Journal of Internal Medicine最新文献

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, but its prevalence and severity remain poorly characterized in the general population. Our aim was to estimate the prevalence of MASLD and the risk of advanced fibrosis in a large Swedish general population cohort.

Methods: From the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort, we analyzed 27,763 participants aged 50-64 years who underwent extensive clinical characterization. MASLD was defined as <48 HU on non-contrast liver computed tomography (CT) imaging. The risk for advanced fibrosis was assessed using the dynamic aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio.

Results: MASLD was present in 18.1% of participants and was more common in men than women (25.5% vs. 11.2%). Prevalence increased with cardiometabolic burden: from 7.0% among those without obesity, hypertension, or Type 2 diabetes mellitus (T2DM) to 70.2% among those with all three conditions. MASLD risk was elevated in individuals with obesity alone (adjusted odds ratio [aOR] 5.56; 95% CI = 4.89-6.31), T2DM alone (aOR = 2.66; 95% CI = 2.13-3.33), or hypertension alone (aOR = 1.78; 95% CI = 1.59-1.99). The combination of all three conferred the highest risk (aOR = 17.1; 95% CI = 14.0-20.9). Among persons with MASLD, 24.8% were classified as at risk for advanced fibrosis. Fibrosis risk was independently associated with hypertension (aOR = 1.44; 95% CI = 1.24-1.66), T2DM (aOR = 1.24; 95% CI = 1.06-1.46), male sex (aOR = 1.20; 95% CI = 1.02-1.42), and alcohol consumption (aOR per gram/day = 1.02; 95% CI = 1.01-1.03).

Conclusions: In Sweden, almost one in five middle-aged adults is affected by MASLD, with a quarter of cases at risk of advanced fibrosis. Male sex, obesity, T2DM, and hypertension are important predictors of the prevalence and severity of MASLD.

Background: Evidence regarding the risk of new-onset myasthenia gravis (MG) following statin therapy initiation is limited.

Objectives: To investigate this potential adverse effect using multinational real-world population-based data.

Methods: A self-controlled case series (SCCS) study was conducted using electronic medical records and claims databases from Hong Kong, the United Kingdom (UK) and Japan. Individuals aged ≥18 years with first diagnosis of MG and initiated statins were included. Conditional Poisson regression compared the risk of MG in different risk periods (up to 2 years after initiation) with non-exposure period, adjusted for age. Pooled results based on meta-analysis across all study sites were reported.

Results: In total, 2267 MG cases were analysed. Combined across all study sites, a significantly increased risk of incident MG was observed during the first year after statin initiation compared to non-exposure period, with a higher risk from Days 0-179 (pooled incidence rate ratio [IRR] [95% CI]: 2.662 [1.276-5.553]) than Days 180-364 (1.407 [1.014-1.954]). No increased risk of MG was observed more than 1 year after statin initiation (1.011 [0.848-1.206]). Moreover, the magnitude of MG risk elevation within the first 180 days after statin initiation was more pronounced with higher intensity statin regimens.

Conclusion: In this multinational SCCS study, statin initiation may be associated with increased risk of new-onset MG during the first 6-12 months, with greater magnitude of risk elevation for higher intensity statin therapy. Consideration of the possibility of new-onset MG may be advisable within first 6-12 months after initiating statins, especially for medium-to-high-intensity statin therapy.

Increased urinary albumin excretion is a strong predictor for cardiovascular events in persons with and without decreased glomerular filtration rate and can be assessed with the urinary albumin-to-creatinine ratio (UACR), which is a selective, sensitive, and convenient method for patients. As UACR levels ≥30 mg/g indicate heightened risk for cardiovascular disease (CVD) and chronic kidney disease (CKD) progression, this biomarker may be used to personalize preventive care. Among individuals with UACR ≥30 mg/g, reducing the UACR by at least 30% from the pretreatment (baseline) value is associated with a reduction in the risk for both cardiovascular and kidney events. Monitoring change in the UACR after drug treatment starts can be used to determine a need for medication adjustments, such as dose escalations, switching drug class, or adding further drug classes in patients with UACR ≥30 mg/g. In this review, we discuss how the biomarker UACR may be used to determine CVD and CKD risk, guide treatment, and monitor treatment response, and that the UACR is an effective tool to personalize medicine in patients with CKD.

Objectives: To describe the rationale, design and data collection procedures of the Swedish CArdioPulmonary bioImage Study (SCAPIS) re-examination, which, in its further scope, aims to quantify and explain the development of atherosclerosis, pathological cardiovascular ageing, longitudinal decline in lung function and the malignant transformation of pulmonary nodules among middle-aged Swedes in the longitudinal SCAPIS.

Methods: SCAPIS re-examination is a prospective observational study reassessing approximately 15,000 participants (50% of the original SCAPIS cohort) from six university hospitals. Participants were aged 55-75 years at follow-up, occurring a median of 8.1 years after the baseline investigation. Standardized protocols replicated baseline imaging and functional assessments, including questionnaires, clinical assessments and extensive computer tomography imaging.

Results: Interim analyses of the first 5000 participants (50% women; median age 65.5 [61.8-69.1] years) indicated an expected age-related increase in the prevalence and treatment of hypertension (from 22% to 37%) and diabetes (from 4% to 8%), together with a modest rise in central adiposity. Body mass index (median 26.6 kg/m²) and the proportion of obesity (22%) remained largely stable, whereas current smoking decreased from 7.5% to 3.4%. The observed patterns were consistent in men and women.

Conclusion: Here we present the rationale, design, methods and management of incidental findings in the SCAPIS re-examination. By integrating serial imaging, functional testing and biomarker profiling, the re-examination will furnish unprecedented insight into cardiopulmonary disease dynamics in an ageing population. These data will underpin personalized risk prediction and inform preventive strategies, while serving as a benchmark for future population-based imaging cohorts.

Excess aldosterone is a key driver of cardiovascular, renal, and metabolic injury, promoting hypertension, myocardial fibrosis, proteinuria, and progressive chronic kidney disease (CKD). Conventional therapies, renin-angiotensin-aldosterone system (RAAS) inhibitors, and mineralocorticoid receptor antagonists attenuate downstream receptor signaling but do not suppress aldosterone biosynthesis, allowing residual hormonal activity that perpetuates tissue damage. The long-term efficacy, endocrine selectivity, and clinical significance of directly inhibiting aldosterone synthesis, however, remain only partly defined, particularly with respect to sustained aldosterone suppression, preservation of cortisol production, and applicability across diverse cardiorenal disorders. This review provides a comprehensive and mechanistically focused synthesis of preclinical and clinical evidence on aldosterone synthase inhibitors (ASIs), examining their pharmacologic specificity, hormonal effects, and emerging therapeutic potential in primary aldosteronism (PA), resistant hypertension, and CKD. Next-generation ASIs-including baxdrostat, lorundrostat, dexfadrostat phosphate, and vicadrostat-demonstrate >100-fold selectivity for CYP11B2 over CYP11B1, enabling potent and reversible aldosterone suppression while maintaining cortisol biosynthesis. Across early-phase trials, these agents consistently reduce aldosterone concentrations, lower systolic and diastolic blood pressure, decrease albuminuria, and normalize potassium balance in PA, with favorable safety and minimal hypothalamic-pituitary-adrenal axis disturbance. Collectively, these findings position ASIs as a selective and mechanistically coherent therapeutic strategy that addresses residual aldosterone activity beyond conventional RAAS blockade. Although current evidence relies largely on surrogate endpoints, ongoing phase III outcome trials will determine whether ASIs can translate mechanistic promise into durable cardiovascular and renal protection, potentially redefining the therapeutic landscape of aldosterone-mediated diseases.

Primary aldosteronism (PA) is a common cause of hypertension. Compared to patients with essential hypertension, untreated PA is associated with a two- to fourfold greater risk of cardiovascular disease, renal failure, and death. PA is caused by increased secretion of aldosterone from one adrenal gland in 30% of the patients and both adrenal glands in 70%. Patients with unilateral PA can be cured by adrenalectomy, whereas patients with bilateral PA should be treated with mineralocorticoid receptor antagonists. With these disease-specific treatments, the long-term prognosis is generally favorable. A major challenge in the management of patients with PA is, however, subtype differentiation, that is, to determine whether the disease is unilateral or bilateral. Adrenal imaging using CT or MRI misclassifies more than one third of patients, and clinical variables—including blood pressure, aldosterone, and renin concentrations—provide limited guidance, underscoring the need for more accurate diagnostic approaches. Adrenal vein sampling is currently considered the gold standard for this purpose, but it is a technically challenging procedure performed only in specialized centers. After adrenalectomy for unilateral PA, histopathological assessment and subtyping are crucial for determining postoperative prognosis. This process is complex and relies on detailed functional analyses that are not always straightforward to interpret. Therefore, new approaches for subtyping PA are required. In this review, we summarize recent advances in the management of patients with PA, with particular focus on the limitations of current approaches to subtype differentiation and the emerging roles of novel techniques, including positron emission tomography, steroidomics, proteomics, and transcriptomics.

The etiology of Alzheimer's disease (AD) remains under active debate. In this perspective, we explore the hypothesis that a primarily infection-caused chronic dysregulation and weakening of human innate immunity via the underexpression, degradation, and inactivation of innate immune proteins necessary for direct antimicrobial effects and regulation of host defense and autophagy could lead to AD. Key evidence relates to the fact that important innate immune proteins such as LL-37—which can bind Aβ and block amyloid formation—as well as Apolipoprotein E, antiviral interferons, and TNF-α can be degraded and deactivated by enzymes produced by the common oral anaerobic pathogen Porphyromonas gingivalis (Pg). Pg produces numerous virulence factors; of particular importance for AD are Pg’s gingipain cysteine proteases. Deleterious effects of chronic Pg infection and gingipains include a systemic downregulation and paralysis of the interferon response, particularly the antiviral interferon-lambda response, which enables replication of endemic herpesviruses. The result is a chronic, low-level viral infectious assault on gut, nerves, and brain causing the production of Aβ antimicrobial peptides, accumulation of Aβ plaques, phosphorylation of Tau, progressive neuroinflammation, and neurodegeneration. The resultant innate immune system dysregulation, as an AD etiology, ties together the well-known amyloid cascade hypothesis and the infectious theory of AD into a unified explanation of the pathology and cause of AD. If this theory holds true, it suggests preventative approaches: (1) test for and eradicate Pg from oral flora, and/or directly deactivate the gingipains; and (2) reduce Herpesvirus exacerbations by the use of antiviral drugs and/or vaccines (e.g., Bacillus Calmette–Guérin).