Journal of Internal Medicine最新文献_第5页

Coexisting inflammatory bowel disease in primary sclerosing cholangitis is associated with higher colorectal cancer and transplant risk 原发性硬化性胆管炎并发炎性肠病与较高的结直肠癌和移植风险相关。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-10-14 DOI: 10.1111/joim.70026

Chengu Niu, Jing Zhang, Prajjwol Bhatta, Kaiwen Zhu, Nagesh Jadhav, Patrick I. Okolo, Asim Mushtaq, Ebubekir Daglilar

Background

Primary sclerosing cholangitis (PSC) is often intertwined with inflammatory bowel disease (IBD), presenting a complex clinical scenario. The coexistence of IBD–PSC complicates disease management and progression, potentially exacerbating outcomes.

Objectives

This study aims to evaluate the specific impact of IBD in patients with PSC, focusing on both liver-related and IBD-specific clinical outcomes.

Methods

This retrospective study, utilizing the TriNetX database, performed propensity score matching to compare clinical outcomes between IBD–PSC and PSC-only patients, as well as IBD–PSC and IBD-only patients. Diagnoses were identified based on International Classification of Diseases-10 coding.

Results

The study analyzed 1941 patients with IBD–PSC, 234,081 with IBD alone, and 628 with PSC alone. Patients with IBD–PSC had significantly higher mortality compared to IBD alone (16.0% vs. 7.5%; hazard ratio [HR]: 2.256, 95% confidence interval [CI]: 1.853–2.747, p < 0.001), as well as increased rates of hospitalization (32.8% vs. 14.5%; HR: 2.641, 95% CI: 2.213–3.152, p < 0.001) and intensive care unit admission (18.7% vs. 5.8%; HR: 3.691, 95% CI: 2.954–4.612, p < 0.001). Colorectal cancer was also more frequent in the IBD–PSC group (2.4% vs. 0.7%; HR: 3.370, 95% CI: 1.846–6.152, p < 0.001). When compared to PSC alone, IBD–PSC patients had a higher rate of liver transplantation (12.3% vs. 8.0%; HR: 1.492, 95% CI: 1.012–2.198, p = 0.042), whereas rates of hepatocellular carcinoma and cholangiocarcinoma were similar between groups.

Conclusions

Patients with coexisting IBD and PSC experience greater clinical severity, including higher mortality, hospitalization, and colorectal cancer risk. They also have increased liver transplant incidence. Further research is needed to explore underlying mechanisms and improve management.

背景：原发性硬化性胆管炎（PSC）常与炎症性肠病（IBD）交织在一起，呈现出复杂的临床情况。IBD-PSC的共存使疾病管理和进展复杂化，潜在地加剧了预后。目的：本研究旨在评估IBD对PSC患者的特异性影响，重点关注肝脏相关和IBD特异性临床结局。方法：本回顾性研究利用TriNetX数据库，进行倾向评分匹配，比较IBD-PSC和单纯psc患者，以及IBD-PSC和单纯ibd患者的临床结果。诊断依据国际疾病分类-10编码。结果：该研究分析了1941例IBD-PSC患者，234,081例IBD单独患者和628例PSC单独患者。IBD-PSC患者的死亡率明显高于单纯IBD患者（16.0% vs. 7.5%）；风险比[HR]: 2.256, 95%可信区间[CI]: 1.853-2.747， p结论：IBD和PSC共存患者的临床严重程度更高，包括更高的死亡率、住院率和结直肠癌风险。他们也增加了肝移植的发生率。需要进一步的研究来探索潜在的机制和改善管理。

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引用次数: 0

Health inequalities in the Nordic countries: A comparative overview and update 北欧国家的卫生不平等：比较概述和最新情况。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-10-11 DOI: 10.1111/joim.70029

Johan Fritzell, Stefan Fors

In this article, we present the state-of-the-art on socioeconomic health inequalities with a focus on the Nordic countries. Health inequalities have increased over time and can be observed for both mortality and morbidity. We show that cross-national comparisons reveal surprisingly high inequalities in the Nordic countries. It is now well established that health and mortality inequalities prevail also at older ages. We show, with data from Sweden, that the interpretation of how mortality inequalities evolve over the life course is markedly different depending on whether we focus on absolute or relative inequalities. Although there is a consensus on basic descriptive facts, disagreements on how these facts are best explained and why they persist and even increase remain. We present a general discussion on how to explain health inequalities, as well as a discussion on why patterns may differ between European regions and across the life course. We introduce a framework for understanding health inequalities, fundamental cause theory and discuss to what extent the evidence aligns with the theory. We review contemporary discussions on health inequalities in light of recent evidence based on novel methods for causal inference. We argue that health inequalities have important ramifications for population health regardless of whether they are primarily shaped by social causation or social selection and end by noting that as modern societies aspire to become more meritocratic, it is possible that socioeconomic position becomes increasingly important for health.

在本文中，我们以北欧国家为重点，介绍了社会经济健康不平等的最新情况。随着时间的推移，保健不平等现象有所增加，在死亡率和发病率方面都可以观察到。我们表明，跨国比较显示北欧国家的不平等程度高得惊人。现已确定的是，健康和死亡率不平等现象在老年人中也普遍存在。我们用瑞典的数据表明，对死亡率不平等在生命过程中如何演变的解释，取决于我们关注的是绝对不平等还是相对不平等。尽管人们对基本的描述性事实达成了共识，但关于如何最好地解释这些事实以及为什么它们持续存在甚至增加的分歧仍然存在。我们就如何解释健康不平等进行了一般性讨论，并讨论了为什么欧洲各区域之间和整个生命过程中的模式可能不同。我们介绍了一个理解健康不平等的框架，基本原因理论，并讨论了证据在多大程度上与理论一致。我们根据基于新因果推理方法的最新证据回顾了当代关于健康不平等的讨论。我们认为，健康不平等对人口健康有着重要的影响，无论它们主要是由社会因果关系还是社会选择形成的，最后我们注意到，随着现代社会渴望变得更加精英化，社会经济地位对健康可能变得越来越重要。

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引用次数: 0

CD71+ erythroid cell expansion in late-onset systemic lupus erythematosus CD71+红细胞在迟发性系统性红斑狼疮中的扩增。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-10-06 DOI: 10.1111/joim.70027

Jian Hao, Yuechen Cui, Jun Du, Jing Cui, Hui-Qi Qu, Fumin Qi, Hui Wang, Na Zhang, Jin Li, Wei Wei

Background

Systemic lupus erythematosus (SLE) mainly affects women of reproductive age. Late-onset SLE patients (lo-SLE, ≥50 years) are generally indolent and have less severe manifestations.

Objective

The present study aims to decode molecular differences underlying the distinct clinical presentations between lo-SLE and early onset SLE patients.

Methods

In a cohort of 243 treatment-naïve Chinese SLE female patients, we carried out clinical analysis and experimental validation studies. RNA-seq was used to identify differentially expressed genes (DEGs) of lo-SLE patients. Reverse transcription quantitative polymerase chain reaction and flow cytometry were utilized to validate DEGs and enriched cell types. The discovery was further compared to findings in a European cohort. The immunosuppressive function of CD71⁺CD235a⁺ erythroid cells (CECs) was evaluated by coculturing peripheral blood mononuclear cells (PBMCs) with CECs.

Results

Differential expression analysis identified a group of hub upregulated genes in lo-SLE patients. These genes, overrepresented in erythrocyte differentiation, are highly enriched in CECs. In our Chinese cohort, CECs abundance in peripheral blood was inversely correlated with disease activity. Increased CECs in treatment-naïve lo-SLE patients may play an immunosuppressive role by inhibiting CD8⁺ T cell function and IFN-γ production. This immunosuppressive role was evidenced by the significant suppression of IL-6, IFN-γ, and IL-17A production by healthy donor's PBMCs cocultured with SLE bone marrow-derived CECs.

Conclusions

This pioneering study has revealed a panel of CECs genes as potential molecular markers for lo-SLE, supporting a novel erythroid modulation theory. These novel findings provide valuable insights into previously unrecognized molecular mechanisms underlying the latent disease activity of lo-SLE.

背景：系统性红斑狼疮（SLE）主要影响育龄妇女。迟发性SLE患者（低SLE，≥50岁）一般表现为懒散，症状较轻。目的：本研究旨在解码低SLE和早发SLE患者不同临床表现的分子差异。方法：对243例treatment-naïve中国SLE女性患者进行临床分析和实验验证研究。RNA-seq用于鉴定低sle患者的差异表达基因（DEGs）。利用逆转录定量聚合酶链反应和流式细胞术验证deg和富集的细胞类型。这一发现与一项欧洲队列研究的结果进行了进一步比较。通过外周血单个核细胞（PBMCs）与CECs共培养，评价CD71+CD235a+红细胞（CECs）的免疫抑制功能。结果：差异表达分析在低sle患者中发现了一组hub上调基因。这些基因在红细胞分化中被过度表达，在CECs中高度富集。在我们的中国队列中，外周血中CECs的丰度与疾病活动性呈负相关。treatment-naïve低sle患者CECs升高可能通过抑制CD8 + T细胞功能和IFN-γ产生发挥免疫抑制作用。通过与SLE骨髓源性CECs共培养的健康供体pbmc显著抑制IL-6、IFN-γ和IL-17A的产生，证明了这种免疫抑制作用。结论：这项开创性的研究揭示了一组CECs基因作为低sle的潜在分子标记，支持了一种新的红细胞调节理论。这些新发现为低系统性红斑狼疮潜伏性疾病活动的分子机制提供了有价值的见解。

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引用次数: 0

Low positive and borderline negative transglutaminase antibody levels are frequently associated with a coeliac disease diagnosis 低阳性和交界阴性的谷氨酰胺转胺酶抗体水平通常与乳糜泻诊断相关。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-25 DOI: 10.1111/joim.70025

Rakel Nurmi, Celina Turunen Beteta, Kalle Kurppa, Heini Huhtala, Katri Lindfors, Laura Kivelä, Katri Kaukinen, Saana Paavola

Background

Due to the expanding screening of coeliac disease (CeD), low positive and borderline negative serum transglutaminase 2 antibody (TGA) values are causing increasing confusion in clinical practice.

Objectives

To investigate the significance of these findings in a well-defined patient cohort.

Methods

Altogether 311 IgA-competent adults, with clinical suspicion or family history of CeD, underwent duodenal sampling and testing for TGA (ImmunoCAP EliA, cut-off 7.0 U/mL) and endomysial antibodies (EmA). TGA values 7.0–14.0 U/mL were defined as low positive and 3.0–6.9 U/mL as borderline negative. Besides conventional histology, small bowel mucosal TGA-targeted IgA deposits and γδ+ intraepithelial lymphocytes (IELs) were determined as CeD-specific markers.

Results

Twenty-eight (9%) individuals had low positive TGA, and 22 (79%) were also positive for EmA. Among those with low positive TGA, all EmA positive and 50% of the EmA negative subjects were diagnosed with CeD. Thirty-nine individuals (13%) had borderline negative TGA, and 36% were positive for EmA. Of these, 79% of EmA positive and 12% of EmA negative subjects were diagnosed with CeD. Additionally, 29% of the subjects with borderline negative TGA and no diagnosis exhibited signs of incipient CeD, including positive IgA deposits, increased density of γδ+ IELs and presence of human leukocyte antigen DQ2/DQ8. All subjects with TGA ≥ 3.2× upper limit of normal (22.4 U/mL) received a CeD diagnosis.

Conclusion

Low positive and borderline negative TGA frequently implies a CeD diagnosis, particularly in EmA positive individuals, or at least may be an indicator of an early stage of the disease.

背景：由于乳糜泻（CeD）筛查的扩大，血清转谷氨酰胺酶2抗体（TGA）低阳性和交界阴性值在临床实践中引起越来越多的混淆。目的：探讨这些发现在明确的患者队列中的意义。方法：对311例临床怀疑或有CeD家族史的iga合格成人进行十二指肠取样，检测TGA （ImmunoCAP EliA，截止值7.0 U/mL）和肌内膜抗体（EmA）。TGA值7.0 ~ 14.0 U/mL定义为低阳性，3.0 ~ 6.9 U/mL定义为交界阴性。除常规组织学外，测定小肠黏膜tga靶向IgA沉积和γδ+上皮内淋巴细胞（IELs）作为ced特异性标志物。结果：28人（9%）TGA低阳性，22人（79%）EmA阳性。在TGA低阳性的受试者中，所有EmA阳性和50% EmA阴性的受试者被诊断为CeD。39例（13%）TGA呈阴性，36%的EmA呈阳性。其中，79%的EmA阳性和12%的EmA阴性受试者被诊断为CeD。此外，29%的TGA阴性且未确诊的受试者表现出早期CeD的迹象，包括IgA阳性沉积，γδ+ IELs密度增加和人白细胞抗原DQ2/DQ8的存在。所有TGA≥3.2×正常上限（22.4 U/mL）的受试者均被诊断为CeD。结论：低阳性和交界性阴性TGA通常意味着CeD诊断，特别是在EmA阳性个体中，或者至少可能是疾病早期的一个指标。

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引用次数: 0

Characterizing VEXAS syndrome in women: Findings from an international multicenter study 妇女VEXAS综合征的特征：来自一项国际多中心研究的发现。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-23 DOI: 10.1111/joim.70023

Rim Bourguiba, Valentin Lacombe, David Beck, Eduardo Martín-Nares, Vincent Jachiet, Thibault Comont, Joris Galland, Mael Heiblig, Alexandre Nguyen, Achille Aouba, Xavier Boulu, Alexandre Curie, Benjamin Terrier, Charles Bescond, Matthew Koster, Yohei Kirino, Olivier Kosmider, Arsene Mekininan, Sophie Georgin-Lavialle

Background

VEXAS syndrome is an autoinflammatory disease caused by somatic UBA1 mutations on the X chromosome, predominantly affecting men.

Objective

To characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes.

Methods

We conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally.

Results

Clinical features, age at onset, UBA1 mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional UBA1-mutated women without typical inflammation are described separately.

Conclusion

VEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.

背景：VEXAS综合征是一种由X染色体上的体细胞UBA1突变引起的自身炎症性疾病，主要影响男性。目的：探讨女性腰痛综合征的特点，并比较腰痛综合征的性别特征。方法：我们进行了一项国际多中心研究，包括12名女性和301名男性，遗传证实为VEXAS综合征。使用标准化病例报告表收集数据。局部进行骨髓分析和分子调查。结果：临床特征、发病年龄、UBA1突变类型、变异等位基因频率和死亡率在性别间具有可比性。在6/8的测试女性中发现获得性X单体。在3/5的受测妇女中存在额外的克隆突变。另外三名没有典型炎症的uba1突变妇女分别被描述。结论：VEXAS综合征影响的女性临床特征与男性相似，支持对表现一致的女性进行UBA1检测的必要性。X单体是常见的，但不是普遍的，提示其他致病机制。

{"title":"Characterizing VEXAS syndrome in women: Findings from an international multicenter study","authors":"Rim Bourguiba, Valentin Lacombe, David Beck, Eduardo Martín-Nares, Vincent Jachiet, Thibault Comont, Joris Galland, Mael Heiblig, Alexandre Nguyen, Achille Aouba, Xavier Boulu, Alexandre Curie, Benjamin Terrier, Charles Bescond, Matthew Koster, Yohei Kirino, Olivier Kosmider, Arsene Mekininan, Sophie Georgin-Lavialle","doi":"10.1111/joim.70023","DOIUrl":"10.1111/joim.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>VEXAS syndrome is an autoinflammatory disease caused by somatic <i>UBA1</i> mutations on the X chromosome, predominantly affecting men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clinical features, age at onset, <i>UBA1</i> mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional <i>UBA1</i>-mutated women without typical inflammation are described separately.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>VEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"516-524"},"PeriodicalIF":9.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Albuminuria is associated with increased risk of dementia, independent of eGFR: The SCREAM project 蛋白尿与痴呆风险增加有关，独立于eGFR：尖叫项目。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-23 DOI: 10.1111/joim.70022

Li Luo, Ron T. Gansevoort, Lyanne M. Kieneker, Yuanhang Yang, Alessandro Bosi, Rudolf A. de Boer, Casper F. M. Franssen, Maria Eriksdotter, Juan-Jesus Carrero, Hong Xu

Background

The association between albuminuria and dementia has been insufficiently studied, possibly due to not considering dementia subtypes, the interplay with estimated glomerular filtration rate (eGFR), and the use of varying albuminuria measurement techniques.

Objectives

This study aimed to investigate the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, measured by the urine albumin-creatinine ratio (ACR) and dipstick.

Methods

The main analysis included 132,869 subjects aged ≥65 years without a history of dementia and with at least one ACR test from the Stockholm Creatinine Measurements (SCREAM) project between 2006 and 2019. The primary and secondary outcomes were the incidence of all-cause dementia and type-specific dementia, respectively. Cox regression models were used to calculate hazard ratios (HRs, 95% CIs).

Results

During a median follow-up of 3.9 (interquartile ranges, 1.8–7.1) years, 9435 (7%) subjects developed incident dementia. After multivariable adjustments, including eGFR, an ACR level of 30–299 and ≥300 mg/g was associated with a 25% (HR, 1.25; 95% CI, 1.19–1.31) and a 37% (HR, 1.37; 95% CI, 1.23–1.51) higher risk of developing all-cause dementia, respectively, compared to an ACR level of <30 mg/g. Higher ACR levels were also associated with an increased risk of mixed, vascular, and unspecified dementia, but not with Alzheimer's disease. These findings were robust in subjects with at least one dipstick proteinuria test.

Conclusion

Increased albuminuria is associated with a higher risk of all-cause dementia, particularly mixed, vascular, and unspecified dementia, independent of baseline eGFR and generalizable across different clinical pathways of albuminuria testing.

背景：蛋白尿和痴呆之间的关系尚未得到充分的研究，可能是由于没有考虑到痴呆亚型、与肾小球滤过率（eGFR）估计的相互作用以及不同蛋白尿测量技术的使用。目的：本研究旨在通过尿白蛋白-肌酐比（ACR）和尿量尺测量egfr不依赖于全因和类型特异性痴呆与蛋白尿相关的风险。方法：主要分析包括132,869名年龄≥65岁，无痴呆病史，并在2006年至2019年期间接受斯德哥尔摩肌酐测量（SCREAM）项目至少一项ACR测试的受试者。主要和次要结果分别是全因痴呆和类型特异性痴呆的发病率。采用Cox回归模型计算风险比（hr, 95% ci）。结果：在中位随访3.9年（四分位数间距1.8-7.1年）期间，9435名（7%）受试者发生了偶发性痴呆。在包括eGFR在内的多变量调整后，ACR水平为30-299和≥300 mg/g与25% （HR, 1.25; 95% CI, 1.19-1.31）和37% (HR, 1.37；结论：蛋白尿增加与全因痴呆的高风险相关，特别是混合性、血管性和未明确的痴呆，与基线eGFR无关，可在不同的蛋白尿检测临床途径中推广。

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引用次数: 0

Oral anticoagulation in patients with gastrointestinal bleeding and new-onset atrial fibrillation: A population-based registry-linkage study 胃肠出血和新发房颤患者的口服抗凝治疗：一项基于人群的登记关联研究

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-23 DOI: 10.1111/joim.70018

Santeri Jolkkonen, Jukka Putaala, Konsta Teppo, Pirjo Mustonen, Jussi Jaakkola, Aapo Aro, Olli Halminen, Ossi Lehtonen, Jari Haukka, Miika Linna, Juha Hartikainen, K. E. Juhani Airaksinen, Mika Lehto

Background

Limited data exist on the prevalence of gastrointestinal bleeding (GIB) in patients with new-onset atrial fibrillation (AF) and the impact of GIB on the initiation of oral anticoagulation (OAC) therapy.

Methods

A population-based registry-linkage study included all patients diagnosed with new-onset AF in Finland during 2010–2018 who had available laboratory data and a definite indication for OAC therapy. The primary outcome was OAC initiation within 90 days following AF diagnosis. Factors associated with OAC initiation were assessed using modified Poisson regression.

Results

Among 117 997 patients with new-onset AF, 6628 (5.6%) had GIB, of which 5336 occurred more than 30 days prior to AF diagnosis, and 1292 were temporally (±30 days) associated with new-onset AF (GIBTAF). Patients with GIB compared to those without GIB were older (mean age 78.3 vs. 75.3 years), more frequently men (48.5% vs. 41.9%), and had more comorbidities. The occurrence of GIB was associated with a lower probability of initiating OAC (RR 0.84, 95% CI 0.81–0.86). Among patients with GIB, an obscure origin of GIB (RR 0.93, 95% CI 0.88–0.99) or GIBTAF reduced the likelihood of OAC initiation (RR 0.72, 95% CI 0.66–0.79). The initiation of OAC did not depend on the known GIB bleeding site (lower vs. upper). Overall, the initiation of OAC therapy increased from 2010 to 2018 but remained consistently lower in patients with GIB.

Conclusion

Prior and concurrent GIB is common among patients with new-onset AF, and despite the overall increasing use of OACs, they remain less utilized in patients with GIB.

背景：关于新发心房颤动（AF）患者胃肠道出血（GIB）的患病率以及GIB对口服抗凝（OAC）治疗开始的影响的数据有限。方法：一项基于人群的登记关联研究纳入了2010-2018年芬兰所有诊断为新发房颤的患者，这些患者具有可用的实验室数据和明确的OAC治疗指征。主要结局是房颤诊断后90天内OAC开始。使用修正泊松回归评估与OAC起始相关的因素。结果：117997例新发房颤患者中，6628例（5.6%）有GIB，其中5336例发生在房颤诊断前30天以上，1292例暂时性（±30天）伴有新发房颤（GIBTAF）。与非GIB患者相比，GIB患者年龄更大（平均年龄78.3岁对75.3岁），男性更常见（48.5%对41.9%），并且有更多的合并症。GIB的发生与较低的OAC发生概率相关（RR 0.84, 95% CI 0.81-0.86）。在GIB患者中，起源不明的GIB （RR 0.93, 95% CI 0.88-0.99）或GIBTAF降低了OAC发生的可能性（RR 0.72, 95% CI 0.66-0.79）。OAC的起始不依赖于已知的GIB出血部位（上出血部位vs下出血部位）。总体而言，从2010年到2018年，OAC治疗的开始量有所增加，但在GIB患者中一直较低。结论：既往和并发GIB在新发房颤患者中很常见，尽管OACs的使用总体上有所增加，但它们在GIB患者中的使用率仍然较低。

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引用次数: 0

Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon 神经内分泌学与成瘾：即将出现的新兴药物疗法。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-23 DOI: 10.1111/joim.70021

Anna Loften, Mehdi Farokhnia, Leandro F. Vendruscolo, Lorenzo Leggio

Alcohol and other substance use disorders (ASUDs) are prevalent and major contributors to global morbidity and mortality. Their impact extends beyond the individual, imposing significant burdens on families, communities, healthcare systems, and society at large. Treatments include psychosocial, behavioral, and pharmacological interventions. However, available pharmacological treatments remain limited, primarily targeting alcohol, tobacco, and opioid use disorders, with a lack of approved pharmacotherapies for other substance use disorders. This gap highlights a critical need to develop novel treatment options. Emerging evidence suggests that bidirectional brain-periphery communications play important roles in the pathophysiology and progression of ASUDs. Gut–brain hormones that are involved in the regulation of feeding and metabolism have been shown to influence reinforcing properties of food, alcohol, and other addictive substances. Additionally, stress-related pathways, especially the hypothalamic–pituitary–adrenal axis, play a significant role in regulating behaviors that are related to ASUDs. Accordingly, feeding- and stress-related neuroendocrine pathways represent novel pharmacotherapeutic targets for ASUDs. This narrative review discusses preclinical and clinical evidence for emerging pharmacotherapies that target ASUD-related neuroendocrine systems. Special emphasis is placed on recent work with glucagon-like peptide-1, ghrelin, fibroblast growth factor-21, amylin, glucocorticoids, and mineralocorticoids.

酒精和其他物质使用障碍（ASUDs）很普遍，是全球发病率和死亡率的主要原因。它们的影响超出了个人，给家庭、社区、卫生保健系统和整个社会带来了沉重的负担。治疗包括心理、行为和药物干预。然而，可用的药物治疗仍然有限，主要针对酒精、烟草和阿片类药物使用障碍，缺乏针对其他物质使用障碍的批准药物治疗。这一差距凸显了开发新的治疗方案的迫切需要。越来越多的证据表明，双向脑外周通讯在asud的病理生理和进展中起着重要作用。参与进食和新陈代谢调节的肠脑激素已被证明能影响食物、酒精和其他成瘾物质的强化特性。此外，应激相关通路，特别是下丘脑-垂体-肾上腺轴，在调节与asud相关的行为中发挥重要作用。因此，喂养和应激相关的神经内分泌通路是asud的新药物治疗靶点。这篇叙述性综述讨论了针对asud相关神经内分泌系统的新兴药物治疗的临床前和临床证据。特别强调最近对胰高血糖素样肽-1、胃饥饿素、成纤维细胞生长因子-21、胰高血糖素、糖皮质激素和矿物皮质激素的研究。

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引用次数: 0

Long-term efficacy of rituximab versus intravenous cyclophosphamide for severe ANCA-associated vasculitis in multicenter REVEAL cohort study 多中心REVEAL队列研究：利妥昔单抗与静脉注射环磷酰胺治疗严重anca相关性血管炎的长期疗效

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-22 DOI: 10.1111/joim.70024

Shogo Matsuda, Takuya Kotani, Daisuke Nishioka, Ayana Okazaki, Yuichi Masuda, Tomoki Taniguchi, Mikihito Shoji, Tsuneyasu Yoshida, Ryosuke Hiwa, Mayu Shiomi, Ryu Watanabe, Muneyuki Hatta, Naoko Ito, Yohei Fujiki, Hirofumi Miyake, Wataru Yamamoto, Motomu Hashimoto, Tohru Takeuchi

Background

The optimal remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study evaluated the effectiveness of rituximab (RTX) as a remission induction therapy for severe AAV compared with intravenous cyclophosphamide (IVCY).

Methods

Patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) treated with systemic glucocorticoids (GCs) and IVCY or RTX as initial remission induction therapy in multicenter REVEAL study between 1991 and 2024 were enrolled. We compared efficacy and safety outcomes between the two groups. Effectiveness was evaluated using all-cause mortality, GC-remission rate, relapse rate, and end-stage renal disease (ESRD) progression rate. Safety was evaluated based on complications from severe infections. Inverse probability of treatment weighting (IPTW) was applied for selection bias.

Results

Of 555 patients with AAV, 178 with severe MPA or GPA were identified (IVCY group: N = 133, RTX group: N = 45). After adjustment by IPTW, no significant differences in baseline clinical characteristics were observed between them. The 10-year survival rate and GC-remission rate at 6 months were significantly higher in the RTX group (p = 0.04, p = 0.017, respectively). ESRD progression and relapse rates were comparable between two groups. Regarding safety, 15.2% of patients in the IVCY group died due to severe infections, whereas none did in the RTX group (p = 0.007).

Conclusions

RTX demonstrated superior efficacy in improving survival and achieving GC remission, with fewer infection-related deaths compared to IVCY in patients with severe AAV. These findings reveal the efficacy and safety of RTX as a remission induction therapy in real-world Japanese clinical practice.

背景：严重抗中性粒细胞细胞质抗体相关血管炎（AAV）的最佳缓解诱导治疗尚不清楚。本研究评估了利妥昔单抗（RTX）与静脉注射环磷酰胺（IVCY）相比作为严重AAV缓解诱导疗法的有效性。方法：纳入1991 ~ 2024年在多中心REVEAL研究中接受系统性糖皮质激素（GCs）和IVCY或RTX作为初始缓解诱导治疗的显微镜下多血管炎（MPA）和肉芽肿病合并多血管炎（GPA）患者。我们比较了两组的疗效和安全性结果。使用全因死亡率、gc缓解率、复发率和终末期肾病（ESRD）进展率来评估有效性。安全性根据严重感染的并发症进行评估。选择偏倚采用处理加权逆概率（IPTW）。结果：555例AAV患者中，重度MPA或GPA患者178例（IVCY组133例，RTX组45例）。经IPTW校正后，两组患者的基线临床特征无显著差异。RTX组10年生存率和6个月gc缓解率显著高于RTX组（p = 0.04, p = 0.017）。两组间ESRD的进展和复发率具有可比性。在安全性方面，IVCY组有15.2%的患者死于严重感染，而RTX组没有患者死于严重感染（p = 0.007）。结论：在严重AAV患者中，与IVCY相比，RTX在改善生存和实现GC缓解方面表现出卓越的疗效，感染相关死亡更少。这些发现揭示了RTX作为缓解诱导疗法在日本临床实践中的有效性和安全性。

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引用次数: 0

Sixty years of experience with hereditary transthyretin amyloidosis: Insights from the Swedish transthyretin amyloidosis registry 六十年的遗传性甲状腺素淀粉样变性经验：来自瑞典甲状腺素淀粉样变性登记的见解。

IF 9.2 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine

Pub Date : 2025-09-17 DOI: 10.1111/joim.70020

Lotta Stenberg, Björn Pilebro, Intissar Anan, Jorge Mejia Baranda, Kristin Samuelsson, Per Eldhagen, Rolf Backlund, Jonas Wixner

Background

Hereditary transthyretin (ATTRv) amyloidosis was first described in Sweden in the late 1960s. Selected patient data have been collected since then and have now been transferred to a national quality registry.

Methods

This is the first report from SveATTR—a longitudinal Swedish web-based registry open for TTR variant carriers and patients with ATTR amyloidosis. The registry covers basic background information, as well as relevant clinical follow-up measures and data on disease-modifying therapies. Data from all ATTRv amyloidosis patients registered through December 2022 were included.

Results

In total, 1055 patients were included, of whom 65% were males and 95% carried the V30M variant. Median age of onset was 64 years, and 79% had a late disease onset (≥50 years). Eighty-seven percent of the patients had peripheral polyneuropathy at onset, whereas 10% had cardiac symptoms, 8% had visual disturbances, and 6% had gastrointestinal symptoms. A total of 159 patients had undergone liver transplantation, and 233 had received a disease-modifying drug. Improved survival was seen for transplanted patients and for patients on drug therapy.

Conclusion

This report highlights the importance of SveATTR for further characterization of the Swedish ATTRv amyloidosis population as well as for evaluating the efficacy of disease-modifying therapies.

背景：遗传性甲状腺转蛋白（ATTRv）淀粉样变症于20世纪60年代末在瑞典首次被报道。从那时起收集了选定的患者数据，现在已转移到国家质量登记处。方法：这是来自sveattr的第一份报告，sveattr是瑞典的一个纵向网络注册中心，面向TTR变异携带者和ATTR淀粉样变患者开放。该登记处包括基本背景信息，以及有关的临床随访措施和疾病改善疗法的数据。纳入了截至2022年12月登记的所有ATTRv淀粉样变患者的数据。结果：共纳入1055例患者，其中65%为男性，95%携带V30M变异。中位发病年龄为64岁，79%为晚发病（≥50岁）。87%的患者发病时有周围多神经病变，10%有心脏症状，8%有视觉障碍，6%有胃肠道症状。共有159名患者接受了肝移植，233名患者接受了疾病缓解药物。移植患者和接受药物治疗的患者生存率均有所提高。结论：本报告强调了SveATTR对进一步表征瑞典ATTRv淀粉样变人群以及评估疾病改善疗法疗效的重要性。

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引用次数: 0