were perioperative changes in hemoglobin, D-dimer and fibrinogen, and complications within 30 days. Intention-to-treat analyses were performed. RESULTS: All patients completed follow-up. Total blood loss was lower with TXA than with placebo (mean ± standard deviation: 221.1 ± 72.4 vs 298.1 ± 90.6 mL; mean difference -77.0 mL; 95% CI, -122.4 to -31.6; P = .001). Intraoperative loss and 24 h drain output were also reduced. Postoperative D-dimer rise was attenuated with TXA (0.31 ± 0.15 vs 0.49 ± 0.22 µg/mL; P = .002); hemoglobin decline was smaller. No thromboembolic, neurologic, or allergic events occurred; no skin-flap necrosis was observed. CONCLUSIONS: Pre-incisional IV TXA safely reduces perioperative bleeding and fibrinolytic activity after reduction mammoplasty. These findings support incorporation of IV TXA into perioperative protocols. LEVEL OF EVIDENCE: 2 (THERAPEUTIC): For image description, please refer to the figure legend and surrounding text.

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

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

PubMed2026

Solutions for engaging priority populations in HIV cure research: a hybrid Delphi consensus-building process.

BACKGROUND: To achieve consensus on barriers and strategies to improve the engagement of three priority populations - Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research. METHODS: We assembled a panel of 54 experts assigned to six groups in a hybrid Delphi process: (1) HIV community members, (2) biomedical researchers, (3) medical providers, (4) funders and private industry members, (5) bioethicists and regulators, and (6) social scientists. Over 18 months, we conducted four iterative survey rounds and three group discussions to identify barriers and strategies to arrive at a consensus on how to engage these priority populations in HIV cure research. RESULTS: For Black and Latino/a/x populations, the panellists identified inadequate outreach and a lack of accessible educational information as primary barriers and emphasised community-driven engagement and partnerships with trusted leaders as key strategies. For cisgender women, logistical hurdles, caregiving responsibilities and time constraints were identified as major barriers, with flexible trial designs and equitable compensation proposed as solutions. For transgender women, the lack of transgender-focused research design, including misrepresentation and exclusion, was identified as a key barrier, while centring transgender-specific needs in study design achieved consensus as the most effective strategy. CONCLUSION: Among all four priority populations, investment in outreach, engagement along the research process, better integration of health needs with research, and enhanced incentives are not novel ideas, but remain obviously ignored in a way that has led to underrepresentation of people in HIV cure research, who carry the greatest burden of HIV in the U.S. SUMMARY: This paper uses a hybrid Delphi process to identify and reach consensus on key barriers and strategies to engage underrepresented groups: Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research across the United States.

Humans↗

PubMed2026

Desmodium styracifolium Total Flavone Capsules for Urolithiasis: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: No oral medication is currently approved for the management of urolithiasis. Guang Jing Qian Cao (Desmodium styracifolium total flavone capsules; hereinafter, Guang Jing), a traditional Chinese herbal extract, has shown clinical benefits for urolithiasis, but randomized clinical trials are needed to assess its effectiveness. OBJECTIVE: To evaluate whether Guang Jing improves stone passage rates (SPRs) compared with placebo in adults with urolithiasis. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 3 randomized clinical trial was conducted at 34 sites in China from December 2017 to April 2020. Participants included adults (aged 18-70 years) with diagnosed ureteral stones. Data analysis was conducted on November 4, 2020. INTERVENTION: Participants were randomized 3:1 to receive oral Guang Jing (0.6 g) or matching placebo 3 times daily for 28 days, in addition to investigator-prescribed background medication. MAIN OUTCOMES AND MEASURES: The primary outcome was SPR by day 28, confirmed by computed tomography. Secondary outcomes included SPR by day 14, stone migration rate, and stone migration distance. Between-group comparisons were performed using the Cochran-Mantel-Haenszel test for categorical outcomes and t tests for continuous outcomes. RESULTS: A total of 606 participants were randomly assigned to receive Guang Jing (n = 458) or placebo (n = 148). Their mean (SD) age was 43.0 (12.0) years, 474 (78.2%) were male, and the mean (SD) stone size was 0.6 (0.1) cm. The SPR by day 28 was significantly higher for the Guang Jing group compared with the placebo group (204 of 457 [44.6%] vs 50 of 148 [33.8%]; relative risk, 1.32 [95% CI, 1.03-1.69]; P = .03), with an absolute risk difference of 10.9 (95% CI, 2.0-19.7) percentage points. No significant between-group differences in SPR by day 14 (Guang Jing vs placebo: 133 [29.1%] vs 33 [22.3%]; P = .14) or stone migration distance (mean [SD], 29.5 [51.8] mm vs 29.7 [43.8] mm; P = .11) were observed. Adverse event rates were similar for the Guang Jing and placebo groups (88 [19.3%] vs 27 [18.2%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, treatment with Guang Jing significantly increased the expulsion of 5- to 10-mm ureteral stones by day 28, with a favorable safety profile. These findings suggest that Guang Jing may be an additional medical expulsive therapy option for appropriately selected patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR-IIR-17013275.

Humans↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child↗

PubMed2026

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72 h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72 h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72 h postoperatively, and the cumulative opioid consumption at 24, 48, and 72 h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p > 0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p > 0.05). Cumulative opioid consumption at 24, 48, and 72 h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p > 0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans↗

PubMed2026

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged ≥65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans↗