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PubMed2026

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31 mm (95% CI -0.63 to 0.02; p = 0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2 = 28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43 mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43 mm; 95% CI -0.70 to -0.16; p = 0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans↗

PubMed2026

Treatment of OSA using mandibular advancement versus CPAP in improving cardiovascular health.

BACKGROUND: Obstructive sleep apnea is a significant risk factor for hypertension. We assessed the relative effectiveness of mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) in reducing 24 h ambulatory blood pressure (BP) and other health-related outcomes over 12 months. METHODS: In a randomized, non-inferiority trial, 321 participants with hypertension and increased cardiovascular risk were recruited for polysomnography. Of these, 220 with moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥15 events/hour) were randomized to MAD or CPAP (1:1). We report the final outcomes at the 12-month follow-up. RESULTS: A total of 180 participants (MAD: 89; CPAP: 91) completed the 12-month follow-up. Median usage for MAD and CPAP was 5.5 and 4.9 h per night, respectively. Compared to baseline, the 24 h mean arterial BP at 12 months decreased by 2.3 mmHg (P = 0.200) in the MAD group and by 1.0 mmHg (P = 0.999) in the CPAP group. The difference between-groups was -0.6 mmHg (95% confidence interval: -2.53 to 1.39, non-inferiority P < 0.019). The MAD group demonstrated a larger reduction in asleep BP compared to the CPAP group. The prevalence of excessive daytime sleepiness in the MAD group decreased from 30.3% at baseline to 10.1% at 12-month follow-up (P = 0.001), and from 38.5% to 7.7% in the CPAP group (P < 0.001). The between-group difference was 10.6% (P = 0.097). No significant within-group or between-group differences were observed in the prevalence of arrhythmias and plasma levels of cardiac biomarkers. CONCLUSION: At 12-month, MAD is non-inferior to CPAP for reducing 24 h mean arterial BP in participants with hypertension and increased cardiovascular risk. TRIAL REGISTRATION: NCT04119999.

Humans↗

PubMed2026

Comparative effectiveness of game-based learning modalities in nursing and medical education: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Game-based learning (GBL) is increasingly used in healthcare education, but educators must choose among diverse modalities (e.g., quiz platforms, apps, serious games and metaverse environments). Comparative evidence on which modalities perform best across learning domains (knowledge, attitudes, and practice) remains limited. AIM: To compare the effects of distinct GBL modalities on knowledge, attitudes, and practice outcomes in nursing and medical education and to explore whether comparative effects differ by learner group (pre-licensure students and in-service professionals). DESIGN: PRISMA-NMA-aligned systematic review and Bayesian network meta-analysis. METHODS: We searched eight databases and trial registries through September 2, 2024, for randomized controlled trials comparing GBL with traditional teaching (TT). Outcomes were transformed to a 0-100 scale and analysed as change from baseline in Bayesian consistency models; random-effects models were selected using deviance information criterion (DIC). Risk of bias was assessed using RoB 2. We report mean differences (MDs) with 95% credible intervals (CrIs) versus TT, ranking probabilities, and subgroup NMAs by learner group. RESULTS: Thirty-one RCTs (n = 3439) were included; 15 contributed complete data to the network. Risk of bias was low in 15 trials and raised some concerns in 16. The network was modest for knowledge (11 trials) and sparse for attitudes (3) and practice (4). Compared with TT, metaverse-based learning showed improved attitudes (MD 15; 95% CrI 12 to 18), based on a single trial. For knowledge and practice, Kahoot-based quizzes (MD 9.1; 95% CrI -8.9 to 27) and app-based learning (MD 4.6; 95% CrI -4.4 to 14) had the highest estimated mean improvements, but credible intervals were wide and included the null for most comparisons. Subgroup rankings differed by learner group, but several comparisons were imprecise and uncertainty was substantial, particularly in sparse networks. CONCLUSIONS: GBL modalities may improve learning outcomes compared with TT, but relative effects appear domain-specific and the certainty of rankings is limited by sparse evidence and imprecision. Future trials should prioritise head-to-head comparisons, robust outcome measurement, and longer-term retention and transfer outcomes in both student and in-service populations.

Humans↗

PubMed2026

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 μg immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 μg/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] μg) compared to the bolus group (300 [200-400] μg; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50 mg/day) or metformin (1000 mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL∶HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD = 0.61 (0.02 to 1.21), p = 0.04; metformin: MD = 0.45 (0.07 to 0.83), p = 0.02], with no significant between-group difference in unadjusted analysis (p = 0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (β = -0.324, p = 0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (β = -1.209, p = 0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans↗

PubMed2026

Spatially resolved multi-omics analysis of indigenous Bacillus-fortified high-temperature Daqu.

Layer-dependent patterns associated with indigenous Bacillus fortification on high-temperature Daqu remain unclear. Here, six indigenous functional Bacillus strains were combined to fortify Daqu at three inoculation levels (QH4, QH5, QH6), with non-fortified as the control (CK). Upper, middle, and lower shelf-layer samples were profiled by physicochemical measurements, volatilomics, organic acid analysis, untargeted metabolomics, 16S/ITS amplicon sequencing, and metagenomics. PERMANOVA showed significant effects of treatment, spatial layer, and their interaction on physicochemical, volatile, bacterial, and fungal profiles (P = 0.001). Among the three inoculation levels, QH5 showed the most balanced performance: QH5_M exhibited the highest observed mean peak temperature (63.3 °C; +4.5 °C relative to CK_M), and its group-mean temperature remained ≥ 60 °C for seven consecutive days. Multi-omics analyses indicated coordinated, non-linear, and layer-dependent differences associated with indigenous Bacillus fortification, with QH5_M showing the most pronounced combined thermal, pyrazine, substrate, microbial, and predicted functional profile. These findings indicate that moderate indigenous Bacillus fortification was associated with distinct layer-dependent thermal and flavor profiles and coordinated microbial, metabolic, and predicted functional differences.

Bacillus↗

PubMed2026

Biological characterization of Candida parapsilosis haploids induced by voriconazole.

OBJECTIVES: Candida parapsilosis is an important opportunistic fungal pathogen causing serious human infections in nosocomial settings. It has long been thought that C. parapsilosis has a diploid genome with a high homozygosity between chromosome homologs. METHODS: In this study, we report the discovery of C. parapsilosis haploids induced by voriconazole, a triazole with broad antifungal activity against fungal pathogens, in an experimental evolutionary assay. RESULTS: The haploid strains were able to undergo auto-diploidization under in vitro culture conditions or during systemic infection at a low frequency. Compared to the progenitor diploid strain, C. parapsilosis haploid and auto-diploid strains exhibited a reduced ability of invasive growth and biofilm formation. Global transcriptional expression analysis indicated that haploid and auto-diploid strains had a similar transcriptomic profile, which showed a remarkable difference from the progenitor diploid strain perhaps due to the loss of chromosome heterozygosity. Moreover, the haploid and diploid strains had distinct fungal burdens in different animal tissues, suggesting the haploid state could have a colonization advantage over the diploids in certain tissues such as the brain and spleen. CONCLUSIONS: The discovery of C. parapsilosis haploids not only sheds lights on the biology of this important fungal pathogen, but also provides a tool for genetic modifications for the field.

Voriconazole↗

PubMed2026

Quantitative assessment of the fingerprint evidential value using machine learning.

Fingerprints as physical evidence have long supported criminal investigation and adjudication. In practice, however, fingerprint identification relies mainly on examiners' experience. Furthermore, expert opinions tend to be categorical, even though the opinions with the same conclusion could differ substantially in evidential strength. To quantitatively assess fingerprint evidential value, this study proposes a machine learning-based framework as an interpretable decision-support tool. A lightweight residual one-dimensional convolutional neural network was constructed, incorporating channel recalibration and a similarity-driven attention mechanism to learn adaptive contribution weights for different matched minutiae (minutiae for short). Controlled experiments revealed that the predicted evidential value increased with the number of minutiae and was significantly influenced by the quality of minutiae. With 10 minutiae, the mean predicted scores were 4.49, 7.00, and 9.09 for blurred, moderately blurred, and clear minutiae, respectively. Multiple regression analysis indicated that replacing a pair of blurred minutiae with a pair of clear minutiae increased the score by 0.492, whereas replacing it with a pair of moderately blurred minutiae increased the score by only 0.216. By mapping predicted scores to graded levels of evidential strength, the framework contributes to a paradigm shift from categorical expert opinions to graded ones, helping courts evaluate fingerprint evidence more scientifically.

Humans↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

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

Free polyphenols and multi-omics traits underlying antioxidant variation across Paeonia lactiflora leaf cultivars.

Leaves of Paeonia lactiflora are underutilized by-products with potential as natural antioxidant sources. In this study, 18 cultivars were evaluated for phytochemical composition and in vitro antioxidant capacity. Total phenolic content correlated strongly with DPPH and ABTS activities, and the comprehensive antioxidant index identified 'Coral Charm' and 'Hangshao' as representative high- and low-antioxidant cultivars, respectively. Untargeted metabolomics detected 2677 metabolites and identified 908 differential metabolites between the two cultivars. Targeted phenolic profiling quantified 27 compounds, among which 11 differed significantly between the two cultivars. Catechin and epicatechin were enriched in 'Coral Charm', with contents of 6.62 and 0.397 ng/mg, respectively, compared with 0.012 and 0.002 ng/mg in 'Hangshao'. (+)-Dihydroquercetin was also more abundant in 'Coral Charm', while caffeic acid showed an upward trend. Proteomic analysis identified 423 differentially expressed proteins, mainly associated with secondary metabolite biosynthesis, redox homeostasis, and central carbon metabolism. Integrated analysis identified pyruvate metabolism as the only pathway significantly enriched in both metabolomic and proteomic datasets. Molecular docking predicted favorable binding between representative phenolics and selected proteins. These findings link cultivar-dependent antioxidant variation in peony leaves with free-phenolic accumulation and pathway-level metabolic differences, supporting the selection and utilization of antioxidant-rich peony leaf resources.

Antioxidants↗

PubMed2026

Type, severity, frequency and management of adverse reactions associated with ultrasound contrast agents: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. MATERIALS AND METHODS: A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. RESULTS: Seventy-four studies encompassing > 1 million adults and > 36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (< 1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. CONCLUSION: UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. PROSPERO REGISTRATION: CRD42023432668. KEY POINTS: Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.

Contrast Media↗

PubMed2026

All-inside repair is an effective treatment for medial meniscus posterior root tears: a systematic review and meta-analysis of biomechanical and clinical evidence.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) reproduce the biomechanics of subtotal meniscectomy. Repair is favored, but the role of all-inside repair (AR) remains unclear relative to transtibial pull-out (TP). This study aimed to review the biomechanical and clinical evidence on AR for MMPRTs. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO). MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Outcomes included patient-reported outcome measures (PROMs), magnetic resonance imaging (MRI), and biomechanical performance. When available, random-effects meta-analysis was performed. RESULTS: Thirteen studies were included. AR restored contact mechanics and showed load to failure comparable to TP, with lower stiffness. Meta-analysis showed lower conversion to total knee arthroplasty with AR versus non-repair (RR 0.18, 95% CI 0.05-0.58), and no significant PROM differences between AR and TP. CONCLUSIONS: AR showed favorable biomechanical properties and improved outcomes versus non-repair. Compared with TP, no significant clinical differences were observed. AR may represent a reasonable option in selected scenarios.

Humans↗

PubMed2026

Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate®; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28 ± 8  years; BMI: 23.8 ± 2.9 kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35°C) to induce ~2% body mass loss (BML), then rehydrated over a 1 h period in a laboratory (~21°C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4 h of seated rest (5 h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2 h after beverage consumption), and all urine produced was collected. RESULTS: During the 5 h rehydration period, there was no effect of trial on total urine volume (FRU: 1266 ± 403 mL, SPO: 1338 ± 361 mL, WAT: 1394 ± 360 mL; P = 0.156) or water retention (FRU: 42 ± 12%, SPO: 37 ± 10%, WAT: 35 ± 11%; P = 0.059). The blood glucose area under the curve differed by trial (P < 0.001), with all beverages significantly different from each other (FRU: 10.12 ± 0.72 mmol/L/2h, SPO: 12.48 ± 1.34 mmol/L/2h, WAT: 7.90 ± 0.47 mmol/L/2h; P < 0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1 h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans↗

PubMed2026

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p > 0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p = 0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p = 0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans↗

PubMed2026

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5 mg/mL, with 75 µg of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2 mg/mL, supplemented with 0.5 mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70 mg (52.5-96.3), vs 96 mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

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↗