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PubMed2026

Temporal shifts in gyrA mutation types and sublineage replacement in ST11 Salmonella enterica serovar Enteritidis over a decade (2014-2023): A genomic epidemiological study in Guangxi, China.

The overuse or abuse of antibiotics drives the global health threat of antimicrobial resistance. Although bans on certain veterinary antibiotics, such as colistin, have proven effective, the impact of fluoroquinolone stewardship on the evolution of the foodborne pathogen Salmonella enterica serovar Enteritidis (S. Enteritidis) remains unclear. Here, we conducted a decade-long (2014-2023) retrospective longitudinal genomic epidemiological analysis of 441 ST11 S. Enteritidis isolates from Guangxi, China, alongside a global reference dataset of 4297 genomes. Our aim was to elucidate the effect of real-world antibiotic stewardship on the shift of gyrA point mutations and lineage distribution. Surveillance identified three global epidemic clade sublineages (GEC-L2, L3, L4), with the multidrug-resistant GEC-L4 (i.e., GC-c or MMC2), characterized by the gyrA mutation with amino acid substitution D87Y, being domestically dominant (70.07%, 309/441). Following China's 2016 ban on the veterinary use of critical fluoroquinolones, the proportion of the highly resistant GEC-L4 sublineage decreased continuously (from 86.84% in 2017 to 56.00% in 2023), while the less resistant GEC-L3 sublineage (i.e., GC-b or MMC1), mainly characterized by gyrA D87G, increased simultaneously (from 13.16% to 44.00%). This phenomenon might be attributed to the fact that the GEC-L4 sublineage exhibited a higher fitness cost compared with the GEC-L3 sublineage, as confirmed by the competition assay. A Random Forest Model validated that the gyrA mutation with amino acid substitution D87Y was the paramount feature for these sublineages' identification. In contrast, global data showed a continuous increase in gyrA mutations (from 8.63% in 2006 to 68.85% in 2024), primarily D87Y (from 1.44% to 31.15%) and D87N (from 4.32% to 22.95%), correlating with rising average fluoroquinolone consumption. This study provides direct genomic evidence that national-level antibiotic stewardship can drive the replacement of highly resistant sublineages with moderately resistant ones. These findings offer crucial scientific evidence for evaluating the impact of antibiotic management policies and inform strategies for the rational use of antimicrobials.

China↗

PubMed2026

Efficacy and Safety of Ultra-Low Starting Dose Febuxostat Titration in Male Patients With Primary Gout.

BACKGROUND: Since gout is a common metabolic arthritis caused by urate crystal deposition, urate-lowering therapy (ULT) is clearly indicated, but the initiation of ULT frequently causes paradoxical acute flares that in turn impair patient adherence. OBJECTIVE: This study sought to assess the effectiveness and safety of an ultra-low-dose initiation strategy for febuxostat (10 mg/day) compared to the standard starting dose (20 mg/day) in reducing initiation-related flares while maintaining long-term urate control. METHODS: 120 male patients with primary gout presenting with acute arthritis were randomly assigned to initiate febuxostat at 10 mg/day (Group A) or 20 mg/day (Group B), with protocol-mandated biweekly titration. The primary outcomes were gout flare frequency over 24 weeks (assessed using Poisson regression), serum uric acid (SUA) target attainment, and the incidence of adverse events. RESULTS: Although both groups achieved comparable target SUA levels by week 24, Group A demonstrated a significantly lower overall flare incidence (36.7% vs. 70.0%; p < 0.001), along with a greater percentage of flare-free patients (70.0% vs. 46.7%; p = 0.016). Multivariable Poisson regression revealed that Group B had an approximately twofold higher risk of flares compared to Group A (Incidence Rate Ratio = 1.95; p = 0.012), with obese patients deriving the most pronounced benefit from the ultra-low-dose approach. To avert one additional flare, the calculated number needed to treat was 4.3. Additionally, the occurrence of clinically significant liver injury (ALT/AST > 3× ULN) was low in both groups, with 3.3% in Group A and 1.7% in Group B. Multivariable regression analysis confirmed that LDL-C is an independent predictor of ALT (β = 12.90, p = 0.009), while febuxostat dosage was not linked to hepatotoxicity. CONCLUSION: Initiating febuxostat at a dose of 10 mg/day with gradual titration demonstrates a superior safety profile by effectively reducing early acute flares without compromising long-term urate control, which is particularly advantageous for high-risk cohorts, including obese patients.

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

Outcomes and Associated Prognostic Factors for Orthograde Canal Obturation Using Ortho MTA III: A Randomised Prospective Clinical Trial.

AIM: To prospectively compare treatment outcomes for orthograde canal obturation using Ortho MTA III (OMTA) with the continuous wave of compaction (CWC) using gutta-percha (GP) and AH Plus sealer, and to identify associated predictive factors. METHODOLOGY: Informed consent was obtained (110 patients), and single- or two-rooted permanent teeth (n = 120) diagnosed with pulp necrosis (or previously treated) and asymptomatic apical periodontitis or chronic apical abscess (periapical index, PAI ≥ 3) were randomly assigned to two groups (n = 60/group). The canals were prepared to a minimal apical size #40 (ISO) based on their initial file size, disinfected and obturated by either CWC or OMTA using an enhanced disinfection protocol (GP disinfected, new gloves after each intraoperative radiograph and before starting obturation). Clinical and periapical radiographic examinations were conducted by two calibrated, independent endodontists during follow-up periods of at least 12 months. Success rates and associated predictive factors (tooth-, operator- and patient-related) were analysed statistically using binary and multiple logistic regression (p < 0.05). RESULTS: The median recall period was 30 months (14-48 months), and 104 teeth were finally analysed (recall rate: 86.67%). No significant differences in success rate were observed between the groups (p > 0.05) under both loose (OMTA: 88.24%, CWC: 83.02%) and strict criteria (OMTA: 64.71%, CWC: 58.49%). Multivariate analysis revealed that age (OR = 5.735, 95% CI: 1.286-25.577, p = 0.022), periapical lesion size (OR = 6.596, 95% CI: 1.397-31.138, p = 0.017) and PAI score (OR = 2.081, 95% CI: 1.047-4.136, p = 0.036) were significant predictors of treatment failure. CONCLUSIONS: Orthograde obturation of infected canals with Ortho MTA III demonstrated comparable success and treatment outcomes to those filled with GP and sealer by CWC, supporting its potential as a clinically viable alternative for the obturation of infected root canals. TRIAL REGISTRATION: cris.nih.go.kr registration number: KCT00099939.

Humans↗

PubMed2026

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans↗

PubMed2026

Hydrogen-rich water combined with traditional Chinese medicine compound in the treatment of kidney stones: a randomized controlled prospective clinical trial.

JOURNAL/mgres/04.03/01612956-202701000-00009/figure1/v/2026-09-13T085902Z/r/image-tiff The formation and development of kidney stones are related to abnormal urine metabolism, oxidative stress and inflammation. Hydrogen-rich water has clear efficacy in antioxidant and improving inflammatory status, while Ye-Shi-Shi-Lin-Formula is a clinically effective traditional Chinese medicine compound preparation for treating kidney stones. This randomized controlled prospective clinical trial from July 2025 to March 2026 at the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine examined the effect of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula on kidney stones. The included 100 patients with kidney stones were randomly divided into blank, hydrogen-rich water, hydrogen-rich water and Chinese medicine, and Chinese medicines groups. The patients received drinking hydrogen-rich water and/or Ye-Shi-Shi-Lin-Formula daily for 12 weeks. All subjects received basic treatment following the guidelines. Imaging examination, urine metabolism testing, renal function, inflammation and oxidative stress index, blood routine and liver function are used to detect the efficacy and safety of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula. Results showed that the total effective rate of kidney stone treatment in blank group, Chinese medicines group, hydrogen-rich water and Chinese medicine group and hydrogen-rich water group was 28%, 76%, 80% and 32%. The Ye-Shi-Shi-Lin-Formula can partially alleviate the oxidative stress, uric acid metabolism and urinary magnesium levels of patients with kidney stone and improve the function of renal tubules. The hydrogen-rich water therapy showed only efficacy in improving glutathione reductase but the combination of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula has shown superior efficacy in improving oxidative stress and related metabolic factors of blood uric acid and urine stones, as well as in renal tubular function. The results indicate that the addition of hydrogen-rich water can improve urinary metabolism and oxidative stress status in the treatment of kidney stones with Ye-Shi-Shi-Lin-Formula. The study was registered at the International Traditional Medicine Clinical Trial Registry (Registration No. ITMCTR2025001446).

Humans↗

PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ≥8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p < 0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p < 0.01), and TCM syndrome score (69.23% vs 30.13%, p < 0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

PubMed2026

Efficacy, tolerability, and threshold effect of atropine eye drops for myopia control: A systematic review and dose-response meta-analysis.

Atropine is an emerging therapy for myopia, yet the optimal concentration for prescription remains uncertain. We searched PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Clinical Trials, and ClinicalTrials.gov registry platforms. We included the randomized clinical trials (RCTs) that compared any dose of atropine against a placebo in myopic children. Among 3566 studies assessed, we identified 33 eligible RCTs involving 6301 children aged 4-18 years, with 10 different concentrations and a mean follow-up time of 19.5 ± 12.3 months. A nonlinear relationship was observed between atropine dosage and treatment efficacy (P < 0.001). Compared to placebo groups, the mean differences in reducing annual spherical equivalent refraction progression for atropine concentrations of 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% were 0.21 diopters (D) (95% CI, 0.13-0.28), 0.35 D (95% CI, 0.23-0.46), 0.42 D (95% CI, 0.28-0.56), 0.45 D (95% CI, 0.30-0.60), and 0.46 D (95% CI, 0.32-0.61) respectively For higher concentrations, the estimates were 0.49 D (95% CI, 0.34-0.63) for 0.1% and 0.99 D (95% CI, 0.66-1.31) for 1%, although these were based on fewer and smaller trials. Higher doses of atropine were associated with decreased amplitude of accommodation (P = 0.02), increased pupil diameters (P = 0.01) and a higher frequency of photophobia (P = 0.02). Our findings suggest that the increase in treatment efficacy with higher concentrations may plateau beyond a certain range, and that the current practice of increasing atropine concentrations for children who show inadequate responses to lower doses should be confined to a specific concentration range. This analysis is limited by the number, design heterogeneity, and sample sizes of available trials for higher concentrations, and by the frequent lack of pre-intervention refractive history in included studies. Therefore, estimates-particularly for doses exceeding 0.1%-should be interpreted with caution.

Humans↗

PubMed2026

New Horizons in the Development of Treatments for Substance Use Disorders.

Substance use disorders (SUDs) are a major public health problem in the United States and cause substantial morbidity and mortality. There are meaningful gaps in the available SUD treatment options, and the development of new therapies is urgently needed. While medications with U.S. Food and Drug Administration approval are available for alcohol, nicotine, and opioid use disorders, there are no approved pharmacotherapies for cannabis, cocaine, or methamphetamine use disorders. Behavioral treatments for SUDs have significant limitations in effectiveness and accessibility, and there is a need for the development of both new behavioral treatment options and new models of treatment delivery. The next generation of treatments for SUDs will likely come from a diverse set of interventions, including new drug classes, new technologies, and new methods of delivery.

Humans↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans↗

PubMed2026

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

Humans↗

PubMed2026

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (≤1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: ≤1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: ≥2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while ≤1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans↗

PubMed2026

Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

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

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points • Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. • A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR ≥ 0.8) showing a relatively lower risk. • Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

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

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

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗