Approximately one-third of people with epilepsy (PWE) experience resistance to treatment, including pharmacological therapies, epilepsy surgery, vagus nerve stimulation (VNS) and dietary interventions such as the ketogenic diet (KD). Emerging evidence suggests that the gut microbiota may influence seizure susceptibility and treatment response through the microbiota-gut-brain axis, potentially contributing to treatment resistance. The MiCrobiota-gut-brain Axis in Resistant Epilepsy project investigates how gut microbial features and associated host epigenetic signatures affect clinical outcomes in PWE undergoing diverse treatment strategies.

This is a multicentre, prospective, longitudinal study involving four clinical centres in Italy and one self-financing partner. Participants aged 3–50 years will be enrolled and stratified into four intervention cohorts: newly diagnosed drug-naïve epilepsy scheduled to start anti-seizure medications, focal drug-resistant epilepsy (DRE) undergoing epilepsy surgery, DRE receiving VNS, and DRE initiating KD. Clinical assessments (including body mass index calculation, self-reported monthly seizure count, dietary evaluation, quality of life scale and gastrointestinal symptoms scale), electroencephalography, MRI and biological sample collection (stool and blood) will be obtained at baseline and longitudinally at two or three timepoints over a 12-month observation period. Gut microbiota changes over time will be assessed via metagenomics (using 16S ribosomal RNA sequencing) and metaproteomics; the associated host DNA methylation profiles will be obtained from blood using Illumina EPIC arrays. Primary endpoints include identification of microbial or host methylation changes predictive of therapeutic response (ie, reduction from baseline in monthly seizure count) to the intervention. Data will be analysed using multivariate models and mixed-effect regression. Further, omics data and corresponding metadata will be integrated using multi-omics approaches to identify molecular signatures biomarkers predictive of treatment response and prognosis in PWE.

The study received ethical approval from the Research Ethic Board (Comitato Etico Territoriale Lombardia 3, ID 4896 – parere numero 4896_17.07.2024_N_bis). All participants or their legal guardians will provide written informed consent. Results will be disseminated through peer-reviewed publications, conference presentations or lay summaries targeting patient organisations.

ClinicalTrials.gov Identifier NCT07010445, registered on 2 May 2025.

To evaluate the effectiveness of a web-based secondary prevention programme for postpartum depression, delivered with or without telephone support, compared with usual care.

We first conducted a randomised controlled superiority trial to test whether the web-based Parents and Babies programme (Toi, Moi, Bébé; TMB) delivered with motivational telephone support (ie, coaching) was superior to the fully automated programme (ie, self-help). TMB incorporated classic and third-wave cognitive–behavioural therapy components and psychoeducation. Then, we tested whether TMB (both treatment modalities combined) was superior to usual care. The usual care comparison group was drawn from the CONCEPTION prospective pan-Canadian perinatal cohort (N=592).

A remote study based at Sainte-Justine Hospital Centre, Quebec, Canada.

Web-based intervention programme participants were women aged ≥14 years at 12–25 weeks’ gestation, with subclinical to moderate clinical Edinburgh Postnatal Depression Scale (EPDS) scores: 9–16. Exclusion criteria were psychosis and self-reported substance abuse. The usual care comparison group was pregnant women ≥18 years old. All participants were living in Canada at study inception.

The primary outcome was EPDS scores at 3 months post partum, accounting for baseline EPDS scores and depression events defined as EPDS ≥13 at 3 months post partum. The secondary outcomes were EPDS scores at 6 months post partum, depression events (EPDS≥13) at 6 months post partum, anxiety symptoms (Generalised Anxiety Disorder 7-item Scale, GAD-7) at 3 and 6 months post partum, accounting for baseline scores for the continuous outcomes; as well as the number of completed intervention modules and well-being scores (WHO 5-Item Well-being Index) at 3 months post partum.

We randomised 510 participants to TMB self-help (n=255) or TMB with coaching (n=255); 211 and 214 participants, respectively, were included in the complete-case intention-to-treat analyses. At baseline, 91% lived with a partner, 71% were university graduates and 42% self-reported GAD-7≥10. Randomisation was successful. First, TMB with coaching was not superior to TMB self-help: at 3 months post partum, EPDS scores were TMB self-help (mean 8.0±4.3) vs TMB with coaching (mean 8.6±4.5); effect size was 0.01 (95% CI 0.00 to 0.03; p=0.16). Second, TMB (regardless of intervention arm) was superior to usual care: in adjusted regression models, EPDS scores were 6.2 units lower (per SD, 95% CI –8.2 to –4.3) in TMB (both treatment modalities combined) than in usual care; and proportions of depression events were 4.7 units lower (per SD on the logit scale, 95% CI –6.6 to –2.7) in TMB (combined) than in usual care. No other group differences were observed.

Our findings suggest that, in women with subclinical to moderate clinical antenatal depressive symptoms, receiving a web-based cognitive–behavioural therapy-based programme in addition to usual care can reduce depression postnatally.

NCT05110456.

The objective of this study was to determine the association between viral subtype/clade and disease severity.

Multicentre retrospective cohort study.

This study used data from the Global Influenza Hospital Surveillance Network (GIHSN). The dataset comprised hospitalised influenza patients with viral sequencing data across 14 countries, collected from August 2022 through October 2023.

A total of 761 hospitalised patients were enrolled during the study period, and 745 patients were included in the analysis. We excluded patients with missing data on explanatory or outcome variables, those infected with viral clades represented by fewer than 11 sequences, and those enrolled at study sites contributing fewer than 5 patients.

Disease severity was defined by admission to intensive care unit (ICU), receipt of non-invasive oxygen supplementation, 3-variable definition (ICU, mechanical ventilation or death) or 4-variable definition (3-variable plus oxygen supplementation).

Outcomes were analysed in association with subtype or clade using the mixed-effects logistic regression models, adjusting for age group, sex, underlying medical conditions, influenza vaccination status, antiviral use, country income level and epidemic period, while study site was included as a random effect.

745 patients were included: 263 A(H1N1)pdm09, 380 A(H3N2), 102 B/Victoria. A(H1N1)pdm09 infection was associated with increased odds of ICU admission (adjusted ORs (aORs) 2.5, 95% CI 1.1 to 5.8) compared with A(H3N2). 6B.1A.5a.2a.1 clade of A(H1N1)pdm09 was associated with increased severity compared with 6B.1A.5a.2a clade (aOR 3.0, 95% CI 1.0 to 9.5) and (aOR 5.4, 95% CI 1.6 to 18.3) for the 3-variable and 4-variable definitions respectively. Among A(H3N2), the (3C.2a1b.2a.)2b clade showed a trend toward increased severity using the 4-variable definition compared with the 2a.1b clade (aOR 2.9, 95% CI 0.8 to 10.0).

This analysis highlights the differential impact of influenza subtypes and clades on disease severity in hospitalised patients. Future research should investigate the role of specific viral mutations of these clades in modulating immune evasion or disease severity. These findings reinforce the GIHSN’s critical role in global surveillance. Ongoing genomic surveillance is crucial for understanding the clinical impact of emerging influenza variants and informing public health responses.

Surgical margins are crucial in determining postoperative local recurrence (LR) in patients with colorectal liver metastasis (CRLM) and hepatocellular carcinoma (HCC). Achieving a margin greater than 1 cm can be challenging due to constraints related to remnant liver reserve, proximity to major vascular structures and tumour depth. We previously published findings from a retrospective study suggesting that additional margin coagulation (AMC) using radiofrequency may reduce LR, and this multicentre randomised clinical trial aims to further assess this hypothesis.

The LIVERATION trial is an international, multicentre, single-blind, randomised, parallel-group, controlled clinical trial involving 698 patients undergoing liver resection for CRLM or HCC. Participants will be randomly assigned in a 1:1 ratio to either AMC (study group) or conventional liver resection (control group) to assess oncological outcomes for both CRLM and HCC. The primary outcome is the incidence of LR. Secondary endpoints include overall survival, disease-free survival, cancer-specific survival, surgical complications and quality of life. Follow-ups occur at 30 days, 90 days, and 1, 2 and 3 years postoperatively.

The LIVERATION trial has been approved by the Ethics Committee at the sponsor site Hospital del Mar de Barcelona, CEIM-PSMAR (Comité de Ética de la Investigación con Medicamentos – Parc de Salut Mar), as well as by the Institutional Ethics Committees in all participating countries. The results of the main trial, along with each of the secondary endpoints, will be submitted for publication in a peer-reviewed journal. The study adheres to national and international guidelines, including the Declaration of Helsinki, and complies with regulations for studies involving biological samples under Law 14/2007 on Biomedical Research. A dissemination strategy has been developed to engage stakeholders and facilitate knowledge transfer to support the use of the findings of the study. LIVERATION is funded by the European Union under the Horizon Europe Framework Programme (Project Number: 101104360).

NCT05492136.

Real-world data and patient-reported outcomes in diabetes in Emilia–Romagna is a multi-centric observational cohort study aimed at improving diabetes care in the Emilia–Romagna region, by exploring trends and predictors of clinical and psychological parameters in a large population of people with diabetes, during and after the COVID-19 pandemic.

The study has a mixed retrospective/prospective design. The retrospective component involves computerised data linkage of administrative and clinical data from the local health authorities of Romagna and Reggio Emilia, and the University Hospital of Parma, covering a population of approximately 100 000 prevalent cases with diabetes, followed throughout the years 2019–2024. The selection of data items collected in the reference time frame is based on the International Consortium for Health Outcomes Measurement (ICHOM) standard set for diabetes, including clinical, lifestyle, social and healthcare service measurements. The prospective component includes primary data collection of indicators of psychological well-being through the WHO-5 Well-Being Index, diabetes distress using the Problem Areas In Diabetes-Short Form and depression through the Patient Health Questionnaire-9, measured at 0–6 months in an overall sample of 455 people with type 2 diabetes. Statistical analysis will include descriptive analysis and multivariate logistic regression using a two-step federated approach.

The study has obtained ethics approval from the Ethics Committee of Romagna and the Ethics Committee of Area Vasta Emilia Nord. The results of the study will be published in scientific journals to evaluate quality and outcomes of diabetes care across the region.

NCT06639100.