ObjectivesTo evaluate the efficacy of two different formulations of glucagon given by three different routes (subcutaneous; SQ, rectal, intranasal; IN) for correcting insulin-induced hypoglycaemia in cats and to describe any adverse effects and compare the time required for administration by each route.MethodsA randomized, nonblinded, sham-controlled crossover study was conducted in six healthy cats, with a 7-day washout period between treatments. Hypoglycemia was induced using a continuous rate infusion (CRI) of rapid-acting Lispro insulin. Glucagon nasal powder (single-dose, ready-to-use) was given intranasally and rectally and compared to subcutaneous glucagon injection and intranasal sham control. Blood glucose concentration (BG) was measured from samples collected at baseline (T-15), after induction of hypoglycemia (T0), and at 5-minute intervals for 30 minutes (min), and then at 15 min intervals for 1 hour (h) following glucagon administration. Plasma glucagon and potassium (K+) concentrations were measured at T-15, T0, and T15 and T30 following glucagon administration. The time taken to prepare and administer each treatment was recorded.ResultsMedian BG was 2.6 mmol/L at T0 and increased significantly following glucagon administration by all routes, reaching peak median concentrations of 11.2 mmol/L (intranasal), 9.7 mmol/L (rectal), and 10.15 mmol/L (subcutaneous). Plasma glucagon concentrations increased markedly by T15, with the highest concentrations observed following intranasal administration (1562 pmol/L), followed by subcutaneous (191.7 pmol/L) and rectal (158 pmol/L) routes of administration. Plasma potassium decreased following insulin administration and increased modestly by T30 following glucagon administration by all routes. No serious adverse effects occurred following glucagon administration.Conclusions and Clinical ImportanceTransmucosal glucagon effectively restores BG towards baseline following insulin-induced hypoglycemia with minimal side effects. The IN route resulted in the highest plasma glucagon and BG concentrations compared to the rectal and subcutaneous routes of administration. Further studies are needed to quantify the efficacy and safety of transmucosal glucagon in diabetic cats in response to spontaneous insulin-induced hypoglycemia.

Cardiovascular diseases (CVDs) remain a major complication of type 1 diabetes mellitus (T1DM). Although healthy lifestyle behaviors are associated with lower cardiovascular risk in the general population and in individuals with type 2 diabetes mellitus, evidence specific to T1DM is limited. This study aimed to examine the associations of individual and composite healthy lifestyle factors with incident CVDs among individuals with T1DM.

This prospective cohort study included participants with T1DM from the UK Biobank who were free of CVDs at baseline. A composite lifestyle score was constructed from six factors: smoking status, alcohol consumption, body mass index (BMI), diet quality, physical activity, and sleep duration. The primary outcomes were incident CVDs, including coronary heart disease (CHD), heart failure (HF), and stroke. Associations were assessed using Cox proportional hazards models, with subgroup analyses stratified by key demographic and clinical characteristics.

Over a median follow-up of 14.38 years, 455 incident CVD events were documented among 1,390 participants with T1DM. Maintaining a BMI of 25 to < 30 kg/m² (HR, 0.65; 95% CI, 0.52-0.81) or 18.5 to < 25 kg/m² (0.59; 0.45-0.78), adhering to a healthy diet (0.83; 0.69-0.99), and obtaining adequate sleep duration (0.77; 0.63-0.92) were independently associated with a reduced risk of CVDs. Compared with participants with a lifestyle score of 0-2, those with a score 4-6 had a significantly lower risk of composite CVDs (0.58; 0.46-0.73), CHD (0.63; 0.49-0.81), and HF (0.49; 0.34-0.70). These associations were generally consistent across subgroups.

Among individuals with T1DM, healthy lifestyle profiles were associated with a lower risk of incident CVDs, particularly through weight management, healthy diet, and adequate sleep duration. These findings support the potential value of incorporating lifestyle assessment and promotion into cardiovascular risk management for individuals with T1DM.

In women with prediabetes after prior gestational diabetes mellitus (GDM), whether intermittent metformin treatment as needed is as effective as continuous use in preventing type 2 diabetes mellitus (T2DM) is unknown. We aimed to test whether an intermittent metformin treatment is non-inferior to continuous metformin strategy for prevention of T2DM in women with prediabetes after GDM.

A randomized, open-label, non-inferiority trial was conducted at three centers in China. Women aged 18-45 years with prior GDM and prediabetes at 4-12 weeks postpartum were randomly assigned to receive lifestyle intervention plus intermittent or continuous metformin treatment. In the continuous group, participants were initially treated with lifestyle intervention and metformin was initiated when lifestyle intervention alone failed to maintain euglycemia and continued without interruption throughout the trial. In the intermittent group, participants were initially treated with lifestyle intervention and metformin was added when they failed to maintain euglycemia and was discontinued if the glycemic status returned to normal. The primary outcome was the difference in incidences of newly diagnosed diabetes between the two groups during the 3-year follow-up, compared against a non-inferiority margin of 10-percentage-point by following the intention-to-treat principle. Secondary outcomes included the percentage of prediabetes remission, changes from baseline in body weight, body mass index, waist circumference, fasting plasma glucose, 2-h plasma glucose, and hemoglobin A1c.

Among the 376 women randomized, 11.5% of women in the intermittent group and 11.1% in the continuous group developed newly diagnosed T2DM after three years (absolute risk difference 0.4% points [95% CI -6.5 to 7.4], meeting criteria for non-inferiority). None of the secondary outcomes were significantly different between the two groups. Women in the continuous group experienced higher rate of metformin-related vitamin B₁₂ deficiency (13.5% vs. 3.7%, P = 0.001).

In postpartum women with prediabetes after GDM, a strategy of intermittent metformin as needed plus lifestyle intervention met the pre-specified 10-percentage-point non-inferiority margin for 3-year T2DM incidence compared with continuous metformin plus lifestyle intervention. The equivalence of the two metformin strategies needs to be confirmed in further trials with a narrower margin and a larger event count.

The study was registered in the Chinese Clinical Trial Registry (ChiCTR-IOR-17012770).

Treatment adherence in type 2 diabetes(T2D) is essential for glycemic control and preventing complications. The aim of the present study was to determine the status of adherence behaviors to diabetes treatment and identify sociodemographic factors associated with these behaviors in patients with type 2 diabetes in southern Iran.

This cross‑sectional study was conducted from November 2022 to January 2023 among patients with type 2 diabetes attending a diabetes clinic in Bandar Abbas. A total of 396 patients were included using systematic sampling. Data were collected using a validated researcher-made questionnaire that assessed sociodemographic characteristics and five treatment-adherence behaviors, including regular medication use, blood glucose monitoring, physician visits, dietary adherence, and physical activity. Associations between demographic and disease-related factors and the outcomes were assessed using multivariable logistic regression, and crude and adjusted odds ratios with 95% confidence intervals were reported. All statistical analyses were performed using SPSS version 24.

Participants (n = 396) had a mean age of 54.4 ± 11.5 years (range: 27-78). Among the treatment adherence behaviors, regular medication use showed the highest level of adherence (86.9%), while regular physical activity had the lowest level (49.7%). In the multivariable analysis, frequent medication use was associated with older age, higher education, higher economic status, and diabetes duration of 6-10 years. Frequent blood glucose monitoring was associated with female sex, older age, and diploma education. Frequent physician visits were associated with older age and longer diabetes duration. Dietary adherence was associated with university education, and frequent physical activity was associated with living alone.

The findings suggest that adherence to treatment among patients with T2Dvaries across different domains and is shaped by individual, social, and clinical factors. It seems that, Lifestyle behaviors such as diet and physical activity are largely influenced by social and environmental contexts, whereas healthcare‑seeking behaviors are more closely linked to disease severity and patients' interaction with the health system.

To reveal the real experience of polypharmacy in middle-aged and elderly patients with type 2 diabetes comorbidity, based on the Common-Sense Model of self-regulation (CSM).

With the method of purposive sampling, 15 middle-aged and elderly patients with type 2 diabetes comorbidity hospitalized in the endocrinology department of a tertiary hospital were selected for semi-structured interviews. Using the Colaizzi's seven-step method to analyze and organize the interview results.

4 themes and 9 subthemes were identified and organized based on the Common-Sense Model of self-regulation: cognitive representation (cognitive struggle in coexistence with medicines, physical discomfort and adjustment, expectations for treatment methods); emotional representation (memory burden, space management burden); coping strategies - negative and positive responses (negative emotions related to polypharmacy, self driven); external factors (family support feels helpful, medical staff support feels relieved).

The psychological experience of middle-aged and elderly patients with type 2 diabetes comorbidity in the course of taking medicine includes the interaction of cognitive and emotional representation, coping strategies and external support system at all levels. Medical personnel should clarify patients' treatment burden, polypharmacy burden, self-management workload, coping strategies and effective support system during the medication process, in order to provide patient-centered medicine care and achieve more ideal emotional and health outcomes.

Sertoli cells (SCs) provide essential metabolic support for spermatogenesis, including lactate production for developing germ cells. While insulin's role in SC glucose metabolism is well-established, its regulation of fatty acid (FA) uptake and oxidation-critical for germ cell support and residual body clearance-remains unknown. Insulin deficiency in diabetes mellitus (DM) impairs male fertility through mechanisms that may involve disrupted SC metabolism.

To determine whether insulin regulates FA uptake and oxidation in SCs and to elucidate mechanistic links between insulin deficiency and impaired spermatogenesis.

The TM4 mouse SC line was cultured under defined in vitro conditions in the presence of insulin (10 µg/mL) versus under insulin-deprived conditions for 18 h. FA metabolism was assessed using RT-qPCR (FAT/CD36, ACADL, and CPT1A), Western blotting, ¹H-NMR spectroscopy, functional FA uptake assay, Oil Red O staining, JC-1 mitochondrial assessment, and Seahorse real-time metabolic analysis.

Insulin deprivation significantly reduced glucose consumption, glutamine consumption, and lactate production. FAT/CD36 expression and FA uptake capacity decreased markedly, with reduced intracellular lipid droplet accumulation. Conversely, FA oxidation enzyme expression (CPT1A, ACADL) remained unchanged, as did mitochondrial membrane potential and oxygen consumption rates with/without etomoxir.

In the TM4 mouse SC line under defined in vitro conditions, insulin selectively regulates FA uptake while maintaining no control over downstream FA oxidation. This dissociation reveals that insulin modulates FA entry for storage and/or biosynthesis, while FA oxidation operates constitutively. Impaired FA uptake under insulin deficiency may compromise SC support for spermatogenesis, providing a mechanistic link to male infertility in DM that requires confirmation in primary SCs and in vivo diabetic models.

Timely treatment in colorectal cancer (CRC) may influence the disease course and, thus, outcomes, but optimal delay thresholds remain uncertain. Identifying pathway-specific time-to-treatment initiation (TTI) effects can guide benchmarks and policies for coordinated, timely care.

To evaluate the association between TTI and 3-year metastasis risk in patients with newly diagnosed nonmetastatic CRC undergoing curative-intent surgery, with attention to variation by treatment pathway.

This cohort study of insured US patients with nonmetastatic CRC used deidentified administrative claims from Optum's Clinformatics Data Mart. Eligible individuals were adults aged 40 years or older with incident nonmetastatic CRC diagnosed during January 1, 2017, to December 31, 2021, who underwent curative-intent surgery within 1 year of diagnosis and had continuous coverage 1 year before and after. Data were analyzed June 2025.

TTI was defined as days from CRC diagnosis to the first receipt of cancer-directed therapy (surgery, chemotherapy, or radiation). Patients were categorized into 4 treatment pathways: surgery with or without radiation, surgery followed by adjuvant therapy with or without radiation, neoadjuvant therapy followed by surgery with or without radiation, and trimodality therapy (neoadjuvant therapy, followed by surgery, followed by adjuvant therapy with or without radiation).

The outcome was 3-year cumulative incidence of metastasis. XGBoost identified optimal TTI thresholds, and Fine-Gray models with death as a competing risk evaluated these thresholds and estimated their associations with metastasis.

Among 11 927 patients (mean [SD] age, 70.7 [10.8] years; 6007 women [50.4%]; 1251 Black [10.5%], 7948 White [66.6%]), 4539 (38.0%) had moderate or severe comorbidity. Over 3 years, 1438 patients (12.1%) developed metastasis. Longer TTIs were associated with higher metastasis risk, varying by treatment pathway. For surgery plus adjuvant therapy, TTIs of 4 to 46 days (subdistribution hazard ratio [sHR], 1.27; 95% CI, 1.04-1.55) and 47 days or longer (sHR, 1.55; 95% CI, 1.08-2.23) were significantly associated with increased risk vs zero to 3 days. For surgery followed by radiation, delays of 223 days or longer showed higher risk (sHR, 2.00; 95% CI, 0.95-4.25) than TTI up to 222 days, although these results were not significant. For neoadjuvant therapy plus surgery, TTI of 68 days or longer were associated with higher risk (sHR, 2.66; 95% CI, 1.02-6.94) than TTI up to 67 days. For patients receiving trimodality therapy, there was no association between TTI and risk of metastasis.

In this cohort study, treatment delays were associated with higher, pathway-specific metastasis risk. These findings support pathway-tailored benchmarks for treatment initiation and highlight the importance of integrated care in reducing delays and improving timely, equitable, cost-effective CRC care.

Pembrolizumab plus chemotherapy, with or without bevacizumab, improves overall survival (OS) in advanced cervical cancer (ACC), but platinum choice and bevacizumab use remain discretionary.

To compare OS by platinum agent and bevacizumab use among patients with ACC receiving first-line pembrolizumab plus chemotherapy in a clinical setting.

This comparative effectiveness study used a retrospective multinational cohort with propensity score matching in the TriNetX Global Collaborative Network. Participants included adults with ACC (International Statistical Classification of Diseases, 10th Revision, Clinical Modification, code C53) treated between January 1, 2015, and October 31, 2024. Patients with prior cancer or contraindications to bevacizumab therapy were excluded. Matching was performed on age, race and ethnicity, body mass index, smoking status, and prior chemoradiotherapy. Data were analyzed from November 19 to 28, 2024.

Cisplatin or carboplatin, with or without bevacizumab, both combined with first-line pembrolizumab plus paclitaxel.

Two comparisons were analyzed: cisplatin vs carboplatin and bevacizumab vs no bevacizumab. The primary outcome was OS, defined as time from treatment initiation to death from any cause. Secondary outcomes were adverse events of special interest, including fistula, bowel perforation, and pulmonary embolism.

Among the 1931 patients receiving first-line pembrolizumab with paclitaxel (mean [SD] age, 54.0 [13.2] years), 623 matched pairs of cisplatin-treated patients (n = 719) and carboplatin-treated patients (n = 1212) were included. The mean (SD) age was 51.2 (12.7) years for cisplatin-treated patients and 50.8 (12.7) years for carboplatin-treated patients; the median follow-up was 10.8 (IQR, 3.7-18.0) months and 9.9 (IQR, 2.5-17.2) months, respectively. The median OS was 25.1 (IQR, 9.2 to not reached) months in both groups (HR, 0.98 [95% CI, 0.81-1.18]; P = .35). Bevacizumab-treated patients (n = 803) and those not receiving bevacizumab (n = 667) yielded 455 matched pairs. The mean (SD) age was 53.6 (13.3) years in the bevacizumab-treated group and 54.3 (13.3) years in the group not receiving bevacizumab; the median follow-up was 11.3 (IQR, 4.4-18.2) months and 8.4 (IQR, 1.6-15.1) months, respectively. Twelve-month OS was 74.8% (95% CI, 70.4%-79.2%) vs 64.5% (95% CI, 59.8%-69.2%), respectively; 24-month OS was 56.2% (95% CI, 50.9%-61.5%) vs 54.0% (95% CI, 48.7%-59.3%), respectively. No increased risk of fistula (odds ratio [OR], 0.94 [95% CI, 0.63-1.40]; P = .76), bowel perforation (OR, 1.21 [95% CI, 0.52-2.82]; P = .67), or pulmonary embolism (OR, 0.62 [95% CI, 0.38-1.01]; P = .052) was observed.

In this comparative effectiveness study of patients with ACC in a clinical setting, cisplatin and carboplatin treatment were associated with similar effectiveness when combined with pembrolizumab. Bevacizumab was associated with early OS benefit, which attenuated over time. These findings warrant prospective validation.

Risk-adapted strategies are central to early breast cancer (EBC) management, particularly in HR+/HER2 - disease. Prosigna/PAM50 combined with clinicopathologic factors refines prognosis, with clearer guidance at ROR extremes, while decisions in the intermediate-risk (i-ROR) group remain challenging. Although adjuvant iCDK4/6 therapy improves outcomes in high-risk patients, eligibility in i-ROR may be overlooked. This study outlines clinicopathologic features, recurrence-free survival, and iCDK4/6 eligibility in i-ROR EBC to support treatment decision-making.

We performed a retrospective analysis of 554 EBC patients who underwent PAM50 testing at Hospital Universitario 12 de Octubre (2015-2024). Clinical, pathological, diagnostic, follow-up, and recurrence data were obtained from records. Kaplan-Meier analyses estimated RFS, while multivariate logistic regression identified predictors of chemotherapy use within i-ROR. Descriptive statistics assessed eligibility for adjuvant ribociclib (NATALEE) and abemaciclib (monarchE).

Among 212 i-ROR patients (38%), 71.7% were postmenopausal, 65.5% Luminal A and 34% Luminal B intrinsic subtypes, and 53.7% node-negative. 68.4% did not receive chemotherapy. There were 11 relapses, predominantly Luminal A (72.7%), node-negative (63.6%), and chemotherapy-naive (90.9%). RFS at 12, 36, and 60 months was 100%, 97.9%, and 96.9%. Chemotherapy use was associated with younger age (p = 0.006), node positivity (p = 0.021), and luminal B subtype (p = 0.001). CDK4/6 eligibility was 44.3% for NATALEE and 14.6% for monarchE, with 10.8% meeting both; chemotherapy use was higher in monarchE-eligible patients (41.9% vs. 31.9%).

This real-world cohort of PAM50 i-ROR HR+/HER2 - EBC patients showed excellent prognosis (5-year RFS > 96%), yet relapses still occurred, highlighting the need for improved risk stratification and consideration of adjuvant therapies, including iCDK4/6.

Serous ovarian carcinoma (SOC) is frequently diagnosed at advanced stages and is associated with poor clinical outcomes, highlighting the urgent need for reliable diagnostic and prognostic biomarkers. Long non-coding RNA MEG3 and the autophagy-related protein Beclin-1 are recognized tumor suppressors; however, their combined diagnostic relevance in SOC remains insufficiently explored. This case-control study included 24 patients with histopathologically confirmed SOC. Paired tumor and adjacent non-tumorous ovarian tissues were analyzed for lncRNA MEG3 expression using quantitative real-time PCR and for Beclin-1 protein expression using immunohistochemistry. Serum CA-125 levels were assessed by ELISA. Associations with clinicopathological parameters were evaluated, and diagnostic performance was analyzed using receiver operating characteristic (ROC) curves. Both lncRNA MEG3 and Beclin-1 were significantly downregulated in SOC tissues compared with adjacent non-cancerous tissues (P < 0.0001). Reduced expression was significantly associated with tumor grade and ascites. The relationship with FIGO stage was not uniform in this cohort and should be interpreted cautiously because of the small sample size and unequal distribution of early and advanced cases. Beclin-1 expression was notably higher in premenopausal patients and in well to moderately differentiated tumors. A strong positive correlation was observed between lncRNA MEG3 and Beclin-1 expression (r = 0.96, P < 0.001), indicating a strong statistical association rather than a proven regulatory interaction. ROC curve analysis suggested diagnostic potential for lncRNA MEG3, Beclin-1, and serum CA-125. The concurrent downregulation of lncRNA MEG3 and Beclin-1 in SOC tissues suggests that these markers may serve as promising complementary biomarkers. However, their clinical utility should be considered preliminary and requires validation in larger, multicenter cohorts with functional studies before routine clinical application can be recommended.