Glioma is an aggressive intracranial malignancy associated with a poor prognosis and high mortality. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic approach for solid tumours; however, its application in glioma is constrained by several significant challenges. This study conducted a systematic review and meta-analysis to synthesise current methodologies and critically evaluate the clinical efficacy of CAR-T-cell-based immunotherapies in patients with glioma. A comprehensive literature search was performed across PubMed, Scopus, Web of Science and Embase using MeSH terms along with relevant keywords. The review process adhered to the PRISMA framework, applying clearly defined inclusion and exclusion criteria. Standard and augmented meta-analyses were employed to evaluate clinical outcomes, associated complications and potential publication bias. The study protocol was prospectively registered in PROSPERO under registration number CRD42022373297. Of 7723 retrieved records, 23 studies encompassing 306 patients with glioma met inclusion criteria. Efficacy analysis of 12 studies (n = 153 evaluable patients) demonstrated a pooled overall response rate of 16.9% (95% confidence interval [CI], 8.0%-32.2%), driven by complete responses in 8.1% (95% CI, 3.5%-17.8%) and partial responses in 13.1% (95% CI, 6.3%-25.5%) of patients. Stable disease was achieved in 46.6% (95% CI, 34.3%-59.3%); progressive disease was observed in 43.9% (95% CI, 27.7%-61.5%). Safety evaluation revealed grade ≥ 3 adverse events in 18.6% (95% CI, 10.0%-33.0%) of treated patients (n = 69 across 9 studies). Cytokine release syndrome affected 29.7% (95% CI, 9.3%-63.3%) (n = 80 across 9 studies), while immune effector cell-associated neurotoxicity syndrome developed in 12.9% (95% CI, 3.6%-37.0%) (n = 59 across 7 studies). This review demonstrated CAR-T-cell therapy to have promise in glioma, but evidence remains limited by heterogeneity and small samples. Larger standardised trials, systematic adverse-event reporting and mechanistic studies on constructs, dosing and combinations are needed. Biomarker discovery will refine patient selection, reduce risk and clarify the therapeutic role of CAR-T cells in glioma.

Medical clearance is still required for many people living with long-term conditions before participating in organised physical activity (PA) despite international guidance suggesting it is usually unnecessary. Existing physical activity readiness tools often direct people towards medical review, creating avoidable barriers. This study aimed to co-create digital, patient-facing guidance to support informed, autonomous decision-making about physical activity without routine medical clearance. This three-phase study used the Knowledge-to-Action framework to develop patient-facing information. Phase 1: Literature review, audit of industry adverse events and stakeholder surveys. Phase 2: Cross-sector workshops with healthcare professionals (HCPs), patient advocates and industry representatives. Phase 3: Creation of consensus statements through patient focus groups, multidisciplinary HCP panel, secondary patient consultation and implementation partner consultation with final consensus validation. Consensus development followed ACcurate COnsensus Reporting Document (ACCORD) principles and Appraisal of Guidelines for Research and Evaluation (AGREE II) criteria. There was cross-sector agreement that current processes are not fit for purpose. Clinicians reported low confidence in providing medical clearance, industry stakeholders identified governance and implementation challenges, and patients expressed concern about worsening symptoms and requested clear, supportive guidance. Through iterative consensus, four headline safety statements and seven symptom-specific statements were developed, addressing musculoskeletal pain, fatigue, shortness of breath, cardiac chest pain, palpitations, diabetes and falls, including practical self-management advice and indicators for seeking medical review. These patient-centred, evidence-based statements offer a credible alternative to routine medical clearance and may reduce barriers to engagement with organised physical activity opportunities for patients and industry providers. Future work will evaluate feasibility, acceptability and safety in real-world settings.

Diabetes affects over 24 million people in Africa, with type 1 and type 2 diabetes being the most recognised forms. Recent studies in sub-Saharan Africa have identified a substantial proportion of children and young adults with clinically diagnosed type 1 diabetes (T1D) who lack evidence of islet autoimmunity despite severe insulin deficiency, suggesting a distinct non-autoimmune insulin-deficient diabetes subtype (NAID). This study aims to characterise the clinical phenotype, assess the underlying pathophysiology and longitudinal progression of this diabetes subtype.

This is a prospective observational study comprising a cross-sectional comparative analysis and a 3-year longitudinal follow-up cohort. The study will recruit 355 children and young adults aged below 25 years with recently (diabetes duration ≤12 months) diagnosed T1D, with an anticipated estimate of 240 NAID and 115 autoimmune T1D cases. In addition, a minimum of 240 age-matched and sex-matched individuals without diabetes will be recruited as healthy controls. Participants will undergo detailed clinical phenotyping, laboratory assessment including islet autoantibody and C-peptide testing and biospecimen collection for biomarker analyses. A nested mechanistic substudy will include a mixed meal tolerance test and pancreatic MRI to assess pancreatic function and structure. Participants with diabetes will be followed for 3 years to assess longitudinal changes in endogenous insulin secretion, glycaemic response and acute metabolic complications. The study will provide the first prospective characterisation of NAID in sub-Saharan Africa and is expected to improve understanding of its clinical phenotype, natural history and underlying biology, thereby informing future diagnostic and therapeutic strategies.

This study protocol was approved by the National Ethics Committee for Human Health Research (IRB No 2026/05/1930/CE/CNERSH/SP/SPA). All participants will provide written informed consent or assent with parental consent, where appropriate, before enrolment into the study. Research findings will be disseminated through peer-reviewed publications, policy briefs, stakeholder meetings and presentations at national and international scientific conferences.

ISRCTN15312527.

Global political declarations play a growing role in shaping health priorities, yet the diplomatic processes through which they are negotiated remain poorly understood across much of the health community. The 4^th United Nations High-Level Meeting on non-communicable diseases (NCDs) and its political declaration provide a revealing illustration of how global health diplomacy operates under contemporary political constraint. Oral diseases entered the declaration through a negotiated process in which technical evidence, existing policy frameworks, and advocacy interacted with discretion, political feasibility, and geopolitical context. The failure to secure consensus on adoption in September 2025, followed by adoption by majority vote in December, underscores both the fragility of multilateral agreement and the willingness of Member States to defend negotiated commitments. Oral diseases have achieved durable political recognition within the global NCD agenda, yet this recognition has yet to be fully translated into corresponding responsibility for financing, delivery, or accountability. Political declarations function primarily as instruments of alignment that stabilise expectations and signal collective intent, while leaving the work of implementation to national health systems. Understanding these dynamics is critical for navigating the space between global commitment and practical change in oral health policy.

Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are common metabolic complications during pregnancy. GDM is an independent risk factor for HDP, while HDP is a major contributor to maternal and perinatal morbidity and mortality. Reliable early tools for identifying women with GDM who are at risk of subsequently developing HDP remain limited. This study aimed to integrate metabolomic, lipidomic, and clinical data to identify reproducible candidate biomarkers associated with subsequently diagnosed HDP in women with GDM and to characterize the accompanying metabolic and lipidomic alterations.

In this prospective exploratory biomarker study, a discovery cohort (n = 128) and a validation cohort (n = 55) were recruited. Serum samples collected at 24-28 weeks of gestation were analyzed using untargeted and targeted metabolomics. Lipidomics was performed to complement the metabolomic analysis and characterize lipid-related alterations. A combined predictive model was constructed using logistic regression, and its predictive performance was evaluated using receiver operating characteristic (ROC) analysis.

Untargeted metabolomics identified lower serum acetyl-L-carnitine (ALC) in the GDMHDP group than in the GDM group, and this difference was confirmed by targeted LC-MS/MS in the validation cohort. The combined ALC-diastolic blood pressure (DBP) model achieved an area under the curve (AUC) of 0.907 in the discovery cohort and 0.886 in the validation cohort. Adding ALC to DBP improved discrimination and reclassification in both cohorts. Multi-omics analysis showed complementary and partly distinct lipid associations with ALC and DBP. Lower ALC was associated with selected ceramide and monolysocardiolipin species, as well as with lipid patterns consistent with altered fatty-acid handling, whereas DBP showed a partly distinct pattern of lipid correlations.

Reduced serum ALC at 24-28 weeks of gestation was reproducibly associated with GDM complicated by HDP. Combining ALC with DBP improved discrimination between GDMHDP and uncomplicated GDM, suggesting complementary metabolic and hemodynamic information. Given the modest number of GDMHDP cases and the single-center design, these findings should be interpreted as exploratory and hypothesis-generating; they support further evaluation of ALC as a candidate metabolic marker but require confirmation in larger independent cohorts.

Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2D), evidence in heart failure (HF) has expanded across diverse trial populations and HF phenotypes but remains fragmented. We therefore performed an integrated systematic review and meta-analysis to evaluate the effects of GLP-1 RAs across the spectrum of HF using complementary trial-level and phenotype-based analyses.

PubMed, Embase, and Web of Science were systematically searched for studies published from inception to August 10, 2025. To provide an integrated assessment across heterogeneous HF populations, treatment effects were evaluated using dual analytical frameworks: trial-level analyses according to study design (dedicated HF with preserved ejection fraction [HFpEF] trials, HF with reduced ejection fraction [HFrEF] trials, and HF subgroups from cardiovascular outcome trials [CVOTs]) and phenotype-based analyses according to left ventricular ejection fraction (HFpEF vs HFrEF using a pragmatic threshold of 40%). A prespecified targeted analysis was conducted to specifically assess the efficacy of semaglutide. The primary outcomes were major adverse cardiovascular events (MACE), and the secondary outcomes included hospitalization for HF (HHF), the composite of cardiovascular death or any worsening HF events, cardiovascular death alone, and all-cause mortality. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random‑effects models.

This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF. In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001). In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019). Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046). Semaglutide showed benefits in HHF and the composite of cardiovascular death or worsening HF events predominantly among overweight or obese patients with HFpEF. GLP-1 RAs also improved functional capacity and quality of life in HFpEF.

GLP-1 RAs were associated with favorable cardiovascular and HF-related outcomes in HFpEF, predominantly among overweight or obese individuals, whereas evidence of benefit in HFrEF remains limited. In trial-level analyses, benefits were primarily observed for atherosclerotic endpoints in HF subgroups from CVOTs. By integrating evidence, this study provides a unified overview of the effects of GLP-1 RAs across the spectrum of HF and supports further phenotype-specific randomized trials, particularly dedicated studies in HFrEF.

Protocol registration PROSPERO (CRD420251079970).

Natural disasters increasingly challenge healthcare systems through both direct injury and secondary infectious disease outbreaks. Following severe flooding in Far North Queensland in early 2025, Australia experienced one of its largest documented outbreak of melioidosis. Prostate abscess is an uncommon but potentially life-threatening manifestation of disseminated melioidosis and presents unique diagnostic and management challenges, particularly in rural and remote communities. This study aimed to describe the presentation, management and outcomes of prostate abscesses occurring during the 2025 flood-associated melioidosis outbreak and to explore the implications for rural surgical practice.

A retrospective observational cohort study was conducted of all patients undergoing drainage of a radiologically confirmed prostate abscess at Cairns Hospital, the tertiary referral centre for Far North Queensland and the Torres Strait, between 1 January and 1 August 2025. Demographic, clinical, microbiological, radiological and perioperative data were collected from electronic medical records.

Nineteen prostate abscess drainage procedures were performed during the study period. Mean age was 66 years (range 40-88 years). Five patients (26%) identified as Aboriginal and/or Torres Strait Islander and six (32%) required transfer from rural or remote hospitals. All patients had at least one recognised risk factor for severe melioidosis, including diabetes mellitus, hazardous alcohol use, smoking, chronic kidney disease, chronic lung disease or malignancy. Burkholderia pseudomallei was isolated in 12 patients (63%) and represented the predominant causative organism. Lower urinary tract symptoms were present in all patients; however, clinical presentation was heterogeneous and frequently included non-urological symptoms. Digital rectal examination was non-tender in all cases and fluctuance was identified in only six patients (32%). Concurrent extra-prostatic infection occurred in 16 patients (84%), most commonly pulmonary involvement. Four patients required intensive care admission and two patients died from disseminated melioidosis despite surgical drainage and intensive medical management.

The 2025 Far North Queensland floods were associated with a marked increase in melioidosis-related prostate abscesses, highlighting the downstream surgical consequences of climate-related natural disasters. Clinical presentation was variable and traditional examination findings lacked sensitivity. Rural clinicians practising in endemic regions should maintain a high index of suspicion, facilitate early cross-sectional imaging and expedite referral to specialist surgical services. The disproportionate burden observed among rural and First Nations patients highlights ongoing inequities in access to healthcare and vulnerability to tropical infectious diseases.

In India, nearly half of patients with tuberculosis (TB) seek care from the private healthcare sector, where concerns regarding quality of TB care, microbiological confirmation, and adherence to Standards for TB Care in India (STCI) continue to exist. The System for TB Elimination in Private Sector (STEPS) model was developed to strengthen quality-assured TB care through a patient-centric single-window approach within private hospitals. This study describes the implementation of a STEPS Centre and its impact on indicators of quality TB care in a private tertiary care hospital in northern India.

A retrospective comparative operational research study was conducted at a private tertiary care hospital in Uttar Pradesh, India. Programmatic indicators from the pre-implementation period (2023) were compared with post-implementation data from 2024 to 2025 following establishment of the STEPS Centre in March 2024. Data were obtained from Nikshay records, laboratory registers, radiology records, and STEPS Centre program records. Indicators assessed included microbiological confirmation, baseline rifampicin resistance testing using Nucleic Acid Amplification Test (NAAT), NAAT offering among clinically diagnosed TB cases, HIV and diabetes mellitus status documentation, and treatment outcomes.

Following implementation of the STEPS Centre, utilization of TB diagnostic services increased substantially. The number of NAATs performed increased from 1485 in 2023 to 2418 in 2025, while chest X-rays increased from 31,405 to 39,353 during the same period. The proportion of microbiologically confirmed TB cases increased from 22% (87/395) in 2023 to 30% (118/392) in 2025. Baseline rifampicin resistance testing using NAAT improved from 11% (43/395) to 65% (256/392) over the period of two years. Among clinically diagnosed TB patients, the proportion offered NAAT increased from 20% to 59%. Documentation of diabetes mellitus status improved from 0% to 91%. TB deaths among notified patients decreased from 3.3% (13/395) in 2023 to 2.3% (9/392) in 2025.

Implementation of the STEPS Centre was associated with improvement in microbiological confirmation, baseline drug resistance testing, co-morbidity assessment, and adherence to STCI recommendations in a private tertiary care hospital. The findings support the potential role of STEPS as a practical and scalable model for strengthen the quality TB care in the private healthcare sector.

To estimate the proportion with low bone status among adults aged 50 years and older attending a community bone health screening programme in rural northern Vietnam, using calcaneal quantitative ultrasound (QUS), and to examine associated factors.

Community-based cross-sectional study.

Kieu Phu, a rural commune of Hanoi, Vietnam (population approximately 60 900), where a one-off community bone health screening programme was conducted between October and December 2025.

A total of 592 community-dwelling adults aged 50 years and older attending the screening programme.

The primary outcome was low bone status, operationally defined as a QUS T-score ≤-2.5. Crude and adjusted ORs were estimated using logistic regression.

The mean age of participants was 74.8 years (SD 7.7) and 58.4% were women. Overall, 355 of 592 participants had low bone status on calcaneal QUS (60.0%, 95% CI 56.0% to 63.8%). In the adjusted model, female sex showed the strongest association with low bone status (adjusted OR 8.71, 95% CI 5.77 to 13.15), and underweight participants had higher odds than those with a body mass index of 18.5-22.9 kg/m² (adjusted OR 2.11, 95% CI 1.15 to 3.87). Age ≥70 years, education level, former occupation, main income source, high sodium intake, hypertension and diabetes mellitus were not independently associated with low bone status.

Low bone status on calcaneal QUS was common among attendees of a rural community screening programme in northern Vietnam and was independently associated with female sex and underweight status. Because participants were screening attendees rather than a probability sample, these findings are not prevalence estimates for the wider rural population. Calcaneal QUS is not equivalent to dual-energy X-ray absorptiometry (DXA)-based diagnosis but may support early risk identification where DXA access is limited, provided screening is linked to accessible confirmatory assessment and referral.

Glucagon plays a pivotal role in hepatic amino acid metabolism; acute high-protein diet feeding and diabetic condition both induce enhanced glucagon secretion. However, it remains unknown whether these two conditions alter hepatic amino acid metabolism through the same or different pathways. In this study, streptozotocin-induced diabetic (STZ-D) and nondiabetic (ND) mice received liquid normal control (LNC) or liquid high-protein (LHP) diet. Plasma and hepatic parameters were analyzed 2 h post-feeding. LHP increased plasma essential amino acids in both groups. Hepatic amino acid accumulation in LHP-fed STZ-D mice was increased compared to that in LNC-fed STZ-D mice but not in ND mice. In addition, LHP reduced hepatic glycogen while the expression of amino acid metabolism and urea cycle genes remained unchanged both in ND and STZ-D mice. Compared with ND mice, STZ-D mice showed upregulation of genes involved in gluconeogenesis and amino acid metabolism, together with an accumulation of early glycolytic intermediates and glycogen. These findings indicate that acute high-protein intake induces non-transcriptional regulation of amino acid metabolism within 2 h. The altered hepatic amino acid profile in STZ-D mice is likely to be driven by increased hepatic amino acid uptake and accelerated gluconeogenesis.