SEARCH · Search PubMed

Results for “Fixation method”

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.

1,331 records · Page 10Linked to original sources

PubMed2026

Esketamine vs. sufentanil for quality of recovery after outpatient gynecological surgery: a randomized clinical trial.

BACKGROUND: Perioperative administration of esketamine has been reported to improve early quality of recovery (QoR). However, data on its effects in outpatient surgery are limited. This study aimed to assess the impact of esketamine on QoR in patients undergoing outpatient gynecological procedures. METHODS: In this investigator-initiated, double-blind, randomized clinical trial, patients aged 18-65 years scheduled for outpatient gynecological surgery under sedation were allocated to receive esketamine (0.2 mg/kg) or sufentanil (0.1 μg/kg) combined with propofol (1.5-3 mg/kg). The primary outcome was quality of recovery on postoperative day (POD) 1. Secondary outcomes included quality of recovery on POD2, sedation success rate, length of post-anesthesia care unit (PACU) stay, injection pain, postoperative pain, nausea and vomiting, fatigue, patient and clinician satisfaction, sleep quality, and anxiety and depression. RESULTS: A total of 126 patients were randomized, with 63 assigned to the esketamine group and 63 to the sufentanil group. Of these, 125 patients were included in the final analysis (62 in the esketamine group and 63 in the sufentanil group), as one patient lacked follow-up data. The mean (SD) QoR-15 score on POD1 was 137.9 (14.5) in the esketamine group and 137.8 (10.7) in the sufentanil group, with no significant difference between groups (absolute difference, 0.2; 95% CI, -4.2 to 4.6; p = 0.93). For secondary outcomes, the esketamine group had a longer PACU stay (median, 28.0 vs. 23.0 min; p < 0.001), a lower incidence of severe injection pain (22.6% vs. 50.8%; p = 0.002), a higher proportion of patients with pain scores ≥ 4 at 30 min postoperatively (30.6% vs. 6.3%; p = 0.001), and higher fatigue scores (median, 3.0 vs. 2.0; p = 0.01). Other secondary outcomes did not differ significantly between groups. CONCLUSION: Among patients undergoing sedation for outpatient gynecological procedures, esketamine did not significantly improve quality of recovery on POD1 compared to sufentanil. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2500098466.

Humans↗

PubMed2026

Perioperative analgesic efficacy of ultrasound-guided erector spinae plane block and posterior transversus abdominis plane block in paediatric patients undergoing open pyeloplasty: A prospective randomised trial.

PURPOSE: Open pyeloplasty in the paediatric population involves extensive tissue dissection and manipulation, resulting in significant postoperative pain. Ultrasound-guided fascial plane blocks have emerged as an important component of multimodal analgesia in abdominal surgeries. This study compared the analgesic efficacy of ultrasound-guided Erector spinae plane block (ESP) and posterior transversus abdominis plane (pTAP) block in children undergoing open pyeloplasty. METHODS: It is a prospective, randomised, double-blind study conducted at a single paediatric centre in a tertiary care hospital in Asia from January 2022 to June 2023. 40 ASA I-II children were randomised to receive either the ESP block (Group E) or the pTAP block (Group T). Both groups received 0.4 ml/kg, 0.2% ropivacaine with 1 mcg/kg dexmedetomidine. Children with an allergy to local anaesthetics, cardiac, renal or hepatic dysfunction and local site infection were excluded. The primary outcome was cumulative 24 h postoperative acetaminophen consumption. Secondary outcomes included the effects on intraoperative hemodynamics, perioperative opioid consumption, FLACC and Watcha scores, time to first rescue analgesia, and any block-related complications. RESULTS: Weight-normalised 24 h postoperative acetaminophen consumption was significantly lower in the ESP group (13.5 ± 4.7 mg/kg) compared to the pTAP group (25.4 ± 8.3 mg/kg), with a mean difference of -12 mg/kg (p < 0.001, 95%CI -16 to -7.6). The median time to first rescue analgesia was significantly longer in the ESP group (18 h [95% CI, 18-24]) than in the TAP group (9 h [95% CI, 6-12]), p < 0.001. Although FLACC scores were significantly lower in the ESP group at 30 min and 12 h postoperatively, the overall longitudinal analysis using a linear mixed-effects model showed no significant difference in the trend of FLACC scores over time between the two groups. There were no block-related complications. CONCLUSION: Ultrasound-guided ESPB provides better, longer-lasting analgesia than posterior TAP block in children undergoing open pyeloplasty. Hence, it may serve as an effective component of multimodal pain management in paediatric open pyeloplasty. CTRI REGISTRATION (CTRI/2022/04/041876) DATED 13/04/2022): https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=67747&EncHid=42257.14515&modid=1&compid=19.

Humans↗

PubMed2026

Effect of Local Anesthetic Solution at Different Temperatures for Epidural Labor Analgesia on Intrapartum Fever: A Randomized Clinical Trial.

BACKGROUND: Whether heating local anesthetic solutions to core body temperature (37°C) for epidural labor analgesia reduces intrapartum fever incidence remains undefined in the current literature. METHODS: This double-blind randomized controlled trial (RCT) enrolled 220 nulliparous parturients (18-35 years, American Society of Anesthesiologists [ASA] physical status II, term singleton pregnancy). Participants were randomized to receive epidural labor analgesia with 0.075% ropivacaine + 0.5 µg/mL sufentanil at 37°C (warmed group) or 22°C (room-temperature group). Epidurals were placed at L3-L4 with a test dose of 3 mL of 1.5% lidocaine at room temperature, followed by programmed bolus epidural analgesia (initial 10 mL, 10 mL/h) and patient-controlled epidural analgesia (PCEA) 5 mL (30-minute lockout). Tympanic temperature was measured every 30 minutes from epidural initiation to delivery, defining intrapartum fever as ≥38°C. The primary outcome was fever incidence, on which the power analysis was based, and also maximum temperature and shivering. Secondary outcomes comprised analgesia onset, block level, labor durations, neonatal Apgar scores, umbilical cord blood pH and BE, and maternal adverse events. RESULTS: A total of 220 parturients were included (warmed group, n = 110; room-temperature group, n = 110). The warmed group had a lower intrapartum fever incidence (15.5% [17/110] vs 30.9% [34/110], relative risk [RR] 0.5 [95% confidence interval {CI}, 0.298-0.840]; P = .007); however, the reduction of 49.8% did not reach the preset clinically meaningful difference of 60% reduction proposed in the power analysis. The maximum body temperature was also lower in the warmed group: median (interquartile range [IQR]) 37.4 (IQR, 37.2-37.7) °C vs 37.6 (IQR, 37.3-38.0) °C, median difference -0.2 (95% CI, -0.3 to -0.1) °C ( P = .006). Shivering incidence was not different between groups (10.9% [12/110] vs 14.5% [16/110]; P = .418). No statistically significant differences were observed between groups in any of the secondary outcomes assessed, including block characteristics, local anesthetic consumption, labor duration, neonatal outcomes, and maternal adverse events. CONCLUSION: Although we found a 50% reduction in the incidence of temperature rise using warmed (37°C) local anesthetics for epidural labor analgesia, this did not reach our preset threshold of 60% reduction.

Humans↗

PubMed2026

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, χ²(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

Humans↗

PubMed2026

HSK21542 for Postoperative Analgesia in Gynecological Surgery: A Pooled Post-Hoc Analysis of Two Phase III Randomized Controlled Trials.

BACKGROUND: Effective postoperative pain management in gynecological surgery is challenging because of complex visceral-somatic pain interactions and the adverse effects of conventional analgesics. HSK21542, a novel peripherally restricted kappa-opioid receptor (KOR) agonist that selectively targets visceral pain pathways enriched with KORs, may provide adequate analgesia without systemic adverse events. METHODS: We conducted a pooled post-hoc analysis of data from two phase III, multicenter, triple-blinded, randomized controlled trials (Study 301, HSK21542 vs placebo; Study 303, HSK21542 vs tramadol vs placebo). Eligible patients undergoing elective gynecological surgery were included. The primary outcome was the summed pain-intensity difference over 12 and 24 hours (SPID 12h and SPID 24h ). Secondary outcomes were pain-relief quality (proportion of patients relieved from severe pain with a pain numerical rating score ≤ 3 between 0 and 24 hours) and rescue-analgesic requirements (number of doses and time to first rescue analgesic). Adverse events were also assessed. RESULTS: A total of 370 patients were analyzed: 150 received HSK21542, 139 received a placebo, and 81 received tramadol. After inverse probability of treatment weighting (IPTW) adjustment, baseline characteristics were well-balanced across treatment groups (all standardized mean differences [SMD] <0.1; see Table 1 for 95% CIs). HSK21542 produced greater reductions in pain intensity over 12 and 24 hours than placebo (least-squares mean differences -8.1 and -16.3 for SPID 12h and SPID 24h , respectively. Both P < .001) and no statistically significant difference was observed between HSK21542 and tramadol ( P > .05). Significantly more patients in the HSK21542 group were relieved from severe pain at 0 to 12 hours (92.7% vs 82.7%, P < .001) and required fewer rescue doses at 0 to 12 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) and 0 to 24 hours (0.00 [IQR 0.00-1.00] vs 1.00 [IQR 0.00-2.00], P < .001) than those in the placebo group, whereas no significant differences with tramadol both in 0 to 12 and 0 to 24 hours. HSK21542 was also associated with significantly lower incidences of nausea (24.7% vs 66.7%) and vomiting (21.3% vs 60.5%) than tramadol. Only one case of dizziness occurred in the tramadol group. CONCLUSIONS: HSK21542 could provide adequate postoperative analgesia with few adverse events in patients undergoing gynecological surgery.

Humans↗

PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans↗

PubMed2026

Magnesium administration for vasospasm prevention in acute aneurysmal SAH: a multicenter randomized controlled trial.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality, with cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) being the primary contributors to poor outcomes. Magnesium sulfate (MgSO₄) has demonstrated neuroprotective and vasodilatory properties in preclinical models. This study aimed to evaluate the effect of targeted serum magnesium (Mg) maintenance on CV and exploratory clinical outcomes following aSAH. We conducted a prospective, multicenter, single-blind RCT across four neurocritical care units in Korea between 2019 and 2024. A total of 121 aSAH patients were randomized to receive either IV MgSO₄or placebo within six hours of admission. Mg was infused to maintain serum concentrations between 2.0 and 3.0 mg/dL for 14 days. The primary outcome was incidence of CV assessed by transcranial doppler. Secondary outcomes included DCI, ICU and hospital length of stay, modified rankin scale (mRS) at 30 days. There was no significant difference in overall CV incidence; however, the Mg group demonstrated significantly lower mean flow velocity and Lindegaard ratio on days 4-9, indicating reduced vasospasm severity. In exploratory multivariable analyses, a median serum Mg concentration > 2.5 mg/dL during the first 14 hospital days was independently associated with lower risks of CV and DCI. No significant differences were found in mRS scores, ICU and hospital stay, or serious adverse events between groups. Early targeted Mg administration improved TCD-derived hemodynamic markers during the peak vasospasm window; however, it did not significantly reduce CV incidence, DCI, ICU or hospital stay, or 30-day functional outcome.

Humans↗

PubMed2026

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1∶1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80±15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56±3.44) mmHg in the tafluprost/timolol group and (5.36±2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of≥15%,≥25%, and≥30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

Humans↗

PubMed2026

Specialized pro-resolving mediator (SPM)-enriched supplementation modulates inflammatory biomarkers in patients with symptomatic knee osteoarthritis: Blood plasma analysis from the GAUDI study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and functional impairment, associated with persistent inflammation, potentially due to impaired resolution. Specialized pro-resolving lipid mediators (SPMs) regulate inflammation resolution and restore homeostasis. The GAUDI study previously demonstrated that SPM supplementation reduces pain and improves quality of life (QoL) in patients with knee OA. This analysis assesses the impact of SPM supplementation on inflammatory biomarkers (IB) and SPM levels and their relationship with clinical outcomes. METHODS: This is a secondary analysis of the GAUDI trial, a randomized, multicenter, double-blind, placebo-controlled study conducted in Spain in adults with symptomatic knee OA who received daily supplementation with SPMs or placebo for 12 weeks. Endpoints included changes in plasma IB and SPM levels and their correlation with clinical outcomes. RESULTS: Changes in IL-1 (15.9 vs. -1.1 pg/ml, p-value: 0.051) and IL-18 (10.3 vs. -1.4 pg/ml, p-value: 0.29) showed a tendency toward reduction in the SPM group compared to the placebo group. Changes in IL-1 and IL-8 positively correlated (r = 0.707, p-value: 0.005 and r = 0.551, p-value: 0.04; respectively) with changes in WOMAC score and negatively correlated (r = -0.797, p-value <0.001 and r = -0.804, p-value <0.001; respectively) with changes in EuroQoL-5 VAS score. Changes in IL-1 (r = 0.554, p-value: 0.048) and IL-6 (r = 0.631, p-value: 0.014 and r = 0.572, p-value: 0.031) correlated with changes in OMERACT-OARSI pain score. No significant differences in IB levels were observed between groups during the intervention. Minor changes in SPM levels point to metabolic pathways at work with SPM supplementation. In patients with a BMI ≥25 kg/m², most IB tended to decrease following SPM consumption. CONCLUSIONS: This analysis suggests a potential association between SPM supplementation, decreased inflammation, and improved pain and QoL in patients with knee OA. Subtle changes in blood plasma SPM levels were detected that indicate, through bioinformatics analysis, a pathway-specific metabolome activation induced by SPM supplementation. TRIAL REGISTRATION: NCT05633849. Registered December 1st, 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Humans↗

PubMed2026

Effects of Lactiplantibacillus plantarum KABP051 Probiotic on Body Composition, Microbiome and Mood in Healthy Overweight Adults.

Obesity and mental health disorders are among the greatest public health challenges of the 21st century. Interestingly, an altered microbiome profile has been associated with both conditions. The aim of this randomized, double-blind, placebo-controlled clinical trial was to evaluate the effects of dietary supplementation with a specific probiotic strain (Lactiplantibacillus plantarum KABP051) on body composition and gut microbiome balance, together with measures of mood state, in a population of healthy overweight subjects. Sixty healthy, moderately stressed, nondepressed and overweight or obese volunteers were supplemented for 12 weeks with probiotic (L. plantarum KABP051; 1 billion colony forming units/day) or placebo (microcrystalline cellulose). The KABP051 group experienced significantly greater improvements compared with placebo on body composition measurements, including a reduction in body weight and waist circumference, which decreased in 1.97 ± 0.77 (mean ± SE) kg and 2.15 ± 0.81 (mean ± SE) cm versus placebo at the end of the intervention (both P < .05, mixed model for repeated measures [MMRM] and post-hoc analysis). Microbiome composition improved in KABP051 group, with significant increase in the relative abundance of Lactiplantibacillus spp. versus placebo. Body fat percentage, profile of mood states fatigue, and confusion sub-scores showed a global trend toward improvement compared with placebo, with the change at 12 weeks being significant in the three measurements in post-hoc analysis (P = .015, P = .014, and P = .016, respectively). No serious adverse events were registered during the intervention period. These results suggest that a specific strain of probiotic bacteria (L. plantarum KABP051) may have both metabolic and psychobiotic effects and may be beneficial for enhancing weight loss and body composition, improving energy (less fatigue) and mood levels while embarking on a healthy lifestyle regimen. ClinicalTrials.gov identifier: NCT06808061.

Humans↗

PubMed2026

Muscle Massage Adding Capacitive Resistive Electric Transfer Therapy in Active or Sham Condition for Post-Exercise Recovery in Athletes: A Crossover Clinical Trial.

The increasing demands of elite sports reduce recovery time, impair performance, and increase injury risk. Efficient lactate transport is essential for postexercise recovery. Capacitive resistive electric transfer (CRET) therapy enhances deep tissue heating, induces vasodilation, and promotes circulation. To evaluate whether adding active CRET to a standardized muscle recovery massage, compared with the same massage plus sham CRET, influences indicators of muscle recovery following a maximal anaerobic effort test. A randomized, single-blind, sham-controlled, and crossover clinical trial was conducted in 25 athletes. Participants completed four visits and, after the maximal power and anaerobic capacity test (Wingate test), received a standardized muscle recovery massage combined with either active CRET or sham CRET. Blood lactate levels, muscle oxygenation, muscle thickness, echogenicity, knee extension force, and muscle activity were assessed before and after the test, after treatment, and 24 hours later. Compared with massage plus sham CRET, massage plus active CRET was associated with lower blood lactate concentration at 60 min postexercise (p = 0.029). Ultrasound-derived muscle thickness and echogenicity also differed between conditions at several time points (p < 0.05). However, no significant differences were observed in Wingate test performance, force, muscle activity, and oxygenation between conditions. In athletes performing repeated Wingate exercise, adding active CRET to massage was associated with lower blood lactate concentration at 60 min postexercise and with differences in ultrasound-derived muscle thickness and echogenicity compared with sham CRET plus massage. However, these between-condition differences were not accompanied by clear short-term functional recovery benefits. TRIAL REGISTRATION: NCT06906146.

Humans↗

PubMed2026

Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19.

INTRODUCTION: Endothelial dysfunction is key in COVID-19 pathogenesis. This randomized, double-blind phase IIb trial investigated continuous intravenous infusion of defibrotide in patients hospitalized with SARS-CoV-2 infection and respiratory failure. METHODS: One-hundred and fifty patients were randomized (2:1) to defibrotide or placebo, stratified by disease severity (WHO COVID-19 severity scale 4/5 vs. 6). The primary endpoint was clinical improvement time (days from first improvement through Day 30). RESULTS: Median clinical improvement time was not significantly different with defibrotide versus placebo (15.0 [IQR: 0-24] vs. 20.0 [IQR: 9-25] days; p = 0.10). Day-30 (23.0% vs. 22.0%) and Day-60 (26.0% vs. 22.0%) mortality, reduction in mean fraction of inspired oxygen during treatment, and median duration of hospitalization did not differ with defibrotide versus placebo. Defibrotide demonstrated favorable safety, with no differences versus placebo in serious adverse events (34.0% vs. 36.0%), hypotension (16.0% vs. 12.0%), or hemorrhage (13.0% vs. 8.0%). Exploratory pre-specified biomarker analyses showed greater early d-dimer reduction and lymphocyte recovery with defibrotide, although these results require validation. CONCLUSION: Continuous intravenous infusion of defibrotide was safe but did not improve clinical outcomes in severe COVID-19. Further analyses will explore mechanistic actions and pharmacokinetics of defibrotide and the pathophysiology of endothelial dysfunction in COVID-19. TRIAL REGISTRATION: EudraCT identifier: 2020-001409-21. CLINICALTRIALS: gov identifier: NCT04348383.

Adult↗

PubMed2026

Effects of acute inflammatory challenge on anhedonia and social reward processing: A randomized controlled trial of endotoxin.

Anhedonia is a core feature of depression that reflects reward system dysfunction. Acute inflammatory challenge has been shown to induce transient anhedonia and reward processing deficits, but its effects on distinct components of social reward processes remain poorly understood. This randomized, double-blind, placebo-controlled study evaluated anhedonia and social reward responsivity following acute inflammatory challenge. Low-dose endotoxin (0.8 ng/kg body weight; n = 18) or placebo (same volume of 0.9% saline; n = 22) was administered to female adults (ages 25-44). Anhedonia (Snaith-Hamilton Pleasure Questionnaire) and blood samples for cytokine assessment were collected pre-infusion and 2 and 4 h post-infusion. Social reward motivation (wanting to engage in a social task) was assessed at a baseline eligibility visit and 2 h post-infusion. Sensitivity to positive social cues (attentional bias toward and recognition of happy faces) was assessed pre-infusion and 2 h post-infusion. Results showed that endotoxin increased anhedonic symptoms (p = .005) and decreased social motivation by 2 h post-infusion (p = .001); within the endotoxin condition, changes in both outcomes were associated with increases in TNF-α (p's < .04). A significant condition-by-time interaction for happy-face recognition (p = .011) was driven by increased accuracy in the placebo (p = .04) but not endotoxin (p = .43) condition. Endotoxin administration did not affect attentional bias toward happy faces. Findings suggest that acute inflammatory challenge induces anhedonia and reduces social motivation, with more limited effects on sensitivity to positive social cues, highlighting specific reward-related pathways through which immune activation may contribute to inflammation-associated depression. Future work could examine whether immune-related changes in social motivation contribute to motivational deficits in depression.

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

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

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2026

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale ≥3.0, n = 12) and controls (n = 10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p = 0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p < 0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p < 0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans↗