European Journal of Internal Medicine最新文献

Peripheral ulcerative keratitis (PUK) is a rare and severe ocular manifestation frequently associated with systemic autoimmune diseases. This retrospective two-center observational study including patients with PUK and a systemic autoimmune disease at two tertiary referral centres aimed to characterize clinical and histopathologic features, treatment strategies, relapses, and ocular outcomes of autoimmune-associated PUK, and to analyse its relationship with systemic disease activity. A total of 24 patients (35 eyes) were identified, 62.5 % female, with a median age of 58.5 years and a mean follow-up of 14.4 years. Rheumatoid arthritis (RA) (45.8 %) and granulomatosis with polyangiitis (GPA) (29.2 %) were the most frequent underlying diseases. PUK preceded or coincided with the diagnosis of systemic disease in 41.7 % of cases. At presentation, 45.8 % had bilateral involvement and 58.3 % had associated scleritis. More than half of patients experienced relapses, with a mean annual relapse rate of 0.43. Corneal complications were common and visual acuity worsened or was severely impaired in 37.5 % and 16.7 % of patients, respectively. Most patients received systemic glucocorticoids and additional immunosuppressive therapy, frequently biologic agents, mainly TNF blockers and rituximab, and 20.8 % underwent ocular surgery. Remarkably, 58.3 % patients had no evidence of systemic activity at PUK onset and 83.3 % of PUK relapses were developed with the autoimmune disease in remission. We conclude that autoimmune-associated PUK may precede systemic diagnosis and often occurs with an inactive systemic disease. These findings emphasize the need for careful autoimmune evaluation in all PUK cases and sustained ophthalmologic surveillance even during remission of the systemic disease.

Background: Combination of GLP-1 receptor agonist (GLP-1 RA) and SGLT2 inhibitor (SGLT2i) is a recommended treatment in national and international diabetes guidelines, and the implementation is restricted by Swiss reimbursement standards. The implications for quality of care is partly dependent on the magnitude of patients affected. The aim was therefore to estimate the proportion of outpatients with type 2 diabetes in tertiary care that would be eligible for the combination therapy based on national treatment recommendations.

Methods: Cross-sectional analysis of patients enrolled in SwissDiab at Kantonsspital St. Gallen with a visit in 2021 or later. Patients with a BMI ≥28 kg/m² and thus eligible for GLP-1 RA were identified, including patients prescribed GLP-1 RA with a BMI ≥28 kg/m² at treatment initiation. Of these, patients with heart failure, chronic kidney disease and/or insufficient glycaemic control were considered eligible for the addition of SGLT2i.

Findings: Of 401 identified patients, 73.1% were eligible for GLP-1 RA. Of these, 61.1% had heart failure, chronic kidney disease and/or insufficient glycaemic control. The prevalence of heart failure was 25.7%, chronic kidney disease 77.7%, and insufficient glycaemic control 37.4%. Overall, 44.6% of the patients would stand to benefit from combination therapy.

Interpretation: That almost half of the patients with type 2 diabetes in tertiary care were eligible for combination therapy with GLP-1 RA and SGLT2i highlight the potential negative impact of restricting access to evidence-based care central for the prevention of cardiorenal outcomes and premature death.

Funding: The current study received unrestricted support from AstraZeneca.

Objectives: Left atrial enlargement (LAE) is a cardiac structural abnormality linked to adverse cardiovascular events, including stroke. However, its independent prognostic role in patients without atrial fibrillation (AF) remains unclear.

Design: prospective cohort study.

Setting: three teaching hospitals in Milan, Italy.

Participants: consecutive adults undergoing transthoracic echocardiography (TTE) between 2012 and 2023. Patients with a history of AF or receiving anticoagulant therapy (for any indication) were excluded.

Interventions: participants underwent TTE in the context of standard clinical practice.

Main outcome measures: LAE was categorized by left atrial volume index (LAVi) as absent (≤34 mL/m²), mild (>34 and ≤41 mL/m²), moderate (>41 and ≤48 mL/m²), or severe (>48 mL/m²). The primary outcome was a composite of cerebrovascular events (CVEs), including ischemic stroke or transient ischemic attack (TIA), within 1 year of the index echocardiogram. Multivariate logistic regression models were used to evaluate the independent association of LAE with 1-year CVEs.

Results: We included 53,109 subjects with a median age of 66 years (48 % female). CVEs occurred in 1318 subjects (2.5 %). In the multivariate analysis, all categories of LAE were associated with 1-year CVEs compared with no LAE (mild: OR 1.21, 95 % CI 1.03 to 1.43; moderate: OR 1.48, 95 % CI 1.20 to 1.83; severe: OR 1.85, 95 % CI 1.54 to 2.22). This association was independent of other relevant predictors.

Conclusions: LAE defined by LAVi is associated with 1-year CVEs in subjects without known AF and ongoing anticoagulation, suggesting that LAVi can serve as a marker to refine CVE risk stratification.

Transthyretin amyloid cardiomyopathy (ATTR-CM) has been traditionally considered a rare and inexorably fatal condition. However, the development of therapies able to slow or halt ATTR-CM progression and increase survival have transformed the management of this condition. As these treatments become more accessible, the need for clinical indicators of disease progression has become increasingly important to guide clinical decision-making and personalise treatment strategies. Changes in widely available parameters have been shown to track disease evolution, which include worsening heart failure symptoms, outpatient diuretic initiation or intensification, decline in the 6-minute walk test, N-terminal pro-B-type natriuretic peptide, estimated glomerular filtration rate, and structural and functional parameters on cardiac imaging. Given the complexity of ATTR-CM, an integrated, multiparametric approach may provide a more precise assessment of disease trajectories and prognosis. Beyond stabilization and suppression of the circulating transthyretin protein, novel therapeutic approaches, including strategies aimed at clearing amyloid deposits, have shown potential for disease regression, even in patients with advanced involvement. With these advancements, ATTR-CM is shifting from an untreatable disease to a manageable condition where both survival and quality of life can be significantly improved. Future randomised controlled trial of disease-modifying treatments in ATTR-CM might use established criteria of disease progression as surrogate endpoints to have sufficient power and consider endpoints that are still clinically meaningful.

Background: To systematically evaluate polypill effects on cardiovascular (CV) risk factors, CV outcomes, and adverse events in CV disease (CVD) prevention populations.

Methods: Systematic searches were conducted in five databases from inception to November 7, 2025, for randomized controlled trials (RCTs) that assessed the effects of polypills for prevention of primary or secondary CVD. Three reviewers independently screened articles, extracted data, assessed risk of bias (RoB) and evaluated GRADE quality of evidence (QoE). Inverse variance meta-analyses were conducted. Primary outcomes included all-cause mortality (ACM), CV death, all-cause hospitalization (ACH), and CV hospitalization (CVH).

Results: Thirteen RCTs (n = 27,836) were included. Seven RCTs investigated primary prevention, three secondary preventions, and three in both populations. When compared to controls, polypills had little to no effect on ACM (RR 0.93, 95 %CI 0.82-1.05, 9 RCTs), stroke (RR 0.61, 95 %CI 0.46-0.81, 4 RCTs), heart failure (RR 0.94, 95 %CI 0.57-1.53, 4 RCTs) and revascularization (RR 0.73, 95 %CI 0.49-1.10, 2 RCTs) and may slightly reduce CV death (RR 0.69, 95 %CI 0.57-0.83, 5 RCTs), CVH (RR 0.80, 95 %CI 0.60-1.06, 2 RCTs), and ACH (RR 0.89, 95 %CI 0.77-1.03, 3 RCTs). Polypills probably reduced MI slightly (RR 0.69, 95 %CI 0.50-0.95, 2 RCTs). Polypills had small, significant reductions of SBP, DBP, total cholesterol, and LDL, and small, non-significant increases of adverse events (AEs), serious AEs and adherence. Subgroup analyses were mostly consistent with main analyses.

Conclusions: In primary and secondary prevention settings, polypills had moderate reductions of CV outcomes, small effects on CV risk factors, and small increases of AEs.