Type 1 diabetes mellitus (T1DM) involves autoimmune β-cell destruction, but insulin resistance may also influence disease outcomes. Vitamin D modulates insulin sensitivity and immune function, and hypovitaminosis D is common in T1DM. This systematic review evaluates clinical and mechanistic evidence on the association between hypovitaminosis D and insulin resistance in T1DM. A Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) framework was applied for a systematic search of PubMed^®, BMJ Journals, Scopus^®, IEEE Xplore^®, and Web of Science™, including articles published until 7 March 2026. Studies assessing vitamin D status and insulin resistance measures in T1DM populations were included. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool and the Newcastle-Ottawa Scale. Narrative synthesis was performed due to methodological heterogeneity. Eight studies (one controlled trial, two prospective cohorts, and five cross-sectional) were included. Hypovitaminosis D prevalence ranged from 47 to 79%. Six studies reported significant associations between low vitamin D levels and markers of insulin resistance, including a positive correlation with estimated glucose disposal rate (eGDR), as well as associations with higher insulin requirements and greater odds of insulin resistance. Mechanistic studies demonstrated preserved β-cell function with sufficient vitamin D and identified vitamin D receptor (VDR) polymorphisms as effect modifiers. Supplementation trials showed conflicting results, and longitudinal analysis revealed no significant association over time. Risk of bias was low in one study, good in five, and fair in two. Hypovitaminosis D is prevalent in T1DM and associated with insulin resistance in cross-sectional studies, with supportive mechanistic evidence. However, interventional and longitudinal data remain inconsistent. Vitamin D may be a marker of metabolic dysregulation, but its therapeutic role in improving insulin resistance requires further robust investigation.

This study aims to assess the predictive value of dietary antioxidants in diabetes-cancer comorbidity using interpretable machine learning (ML) models and to identify key clinical factors. Data were sourced from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 cycles, including 44 dietary antioxidants, as well as demographic, lifestyle, and health-related features. 8 ML models (Random Forest, light Gradient Boosting Machines [LightGBM], Logistic Regression, Decision Tree, Multilayer Perceptron, Naïve Bayes, Kernel k-Nearest Neighbors, and Support Vector Machine with Radial Basis Function) were trained, with preprocessing steps for multicollinearity, class imbalance (SMOTE), and data normalization. Model performance was evaluated using AUC, accuracy, Brier scores, and calibration plots. SHapley Additive exPlanations (SHAP) values were applied to interpret feature importance. Data from 8644 participants were analyzed, including 272 individuals with confirmed diabetes-cancer comorbidity. After removing collinear features, the ML model included 30 dietary antioxidant features and 10 baseline features. The Random Forest model achieved optimal performance (AUC = 0.996, accuracy = 0.978, brier score = 0.0241), followed by LightGBM (AUC = 0.993). SHAP analysis revealed that while advanced age, cardiovascular disease, and hypertension were the primary drivers of comorbidity probability, dietary antioxidants are also influential factors. Specifically, polyphenols (daidzein, malvidin, pelargonidin, cyanidin) and essential minerals (magnesium) emerged as the most influential nutritional features. The high accuracy of the Random Forest and LightGBM models underscores their clinical utility in risk stratification for diabetes-cancer comorbidity. While advancing age and cardiometabolic dysfunction primarily drives the probability of diabetes-cancer comorbidity. This study establishes dietary antioxidants, particularly polyphenols such as daidzein and malvidin, as predictive factors for diabetes-cancer comorbidity.

Diabetes is a significant disease that affects individuals of all ages and may lead to the development of systemic and ocular complications, ultimately resulting in a poor quality of life (QoL). The use of health-related quality of life (HRQoL) measures is important for identifying disparities and those at risk, thereby promoting early intervention. This study aimed to examine the HRQoL and associated factors in Ghanaian children and adolescents with type 1 diabetes mellitus (T1DM).

A cross-sectional study involving children and adolescents with T1DM aged 5-19 years was conducted. Demographic and clinical data of participants were recorded. Participants completed the PedsQL Generic Scales questionnaires. SPSS Version 25.0 was used in analyzing the data. Logistic regression was used in analyzing risk factors associated with poor QoL. p-values < 0.05 were considered statistically significant.

Data from 46 children and adolescents with T1DM were analyzed. A female preponderance of 35/46 (76.1%) was observed. The overall mean HRQoL score for participants was 73.9 ± 18.7. Sex was the only risk factor associated with poor self-reported HRQoL in children and adolescents with T1DM. Female children and adolescents with T1DM were 13 times more likely to have poor self-reported HRQoL compared with their male counterparts (OR = 13.2; 95% CI = 1.9-91.0; p = 0.009). There were no significant associations with age, duration of diabetes, glycemic control, number of hypoglycemic and diabetic ketoacidosis episodes, hypertension, or nephropathy.

Self-reported QoL of children and adolescents with T1DM was poor. Female children and adolescents with T1DM are more likely to have poor self-reported QoL.

Metformin is derived from the plant Galega officinalis with the blood-glucose-lowering properties. Although its early development was hindered by the toxicity issues associated with other guanidine derivatives and the rise of insulin therapies, it ultimately established its position as a first-line oral hypoglycemic agent for addressing insulin resistance and managing hyperglycemia through extensive clinical validation. With a nearly 70-year history in diabetes treatment, the mechanisms by which metformin modulates blood glucose have been widely studied and refined. Recent investigations into combination therapies, fixed-dose formulations, and novel applications underscores a broader therapeutic potential beyond glycemic control. This paper aims to review the development trajectory of metformin, consolidate the latest evidence for its clinical benefits, and critically appraise its future directions and constraints.

Objective biomarkers that reflect systemic inflammation in pediatric allergic rhinitis to support clinical diagnosis. We aimed to evaluate serum levels of endocan (a marker of endothelial activation) and eosinophil-derived neurotoxin (EDN; reflecting eosinophil degranulation) in children with AR and investigate their diagnostic performance and associations with disease severity and conventional inflammatory markers. In this prospective case-control study, 85 children with AR and 67 healthy controls were enrolled. Serum endocan and EDN were measured via sandwich ELISA. Primary outcomes included group comparisons of biomarker levels and their diagnostic accuracy determined by receiver operating characteristic (ROC) curve analysis. Serum endocan and EDN levels were significantly elevated in children with AR compared to controls (both p < 0.001). Both biomarkers demonstrated high diagnostic performance, with an area under the curve (AUC) of 0.931 for endocan and 0.929 for EDN, showing greater diagnostic accuracy than absolute eosinophil counts (AUC, 0.871). Endocan and EDN showed a strong intercorrelation (r = 0.88, p < 0.001) and significant positive correlations with total IgE and eosinophil counts. However, no significant associations were observed between these biomarkers and disease severity, symptom control scores, or allergen sensitization patterns.

Serum endocan and EDN are significantly elevated in children with AR and demonstrate high diagnostic discrimination in this cohort. These findings suggest that endocan and EDN may serve as promising complementary biomarkers for the objective assessment of allergic inflammation in children, although further multicenter studies are needed to confirm their clinical utility.

• Allergic rhinitis (AR) is common in childhood and involves systemic inflammatory pathways; however, objective biomarkers to support diagnosis in pediatric practice remain limited. • Endocan and eosinophil-derived neurotoxin (EDN) reflect endothelial activation and eosinophil degranulation, respectively, and have been studied in other atopic and inflammatory conditions.

• This study concurrently evaluates serum Endocan and EDN in children with AR in a prospective case-control design. • Both biomarkers demonstrated high discriminatory performance (AUC∼ 0.93 in this cohort) and showed greater diagnostic accuracy than absolute eosinophil counts . • Endocan and EDN are largely independent of generalized systemic inflammatory indices (NLR, SII, SIRI), supporting specificity for the endothelial- eosinophilic axis in pediatric AR.

Chronic inflammation plays a pivotal role in carcinogenesis, particularly in upper gastrointestinal (UGI) cancers. However, the contribution of dietary inflammation to UGI cancer risk in the Chinese population remains insufficiently explored. This study investigated the association between energy-adjusted dietary inflammatory index (E-DII) and UGI cancer incidence in high-risk regions of China.

This prospective cohort study included 43,153 participants enrolled between 2017 and 2019 in the National Cohort of Esophageal Cancer. The E-DII score, based on 22 dietary parameters, quantified dietary inflammation. Cox proportional hazards regression models were used to assess the relationship between E-DII scores and incident UGI cancer, with adjustments for age, sex, residence, lifestyle factors, medical history, and pathological diagnoses. Subgroup and sensitivity analyses were conducted to address potential confounding effects.

Over a median follow-up of 55 months, 527 participants developed UGI cancer. Higher E-DII scores were associated with increased UGI cancer risk (hazard ratio [HR] for highest vs. lowest quartile: 1.75; 95% confidence interval [CI]: 1.28-2.40; P for trend = 0.001). Significant associations were observed for esophageal cancer (HR = 1.81; 95% CI 1.03-3.18; P for trend = 0.050) and gastric cancer (HR = 1.69; 95% CI 1.16-2.47; P for trend = 0.009). Subgroup analyses and sensitivity tests confirmed the robustness of these findings.

This study highlights the role of dietary inflammation in increasing UGI cancer risk and suggests that promoting anti-inflammatory dietary patterns may serve as an effective preventive measure in high-risk populations.

Most novel anti-cancer therapies involve combining multiple immuno-oncology and/or targeted drugs. The historical paradigm of exploring combination regimens only after approval of the individual drugs is changing rapidly leading to clinical development of 'novel-novel' combination therapies consisting of at least two investigational agents.

Initiating those combination efforts early in development is an important strategy to accelerate evolution of the standard of care for high unmet need cancer indications. However, there are specific challenges associated with such development programs, with additional complexity if more than one company is involved. Representing a consortium of major oncology drug developers, we critically discuss those challenges and suggest potential solutions to encourage the development of novel multi-company combination therapies for solid and hematological tumors. The areas covered include trial strategies for early and late clinical development, including dose/regimen optimization, statistical considerations, optimizing safety profiles, dose modification approaches, contribution of components, choice of standard of care backbone and comparator regimens as well as regulatory strategies.

To assess the benefit of the new 'SURC' model, allowing patients having systemic anti-cancer therapy (SACT) to be seen acutely for assessment of adverse events, as well as scheduled early review in their treatment course. It also assessed the effect of the COVID-19 pandemic on this service.

Data was collected prospectively between 2020 and 2023 and then analysed retrospectively. The clinic was implemented at Ballarat Regional Integrated Cancer Centre (BRICC). It also included two outreach sites: Primary outcomes were the number of interactions by patients with SURC; secondary outcomes included the number of admissions, type of cancer involved, and reasons for contacting SURC.

This study demonstrated benefit for patients with cancer from a regional area who presented with acute complications of their treatment. Presentations requiring hospital admissions and further assessment in ED were lower compared to the pre-SURC period, with most patients being treated comprehensively in the SURC environment. The study demonstrated the utility of early SACT review as there was a decrease in the number of treatment disruptions due to early recognition of complications of each patient's regimen. There was also a gradual increase in patient presentations to the clinic during the duration of the study, reflecting the growing awareness and confidence in the service from both healthcare providers and patients alike.

This study demonstrates the benefit of the novel SURC model to patients living in regional areas with cancer who either develop acute complications or are routinely reviewed early during their course of treatment. Although this study was limited to only one public health service provider, we feel this new proactive paradigm for acute cancer care will become increasingly adopted across Australia, given its proven ability to look after patients undergoing SACT more efficiently in addition to reducing hospital admissions.

Esophageal cancer is a global burden, and multiple international societies exist to address the issue in international collaboration. This study aims to analyze the characteristics of esophageal cancer and robot-assisted minimally invasive esophagectomy (RAMIE) across geographic areas. We performed a retrospective analysis of the Upper GI International Robotic Association (UGIRA) international database from January 2016 to April 2024. Forty centers worldwide that were known to perform RAMIE were involved in establishing this consortium. The patient characteristics, surgical techniques, and short-term outcomes of RAMIE were compared by each regional area (Europe, Asia, North America, and South America). A total of 3,916 RAMIE cases were registered in the UGIRA database (2,643 in Europe, 1,130 in Asia, 111 in North America, and 32 in South America). The median age was 66 years, and 80.5% of patients were male. Notably, Asia had a high prevalence of squamous cell carcinoma (91.2%) and predominant use of the McKeown approach (94.9%). BMI was lower in Asia, whereas comorbidities were more common in Western countries across all types. The use of neoadjuvant chemotherapy and radiation was lower in Asia (48.2% and 20.8 %, respectively). Postoperative complications also differed by region; pneumonia was most common in Europe and South America, cardiopulmonary complications in North America, and recurrent nerve injury in Asia. In conclusion, regional differences were observed in baseline characteristics, treatment approaches, and complication patterns in patients treated by RAMIE for esophageal cancer. Recognizing these variations is essential for fostering mutual understanding and advancing the field through international collaboration.

Accurate assessment of submucosal invasion depth in pT1b-SM esophageal squamous cell carcinoma (ESCC) is critical to determine the need for additional treatment after endoscopic resection (ER). However, the reliability of submucosal invasion depth measurement has not been sufficiently validated. This study aimed to evaluate interobserver agreement in measuring invasion depth and to identify a reliable and reproducible assessment method.

Thirty-four pT1b-SM ESCC specimens obtained by ER were independently assessed by three pathologists. Invasion depth was measured using three methods on hematoxylin and eosin (H&E)- and desmin-stained slides: Method 1, from an imaginary line representing the original level of the muscularis mucosae; Method 2, from a reconstructed trajectory based on disorganized muscularis mucosae; and Method 3, from a line connecting the lowest visible ends of the disrupted muscularis mucosae, with each method measuring perpendicular to the deepest point of invasion. The lesions were classified as pT1a-MM, pT1b-SM1 (≤200 μm), or pT1b-SM2 (>200 μm). Interobserver agreement was assessed using Fleiss' κ and intraclass correlation coefficients (ICC).

Moderate to substantial agreement was observed across all methods. Method 3 (κ = 0.678, ICC = 0.789) achieved the highest agreement on H&E-stained slides, whereas Method 2 (κ = 0.615, ICC = 0.801) on desmin-stained slides demonstrated comparable reliability.

A stepwise approach using Method 3 on H&E-stained slides as a first-line method and Method 2 on desmin-stained slides as a complementary option when the muscularis mucosae is disrupted or ambiguous demonstrated high interobserver agreement and may enhance reproducibility in routine pathological practice.