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.
{"title":"Health inequalities in the Nordic countries: A comparative overview and update","authors":"Johan Fritzell, Stefan Fors","doi":"10.1111/joim.70029","DOIUrl":"10.1111/joim.70029","url":null,"abstract":"<p>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.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 6","pages":"591-603"},"PeriodicalIF":9.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273248","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}
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.
{"title":"CD71+ erythroid cell expansion in late-onset systemic lupus erythematosus","authors":"Jian Hao, Yuechen Cui, Jun Du, Jing Cui, Hui-Qi Qu, Fumin Qi, Hui Wang, Na Zhang, Jin Li, Wei Wei","doi":"10.1111/joim.70027","DOIUrl":"10.1111/joim.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The present study aims to decode molecular differences underlying the distinct clinical presentations between lo-SLE and early onset SLE patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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<sup>+</sup>CD235a<sup>+</sup> erythroid cells (CECs) was evaluated by coculturing peripheral blood mononuclear cells (PBMCs) with CECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 6","pages":"637-655"},"PeriodicalIF":9.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237424","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}
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.
{"title":"Low positive and borderline negative transglutaminase antibody levels are frequently associated with a coeliac disease diagnosis","authors":"Rakel Nurmi, Celina Turunen Beteta, Kalle Kurppa, Heini Huhtala, Katri Lindfors, Laura Kivelä, Katri Kaukinen, Saana Paavola","doi":"10.1111/joim.70025","DOIUrl":"10.1111/joim.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate the significance of these findings in a well-defined patient cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 6","pages":"617-625"},"PeriodicalIF":9.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136019","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}
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.
{"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}
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.
{"title":"Albuminuria is associated with increased risk of dementia, independent of eGFR: The SCREAM project","authors":"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","doi":"10.1111/joim.70022","DOIUrl":"10.1111/joim.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"489-503"},"PeriodicalIF":9.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123995","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}
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。
{"title":"Oral anticoagulation in patients with gastrointestinal bleeding and new-onset atrial fibrillation: A population-based registry-linkage study","authors":"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","doi":"10.1111/joim.70018","DOIUrl":"10.1111/joim.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"450-463"},"PeriodicalIF":9.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124036","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}
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.
{"title":"Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon","authors":"Anna Loften, Mehdi Farokhnia, Leandro F. Vendruscolo, Lorenzo Leggio","doi":"10.1111/joim.70021","DOIUrl":"10.1111/joim.70021","url":null,"abstract":"<p>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.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"392-423"},"PeriodicalIF":9.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124016","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}
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。
{"title":"Long-term efficacy of rituximab versus intravenous cyclophosphamide for severe ANCA-associated vasculitis in multicenter REVEAL cohort study","authors":"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","doi":"10.1111/joim.70024","DOIUrl":"10.1111/joim.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 555 patients with AAV, 178 with severe MPA or GPA were identified (IVCY group: <i>N</i> = 133, RTX group: <i>N</i> = 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 (<i>p</i> = 0.04, <i>p</i> = 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 (<i>p</i> = 0.007).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"504-515"},"PeriodicalIF":9.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123967","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}
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.
{"title":"Sixty years of experience with hereditary transthyretin amyloidosis: Insights from the Swedish transthyretin amyloidosis registry","authors":"Lotta Stenberg, Björn Pilebro, Intissar Anan, Jorge Mejia Baranda, Kristin Samuelsson, Per Eldhagen, Rolf Backlund, Jonas Wixner","doi":"10.1111/joim.70020","DOIUrl":"10.1111/joim.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is the first report from SveATTR—a longitudinal Swedish web-based registry open for <i>TTR</i> 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"478-488"},"PeriodicalIF":9.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074172","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}
Benjamin Sasko, Nikolaos Pagonas, Martin Christ, Jan Wintrich, Oliver Ritter, Christian Ukena, Innas Sultana, Simin Delalat, Ibrahim El-Battrawy, Theodoros Kelesidis, Nazha Hamdani
Background
High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDLox) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health.
Methods
We assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHDLox). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated.
Results
ACS patients had nHDLox levels 140% higher than healthy controls (p < 0.001). Higher nHDLox levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function.
Conclusion
HDLox levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.
{"title":"Oxidized high-density lipoprotein associates with cardiometabolic dysfunction in coronary artery disease and acute coronary syndrome","authors":"Benjamin Sasko, Nikolaos Pagonas, Martin Christ, Jan Wintrich, Oliver Ritter, Christian Ukena, Innas Sultana, Simin Delalat, Ibrahim El-Battrawy, Theodoros Kelesidis, Nazha Hamdani","doi":"10.1111/joim.70019","DOIUrl":"10.1111/joim.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDL<sub>ox</sub>) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHDL<sub>ox</sub>). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ACS patients had nHDL<sub>ox</sub> levels 140% higher than healthy controls (<i>p</i> < 0.001). Higher nHDL<sub>ox</sub> levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HDL<sub>ox</sub> levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical trial registration</h3>\u0000 \u0000 <p>DRKS00014037</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 5","pages":"464-477"},"PeriodicalIF":9.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028602","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}
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