The impact of anaesthesia modality on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) remains uncertain. Emerging evidence suggests that anaesthetic agents and techniques may influence tumour biology and recurrence through immunomodulatory and neuroendocrine pathways. However, prospective randomised trials comparing spinal and general anaesthesia in this population are lacking.

This single-centre, prospective, parallel-arm randomised controlled trial will enrol 370 patients with clinically suspected high-risk NMIBC undergoing transurethral resection of bladder tumour. Participants will be randomised 1:1 to receive either spinal or general anaesthesia. The primary endpoint is time to recurrence over a 104-week follow-up period. Secondary endpoints include time to progression, Bacillus Calmette–Guérin (BCG) unresponsiveness and a composite oncological event. Additional secondary outcomes include postoperative opioid consumption (morphine equivalents), obturator jerk occurrence, acute urinary retention and tolerance to immediate intravesical chemotherapy. Safety outcomes will include treatment-emergent adverse events, Clavien-Dindo graded surgical complications, haemorrhagic events and anaesthesia-related risks. Exploratory endpoints involve perioperative biomarker analyses. Data will be analysed on an intention-to-treat basis.

Recruitment has not yet started. It is expected to begin in December 2025 and to be completed by June 2029. The planned follow-up period for each participant is 104 weeks. This manuscript is based on protocol V.1.0, dated March 2025. Results will be disseminated through peer-reviewed journals and conference presentations

NCT06982690.

Gestational diabetes mellitus (GDM) is common in pregnancy and is increasing in prevalence. It is associated with an increased risk of maternal and perinatal complications if not diagnosed and managed early. Most guidelines suggest making a diagnosis of GDM using an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy at which stage there still is an increased risk of complications. Increased beta-cell secretory product concentrations have been observed prior to changes in glycaemia and can potentially be used as an early marker to diagnose and assess risk of developing GDM.

The study was a prospective, longitudinal cohort study. OGTTs were carried out at visit one: 16–18 weeks and visit two: 24–28 weeks gestation in pregnant women with at least one risk factor for GDM [Body Mass Index >30 kg/m², previous macrosomic baby (>4.5 kg), previous GDM, first degree relative with type 2 diabetes mellitus (T2DM)]. Blood sampling was performed at fasting, 30 min, 1 and 2 hours following a 75-g oral glucose load. Samples were analysed for glucose, total and intact proinsulin, insulin and C-peptide. Hormonal concentrations at visit 1 were compared between those that remained normal glucose tolerant (NGT) and those that progressed to GDM at visit 2 using receiver operator characteristic (ROC) area under the curve (AUC) to assess for discrimination between the two groups.

Unfortunately, a smaller than planned sample size was recruited due to the start of COVID-19 pandemic midway through the study. 83 pregnant women had OGTT at visit 1. Of these, 12 reached the threshold for GDM at visit 1 and were excluded. In total, data from 66 patients were included for analysis (5 Did Not Attend). Visit 1 hormone comparisons were carried out between 51 who remained NGT and 15 who progressed to GDM at visit 2. There were no significant differences at each time point in ROC AUC between the two groups for total and intact proinsulin and insulin. However, there were significant differences observed in C-peptide ROC AUC at 30 (p=0.041) and 60 min (p=0.003) between the two groups.

This study did not demonstrate significant increase in early proinsulin concentrations in patients that developed GDM. However, there were differences in C-peptide concentrations. The COVID-19 pandemic restricted the recruitment of patient numbers and further studies in a larger cohort will be needed to validate these findings.

ISRCTN16416602.