Incretin-based drugs, including glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, are increasingly used in the management of type 2 diabetes mellitus and obesity. While these agents have shown cardiovascular benefits, their effects on both cardiovascular outcomes and cardiac structure and function remain uncertain—particularly in patients with and without a history of heart failure (HF).

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S)), as well as clinical trial registries from their inception and onwards to identify relevant randomised trials. The literature search is scheduled for July 2025. Two review authors will independently extract data and assess risk of bias. We will include randomised controlled trials assessing the effects of cagrilintide/semaglutide, liraglutide, semaglutide and tirzepatide in patients with and without a history of HF. The primary outcome will be cardiovascular mortality. Secondary outcomes will include HF hospitalisation, myocardial infarction, stroke, heart rate, systolic blood pressure, N-terminal pro B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume. Data will be synthesised by aggregate data meta-analyses and trial sequential analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool, version 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

As this study is a systematic review based on secondary analysis of published data, ethical approval is not required. Findings will be published in international peer-reviewed scientific journals.

CRD420251003374.

Glaucoma is the second leading cause of moderate to severe visual impairment worldwide, primarily affecting peripheral vision and increasing the risk of falls due to impaired balance and mobility. While traditional physical training (PT) is used for fall prevention, its effectiveness may be limited by low patient engagement. Action video games (AVGs) may offer a more engaging alternative for improving balance and mobility in individuals with glaucoma.

This prospective, two-arm, single-blind, active-control trial will involve 56 patients with glaucoma with moderate to severe peripheral field loss and intact cognitive function, who have not previously undergone balance training. Participants will be randomly assigned in a 1:1 ratio to either a physically interactive action video-game training (AVG) group or a conventional PT group. The AVG group will use a Nintendo Switch gaming station for 20 sessions of 45 min each, conducted two to three sessions per week over 8 weeks. These sessions will involve standing game exercises using game controllers or body sensors, focusing on muscle stretching and strengthening, balance improvement and fitness. The PT group will engage in traditional PT for the same duration and frequency. The primary outcome is the change in mobility function after 20 sessions, measured by the narrow path walking test. Secondary outcomes include balance function (modified Clinical Test of Sensory Interaction and Balance, motor control test, landing balance test, five-time sit-to-stand test and time up and go test), visual cognition (reaction time test and useful field of view test) and patient-reported outcomes (validated questionnaires). Exploratory outcomes include fall frequency, fear of falling, visual function and serum brain-derived neurotrophic factor levels (one of the biomarkers related to exercise). Assessments will occur at seven time points: baseline (T1), after 10 sessions (T2), after 20 sessions (T3), 1-month post-training (T4) and 3, 6 and 9 months after all training sessions (T5–T7).

The human ethics approval was obtained from the respective ethics board of the Hong Kong Polytechnic University (ID: HSEARS20210722001). The study protocol will conform to the principles of the Declaration of Helsinki. Results will be disseminated through peer-reviewed journals and conferences.

NCT06000865.

For patients with perihilar cholangiocarcinoma (pCCA), surgical resection remains the sole treatment modality that can potentially result in cure. Unfortunately, the majority of patients present with unresectable tumours or are excluded from surgical treatment due to complications like cholangitis affecting their performance status. In the Netherlands, recommended first-line treatment for patients with unresectable pCCA is palliative chemotherapy with gemcitabine and cisplatin. This regimen yields an estimated median overall survival (OS) of 11.7–15.2 months, highlighting the urgent need for novel treatment options. The STRONG I trial, a phase I study in patients with unresectable pCCA, was completed in 2020. Its aim was to assess the feasibility and toxicity profile of adding stereotactic body radiation therapy (SBRT) to chemotherapy. SBRT, delivered in 15 fractions of 4.0 Gray (Gy), was considered to be feasible and safe, with no dose-limiting toxicity being observed. The 1-year local tumour control rate was 80% and the 1-year OS rate 100%, with maintenance of quality of life (QoL). These results encouraged us to initiate the STRONG II trial, aiming to investigate the efficacy of adding SBRT to chemotherapy in a larger patient cohort.

STRONG II is a single-arm, multicentre phase II study. Patients with non-metastatic unresectable pCCA (T1-4, N0-2) are eligible. A total of 30 patients will be enrolled in six academic centres in the Netherlands and two in Belgium. SBRT will be delivered in 15 fractions of 4.0–4.5 Gy. The primary endpoint is local tumour control, defined by Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1. Secondary endpoints include toxicity, biliary stent-related events, progression-free survival, OS and QoL using the EuroQoL five-dimensional, five-level (EQ-5D-5L) questionnaire, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and the EORTC Biliary Module (QLQ-BIL21). In addition, we will explore the predictive value of the peripheral immunological status (immune-related proteins and serum functional immunological status assay) and its dynamics in determining survival outcomes. For this explorative translational study, two blood samples will be collected, one before the start of chemotherapy and another after completing chemotherapy.

Approval of the study was obtained on 5 June 2024 by the Medical Ethics Review Committee of Erasmus Medical Center Rotterdam, the Netherlands (ID: NL86210.078.24). The anticipated time frame for patient enrolment is July 2024 to December 2027. The main study findings will be published in peer-reviewed medical journals, and presented at national and international conferences.

NCT06493734 (ClinicalTrials.gov).

Our study was designed to assess whether paired normal-tumour testing increased access to targeted therapy, clinical trials and influenced cancer screening recommendations given to patients and their families.

Prospective cohort study.

Academic cancer centre in the Pacific Northwest region of the USA.

Patients newly diagnosed between 01 January 2021 and 31 December 2022 with cancers of the oesophagus, gastro-oesophageal junction and stomach (CEGEJS) were included. All other cancer diagnoses such as head and neck, duodenal and lower gastrointestinal tract cancers were excluded.

Paired germline and tumour genetic test within 90 days of new patient visit.

Number of targeted therapies received (or not) when eligible, follow-up treatment data and number of inherited predispositions to cancers identified. No secondary outcome measures.

Of 42 patients, 32 (76.2%) were eligible for at least one targeted therapy. 19 patients received immunotherapy, when 16 had a biomarker predicting immunotherapy benefit, and benefit of immunotherapy was unclear for 3. Another 11 did not have this biomarker, and 6 of them received immunotherapy. Six pathogenic variants were identified in four high-risk genes. By 01 January 2024, 18 patients (42.9%) had died of complications of cancer.

More than 75% of patients who received tumour testing were eligible for a targeted therapy regardless of their stage at diagnosis, emphasising the need to expand access to testing with staging workup to improve survival outcomes. Six families received personalised screening recommendations, thanks to this study.