Retinal fibrosis is a blinding complication of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD) and idiopathic epiretinal membrane (iERM), yet effective therapies remain lacking. The purpose of this study was to investigate the role of BMP2 and BMP4 (BMP2/4)-activin receptor-like kinase (ALK) signaling in retinal fibrosis. BMP2 was detected in the vitreous of PDR, PVR, and rhegmatogenous retinal detachment (RRD) samples at concentration of 70, 180, and 85 pg/mL respectively, whereas it was present only at trace levels or was undetectable in the vitreous of macular hole and idiopathic ERM samples (~0.1 pg/mL). PDR, PVR, and idiopathic ERMs exhibited strong immunoreactivity for BMP2, BMP4, ALK3 (Bmpr1a), pSMAD1/5/9, and pSMAD4. Formation of preretinal fibronectin-containing membranes resulted from intravitreal injection of wild-type mice with BMP2 and similar membranes formed in mice expressing constitutively active ALK3 (caBmpr1a). The presence of preretinal membrane in caBmpr1a was confirmed by optical coherence tomography. The limited hyperoxia-induced proliferative retinopathy (LIHPR) model demonstrated a progressive increase in the retinal expression of BMP2 and BMP4and development of preretinal membrane. Administration of BMP/ALK inhibitor LDN193189 induced regression of the preretinal membrane in LHIPR. BMP2 and BMP4 induced a significant increase in the expression of Glial Fibrillary Acidic Protein (GFAP), fibronectin, and collagen-VI in cultured rat Muller glial cells, and increased fibronectin was reversed by BMP/ALK inhibition. BMP2 also significantly upregulated fibronectin and activated matrix metalloproteinase-2 in human retinal endothelial cells. These findings support BMP2/4-ALK signaling as a potential mediator and therapeutic target in retinal fibrosis.

Real-time continuous glucose monitoring (rtCGM) improves short-term glycemic control in diabetes. However, scant evidence exists regarding rtCGM's longer-term benefits for glycemia or kidney health.

To evaluate whether rtCGM initiation and sustained use is associated with improved glycemic control and kidney markers in high-risk adults with type 2 diabetes (T2D).

This comparative effectiveness research study compared glycemic control and kidney markers among high-risk adults with T2D initiating and sustaining use of rtCGM (rtCGM arm) vs no initiation (controls) using inverse probability-weighted marginal structural models to estimate per-protocol outcomes of an emulated target trial. Target trial eligibility criteria were as follows: age of 19 years or older, T2D, no prior CGM use, and poor glycemic control (hemoglobin A1c [HbA1c] >8%) or emergency department or inpatient treatment for hypoglycemia. Baseline was defined by the rtCGM initiation date and applied to temporally matched CGM-naive controls who met the eligibility criteria, sampled monthly from risk sets from January 1, 2015, to June 30, 2023. Data were censored at nonadherence to the target trial protocol (eg, rtCGM arm discontinued use or controls initiated CGM), coverage gaps, death, or after 36 months of follow-up. Data analysis was performed July 2025 to March 2026.

rtCGM use.

Cumulative differences for HbA1c, urinary albumin-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR).

The study included 25 648 individuals (2771 in the rtCGM arm and 22 877 in the control arm) who were target trial eligible (mean [SD] age, 61.5 [13.1] years; 13 885 [54.7%] male). The mean (SD) baseline HbA1c level was 9.5% (1.5%). After 36 months of follow-up, the rtCGM arm had an approximately 0.8-percentage point lower HbA1c level than controls (7.83% [95% CI, 7.55%-8.11%] vs 8.58% [95% CI, 8.49%-8.66%], P < .001). There was substantial attrition during follow-up; 1228 (44.3%) in the rtCGM arm were censored due to discontinuation and 4284 (18.7%) in the control group were censored due to CGM initiation. There were no significant differences in UACR between arms initially; however, by the end of 36 months, rtCGM initiators had a UACR of 125.3 mg/g (95% CI, -196.6 to -54.0 mg/g; P = .001) lower than that of controls. There were no differences in eGFR during follow-up.

In this comparative effectiveness study using a target trial emulation, sustained, longer-term use of rtCGM was associated with durable improvements in glycemic control and later regression of UACR. By addressing glycemic deterioration, rtCGM may extend the time before pharmacologic escalation is required and potentially delay diabetic kidney disease progression.

Type 1 diabetes (T1D) in children and adolescents has been associated with alterations in attentional and executive functioning. Acute metabolic complications, particularly diabetic ketoacidosis (DKA) and clinically significant hypoglycemia (CSH), may adversely affect neurocognitive development. This study evaluated the associations between acute metabolic events and attentional functioning in pediatric patients with T1D.

The study included 117 children and adolescents with T1D (55 females, 62 males; mean age 12.86 ± 3.16 years). Participants were stratified according to the presence of DKA and CSH. Cognitive functioning was assessed using the MOXO Continuous Performance Test (MOXO-CPT), which evaluates sustained attention, timeliness, impulsivity, and hyperactivity. Associations between cognitive performance and clinical variables were analyzed using ANOVA, ANCOVA, and multivariable regression models.

Patients with a history of CSH demonstrated significantly lower sustained attention (p < 0.001) and timeliness scores (p < 0.001) compared with controls. DKA was associated with poorer impulsivity scores (p = 0.008). After adjustment for age, sex, HbA1c, diabetes duration, and treatment modality, the differences in sustained attention and timeliness, whereas the association with impulsivity was attenuated.

Acute metabolic complications in pediatric T1D were associated with domain-specific alterations in attentional functioning. CSH was primarily related to impaired sustained attention and timeliness, whereas DKA was associated mainly with impulsivity. Early identification of attentional difficulties may support individualized diabetes care and improve long-term metabolic safety.

Ulcerative colitis (UC) is characterized by chronic gastrointestinal inflammation often requiring corticosteroids, both of which may increase long-term cardiometabolic risk. Early colectomy, by eliminating these exposures, may mitigate this risk, though data are limited.

We performed a matched cohort study using the Swedish National Patient Register and ESPRESSO histopathology cohort, identifying individuals aged ≥18 with incident UC (2006-2021, follow-up through 2023). Patients who underwent total colectomy within two years of diagnosis (early colectomy) were matched 1:1 to those without early colectomy using propensity score matching. The primary outcome was incident cardiovascular disease (CVD), with type 2 diabetes mellitus (DM2) assessed as a secondary outcome. Kaplan-Meier and Cox proportional hazards models were used for analyses.

Among 1,832 individuals (median age 45 years, 64.6% male, median post-matching follow-up of 9 years), early colectomy was associated with a significantly lower cumulative incidence of CVD on unadjusted Kaplan-Meier analysis (p=0.02). The CVD incidence rate was 9.1 per 1,000 person-years in the early colectomy group versus 13.0 in controls; after adjustment for baseline covariates, early colectomy was associated with a 32% lower risk of CVD, though this did not reach statistical significance (aHR 0.68, 95% CI 0.44-1.06). A numerically lower risk of DM2 was also observed (incidence rate: 5.5 vs 5.8 per 1,000 person-years; aHR 0.76, 95% CI 0.39-1.48); findings were consistent across sensitivity analyses.

Early colectomy was associated with numerically lower risks of CVD and DM2 in UC, raising the possibility that earlier surgical intervention may mitigate long-term cardiometabolic risk beyond established IBD-related benefits, though confirmation in larger studies is needed.

Type 2 diabetes mellitus (T2DM) is associated with abnormal ventricular repolarization and increased arrhythmic risk. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors may exert electrophysiological effects beyond glycemic control. We investigated changes in electrocardiographic (ECG) markers of ventricular repolarization after dapagliflozin initiation in SGLT-2 inhibitor-naïve patients with T2DM according to heart failure (HF) phenotype.

In this prospective, non-randomized, controlled observational study, 700 patients with T2DM were enrolled between June 2023 and February 2026. Patients initiating dapagliflozin (n = 350) were classified as HFrEF (LVEF <50%, n = 87), HFpEF (LVEF ≥50% with HF, n = 93), or no HF (LVEF ≥50% without HF, n = 170); 350 controls continued pre-existing antidiabetic therapy. Twelve-lead ECG and echocardiography were performed at baseline and 3 months. Prespecified endpoints included QT, QTc, QT dispersion, Tp-e, Tp-e/QT, and Tp-e/QTc. Inverse probability of treatment weighting and Holm-Bonferroni correction were applied.

Dapagliflozin was associated with greater reductions in all prespecified ECG parameters than controls (all between-group p <0.001; Cohen's d = 0.48-1.08), with consistent findings after IPTW. Reductions were greatest in HFrEF (QTc = -14.3 ms; Tp-e = -9.1 ms), followed by HFpEF (-11.2 and -7.4 ms) and no HF (-7.6 and -3.8 ms); all between-subgroup comparisons p <0.001. HFrEF independently predicted greater QTc reduction (β = -4.8 ms vs no HF, p < 0.001). Change in Tp-e correlated weakly with HbA1c change (r = -0.145, p = 0.037). LVEF increased in HFrEF (+3.2%) and HFpEF (+0.9%).

Dapagliflozin initiation was associated with reductions in multiple ECG markers of ventricular repolarization, with the greatest changes observed in HFrEF. These findings concern surrogate ECG measures and do not establish a reduction in clinical arrhythmic events. Confirmation in prospective randomized trials is warranted.

Cardiometabolic risk factors (CMRF) have traditionally been overlooked in alcohol-related liver disease (ALD) and their prognostic impact in alcohol-related hepatitis (AH) remains poorly defined. We evaluated the influence of CMRF burden and therapeutic control on complications and mortality in AH.

We prospectively enrolled 100 patients with biopsy-proven AH. CMRF (obesity, hypertension, diabetes, hyper-triglyceridaemia, low HDL cholesterol) and therapeutic control prior to admission were assessed. A cardiometabolic burden (CMB) score (0-10), incorporating CMRF number and control, was constructed. External validity was tested in an independent multicentre cohort of 332 patients with clinically diagnosed AH.

In the primary cohort, patients with CMRF had higher 1-year mortality than those without (48% vs. 25%, p = 0.030) and more frequent in-hospital complications. Clustered CMRF (≥ 3) independently predicted 1-year mortality after adjustment for MELD, age and sex (HR = 4.1, 95% CI: 1.66-10, p = 0.002). Increasing CMB scores (≥ 5) similarly associated with higher mortality (HR = 4.4, 95% CI: 1.76-11, p = 0.002). These findings were reproduced in the external cohort, where ≥ 3 CMRF predicted 1-year mortality (HR = 3.0, 95% CI: 1.97-4.7, p < 0.001). Furthermore, ≥ 3 CMRF independently predicted 1-year mortality beyond MELD and Lille response in treated patients (HR = 2.6, 95% CI: 1.46-4.5, p = 0.001).

Clustered (≥ 3) and poorly controlled CMRF significantly impair survival and increase complication rates in AH. These findings, confirmed in an independent multicentre cohort, support integrating systematic cardiometabolic evaluation into routine clinical ALD management.

Type 2 diabetes mellitus (T2DM) alters bone quality at the matrix level in ways that current methods do not fully capture. Raman spectroscopy provides molecular information on bone composition and is well suited to probing such alterations. Full-spectrum Raman data were acquired from cortical bone of fresh-frozen cadaveric femurs from 60 non-diabetic and 60 T2DM donors (equal numbers of men and women, aged 50-97 years), followed by uniaxial tensile testing. Machine learning (ML) models (random forest [RF], gradient boosting machine [GBM], adaptive boosting [AdaBoost], stacking) and a one-dimensional convolutional neural network (1D CNN) were trained on the full spectrum to predict tensile properties. A combined 1D CNN and multilayer perceptron (MLP) model that added clinical variables (age, sex, group) reached the highest performance, with R² values from 0.83 to 0.89, while spectral-only models also performed well. These findings show that full-spectrum Raman analysis with deep learning (DL) predicts tensile mechanical behavior of human cortical bone. SHapley Additive exPlanations (SHAP) analysis further showed that collagen associated spectral regions, rather than mineral-related regions, were the primary contributors to the model predictions.

Pyoderma is considered a secondary complication of diabetes mellitus (DM), yet the relationship remains unclear. One study found 22% of diabetic dogs with dermatopathy had no other comorbidities while cats have not been evaluated.

This study evaluated the association of DM and pyoderma in dogs and cats by identifying comorbidities.

This retrospective study analysed canine and feline DM cases from August 2019 to November 2022 at Iowa State University and Colorado State University. We analysed cytologically confirmed pyoderma and assessed the prevalence of comorbidities, including allergies, thyroid and adrenal disease, neoplasia and other dermatological disorders.

Pyoderma was prevalent in 7.6% (61 of 805) dogs and 4.0% (15 of 372) cats with concurrent DM. Of 61 dogs, two (3.3%) lacked comorbidities which was considered protective (odds ratio [OR] = 0.06; 95% CI 0.01-0.29; p < 0.001). Allergic dermatitis was the most common comorbidity (70.5%) in dogs with increased odds (OR = 9.15; 95% CI 4.25-19.72; p < 0.001). Among 15 cats, one (6.7%) lacked comorbidities (OR = 0.04; 95% CI 0.01-0.34; p = 0.003), while allergic dermatitis appeared most frequent and increased odds (73.3%; OR = 18.67; 95% CI 4.81-72.44; p < 0.001). West Highland white terriers (OR = 4.59; 95% CI 1.43-14.77; p = 0.011) and domestic medium hair cats (OR = 7.31; 95% Cl 1.05-50.68; p = 0.044) had increased odds of pyoderma.

This study suggests that pyoderma in DM cats and dogs is uncommon as pyoderma owing to DM alone being seen in only 0.25% of dogs and 0.27% of cats.

BackgroundThe widespread success of tobacco control policy and smoking cessation campaigns has led to considerable reductions in lung cancer mortality. However, it is currently not known how many more deaths might have occurred if not for the substantial progress made in lung cancer control.MethodsIn this retrospective study, we used age-specific population counts and lung cancer mortality rates from 1950 to 2019 (from 48 countries) from the Global Cancer Observatory. We estimated age-standardized mortality rates (ASMR), standardized to the WHO (2000-2025) Standard Population. Peak mortality was defined as the year when the maximum ASMR was reached for each country and sex. For each year in the period following peak mortality, the expected number of lung cancer deaths was estimated using peak-year age-specific mortality rates and age-specific population counts for that year. The number of avoided deaths was estimated as the difference between expected and observed lung cancer deaths in that period.ResultsLung cancer mortality peaked for males in all 48 countries but has yet to peak for females in 11 countries. There have been 3.08 million avoided lung cancer deaths since mortality rates peaked for many countries (2.93 million for males, 0.15 million for females). Across these countries, 21.4% and 4.3% of expected lung cancer mortality has been avoided since mortality peaked for males and females, respectively. Fourteen countries have reduced lung cancer mortality more than 25% for men, while only two countries have for women. There have been statistically significant reductions in lung cancer deaths for 46 out of 48 (96%) countries for men and 14 out of 48 (29%) countries for women.ConclusionThere has been a substantial number of lung cancer deaths avoided since mortality rates peaked for many countries, though the reduction in mortality has not been observed in all countries or equally for males and females.

Understanding how women navigate fertility-related decisions after a breast cancer diagnosis is critical for patient-centered survivorship care in low-resource settings. This study explored young women's fertility-related perspectives and, importantly, how their experiences point to system-level gaps in oncofertility counseling and access to fertility preservation at a periurban cancer center in Uganda.

A qualitative phenomenologic study design was used. Twenty young adult women diagnosed with breast cancer were purposively selected from St Francis Hospital Nsambya, in Kampala, Uganda. Data were collected through face-to-face, semistructured, in-depth interviews guided by an interview schedule. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis to systematically identify themes, subthemes, and illustrative quotes from participants' narratives.

Four major themes emerged from the analysis: (1) Cultural and Societal Significance of Motherhood-childbearing held significant personal and cultural importance, affecting participants' identity and relationship decisions; (2) Need for Comprehensive Fertility Counseling-participants expressed the necessity for timely, empathetic, and detailed fertility information from health care providers and self-esteem; (3) Uncertainty about ika Fertility-considerable anxiety was expressed regarding potential infertility and adverse treatment effects on future offspring, resulting in difficult prioritization between survival and reproduction; and (4) Beyond reach-significant barriers, including high costs, lack of health insurance, and limited service availability, restricted participants' ability to pursue fertility preservation.

Young women with breast cancer in Uganda experience profound fertility-related distress shaped by sociocultural expectations and by health system constraints. Limited integration of oncofertility counseling into routine oncology care, gaps in provider communication, and restricted access to affordable fertility preservation (infrastructure constraints, high out-of-pocket costs, insurance exclusions, and geographic centralization) complicate decision making and highlight priorities for equitable service delivery.