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Prevalence and risk factors for metabolic dysfunction-associated steatotic liver disease in Sweden: Insights from the SCAPIS cohort. 瑞典代谢功能障碍相关脂肪变性肝病的患病率和危险因素:来自SCAPIS队列的见解
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-02-05 DOI: 10.1111/joim.70071
Oumarou Nabi, Jonas Spaak, Göran Bergström, Gunnar Engström, Carl Johan Östgren, Andrei Malinovschi, Joel Kullberg, Anders Blomberg, Tomas Jernberg, Daniel P Andersson, Hannes Hagström

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.

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引用次数: 0
Myasthenia gravis following the initiation of statin therapy: A multinational self-controlled case series study. 开始他汀类药物治疗后的重症肌无力:一项多国自主病例系列研究。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-02-05 DOI: 10.1111/joim.70072
Vincent Ka Chun Yan, Wanchun Xu, Yuta Taniguchi, Kwun Kei Fung, Koon Ho Chan, Gary Kui Kai Lau, Celine Sze Ling Chui, Francisco Tsz Tsun Lai, Xue Li, Masao Iwagami, Rie Masuda, Nanako Tamiya, Sreemanee Raaj Dorajoo, Jing Wei Neo, Esther Wai Yin Chan, Ian Chi Kei Wong, Eric Yuk Fai Wan

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.

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引用次数: 0
The urinary albumin-to-creatinine ratio can direct personalized prevention and treatment for cardiovascular and chronic kidney disease. 尿白蛋白/肌酐比值可以指导心血管和慢性肾脏疾病的个性化防治。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-02-03 DOI: 10.1111/joim.70066
Holly J Kramer, George L Bakris

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.

尿白蛋白排泄量的增加是肾小球滤过率降低或未降低的患者心血管事件的一个强有力的预测因素,可以用尿白蛋白与肌酐比(UACR)来评估,这对患者来说是一种选择性、敏感性和便便性的方法。由于UACR水平≥30mg /g表明心血管疾病(CVD)和慢性肾脏疾病(CKD)进展的风险增加,该生物标志物可用于个性化预防保健。在UACR≥30mg /g的个体中,将UACR从预处理(基线)值降低至少30%与心血管和肾脏事件的风险降低相关。药物治疗开始后监测UACR的变化可用于确定是否需要药物调整,如剂量升级、切换药物类别或在UACR≥30 mg/g的患者中增加药物类别。在这篇综述中,我们讨论了生物标志物UACR如何用于确定CVD和CKD风险、指导治疗和监测治疗反应,以及UACR是CKD患者个性化用药的有效工具。
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引用次数: 0
The Swedish CArdioPulmonary bioImage Study re-examination: Rationale, design, methods, and management of incidental findings. 瑞典心肺生物影像研究复查:基本原理、设计、方法和意外发现的处理。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-01-20 DOI: 10.1111/joim.70068
Elin Good, Göran Bergström, Anders Blomberg, Viiu Blöndal, Gunnar Engström, Erika Fagman, Klas Gränsbo, Shabab Hasan, Shadi Jalali, Tomas Jernberg, Åse Johnsson, Ioannis Katsoularis, Jeanette Kuhl, Andrei Malinovschi, Lina Malm, Vibeke Sparring, Eva Swahn, Richard Ssegonja, Jelmer Westra, Mischa Woisetschläger, Carl Johan Östgren, Emil Hagström

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.

目的:描述瑞典心肺生物图像研究(SCAPIS)复核的基本原理、设计和数据收集程序,在进一步的范围内,旨在量化和解释瑞典中年人在纵向SCAPIS中的动脉粥样硬化、病理性心血管老化、肺功能纵向下降和肺结节恶性转化的发展。方法:scapi重新检查是一项前瞻性观察性研究,重新评估了来自六所大学医院的约15,000名参与者(占原始scapi队列的50%)。随访时,参与者的年龄为55-75岁,基线调查后的中位数为8.1年。标准化方案复制了基线成像和功能评估,包括问卷调查、临床评估和广泛的计算机断层扫描成像。结果:前5000名参与者(50%为女性,中位年龄65.5[61.8-69.1]岁)的中期分析表明,高血压和糖尿病的患病率和治疗(从22%到37%)和糖尿病(从4%到8%)的预期年龄相关增加,同时中心性肥胖略有上升。身体质量指数(中位数26.6 kg/m2)和肥胖比例(22%)基本保持稳定,而目前吸烟人数从7.5%下降到3.4%。观察到的模式在男性和女性中是一致的。结论:本文介绍scapi复检的基本原理、设计、方法和意外发现的处理。通过整合系列成像,功能测试和生物标志物分析,重新检查将为老龄化人口的心肺疾病动态提供前所未有的见解。这些数据将支持个性化的风险预测,并为预防策略提供信息,同时作为未来基于人群的成像队列的基准。
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引用次数: 0
Correction to "Soluble urokinase plasminogen activator receptor and interleukin-6 improve prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes". 对“可溶性尿激酶纤溶酶原激活物受体和白介素-6改善1型糖尿病全因死亡率和主要不良心血管事件的预测”的更正。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-01-14 DOI: 10.1111/joim.70065
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引用次数: 0
Identifying subjects at risk of liver cirrhosis via a range of thresholds for common fibrosis markers: A Welsh general population-based cohort study 通过一系列常见纤维化标志物的阈值来确定有肝硬化风险的受试者:一项基于威尔士普通人群的队列研究。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-01-07 DOI: 10.1111/joim.70064
Trevor A. Hill, Joe West, Joanne R. Morling, Colin J. Crooks

Background

Liver disease is on the increase worldwide, with cirrhosis and liver cancer accounting for around 3.5% of all deaths.

Objectives

Investigate the prognostic utility of three non-invasive liver fibrosis markers in the Welsh primary care population for identification of those at risk of cirrhosis or hepatocellular carcinoma (HCC).

Methods

Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000–2017), we identified people with liver blood tests allowing calculation of three commonly used liver fibrosis markers: aspartate transaminase to alanine transaminase (AST/ALT) ratio, AST to platelet ratio index (APRI) and fibrosis-4 index (FIB-4). We modelled 10-year risk of cirrhosis/HCC across a range of thresholds using competing risk survival analysis and compared their prognostic value using decision curve analysis (DCA).

Results

Blood tests enabling calculation of FIB-4, APRI and AST/ALT were available for 203,005 people. At commonly utilized cut-points to detect advanced fibrosis/cirrhosis of 3.25, 1.5 and 1.0 for FIB-4, APRI and AST/ALT, respectively, the 10-year risks of cirrhosis/HCC were 4.7%, 16% and <1%. DCA demonstrated the APRI has the greatest net benefit for estimating cirrhosis/HCC risk over 10 years, in a general population compared to AST/ALT or FIB-4. In higher risk subgroups, a greater proportion of at-risk patients were captured for fewer referrals. This was also observed in groups with combinations of risk factors.

Conclusion

At risk thresholds often used for referral, liver fibrosis markers had prohibitively high false positive rates unless restricted to subgroups at increased risk of developing severe liver disease.

背景:肝脏疾病在世界范围内呈上升趋势,肝硬化和肝癌约占所有死亡人数的3.5%。目的:研究三种非侵入性肝纤维化标志物在威尔士初级保健人群中用于识别肝硬化或肝细胞癌(HCC)风险的预后效用。方法:使用斯旺西大学(Swansea University)的安全匿名信息链接(SAIL)数据库(2000-2017),我们确定了进行肝脏血液检查的人群,允许计算三种常用的肝纤维化标志物:天冬氨酸转氨酶与丙氨酸转氨酶(AST/ALT)比率、AST与血小板比率指数(APRI)和纤维化-4指数(FIB-4)。我们使用竞争风险生存分析对不同阈值的肝硬化/HCC 10年风险进行建模,并使用决策曲线分析(DCA)比较其预后价值。结果:可计算FIB-4、APRI和AST/ALT的血液检查有203,005人。在常用的检测晚期纤维化/肝硬化的切割点上,FIB-4、APRI和AST/ALT分别为3.25、1.5和1.0,肝硬化/HCC的10年风险分别为4.7%、16%。结论:在通常用于转诊的风险阈值上,肝纤维化标志物具有高得令人难以置信的假阳性率,除非仅限于发生严重肝病风险增加的亚组。
{"title":"Identifying subjects at risk of liver cirrhosis via a range of thresholds for common fibrosis markers: A Welsh general population-based cohort study","authors":"Trevor A. Hill,&nbsp;Joe West,&nbsp;Joanne R. Morling,&nbsp;Colin J. Crooks","doi":"10.1111/joim.70064","DOIUrl":"10.1111/joim.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liver disease is on the increase worldwide, with cirrhosis and liver cancer accounting for around 3.5% of all deaths.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Investigate the prognostic utility of three non-invasive liver fibrosis markers in the Welsh primary care population for identification of those at risk of cirrhosis or hepatocellular carcinoma (HCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000–2017), we identified people with liver blood tests allowing calculation of three commonly used liver fibrosis markers: aspartate transaminase to alanine transaminase (AST/ALT) ratio, AST to platelet ratio index (APRI) and fibrosis-4 index (FIB-4). We modelled 10-year risk of cirrhosis/HCC across a range of thresholds using competing risk survival analysis and compared their prognostic value using decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Blood tests enabling calculation of FIB-4, APRI and AST/ALT were available for 203,005 people. At commonly utilized cut-points to detect advanced fibrosis/cirrhosis of 3.25, 1.5 and 1.0 for FIB-4, APRI and AST/ALT, respectively, the 10-year risks of cirrhosis/HCC were 4.7%, 16% and &lt;1%. DCA demonstrated the APRI has the greatest net benefit for estimating cirrhosis/HCC risk over 10 years, in a general population compared to AST/ALT or FIB-4. In higher risk subgroups, a greater proportion of at-risk patients were captured for fewer referrals. This was also observed in groups with combinations of risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>At risk thresholds often used for referral, liver fibrosis markers had prohibitively high false positive rates unless restricted to subgroups at increased risk of developing severe liver disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 3","pages":"398-413"},"PeriodicalIF":9.2,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aldosterone synthase inhibitors across the translational spectrum: Mechanistic foundations and emerging clinical applications. 醛固酮合成酶抑制剂的翻译谱:机制基础和新兴临床应用。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-01-05 DOI: 10.1111/joim.70061
Matteo Merlo, Francesca Zoccatelli, Gabriele Costa, Lucia Panepinto, Simonetta Friso, Luigi Marzano

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.

过量的醛固酮是心血管、肾脏和代谢损伤的关键驱动因素,可促进高血压、心肌纤维化、蛋白尿和进行性慢性肾脏疾病(CKD)。常规疗法、肾素-血管紧张素-醛固酮系统(RAAS)抑制剂和矿化皮质激素受体拮抗剂会减弱下游受体信号,但不会抑制醛固酮的生物合成,导致残留的激素活性使组织损伤持续存在。然而,直接抑制醛固酮合成的长期疗效、内分泌选择性和临床意义仍然只是部分确定,特别是在持续抑制醛固酮、保持皮质醇产生和适用于各种心肾疾病方面。本文综述了醛固酮合成酶抑制剂(ASIs)的临床前和临床证据,研究了它们在原发性醛固酮增多症(PA)、顽固性高血压和慢性肾病中的药理学特异性、激素效应和新出现的治疗潜力。下一代asis -包括巴洛司他、洛诺司他、磷酸右法罗司他和维卡罗司他-对CYP11B2的选择性是CYP11B1的100倍,在维持皮质醇生物合成的同时实现了有效和可逆的醛固酮抑制。在早期试验中,这些药物持续降低醛固酮浓度,降低收缩压和舒张压,减少蛋白尿,并使PA钾平衡正常化,具有良好的安全性和最小的下丘脑-垂体-肾上腺轴干扰。总的来说,这些发现表明ASIs是一种选择性和机制上一致的治疗策略,可以解决传统RAAS阻断之外的残留醛固酮活性。尽管目前的证据在很大程度上依赖于替代终点,但正在进行的III期结局试验将确定ASIs是否能将机制承诺转化为持久的心血管和肾脏保护,从而有可能重新定义醛固酮介导疾病的治疗前景。
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引用次数: 0
Non-steroidal anti-inflammatory drugs versus acetaminophen and risk of venous thromboembolism: An active comparator new user cohort study 非甾体抗炎药与对乙酰氨基酚和静脉血栓栓塞的风险:一个活跃的比较新用户队列研究。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2026-01-03 DOI: 10.1111/joim.70063
Yuichiro Matsuo, Akira Okada, Hideo Yasunaga

Background

Previous observational studies have reported an increased risk of venous thromboembolism (VTE) among non-steroidal anti-inflammatory drug (NSAID) users compared with non-users. However, these studies may have been subject to bias due to unmeasured confounders related to patient conditions requiring NSAIDs. We employed an active comparator new user cohort design, using acetaminophen as the active comparator.

Methods

New users of either NSAIDs or acetaminophen aged 18–65 years were identified from a Japanese health insurance claims database. The adjusted hazard ratio (aHR) of VTE among new NSAID and acetaminophen users within 60 days of prescription was calculated using propensity score overlap weighting and Cox regression. To examine how a naïve comparison between users and non-users of NSAIDs might affect the results, we repeated the analysis using non-users of NSAIDs as the comparator group instead of acetaminophen users.

Results

Among 4,282,421 new NSAID users and 2,728,202 new acetaminophen users, 1504 (0.022%) developed VTE during follow-up. New NSAID users had a significantly lower incidence of VTE compared with new acetaminophen users (aHR, 0.70; 95% confidence interval [CI], 0.62–0.80). When compared with non-users, NSAID users had a significantly higher incidence of VTE (aHR, 3.18; 95% CI, 2.85–3.55).

Conclusion

Although new NSAID users had a lower incidence of VTE than new acetaminophen users, they had a higher incidence compared with non-users. Assuming that acetaminophen does not increase VTE risk, these findings suggest that NSAIDs themselves may not increase VTE risk.

背景:先前的观察性研究报道了非甾体抗炎药(NSAID)使用者与非使用者相比,静脉血栓栓塞(VTE)的风险增加。然而,这些研究可能由于与需要非甾体抗炎药的患者状况相关的未测量混杂因素而存在偏倚。我们采用主动比较剂新用户队列设计,使用对乙酰氨基酚作为主动比较剂。方法:从日本健康保险索赔数据库中确定年龄在18-65岁的非甾体抗炎药或对乙酰氨基酚的新使用者。采用倾向评分重叠加权和Cox回归计算处方60天内NSAID和对乙酰氨基酚新使用者VTE的调整风险比(aHR)。为了检验使用者和非NSAIDs使用者之间的naïve比较如何影响结果,我们使用非NSAIDs使用者而不是对乙酰氨基酚使用者作为比较组重复了分析。结果:在4,282,421名NSAID新使用者和2,728,202名对乙酰氨基酚新使用者中,1504名(0.022%)在随访期间发生静脉血栓栓塞。新的非甾体抗炎药服用者与新的对乙酰氨基酚服用者相比,静脉血栓栓塞发生率显著降低(aHR, 0.70; 95%可信区间[CI], 0.62-0.80)。与非使用者相比,非甾体抗炎药使用者的静脉血栓栓塞发生率显著高于非甾体抗炎药使用者(aHR, 3.18; 95% CI, 2.85-3.55)。结论:尽管新的非甾体抗炎药服用者的静脉血栓栓塞发生率低于新的对乙酰氨基酚服用者,但与非服用者相比,他们的发生率更高。假设对乙酰氨基酚不会增加静脉血栓栓塞风险,这些发现表明非甾体抗炎药本身可能不会增加静脉血栓栓塞风险。
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引用次数: 0
Emerging methods for subtype differentiation in primary aldosteronism 原发性醛固酮增多症亚型分化的新方法。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2025-12-30 DOI: 10.1111/joim.70055
Oskar Ragnarsson, C. Christofer Juhlin, Tobias Åkerström, Per Dahlqvist, Henrik Falhammar, Per Hellman

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.

原发性醛固酮增多症(PA)是高血压的常见病因。与原发性高血压患者相比,未经治疗的PA与心血管疾病、肾衰竭和死亡的风险增加2 - 4倍相关。PA是由30%的患者单侧肾上腺分泌醛固酮增多引起的,70%的患者双侧肾上腺分泌醛固酮增多。单侧肾上腺皮质激素患者可通过肾上腺切除术治愈,而双侧肾上腺皮质激素患者应使用矿皮质激素受体拮抗剂治疗。使用这些疾病特异性治疗,长期预后通常是有利的。然而,PA患者管理的一个主要挑战是亚型分化,即确定疾病是单侧还是双侧。使用CT或MRI进行肾上腺成像对超过三分之一的患者进行了错误分类,并且临床变量(包括血压、醛固酮和肾素浓度)提供的指导有限,强调需要更准确的诊断方法。肾上腺静脉取样目前被认为是这一目的的金标准,但它是一个技术上具有挑战性的程序,只有在专门的中心进行。单侧肾上腺切除术后,组织病理学评估和分型是决定术后预后的关键。这个过程是复杂的,依赖于详细的功能分析,并不总是直截了当的解释。因此,需要新的PA亚型方法。在这篇综述中,我们总结了PA患者管理的最新进展,特别关注当前亚型分化方法的局限性和新技术的新兴作用,包括正电子发射断层扫描、类固醇组学、蛋白质组学和转录组学。
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引用次数: 0
The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease 牙龈卟啉单胞菌先天免疫失调在阿尔茨海默病病因学中的作用。
IF 9.2 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2025-12-22 DOI: 10.1111/joim.70060
Annelise E. Barron, Jennifer S. Lin, Mark I. Ryder, Peter Bergman

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).

阿尔茨海默病(AD)的病因学仍然存在激烈的争论。从这个角度来看,我们探索了一种假设,即主要是感染引起的人类先天免疫的慢性失调和减弱,通过直接抗菌作用和调节宿主防御和自噬所必需的先天免疫蛋白的低表达、降解和失活,可能导致AD。关键证据表明,重要的先天免疫蛋白,如ll -37(可以结合a - β并阻断淀粉样蛋白的形成)、载脂蛋白E、抗病毒干扰素和TNF-α,可以被常见的口腔厌氧病原体牙龈卟啉单胞菌(Pg)产生的酶降解和失活。Pg产生大量毒力因子;对AD特别重要的是Pg的牙龈蛋白酶半胱氨酸蛋白酶。慢性Pg感染和牙龈疼痛的有害影响包括干扰素反应的系统性下调和瘫痪,特别是抗病毒干扰素-lambda反应,这使得地方性疱疹病毒的复制成为可能。其结果是对肠道、神经和大脑的慢性、低水平病毒感染攻击,导致a β抗菌肽的产生、a β斑块的积累、Tau蛋白的磷酸化、进行性神经炎症和神经退行性变。由此产生的先天免疫系统失调,作为阿尔茨海默病的病因,将众所周知的淀粉样蛋白级联假说和阿尔茨海默病的感染理论联系在一起,形成了对阿尔茨海默病病理和病因的统一解释。如果这一理论成立,它建议预防方法:(1)检测和根除口腔菌群中的Pg,和/或直接使牙龈疼痛消失;(2)通过使用抗病毒药物和/或疫苗(例如卡介苗-谷氨酰胺芽孢杆菌)减少疱疹病毒的恶化。
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Journal of Internal Medicine
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