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PubMed2026

Clinical Outcomes and Patient Experiences With Celiprolol Therapy in Vascular Ehlers-Danlos Syndrome: The First Non-European Cohort.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder caused by heterozygous pathogenic variants in COL3A1. European studies have shown that celiprolol may reduce the risk of life-threatening vascular events, but outcomes in non-European populations and the therapy's psychological impact remain unclear. We conducted a retrospective cohort study of individuals aged ≥ 20 years with genetically confirmed vEDS in a single referral center in Japan between 2000 and 2024. Clinical, molecular, and treatment data were obtained from medical records, and semi-structured interviews were conducted with a subset of participants to assess patient experiences. Twenty-six patients were included. The mean age at celiprolol initiation was 36.9 years, with a mean follow-up of 96.6 months. All patients received celiprolol, and 61.5% reached the target dose (400 mg/day). One patient died of hepatic artery rupture; vascular events occurred in 11, while 14 remained event-free. No significant associations were observed between vascular event occurrence and genotype or celiprolol dose. Interviews with 11 patients revealed that celiprolol use provided emotional reassurance and promoted a more proactive approach to disease management. Celiprolol therapy may reduce fatal vascular events in vEDS and have a positive psychological impact, though nonfatal vascular complications remain frequent.

Humans↗

PubMed2026

Diagnostic performance of intraoperative in vivo hyperspectral imaging for meningioma grading and molecular alterations: results from a prospective feasibility study.

OBJECTIVE: Hyperspectral imaging (HSI) is an emerging intraoperative, noninvasive, contrast agent-free imaging modality that enables quantitative assessment of tissue composition. The present study aimed to investigate whether HSI-derived tissue parameters correlate with WHO grade and molecular markers of aggressiveness in cranial meningiomas. METHODS: In this prospective study, intraoperative in vivo HSI was performed using the TIVITA tissue system, capturing spectral signatures between 500 and 1000 nm. Quantitative tissue parameters included tissue oxygen saturation (StO2), near-infrared perfusion index, organ hemoglobin index (OHI), and tissue water index (TWI). HSI parameters were correlated with histopathological WHO grade and molecular alterations, including CDKN2A/B deletion, TERT promoter mutation, and 1p/22q loss. Group differences were analyzed using one-way ANOVA, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Forty-six meningiomas were included, comprising WHO grade 1 (n = 35) and WHO grade 2-3 (n = 11) tumors. TWI was significantly higher in WHO grade 2-3 meningiomas compared with WHO grade 1 tumors (mean 0.49 [SD 0.12] vs 0.38 [SD 0.17], p = 0.048). ROC analysis demonstrated an area under the ROC curve (AUC) of 0.71 (95% CI 0.56-0.86, p = 0.036) for TWI in discriminating higher-grade disease. A TWI cutoff ≥ 0.367 identified all WHO grade 2-3 meningiomas with 100% sensitivity and 100% negative predictive value. In a molecular subgroup (n = 15), OHI appeared higher in tumors with homozygous CDKN2A/B deletion than in nondeleted tumors (mean 0.77 [SD 0.04] vs 0.62 [SD 0.10]). However, only 3 CDKN2A/B-deleted cases were available, and these findings should be considered descriptive. ROC analysis yielded an AUC of 0.89 (95% CI 0.71-1.00). An OHI cutoff ≥ 0.712 identified all three CDKN2A/B-deleted tumors (100% sensitivity), with 83.3% specificity and 86.7% accuracy. CONCLUSIONS: The present investigation demonstrated that HSI-derived tissue water and hemoglobin metrics provide biologically meaningful information in meningiomas. Low tissue water content appeared to rule out higher-grade diseases in this first subset cohort, while elevated hemoglobin showed a potential association with CDKN2A/B deletion in a small exploratory subgroup. These findings support the potential of HSI as a real-time noninvasive tool for intraoperative risk stratification and should be evaluated in large-scale studies. German Clinical Trials Register no. DRKS00036771 (www.drks.de).

Humans↗

PubMed2026

Divergent evolutionary strategies in spider venoms: A comparative proteomic profiling of four sympatric species from Yunnan.

Spider venoms comprise complex cocktails of bioactive molecules evolved for predation and defense, representing a valuable resource for biological research and pharmaceutical discovery. In this study, we performed a systematic analysis of venom gland extracts from four common spider species indigenous to Yunnan, China: Agelena limbata, Hippasa lycosina, Lycosa grahami, and Sinopoda pengi. Using an integrated transcriptomic and proteomic targeted profiling approach, we successfully annotated 141 distinct toxins. Comparative analysis revealed significant interspecific heterogeneity, suggesting distinct evolutionary trajectories and "weapon system economics." Both A. limbata and L. grahami exhibited a "peptide-dominant" profile anchored by neurotoxic peptides and isomerases, optimized for rapid chemical paralysis. In contrast, S. pengi displayed a distinct "protein-dominant" signature enriched with high-molecular-weight enzymes and CAP superfamily proteins, likely functioning to facilitate tissue degradation and toxin diffusion. Occupying an intermediate position, H. lycosina demonstrated a hybrid composition. These findings suggest that although these species share the same geographical range, their venom systems have undergone divergent evolutionary adaptations driven by specific ecological niches and hunting strategies. This study represents the first systematic proteomic characterization of these venom components, providing a valuable reservoir of molecular candidates while highlighting the bioinformatic nuances of analyzing whole-gland homogenates.

Animals↗

PubMed2026

Fourteen-Day Amoxicillin- or Tetracycline-Containing Bismuth Quadruple Therapy versus 14-Day Metronidazole-Based Triple Therapy as the Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial.

BACKGROUND/AIMS: Combination therapy comprising a proton pump inhibitor (PPI), amoxicillin, and metronidazole (PAM) is used to treat clarithromycin-resistant Helicobacter pylori in the Republic of Korea, but eradication rates are decreasing due to an increasing incidence of clarithromycin resistance. We compared PAM, bismuth compounds plus PAM (PAM-B), and the combination of PPI, bismuth compounds, metronidazole, and tetracycline (PBMT) to determine whether PAM-B can achieve an eradication rate higher than that of PAM and comparable to that of PBMT. METHODS: This prospective multicenter study enrolled patients with clarithromycin-resistant H. pylori infections in the Busan and Gyeongsangnam-do of the Republic of Korea between December 2022 and February 2024. RESULTS: In the intention-to-treat (ITT) analysis, the eradication rate was significantly lower in the PAM group (68.2%) than in the PAM-B group (84.8%, p=0.024), whereas the difference from the PBMT group (81.8%) was not significant (p=0.070). The rate remained lowest in the PAM group (75.4%) in the per-protocol (PP) analysis (PAM-B, 96.5%, p=0.001; PBMT, 94.6%, p=0.004). Eradication rates were comparable between the PAM-B and PBMT groups in both the ITT (p=0.640) and PP analyses (p=0.633). Nausea and vomiting were significantly less frequent in the PAM-B group than in the PBMT group (6.8% vs 25.0%; p=0.007). Severe adverse events were rare, and all symptoms resolved after treatment discontinuation. CONCLUSIONS: PAM-B yielded eradication rates higher than those of PAM and comparable to those of PBMT, with no significant increase in the incidence of adverse events, suggesting the potential of PAM-B as a first-line treatment for clarithromycin-resistant H. pylori infection. Further large-scale studies are needed to validate these results. Registered retrospectively with the Clinical Research Information Service (CRIS; KCT0012265).

Humans↗

PubMed2026

Adherence and efficacy of the 0 - 7 - 21-day versus the 0 - 1 - 6-month hepatitis B vaccination schedules among people who use drugs: a two-year randomized controlled trial.

BACKGROUND: To compare the adherence and efficacy between the 0 - 7 - 21-day and the 0 - 1 - 6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20 µg per-dose vaccine was used. HBV surface antibody (anti-HBs), surface antigen, and core antibody were tested at months 7, 15, and 22 after the first dose. RESULTS: Third-dose coverage was significantly higher in the 0 - 7 - 21-day group (74.40%) than in the 0 - 1 - 6-month group (51.58%, p < 0.001), mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0 - 1 - 6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0 - 7 - 21-day schedule (74.23%, 49.40%, and 40.95%; all p < 0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p = 0.018). CONCLUSIONS: The 0 - 7 - 21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900022403).

Humans↗

PubMed2026

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-α-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage↗

PubMed2026

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals↗

PubMed2026

PdIr bimetallic nanozyme engineered metal-organic frameworks integrated dual-mode sensor toward Stx2 detection in food.

Shiga toxin II (Stx2) has attracted extensive attention due to its toxicity and pathogenicity, making the development of sensitive detection methods urgent. This study constructed a dual-mode sensing platform for the sensitive detection of Stx2 in food. Composite material UIO-66@PdIr with peroxidase-like activity and fluorescent properties was synthesized and combined with cDNA as the signal probe, while aptamer-modified magnetic beads served as the capture probe. Specific binding of Stx2 to the aptamer triggered the release of the signal probe, enabling colorimetric and fluorescence signal readout. The colorimetric mode showed a linear range of 0.05-100 ng/mL with an LOD of 0.039 ng/mL, and the fluorescence mode exhibited 0.01-1000 ng/mL with an LOD of 0.0097 ng/mL. Additionally, this method was successfully applied to the detection of Stx2 in food, and the recovery rates were 94.33% ∼ 102.20%. It indicated that the constructed sensor holds great practical potential for Stx2 detection.

Food Contamination↗

PubMed2026

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged ≥21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for ≥60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10·0 months (IQR 4·6-17·2); median follow-up for progression-free survival was 11·0 months (IQR 4·8-18·4) for STRIDE plus lenvatinib plus TACE and 8·3 months (4·1-15·5) for TACE. Median progression-free survival was 13·0 months (95% CI 12·2-16·7) for STRIDE plus lenvatinib plus TACE versus 9·8 months (8·0-11·4) for TACE (HR 0·70 [95% CI 0·57-0·86]; p=0·0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24·6 months (IQR 16·5-31·5) for STRIDE plus lenvatinib plus TACE and 22·9 months (14·9-30·2) for TACE, median overall survival was 39·5 months (95% CI 34·1-not reached) for STRIDE plus lenvatinib plus TACE and 34·7 months (28·8-not reached) for TACE (HR 0·84 [95% CI 0·65-1·09]; p=0·18). At this data cutoff, median progression-free survival was 12·9 months (95% CI 10·2-15·9) for STRIDE plus TACE and 8·1 months (6·5-10·2) for the first 175 participants randomised to TACE (HR 0·71 [95% CI 0·56-0·91]), with median follow-up of 10·3 months (IQR 4·6-23·7) for STRIDE plus TACE and 7·7 months (3·0-18·5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult↗

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

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans↗

PubMed2026

Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.

Central nervous system (CNS) injuries are the leading cause of permanent disability and premature death in adults worldwide, with their incidence continuing to rise amid social development. These injuries not only severely impair the quality of life but also impose a heavy burden on the global public health system. Current clinical interventions, such as decompression and thrombolysis, can alleviate primary injury but fail to effectively reverse the secondary neuroinflammatory damage. Traditional anti-inflammatory therapies, which cannot block the upstream source of the inflammatory cascade, have led to repeated failures in global clinical translation research over the past decades. Gasdermins were first characterized in studies of systemic inflammatory diseases. These proteins form transmembrane pores to drive the release of proinflammatory factors and inflammatory cell death, serving as key mediators of host innate immunity. Recent studies have revealed that gasdermins play critical roles in regulating the initiation and amplification of neuroinflammation following CNS injury. To clarify the therapeutic potential of gasdermins as targets for injury repair, this review systematically summarizes the structure and function of gasdermins, as well as their cell-specific activation and regulatory mechanisms. We further elaborate on their pathological roles in these injuries and the corresponding therapeutic strategies, aiming to provide a theoretical reference for basic research and clinical translation in this field.

Humans↗

PubMed2026

Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard®) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n = 53) or an untreated control group (n = 51). Clinical evaluations were performed on Days 0, 15 (±2), 30 (±2), and 45 (±2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p < .001), with large effect sizes at the final visit for all outcomes (r = 0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals↗

PubMed2026

Pharmacokinetics of injectable favipiravir: phase I, randomized, double-blind, placebo-controlled study in healthy East Asian subjects.

Favipiravir, an oral antiviral medication, has been approved in Japan for the treatment of patients with novel or re-emerging influenza and severe fever with thrombocytopenia syndrome (SFTS). Randomized, double-blind, placebo-controlled trials were conducted in an East Asian population to characterize the pharmacokinetics and tolerability of an injectable favipiravir formulation. In the single-ascending dose trial, subjects received a single intravenous (IV) dose of 300-2,400 mg of favipiravir. In the multiple dose trial, 1,800 mg was administered twice daily on the first day, followed by 800 mg twice daily for the subsequent 10 days, which is the approved tablet dose for SFTS in Japan. This multiple-dose trial was divided into a cohort receiving intravenous administration throughout the treatment period (IV cohort) and a cohort switching to oral administration from Day 6 (Switching cohort). After a single administration of ≤2,400 mg, the pharmacokinetic parameters increased in a dose-dependent manner but showed slight deviation from linearity. The geometric mean maximum plasma concentration following a single 2,400 mg dose was 126 (range: 110 to 138) μg/mL. In the IV cohort, the trough (at 12 h post-dose) plasma concentrations were maintained at approximately 85 μg/mL after Day 2. These concentrations were approximately 20% higher than those achieved with the same oral doses. In the Switching cohort, these concentrations were maintained throughout the treatment. No serious adverse events were observed. These findings support advancing injectable favipiravir into clinical evaluation.CLINICAL TRIALSThis study is registered with the Japan Registry of Clinical Trials as jRCT2071210042 and jRCT2071210126.

Humans↗

PubMed2026

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24 mg single dose; MAD: 12 mg once daily (QD) for 7 days in healthy subjects) and phase IIa studies (0.75 to 6 mg once or twice daily for 4 weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24 h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5 h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12 h post-administration, with FEV1 peaking at approximately 2 h post-dose and returning to baseline levels by 12 h, which supports a twice-daily dosing regimen for the future, and peak FEV₁ improvements ranging from 186 to 272 ml across dose groups after 4 weeks of treatment. Moreover, twice-daily 3 and 6 mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult↗

PubMed2025

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans↗

PubMed2026

Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged ≥ 18 years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n = 42 VH, and n = 71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p = 0.04). VANH was associated with a significantly shorter operative time (median 55 min versus 65 min; p = 0.005), less blood loss (median 50 mL vs. 150 mL; p < 0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p = 0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p < 0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p = 0.34), readmission (VH 4.8% vs. VANH 8.5%; p = 0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans↗

PubMed2026

Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.

To evaluate the efficacy and safety of the flexible ureteroscopy (fURS) with a flexible and negative suction ureteral access sheath (FANS) versus traditional sheath for patients with infectious upper urinary tract stones (IUUTS). A total of 185 patients were enrolled, with 93 assigned to the FANS group and 92 to the traditional UAS group. The primary outcome was the stone-free rate (SFR) at the first postoperative day. Secondary outcomes included the SFR at 30 days postoperatively, operative time, hemoglobin reduction, length of hospital stay, quality of life (QoL) improvement, incidence of ureteral stricture at 3 months, and surgery-related complications. No significant differences were observed between the two groups in baseline demographics or preoperative clinical characteristics (P > 0.05). The FANS group had significantly lower white blood cell count, C-reactive protein, and procalcitonin levels at 6 and 24 h postoperatively (all P < 0.05). Mean operative time was significantly shorter (P < 0.001), QoL improvement was obviously greater (P < 0.001), and average hospital stay was shorter in the FANS group (P < 0.001). The SFRs on postoperative day 1 and at 30 days were both significantly higher in the FANS group (both P < 0.05). At 3 months, ureteral strictures occurred in three patients in the traditional UAS group and one in the FANS group, a difference that was not statistically significant (P > 0.05). The overall complication rate was significantly lower in the FANS group (P < 0.05). For patients with IUUTS, fURS combined with FANS effectively improves stone clearance efficiency and reduces the risk of postoperative infection.

Humans↗