Invasive arterial blood pressure monitoring is critical for perioperative and critically ill patients, yet traditional radial artery cannulation near the wrist joint is prone to catheter dysfunction (eg, kinking, occlusion) due to positional changes, compromising accuracy and patient safety. This trial hypothesises that modifying the cannulation site to 1.5–2.5 cm proximal to the radial styloid process may enhance catheter stability.

This is a prospective, parallel-group, randomised, controlled, analyst-blinded trial. A total of 486 participants (243 per group) will be enrolled at the Sixth Affiliated Hospital, Sun Yat-sen University. Eligible patients (18–75 years, American Society of Anesthesiologists physical status I–III, requiring elective surgery with radial artery cannulation) will be randomised 1:1 to the modified group (1.5–2.5 cm proximal to the radial styloid process) or the conventional group (traditional site). The primary outcome is the incidence of arterial catheter dysfunction (defined by criteria such as blood sampling difficulty, position-dependent waveform or improved waveform post-square wave test). Secondary outcomes include frequency of catheter dysfunction, damping abnormality rate, first-puncture success rate, number of arterial punctures, arterial cannulation time, complication incidence and blood pressure measurement differences.

This study protocol (V.4.0) was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University in Guangzhou, China on 2 September 2025. The first participant was recruited on 15 September 2025, with an estimated completion date of 31 December 2025. Informed consent will be obtained from all participants. Findings will be published in peer-reviewed journals.

NCT06566456.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders globally, affecting 11–13% of women during reproductive age. PCOS is associated with an elevated risk of reproductive, metabolic, endocrine and mental health features. While lifestyle changes are first-line treatment for managing PCOS, metformin is often recommended for individuals with a body mass index (BMI) ≥25 kg/m². The aim of the metformin use in polycystic ovary syndrome (MET-PCOS) trial is to determine whether a metformin dose of 1500 mg per day or 2250 mg per day is superior in managing biochemical and clinical outcomes in PCOS.

MET-PCOS is a double-blind randomised controlled trial with two arms. It will be carried out at the Reproductive Medicine Unit at Helsinki University Hospital, starting from November 2025. Participants aged 18–37 years with a BMI≥25 kg/m² meeting the updated 2023 Rotterdam criteria for a PCOS diagnosis will be included. The participants (n=184) will be allocated (1:1) to a metformin dose of 1500 mg or 2250 mg per day. Outcomes include anthropometry, metabolic outcomes, hyperandrogenism, polycystic ovary morphology, menstrual cyclicity, mental health and gastrointestinal adverse effects. Measurements for study endpoints will be undertaken at baseline, 14 and 26 weeks.

The Finnish Medicines Agency has authorised the clinical trial (FIMEA/2025/00755) and the Regional Committee Medical Research Ethics, Finland (T7323/2024) has approved the trial protocol. This study will guide care providers in selecting the ideal metformin dose for individuals with PCOS.

NCT07120815, EU trial number: 2023-509259-15-01.

Tongxinluo capsule (TXL) is widely used in China as an adjunctive therapy for patients with acute coronary syndromes (ACS) who underwent percutaneous coronary intervention (PCI), collectively referred to as ACS-PCI. However, current evidence on its therapeutic effects and safety remains limited and insufficiently synthesised. This review aims to evaluate the therapeutic effects and safety of adding TXL to Western medical therapy (WM) in this population.

A systematic literature search was performed in PubMed, the Cochrane Library, CNKI, VIP and Wanfang from inception to August 2024; a rapid supplemental search was conducted up to November 2025, without language restrictions, to identify randomised controlled trials (RCTs) evaluating the therapeutic effects and safety of adding TXL to WM in patients with ACS-PCI. Dichotomous outcomes were summarised using risk ratios (RRs) with 95% CIs; absolute risk reductions (ARRs) were estimated as risk differences, and corresponding numbers needed to treat (NNTs) were calculated. Continuous outcomes were summarised using mean differences (MDs) with 95% CIs. All meta-analyses were performed using a random-effects model. The included studies generally had limitations in methodological quality, heterogeneity across analyses was low to moderate and the potential for publication bias could not be excluded. The evidence certainty for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Eighteen RCTs involving 1800 participants were included. Low-certainty evidence indicated that adding TXL to WM may reduce the risks of restenosis (RR=0.30, 95% CI 0.10 to 0.91; ARR=0.056, NNT=18), revascularisation (RR=0.28, 95% CI 0.10 to 0.80; ARR=0.069, NNT=15), myocardial infarction (RR=0.44, 95% CI 0.20 to 0.98; ARR=0.033, NNT=31), angina (RR=0.32, 95% CI 0.17 to 0.61; ARR=0.076, NNT=14) and other cardiovascular events (RR=0.41, 95% CI 0.24 to 0.71; ARR=0.075, NNT=14). It also improved Seattle Angina Questionnaire scores (MD=8.82, 95% CI 6.58 to 11.05) and quality of life (qualitative synthesis). However, no statistically significant reductions were observed for sudden cardiac death (RR=0.39, 95% CI 0.12 to 1.27; ARR=0.022, NNT=45), or non-cardiovascular adverse events (RR=0.67, 95% CI 0.32 to 1.40; ARR=0.043, NNT=24) when TXL was added to WM.

Current evidence suggests that adjunctive TXL may reduce key cardiovascular events and improve symptoms and quality of life in patients with ACS-PCI, without increasing the risk of non-cardiovascular adverse events. However, all findings are based on low-certainty evidence. These results provide preliminary support for the use of TXL as an adjunctive therapy, but high-quality, multicentre RCTs are needed to confirm these effects and inform clinical guidelines.

CRD42024509453.

The predictive value of carotid-femoral pulse wave velocity (cfPWV) for cardiovascular (CV) events in individuals with blood pressure (BP) 120–159/80–99 mm Hg, where more accurate risk stratification has the greatest clinical effect, is unknown. This study aims to determine whether cfPWV improves the prediction of CV events beyond traditional risk factors in individuals with moderate BP.

A systematic review and meta-analysis.

PubMed and EMBASE were searched through April 2023.

We included prospective, population-based cohort studies with ≥1 year follow-up that directly measured cfPWV as an index of arterial stiffness and reported incident CV disease (CVD), atherosclerotic CVD (ASCVD), coronary heart disease, stroke or all-cause mortality outcomes.

Individual participant data from 11 cohorts (n=15 987) were harmonised and analysed using two-stage random-effects meta-analysis. Incremental predictive and clinical utility analyses compared 10-year risk models with and without cfPWV.

There were 1279 first atherosclerotic CV events over a median follow-up of 9.9 years. A 1-SD increase in log_e(cfPWV) was associated with a 1.21-fold (95% CI 1.08 to 1.36) increase in risk of ASCVD. Adding cfPWV to traditional risk factors improved ASCVD prediction: change in discrimination (C-index): 0.0048 (95% CI 0.0002 to 0.0094), p=0.041. In hypothetical populations of 100 000 individuals with moderate BP, cfPWV-guided treatment could reduce event rates by 2.7% and 3.1% under European and US guidelines, respectively.

Adding cfPWV to traditional CV risk factors may improve the prediction and classification of first CV events in individuals with moderate BP. Additional screening with cfPWV could enhance risk stratification for antihypertensive treatment initiations.

Low anterior resection syndrome (LARS) is a common functional complication after sphincter-preserving surgery for rectal cancer that significantly impairs the quality of life. Current postoperative management strategies are suboptimal, and effective preventive approaches are lacking. This study aims to evaluate the impact of a mobile-based, knowledge-enhanced digital intervention for reducing the incidence of major LARS.

This is a multicentre, open-label, parallel-group, randomised controlled trial to be conducted across three academic medical centres in Korea.

A total of 300 adult patients who underwent low anterior resection or stoma reversal after rectal cancer surgery will be randomly assigned in a 1:1 ratio to the intervention group (mobile digital programme) or the control group (standard educational materials). The digital programme includes daily symptom monitoring, exercise suggestions, dietary recommendations and structured feedback from healthcare providers during clinical visits based on outcomes. The primary outcome is the incidence of major LARS (score ≥30) at 12 months postoperatively. Secondary outcomes include longitudinal changes in LARS score, quality of life (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30), EORTC QLQ-Colorectal Cancer 29 (CR29)), European Quality of Life 5 Dimensions Level Version (EQ-5D-5L), patient satisfaction and programme adherence. Statistical analyses will include stratified chi-squared tests and mixed-effects models based on the intention-to-treat principle.

The trial received ethical approval from the Institutional Review Board of the National Cancer Centre, Korea. Written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed publications and conference presentations.

NCT07041515.

To investigate whether systemic lupus erythematosus (SLE) increases the risk of cataract development and to evaluate the impact of corticosteroid use and dosage on this risk.

Nationwide retrospective cohort study.

Using Taiwan’s National Health Insurance (NHI) database, which covers over 99.9% of the population.

The SLE cohort included 30 501 newly diagnosed adults from 2011 to 2020. For each patient with SLE, four individuals without SLE were selected from the NHI database using frequency matching by age (in 5 year intervals), gender and index year of diagnosis, resulting in a comparison cohort of 122 004 individuals.

The primary outcome was incident cataract. Secondary outcomes included risk stratification by age, sex, comorbidities and corticosteroid dose.

SLE patients had a higher incidence of cataracts than non-SLE individuals (adjusted HR (aHR) = 1.73, 95% CI 1.66 to 1.81). Stratified analyses showed elevated risks in women (aHR=1.74, 95% CI 1.66 to 1.83), men (aHR=1.68, 95% CI 1.52 to 1.86), and across age groups 20–49 years (aHR=2.32, 95% CI 2.11 to 2.56), 50–64 years (aHR=1.60, 95% CI 1.51 to 1.69), and ≥65 years (aHR=1.50, 95% CI 1.36 to 1.66). Analysis of corticosteroid exposure revealed that cumulative dose showed a trend towards increased risk at high exposure (adjusted OR (aOR) = 1.14, 95% CI 0.99 to 1.31), while average daily dose demonstrated a dose–response effect: 1–5 mg/day (aOR=1.31, 95% CI 1.13 to 1.52) and ≥5 mg/day (OR=2.48, 95% CI 2.16 to 2.86).

Adults with SLE have an increased risk of developing cataracts compared with matched controls, and higher average daily corticosteroid doses are associated with this risk. These findings highlight the need for careful monitoring of ocular complications in SLE patients.

Neonatal death and later disability remain common sequelae of hypoxic-ischaemic encephalopathy (HIE) despite the now standard use of therapeutic hypothermia (HT). New therapeutic approaches to brain protection are required. Melatonin is an indolamine hormone with free-radical scavenging, antiapoptotic, anti-inflammatory and gene regulatory neuroprotective properties, which has extensive preclinical evidence of safety and efficacy. Pharmacokinetic (PK) data suggest it is necessary to reach melatonin levels of 15–30 mg/L within 6–8 hours of hypoxia-ischaemia for brain protection. We developed a novel Good Manufacturing Practice (GMP) grade melatonin in ethanol 50 mg/mL solution for intravenous use. In preclinical studies, ethanol is an adjuvant excipient with additional neuroprotective benefit; optimised dosing protocols can achieve therapeutic melatonin levels while limiting blood alcohol concentrations (BACs).

The Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study is a first-in-human, international, multicentre, phase 1 safety study of intravenous melatonin in babies with moderate/severe HIE receiving HT. Sixty babies will be studied over two phases: a dose escalation study including four dose levels to establish the recommended phase 2 dose (RP2D), followed by a 6-month cohort expansion study of RP2D to further characterise PKs and affirm safety. Participants will receive a 2-hour intravenous infusion of melatonin within 6 hours of birth, followed by five maintenance doses every 12 hours to cover the period of HT. Plasma melatonin and BACs will be monitored. The RP2D will be based on the attainment of therapeutic melatonin levels while limiting BACs and the frequency of dose-limiting events (DLEs). A Bayesian Escalation with Overdose Control approach will be used to estimate the risk of DLE per dose level, with a target level of

Approval has been given by the London Central National Health Service Health Research Authority Ethics Committee (25/LO/0170) and UK Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. Separate approvals have been sought in Ireland and Australia. Dissemination will be via peer-reviewed journals, conference presentations, public registries and plain language summaries for parent/legal guardian(s), in accordance with national requirements.

ISRCTN61218504. EU CT: 2025-520538-49-00.

Publication based on the UK protocol V.3.0, 08 May 2025

Although caesarean sections (CSs) are essential for the management of obstructed labour and other obstetric complications, postoperative pain, delayed recovery and complication risks continue to be significant challenges in perioperative management. Improvements in traditional medications and surgical techniques have helped, yet issues, including medication side effects and extended recovery times, persist. Therefore, it is particularly important to seek non-pharmacological interventions, such as acupoint stimulation, to optimise the perioperative management of CS. The aim of this systematic review protocol is to synthesise the available evidence and assess the effect of acupoint stimulation in the perioperative period of CS.

We plan to search PubMed, Web of Science, EMBASE, Scopus, the Cochrane Library and China National Knowledge Infrastructure, from their inception to August 2025. Primary outcome indicators will include pain, time to first defecation, time to first bowel movement and time to return of bowel sounds. Secondary outcome indicators will include postoperative complications, such as nausea and vomiting, bloating, anxiety and depression, as well as length of hospital stay and morphine consumption. Subgroup analyses, meta-regression and sensitivity analyses will be used to investigate the potential sources of heterogeneity and to test the stability of the results. Trial sequential analysis will be introduced to enhance the reliability of the evidence.

No ethical approval is required as this study synthesises the existing published data. Results will be disseminated through peer-reviewed publications and conference presentations. Any protocol amendments will be documented in PROSPERO and detailed in the final publication.

CRD42024558572.