• Diabetes Mellitus Facilitates Gallstone Formation Through CXCR2-NETs-Mediated Liver-Bile Barrier Damage.
    3 weeks ago
    Gallstone disease is a major health burden worldwide, and diabetes is believed to increase the risk of gallstone formation. This study investigates how diabetes promotes gallstone formation and elucidates the underlying mechanism.

    Data from the National Health and Nutrition Examination Survey and Mendelian randomization analyses were used to identify the causal relationship between diabetes and gallstones. Through the integration of multi-omics sequencing and molecular dynamics simulation, CXCR2 was identified as a molecular bridge linking both diseases. Animal models were established, and Western blotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay were employed to explore the relevant mechanisms.

    Clinical data demonstrated that diabetes is an independent risk factor for gallstones. Animal experiments revealed that diabetes upregulated the expression of CXCR2 in hepatic neutrophils, thereby promoting the formation of neutrophil extracellular traps (NETs). Excessive NETs disrupted the tight junctions between hepatocytes, allowing NETs to enter the bile and accelerate gallstone formation. Moreover, sarcosine inhibited CXCR2 expression, reduced NETs production, and decreased gallstone formation.

    Diabetes promotes NETs formation through CXCR2 activation, which damages the liver-bile barrier and facilitates gallstone development. Sarcosine may serve as a potential therapeutic agent, providing a theoretical basis for clinical intervention.
    Diabetes
    Care/Management
  • Traditional Chinese Medicine Intervention for Managing Type 2 Diabetes in Elderly Urban Populations: A Randomized Controlled Trial.
    3 weeks ago
    To assess the effectiveness of Western medicine and TCM treatment for the improvement of glycaemia control, quality of life, and reducing complications among type 2 diabetes elderly patients in an urban community, a total of 132 elderly patients with type 2 diabetes (aged ≥ 60 years) were randomly allocated to either treatment or placebo control. The intervention group received a comprehensive TCM treatment regimen, including herbal medicine, acupuncture, massage, and dietary therapy, along with lifestyle changes. The control received the standard Western medical treatment. Blood glucose levels were measured upon arrival and again 2 h later. Glycated haemoglobin (HbA1c) was monitored over the duration of the study. In addition, lipid profiles were assessed. Quality of life was evaluated using the Diabetes-Specific Quality of Life Scale (DSQL). Other complications were also recorded. The secondary outcomes measured other kinds of social support (Social Support Rate Scale, SSRS) and health risk (WONCA scale). Compared to the control group, those in the TCM intervention group had better glycemic management, with significant improvements in fasting blood glucose (FBG) (6.82 ± 0.94 vs. 9.34 ± 1.43 mmol/L, P < 0.05) and HbA1c (6.51 ± 0.65% vs. 7.82 ± 0.88%, P < 0.05). Furthermore, the TCM intervention group had better lipid profiles and a higher DSQL score (21.25 ± 3.65 vs. 28.32 ± 4.89, P < 0.05). Finally, they did not suffer from TCM complications (1.52% vs. 10.61%, P < 0.05). Those in the intervention group also had significantly higher social support scores (SSRS; P < 0.05). Therefore, using TCM together with other treatments has a greater effect on the blood glucose, life quality, and diabetic complications of older diabetic patients in a community.
    Diabetes
    Diabetes type 2
    Care/Management
    Advocacy
  • Predicting checkpoint inhibitor-associated autoimmune diabetes: prospects and limitations.
    3 weeks ago
    Checkpoint inhibitor-associated autoimmune diabetes (CIADM) is a life-altering and potentially life-threatening complication of immune checkpoint inhibitor (ICI) treatment in patients with cancer. Risk factors and predictors of this complication remain largely unknown. In this issue of the JCI, Wu et al. examined serum and PBMCs from 14 ICI-treated patients who developed CIADM and 28 matched controls. They identified several variables that were present prior to ICI treatment, including reduced pancreatic volume, islet autoantibodies, and biomarkers indicating immune cell activation, that together are highly predictive of development of CIADM. These findings could have profound clinical implications including treatment decisions, monitoring, and potential future prevention strategies.
    Diabetes
    Cancer
    Diabetes type 1
    Care/Management
  • The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications.
    3 weeks ago
    GLP-1 receptor agonist (GLP-1RA) medications have transformed the treatment of type 2 diabetes (T2D) and obesity, with robust evidence for cardiovascular and renal benefits. Nevertheless, GLP-1RA therapy is associated with a pattern of adverse events affecting their safety and tolerability. Here, we delineate mechanisms potentially leading to adverse responses to GLP-1RAs, describe the impact of side effects on treatment persistence, discuss potential mitigation strategies, and identify areas requiring further studies. Concerns that GLP-1RAs raise the risk for acute pancreatitis and pancreatic cancer have been dispelled by long-term clinical trials. However, GLP-1RAs may confer an increased risk for thyroid cancer. Sight-threatening eye complications resulting from rapid reductions in glycemia may be avoided by retinal screening and ophthalmologic treatment before GLP-1RA initiation. The slowing of gastric emptying with GLP-1RA treatment increases the propensity for retained gastric contents, which could increase the risk of aspiration during upper gastrointestinal endoscopy or general anesthesia. These risks may, however, be elevated in individuals with long-standing T2D even in the absence of GLP-1RA treatment. Improved pharmacovigilance and a more standardized, quantitative assessment of adverse events in clinical trials, particularly in the assessment of gastrointestinal symptoms, would facilitate definition of the benefit-risk relationship for individual medications and indications.
    Diabetes
    Cancer
    Diabetes type 2
    Care/Management
  • Improving Services for Paediatric Brain Tumour Survivors: Engaging Stakeholders and Decision-Makers in Collaborative Workshops to Translate Solutions Into Practice.
    3 weeks ago
    Paediatric brain tumour survivors (PBTS) may experience psychosocial, academic, and employment difficulties after care due to physical and neurocognitive sequelae. Despite clear needs, PBTS do not receive appropriate services and guidance. This study aimed to identify strategies to translate previously prioritised solutions from PBTS and their parents into practice. The specific objectives were to select the two most feasible solutions for effective implementation and to describe the main elements and institutional strategies that could support their adoption.

    This study employed a mixed-methods design. We conducted a survey and two 2-h online workshops with 15 professionals and 5 decision-makers from various sectors (health, education, and non-profit organisations) in Quebec, Canada. Survey data were collected using Likert scales and single-response multiple-choice statements. We used frequencies and percentages to identify the two highest-rated solutions. The workshops were video-recorded, and after each session, we collected information on the topics discussed using pre-established grids. This information was then reorganised into overarching themes using a worksheet and verbatim excerpts to describe actions and propose recommendations for implementation.

    The chosen solutions were to (1) provide ongoing evaluations for PBTS and (2) provide counselling to help PBTS understand their needs and advocate for services. Three overarching themes emerged from workshops: cross-sectoral awareness actions, long-term evaluation and follow-up strategies, and liaison efforts. The key actions proposed for implementing these solutions included providing meetings and counselling involving diverse sectors, providing systematic consultations and inter-sector co-designed tools, and developing the role of a cross-sectoral team or a pivot/liaison person.

    The workshops provided actionable insights for implementing services for PBTS. Future interventions should focus on developing pilot projects based on the main actions identified by participants. These initiatives could improve aftercare services for PBTS and optimize their long-term rehabilitation.
    Cancer
    Access
    Advocacy
  • CT-based radiomics-clinical machine-learning model to predict completeness of cytoreduction in colorectal peritoneal metastases.
    3 weeks ago
    Completeness of cytoreduction (CC) remains the strongest prognostic determinant after cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) yet accurate pre-operative prediction remains difficult. This study aimed to develop and validate a radiomic-clinical machine-learning model to predict cytoreduction completeness.

    83 patients who underwent CRS ± HIPEC for CPM (2008-2025) were retrospectively analysed. Pre-operative contrast-enhanced CT scans were manually segmented in ITK-SNAP, and radiomic features were extracted using PyRadiomics. Clinical variables were modelled alone and in combination with radiomics features using a nested five-fold cross-validated machine-learning pipeline incorporating least absolute shrinkage and selection operator (LASSO) logistic regression, random forest (RF) and gradient-boosted classifiers (GBC) algorithms. The primary endpoint was incomplete cytoreduction (iCC). Model discrimination (AUROC, AUPRC), Brier score and calibration were assessed.

    iCC occurred in 17 of 83 patients (20.5%). Independent predictors of iCC were high radiological PCI (≥15), upper-abdominal disease, absence of pre-operative chemotherapy and normal CEA (≤5 ng/mL). The radiomic-clinical model achieved the best performance (AUROC 0.90, AUPRC 0.69, Brier 0.077, sensitivity 0.83, specificity 0.92), outperforming clinical-only (AUROC 0.82-0.86) and radiomic-only (AUROC 0.69-0.75) models. Key radiomic predictors of iCC-low sphericity, high maximum 2D diameter and high zone entropy-reflected morphological irregularity and heterogeneity of CPM. Integrated models demonstrated superior calibration indicating stable and reliable probability estimates.

    A CT-based radiomic-clinical model accurately predicts CC pre-operatively. This exploratory proof-of-concept model supports multicentre external validation to enhance decision-making for CRS ± HIPEC in CPM.
    Cancer
    Access
    Care/Management
    Advocacy
  • Robot-assisted partial nephrectomy for hilar versus non-hilar renal tumors: a systematic review and meta-analysis.
    3 weeks ago
    We conducted this comprehensive systematic review and meta-analysis to assess surgical outcomes, kidney function preservation, and cancer control efficacy when comparing robot-assisted partial nephrectomy (RAPN) outcomes between renal hilar masses and peripherally located tumors. We performed an exhaustive search strategy utilizing four major electronic databases to capture all relevant comparative investigations published up to August 2025. Meta-analytical calculations were executed through Review Manager (RevMan) version 5.4 software platform. Our investigation synthesized data from eight research studies, including 7064 participants (1292 presenting hilar masses, 5772 with peripheral lesions). Comparative analysis revealed that RAPN procedures for hilar lesions demonstrated significantly longer surgical duration (WMD 22.18 min, 95% CI 16.86 to 27.51; p < 0.00001), greater intraoperative hemorrhage (WMD 31.66 ml, 95% CI 10.10 to 53.21; p = 0.004), higher blood transfusion requirements (OR 1.68, 95% CI 1.14 to 2.49; p = 0.009), prolonged renal clamping duration (WMD 4.89 min, 95% CI 2.80 to 6.97; p < 0.00001), increased severe adverse events (OR 1.44, 95% CI 1.03 to 2.01; p = 0.03), and diminished probability of optimal surgical outcomes (OR 0.45, 95% CI 0.25 to 0.84; p = 0.01). However, both patient cohorts exhibited equivalent outcomes regarding hospitalization duration, total adverse events, surgical approach conversion frequencies to open procedures or radical nephrectomy, postoperative kidney function deterioration, positive surgical margin (PSM), and tumor recurrence patterns, showing no statistically meaningful disparities. While technically more demanding and associated with increased perioperative morbidity, RAPN for hilar tumors is a safe and effective procedure that provides crucial renal functional and oncological outcomes comparable to those of RAPN for non-hilar tumors.
    Cancer
    Access
  • Prognostic significance of tumor fraction in advanced sarcoma: highlighting a novel circulating biomarker.
    3 weeks ago
    Circulating tumor DNA (ctDNA) tumor fraction (TF), the proportion of ctDNA within total cell-free DNA, is emerging as a simple and powerful biomarker across cancers. While recent studies in carcinomas established its prognostic value, its role in sarcomas remains unknown. We analyzed 192 patients with advanced soft tissue sarcomas enrolled in the French BIP (NCT02534649) and STING (NCT04932525) precision medicine programs, using the FoundationOne® Liquid CDx assay to quantify TF. Patients were stratified at a 10% cutpoint, consistent with prior reports. Median overall survival was 6.3 months for patients with TF ≥ 10% compared to 12.9 months for those with TF < 10% (p = 0.01). On multivariate analysis adjusting for histology, grade, performance status, and metastatic burden, high TF remained an independent predictor of poor survival (HR 2.0, 95% CI 1.1-3.5, p = 0.017). Unlike carcinomas, sarcomas currently lack validated circulating biomarkers. Our findings demonstrate that ctDNA TF provides non-invasive, real-time prognostic information in this rare and heterogeneous tumor type, with potential applications for patient stratification, treatment planning, and clinical trial design. Prospective validation is warranted to define standardized TF thresholds and support its integration into sarcoma care.
    Cancer
    Access
    Care/Management
    Advocacy
  • Rapid efficacy of efgartigimod for generalized myasthenia gravis patients in acute exacerbations/worsening: multicenter real-world retrospective study.
    3 weeks ago
    Acute exacerbations/worsening of generalized myasthenia gravis (gMG) require urgent intervention to prevent progression to life-threatening myasthenic crisis. This multicenter study evaluate the efficacy and safety of efgartigimod in gMG patients experiencing acute exacerbations/worsening to validate its potential as a rapid-acting therapeutic option.

    In this multicenter retrospective study (Jan 2024-Feb 2025), 61 gMG patients with acute exacerbations/worsening received weekly efgartigimod infusions for 4 weeks. Efficacy was assessed at baseline (W0) and weekly throughout the treatment cycle (W1-W7) using Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, along with prednisone dosage reductions. Safety assessments were concurrently performed.

    Median age was 56 years (range: 39-68 years). Pulmonary infection (16/61, 26.2%) was the predominant trigger of myasthenic crisis (MC) red flgs. Median duration from symptom deterioration to efgartigimod initiation was 18 days. Clinical meaningful improvement occurred in 81.9% at W1 (post-single dose), 98.1% at W4, and 91.9% at W7. MG-ADL and QMG scores decreased substantially from baseline (W4: 80.86% and 55.81% reduction; W7: 70.78% and 47.76% reduction), Patients with MC red flags achieved comparable outcomes. Greater MG-ADL imrovements were observed in those with thymoma history, severe MGFA classification, prior MC, or MC red flags. No treatment-related allergic reactions, infections, or serious adverse events were observed.

    Efgartigimod demonstrates rapid, significant efficacy in gMG acute exacerbations/worsening, supporting its role as a valuable therapeutic option for this high-risk population.
    Cancer
    Access
    Care/Management
    Advocacy
  • Caregiver health literacy in head and neck cancer and its relationship with caregiver and patient psychological distress.
    3 weeks ago
    Describe caregiver health literacy and assess its association with mental health outcomes of head and neck (HNC) dyads.

    This single institution cross-sectional cohort study involved 100 dyads from October 2020 to July 2021. Ordinary least squares regression was used to examine the association between caregiver health literacy using the Health Literacy of Caregivers Scale- Cancer (HLCS-C) and depression (PHQ-8), anxiety (GAD-7), quality of life (UW-QOL), and perceived stress (PSS) among caregivers and care recipients.

    Higher caregiver scores in the proactiveness domain were linked with lower caregiver PSS scores (β = -0.45, 95% confidence interval [CI]: -0.85 to -0.05). Higher caregiver self-care correlated with higher caregiver depression (β = 0.99, 95% CI: 0.72 to 1.27), anxiety (β = 0.76, 95% CI: 0.39-1.13), and perceived stress (β = 1.06, 95% CI: 0.63 to 1.50). Caregivers having sufficient information about cancer was linked to lower care recipient QOL [physical QOL (β = -3.08, 95% Cl: -4.84 to -1.33); socio-emotional QOL (β = -1.88, 95% CI: -3.54 to -0.22)] and higher care recipient depression (β = 0.80, 95% Cl: 0.18 to 1.41). Caregivers having higher social support was associated with lower care recipient depression (β = -0.59, 95% Cl: -1.12 to -0.07).

    Our findings suggest that caregiver health literacy may affect HNC mental health outcomes, with certain HLCS-C domains-self-care and adequate information- were linked to poorer outcomes. Encouraging a balanced information seeking behavior and strong social support among caregivers may lessen the psychological burden for both HNC caregivers and patients.
    Cancer
    Mental Health
    Access
    Care/Management
    Advocacy
    Education