Maria Dons, Charlotte Näslund-Koch, Morten Sengeløv, Sofie Bøgh-Sørensen, Kristoffer Grundtvig Skaarup, Marianne Bengtson Løvendorf, Filip Soeskov Davidovski, Anne Marie Reimer Jensen, Brittany N. Weber, Lise Lotte Gluud, Claus Zachariae, Lone Skov, Tor Biering-Sørensen
Background
Individuals with psoriasis have a high prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), yet the association between MASLD as a cardiometabolic risk factor and cardiac manifestations in this population remains unclear.
Objectives
We aimed to evaluate associations between MASLD, cardiometabolic risk factors, and cardiac structure and function in adults with psoriasis.
Methods
We performed a cross-sectional analysis of 255 adults with psoriasis prospectively enrolled. Participants underwent transthoracic echocardiography and transient elastography. MASLD was defined by hepatic steatosis with a controlled attenuation parameter of ≥250 dB/m and the presence of ≥1 cardiometabolic risk factor(s), excluding other liver disease causes. Cardiac structure and function were compared between individuals with psoriasis and MASLD and those without MASLD. Associations between MASLD and myocardial dysfunction were assessed in uni- and multivariable regression models.
Results
MASLD was present in 92 participants (36.1%), of whom 5 (5.4%) had evidence of increased liver stiffness. Those with MASLD exhibited higher blood pressure, body mass index (BMI), and more adverse cardiometabolic profiles. MASLD was associated with cardiac structural changes and worse diastolic and systolic function. After adjusting for age, sex, and BMI, most associations were attenuated. In fully adjusted models, higher BMI and diabetes, but not MASLD, were independently associated with myocardial dysfunction.
Conclusions
In adults with psoriasis, the association between MASLD and cardiac structural and functional changes was attenuated after adjusting for BMI and cardiometabolic risk factors, underscoring the importance of cardiometabolic risk factor control, in particular of obesity and diabetes, in psoriasis with concomitant MASLD.
{"title":"Metabolic dysfunction-associated steatotic liver disease, cardiometabolic risk factors, and cardiac manifestations in psoriasis: A cross-sectional study of 255 patients","authors":"Maria Dons, Charlotte Näslund-Koch, Morten Sengeløv, Sofie Bøgh-Sørensen, Kristoffer Grundtvig Skaarup, Marianne Bengtson Løvendorf, Filip Soeskov Davidovski, Anne Marie Reimer Jensen, Brittany N. Weber, Lise Lotte Gluud, Claus Zachariae, Lone Skov, Tor Biering-Sørensen","doi":"10.1111/joim.70053","DOIUrl":"10.1111/joim.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Individuals with psoriasis have a high prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), yet the association between MASLD as a cardiometabolic risk factor and cardiac manifestations in this population remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to evaluate associations between MASLD, cardiometabolic risk factors, and cardiac structure and function in adults with psoriasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional analysis of 255 adults with psoriasis prospectively enrolled. Participants underwent transthoracic echocardiography and transient elastography. MASLD was defined by hepatic steatosis with a controlled attenuation parameter of ≥250 dB/m and the presence of ≥1 cardiometabolic risk factor(s), excluding other liver disease causes. Cardiac structure and function were compared between individuals with psoriasis and MASLD and those without MASLD. Associations between MASLD and myocardial dysfunction were assessed in uni- and multivariable regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MASLD was present in 92 participants (36.1%), of whom 5 (5.4%) had evidence of increased liver stiffness. Those with MASLD exhibited higher blood pressure, body mass index (BMI), and more adverse cardiometabolic profiles. MASLD was associated with cardiac structural changes and worse diastolic and systolic function. After adjusting for age, sex, and BMI, most associations were attenuated. In fully adjusted models, higher BMI and diabetes, but not MASLD, were independently associated with myocardial dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In adults with psoriasis, the association between MASLD and cardiac structural and functional changes was attenuated after adjusting for BMI and cardiometabolic risk factors, underscoring the importance of cardiometabolic risk factor control, in particular of obesity and diabetes, in psoriasis with concomitant MASLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"283-299"},"PeriodicalIF":9.2,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627392","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}
Martin Lindgren, Helen Sjöland, Demir Djekic, Josefina Robertson, Maria Åberg, Erik Thunström, Zacharias Mandalenakis, Jon Edqvist, Christina E. Lundberg, Martin Adiels, Annika Rosengren
Background
The long-term risk across severity strata of people infected with SARS-CoV-2 has not yet been comprehensively described.
Methods
Using nationwide registries, all COVID-19 cases in Sweden with <2 vaccine doses, with and without initial hospitalization (February 1, 2020 to June 30, 2022), were identified and matched with non-COVID comparators. Participants were followed during the early, intermediate, long-term, and extended phases (365+ days) regarding death, acute myocardial infarction (AMI), ischemic stroke (IS), or heart failure (HF), and a composite of major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using Cox proportional hazard regression adjusted for age, sex, obesity, hypertension, need of assisted living, Nordic origin, education, and Charlson Comorbidity Index.
Results
We identified 1,024,623 nonhospitalized (mean age: 40.4 years, 48.1% men) and 49,855 hospitalized (mean age: 58.8 years, 58.9% men) COVID-19 cases who were matched with 1,022,266 and 249,142 non-COVID comparators, respectively. Overall, nonhospitalized cases had no remaining risk of MACE past the early phase following COVID-19 infection. Among hospitalized cases, the risk of MACE remained elevated into the long-term and extended follow-up period (HRs 1.70 [confidence interval (CI) = 1.56–1.86] and 1.62 [CI = 1.51–1.72]) compared with comparators. After 365 days, they had a persistently increased risk of death (HR = 1.75, CI = 1.62–1.89), IS (HR = 1.40, CI = 1.18–1.67), HF (HR = 2.07, CI = 1.74–2.45), and AMI (HR = 1.28, CI = 1.07–1.53), compared with non-COVID comparators.
Conclusions
Hospitalized COVID-19 cases continued to have a nearly doubled risk of cardiovascular events and death after the first year of follow-up, whereas nonhospitalized cases had risks comparable to population comparators.
背景：SARS-CoV-2感染人群不同严重程度的长期风险尚未得到全面描述。结果：我们确定了1,024,623例未住院（平均年龄：40.4岁，男性48.1%）和49,855例住院（平均年龄：58.8岁，男性58.9%）的COVID-19病例，他们分别与1,022266例和249,142例非covid比较者匹配。总体而言，未住院的病例在COVID-19感染后的早期阶段没有剩余的MACE风险。在住院病例中，与比较组相比，MACE的风险在长期随访和延长随访期间仍然升高（hr为1.70[置信区间(CI) = 1.56-1.86]和1.62 [CI = 1.51-1.72]）。365天后，与非covid比较者相比，他们的死亡风险持续增加（HR = 1.75, CI = 1.62-1.89）、IS （HR = 1.40, CI = 1.18-1.67）、HF （HR = 2.07, CI = 1.74-2.45）和AMI （HR = 1.28, CI = 1.07-1.53）。结论：住院的COVID-19病例在随访一年后心血管事件和死亡的风险几乎翻了一番，而非住院病例的风险与人群比较者相当。
{"title":"Long-term risk of cardiovascular events after COVID-19 in the Swedish adult population—A matched cohort study","authors":"Martin Lindgren, Helen Sjöland, Demir Djekic, Josefina Robertson, Maria Åberg, Erik Thunström, Zacharias Mandalenakis, Jon Edqvist, Christina E. Lundberg, Martin Adiels, Annika Rosengren","doi":"10.1111/joim.70048","DOIUrl":"10.1111/joim.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The long-term risk across severity strata of people infected with SARS-CoV-2 has not yet been comprehensively described.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using nationwide registries, all COVID-19 cases in Sweden with <2 vaccine doses, with and without initial hospitalization (February 1, 2020 to June 30, 2022), were identified and matched with non-COVID comparators. Participants were followed during the early, intermediate, long-term, and extended phases (365+ days) regarding death, acute myocardial infarction (AMI), ischemic stroke (IS), or heart failure (HF), and a composite of major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using Cox proportional hazard regression adjusted for age, sex, obesity, hypertension, need of assisted living, Nordic origin, education, and Charlson Comorbidity Index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 1,024,623 nonhospitalized (mean age: 40.4 years, 48.1% men) and 49,855 hospitalized (mean age: 58.8 years, 58.9% men) COVID-19 cases who were matched with 1,022,266 and 249,142 non-COVID comparators, respectively. Overall, nonhospitalized cases had no remaining risk of MACE past the early phase following COVID-19 infection. Among hospitalized cases, the risk of MACE remained elevated into the long-term and extended follow-up period (HRs 1.70 [confidence interval (CI) = 1.56–1.86] and 1.62 [CI = 1.51–1.72]) compared with comparators. After 365 days, they had a persistently increased risk of death (HR = 1.75, CI = 1.62–1.89), IS (HR = 1.40, CI = 1.18–1.67), HF (HR = 2.07, CI = 1.74–2.45), and AMI (HR = 1.28, CI = 1.07–1.53), compared with non-COVID comparators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hospitalized COVID-19 cases continued to have a nearly doubled risk of cardiovascular events and death after the first year of follow-up, whereas nonhospitalized cases had risks comparable to population comparators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"241-254"},"PeriodicalIF":9.2,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627351","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}
Maria Bygdell, Erik Bülow, Simon B. Larsson, Robert Sigström, Huiqi Li, Jari Martikainen, Ailiana Santosa, Lisa Lundberg-Morris, Susannah Leach, Magnus Gisslén, Carl Bonander, Jörgen Månsson, Kristoffer Strålin, Fredrik Nyberg
Background and objective
Post-infectious sequelae can increase burden on healthcare systems. We aimed to assess the long-term effect of COVID-19 on healthcare utilization across all levels of care.
Methods
In this register-based cohort study, we included all adult (≥18 years) residents in Sweden's two largest counties with a registered COVID-19 index date between 31 January 2020 and 9 February 2022. Each exposed individual was matched 1:1 to a control without registered COVID-19 on index date based on gender, birth year, vaccination status and the change in number of healthcare contacts between 2018 and 2019. We counted the number of healthcare contacts across all levels of care during the pre-index (13–1 months) and post-index (4–15 months) full-year periods. A difference-in-difference (DID) analysis was used to assess changes in the number of healthcare contacts and specific diagnoses, between each individual's pre- and post-periods, as well as comparing individuals with and without COVID-19.
Results
The study included 753,905 matched pairs, comprising 1,415,432 unique individuals. Trends in healthcare contacts were parallel between the matched groups prior to the index date. The DID analysis revealed a mean increase of 0.33 (95%CI 0.30–0.36) healthcare contacts following COVID-19, mainly observed from a smaller proportion of the population (5%) and by contacts with primary healthcare. The largest diagnosis-specific difference was observed for reactions to severe stress (0.02, 0.01–0.03). The estimate varied across gender, acute COVID-19 severity, virus variant period and vaccination status.
Conclusion
This study demonstrates increased healthcare utilization after COVID-19 in a smaller proportion of the population.
{"title":"Change in healthcare utilization before and after COVID-19 using data from 1.5 million individuals","authors":"Maria Bygdell, Erik Bülow, Simon B. Larsson, Robert Sigström, Huiqi Li, Jari Martikainen, Ailiana Santosa, Lisa Lundberg-Morris, Susannah Leach, Magnus Gisslén, Carl Bonander, Jörgen Månsson, Kristoffer Strålin, Fredrik Nyberg","doi":"10.1111/joim.70051","DOIUrl":"10.1111/joim.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and objective</h3>\u0000 \u0000 <p>Post-infectious sequelae can increase burden on healthcare systems. We aimed to assess the long-term effect of COVID-19 on healthcare utilization across all levels of care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this register-based cohort study, we included all adult (≥18 years) residents in Sweden's two largest counties with a registered COVID-19 index date between 31 January 2020 and 9 February 2022. Each exposed individual was matched 1:1 to a control without registered COVID-19 on index date based on gender, birth year, vaccination status and the change in number of healthcare contacts between 2018 and 2019. We counted the number of healthcare contacts across all levels of care during the pre-index (13–1 months) and post-index (4–15 months) full-year periods. A difference-in-difference (DID) analysis was used to assess changes in the number of healthcare contacts and specific diagnoses, between each individual's pre- and post-periods, as well as comparing individuals with and without COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 753,905 matched pairs, comprising 1,415,432 unique individuals. Trends in healthcare contacts were parallel between the matched groups prior to the index date. The DID analysis revealed a mean increase of 0.33 (95%CI 0.30–0.36) healthcare contacts following COVID-19, mainly observed from a smaller proportion of the population (5%) and by contacts with primary healthcare. The largest diagnosis-specific difference was observed for reactions to severe stress (0.02, 0.01–0.03). The estimate varied across gender, acute COVID-19 severity, virus variant period and vaccination status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates increased healthcare utilization after COVID-19 in a smaller proportion of the population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"255-270"},"PeriodicalIF":9.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627334","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}
Xiaoying Kang, David Bergman, Jiangwei Sun, Karin Wirdefeldt, Jonas F. Ludvigsson
Background
The microbiota–gut–brain axis has been implicated in dementia. Yet whether dementia is associated with microscopic colitis (MC), an age-related inflammatory colonic disease involving gut dysbiosis, remains unknown.
Methods
Using the nationwide ESPRESSO cohort in Sweden, we compared MC patients histologically diagnosed 1990–2017 and aged ≥30 years to their population-based comparators and siblings, separately. MC association with incident and prevalent dementia diagnosis, respectively, was investigated in a matched cohort and a matched case-control design.
Findings
Following 13,037 MC patients and 61,710 population comparators for a median of ∼10 years, we observed 4674 incident dementia cases (46% were Alzheimer's disease [AD]). During the first 5 years since biopsy, MC was associated with a 19% higher dementia risk (adjusted hazard ratio [aHR]: 1.19; 95% confidence interval [CI]: 1.07–1.32). This short-term association applied to both AD and vascular dementia and appeared stronger as compared to siblings (aHR: 1.55; 95% CI: 1.22–1.97). After 5 years, it attenuated to null in both comparisons, regardless of dementia subtype. Prior dementia was less prevalent in MC (adjusted odds ratio [aOR]: 0.73; 95% CI: 0.65–0.82). This inverse association was independent from medications commonly prescribed in MC but was not supported by sibling findings (aOR: 1.11; 95% CI: 0.81–1.51).
Conclusions
MC patients may be more vulnerable to dementia diagnosis in early disease course. The intriguing inverse association between MC and preexisting dementia implies a possible underdiagnosis of MC in demented population and warrants further investigation.
{"title":"Microscopic colitis is associated with an increased risk of dementia in a Swedish population","authors":"Xiaoying Kang, David Bergman, Jiangwei Sun, Karin Wirdefeldt, Jonas F. Ludvigsson","doi":"10.1111/joim.70046","DOIUrl":"10.1111/joim.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The microbiota–gut–brain axis has been implicated in dementia. Yet whether dementia is associated with microscopic colitis (MC), an age-related inflammatory colonic disease involving gut dysbiosis, remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the nationwide ESPRESSO cohort in Sweden, we compared MC patients histologically diagnosed 1990–2017 and aged ≥30 years to their population-based comparators and siblings, separately. MC association with incident and prevalent dementia diagnosis, respectively, was investigated in a matched cohort and a matched case-control design.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Following 13,037 MC patients and 61,710 population comparators for a median of ∼10 years, we observed 4674 incident dementia cases (46% were Alzheimer's disease [AD]). During the first 5 years since biopsy, MC was associated with a 19% higher dementia risk (adjusted hazard ratio [aHR]: 1.19; 95% confidence interval [CI]: 1.07–1.32). This short-term association applied to both AD and vascular dementia and appeared stronger as compared to siblings (aHR: 1.55; 95% CI: 1.22–1.97). After 5 years, it attenuated to null in both comparisons, regardless of dementia subtype. Prior dementia was less prevalent in MC (adjusted odds ratio [aOR]: 0.73; 95% CI: 0.65–0.82). This inverse association was independent from medications commonly prescribed in MC but was not supported by sibling findings (aOR: 1.11; 95% CI: 0.81–1.51).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MC patients may be more vulnerable to dementia diagnosis in early disease course. The intriguing inverse association between MC and preexisting dementia implies a possible underdiagnosis of MC in demented population and warrants further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"216-227"},"PeriodicalIF":9.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601605","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 Linda Zignego, Laura Gragnani, Marcella Visentini, Riccardo Bomben, Luca Arcaini, Clodoveo Ferri, Valter Gattei, Cesare Mazzaro
Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involves B-cell lymphoproliferation and autoantibody production. CG may lead to systemic vasculopathy, ranging from mild symptoms (purpura, asthenia, and arthralgia) to severe complications such as skin ulcers, peripheral neuropathy, renal involvement, and non-Hodgkin lymphoma. Compared to MC, Type I is more often marked by severe cutaneous involvement (ulcers, gangrene), hyperviscosity, and a higher risk of morbidity due to the underlying hematologic malignancy. Management of Type I requires control of vasculopathy and treatment of the hematologic neoplasm, whereas MC demands antiviral therapy in all HCV-associated or hepatitis B virus–associated cases. Severe vasculopathy in both types may benefit from corticosteroids, immunomodulators, anti-CD20 monoclonal antibodies, and plasma exchange. A multidisciplinary approach is essential for addressing both etiology and complications, thereby improving outcomes. This review summarizes the pathophysiology, clinical features, recent etiopathogenetic insights, and therapeutic advances related to the various forms of CG.
{"title":"Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management","authors":"Anna Linda Zignego, Laura Gragnani, Marcella Visentini, Riccardo Bomben, Luca Arcaini, Clodoveo Ferri, Valter Gattei, Cesare Mazzaro","doi":"10.1111/joim.70042","DOIUrl":"10.1111/joim.70042","url":null,"abstract":"<p>Cryoglobulinemia (CG) is defined by the presence of serum immunoglobulins that precipitate below 37°C and redissolve upon rewarming. It is classified into three types based on immunoglobulin composition. Type I, a rare form, involves monoclonal IgM or IgG and is linked to lymphoproliferative disorders. Types II and III are known as mixed CG (MC): Type II consists of polyclonal IgG and monoclonal IgM with rheumatoid factor (RF) activity, whereas Type III includes polyclonal IgG and polyclonal IgM with RF activity. MC is predominantly associated with hepatitis C virus (HCV) infection and involves B-cell lymphoproliferation and autoantibody production. CG may lead to systemic vasculopathy, ranging from mild symptoms (purpura, asthenia, and arthralgia) to severe complications such as skin ulcers, peripheral neuropathy, renal involvement, and non-Hodgkin lymphoma. Compared to MC, Type I is more often marked by severe cutaneous involvement (ulcers, gangrene), hyperviscosity, and a higher risk of morbidity due to the underlying hematologic malignancy. Management of Type I requires control of vasculopathy and treatment of the hematologic neoplasm, whereas MC demands antiviral therapy in all HCV-associated or hepatitis B virus–associated cases. Severe vasculopathy in both types may benefit from corticosteroids, immunomodulators, anti-CD20 monoclonal antibodies, and plasma exchange. A multidisciplinary approach is essential for addressing both etiology and complications, thereby improving outcomes. This review summarizes the pathophysiology, clinical features, recent etiopathogenetic insights, and therapeutic advances related to the various forms of CG.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"196-215"},"PeriodicalIF":9.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627301","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}
Valentine Pagis, Quentin Astouati, Lucas Pacoureau, Yann Nguyen, Pierre Bay, Antoine Roux, Laure Gallay, Vincent Cottin, Benjamin Terrier, Alain Meyer, Charles Cerf, Mathilde Neuville, Baptiste Hervier, Arthur Renaud, Benoit Suzon, Nicolas Schleinitz, Thomas Papo, Pascaline Priou, Arsène Mekinian, Audrey Ullmer, Erwan Oehler, Noémie Gensous, Alice Berezne, Luc De Saint Martin, Thierry Marhadour, Mickaël Martin, Amélie Servettaz, Maxime Samson, Laurent Gilardin, Pierre Charles, Juliette Woessner, Thierry Carmoi, Baptiste Dilly, Wladimir Mauhin, Nicolas Baillet, Sébastien Humbert, Benjamin Thoreau, Marine Lemaitre, Claire Le Pendu, Pierre Loiseau, Thomas Quemeneur, Elodie Blanchard, Nicol Voermans, David Launay, Hilario Nunes, Olivier Benveniste, Yurdagul Uzunhan, Yves Allenbach
Objectives
Anti-MDA5 dermatomyositis (anti-MDA5 DM) is the most severe subtype of dermatomyositis, due to its pulmonary involvement. Current treatment involves corticosteroids and immunosuppressants, but variability in responses exists. This study aims to evaluate the efficacy and safety of Janus kinase (JAK)– and calcineurin–inhibitor combination (JAK–CNI) in anti-MDA5 DM patients.
Methods
A nested case–control study was conducted within a retrospective cohort of 234 anti-MDA5 DM patients. Patients receiving JAK–CNI were matched 1:2 with comparators. All-cause mortality or transplant within a year was compared using Cox proportional hazards models. Infectious and noninfectious side effects were also assessed.
Results
Twenty-seven patients receiving JAK–CNI were compared to 52 matched controls. Almost all these patients had pulmonary involvement. Thirty-nine (49%) died or were transplanted during follow-up. No significant improvement in survival or transplant-free survival was observed with JAK–CNI compared with comparators (hazard ratios 1.02, 95% confidence intervals [0.48–2.16]). Results were consistent regardless of intensive care unit (ICU) admission status and when analyses were restricted to patients with rapidly progressive interstitial lung disease. A trend toward a beneficial effect of the JAK–CNI combination was observed in non-ICU patients. Infectious complications were frequent (n = 49, 62%), with no excess risk in patients receiving JAK–CNI.
Conclusion
JAK–CNI showed a similar outcome to other immunosuppressive combinations. However, as the study included the most severe cases, the potential benefit of early JAK–CNI introduction in less severe forms cannot be dismissed, as suggested by the nonsignificant trend in non-ICU patients. Future studies are needed to clarify the optimal timing and patient selection for JAK–CNI therapy in anti-MDA5 DM.
{"title":"Janus kinase and calcineurin-inhibitor combination in anti-MDA5 dermatomyositis: No significant survival benefit but reassuring safety profile","authors":"Valentine Pagis, Quentin Astouati, Lucas Pacoureau, Yann Nguyen, Pierre Bay, Antoine Roux, Laure Gallay, Vincent Cottin, Benjamin Terrier, Alain Meyer, Charles Cerf, Mathilde Neuville, Baptiste Hervier, Arthur Renaud, Benoit Suzon, Nicolas Schleinitz, Thomas Papo, Pascaline Priou, Arsène Mekinian, Audrey Ullmer, Erwan Oehler, Noémie Gensous, Alice Berezne, Luc De Saint Martin, Thierry Marhadour, Mickaël Martin, Amélie Servettaz, Maxime Samson, Laurent Gilardin, Pierre Charles, Juliette Woessner, Thierry Carmoi, Baptiste Dilly, Wladimir Mauhin, Nicolas Baillet, Sébastien Humbert, Benjamin Thoreau, Marine Lemaitre, Claire Le Pendu, Pierre Loiseau, Thomas Quemeneur, Elodie Blanchard, Nicol Voermans, David Launay, Hilario Nunes, Olivier Benveniste, Yurdagul Uzunhan, Yves Allenbach","doi":"10.1111/joim.70047","DOIUrl":"10.1111/joim.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Anti-MDA5 dermatomyositis (anti-MDA5 DM) is the most severe subtype of dermatomyositis, due to its pulmonary involvement. Current treatment involves corticosteroids and immunosuppressants, but variability in responses exists. This study aims to evaluate the efficacy and safety of Janus kinase (JAK)– and calcineurin–inhibitor combination (JAK–CNI) in anti-MDA5 DM patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A nested case–control study was conducted within a retrospective cohort of 234 anti-MDA5 DM patients. Patients receiving JAK–CNI were matched 1:2 with comparators. All-cause mortality or transplant within a year was compared using Cox proportional hazards models. Infectious and noninfectious side effects were also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-seven patients receiving JAK–CNI were compared to 52 matched controls. Almost all these patients had pulmonary involvement. Thirty-nine (49%) died or were transplanted during follow-up. No significant improvement in survival or transplant-free survival was observed with JAK–CNI compared with comparators (hazard ratios 1.02, 95% confidence intervals [0.48–2.16]). Results were consistent regardless of intensive care unit (ICU) admission status and when analyses were restricted to patients with rapidly progressive interstitial lung disease. A trend toward a beneficial effect of the JAK–CNI combination was observed in non-ICU patients. Infectious complications were frequent (<i>n</i> = 49, 62%), with no excess risk in patients receiving JAK–CNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>JAK–CNI showed a similar outcome to other immunosuppressive combinations. However, as the study included the most severe cases, the potential benefit of early JAK–CNI introduction in less severe forms cannot be dismissed, as suggested by the nonsignificant trend in non-ICU patients. Future studies are needed to clarify the optimal timing and patient selection for JAK–CNI therapy in anti-MDA5 DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 2","pages":"228-240"},"PeriodicalIF":9.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585529","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}
Birger Sourander, Kirsten Mehlig, Fredrik Olsen, Martin Lindgren, Ulrika Snygg-Martin, Magnus Gisslén, Annika Rosengren, Maria Åberg, Josefina Robertson
Background
Obesity and poor physical fitness in youth are established risk factors for future cardiovascular disease and cancer. However, their potential impact on the risk of severe bacterial infections later in life remains unclear.
Methods
This register-based cohort study followed almost 1 million Swedish conscripts (mean age 18.3 years) over a period of three decades. Measured body mass index (BMI) and cardiorespiratory fitness (CRF) at conscription to military service served as exposure variables, whereas outcomes included morbidity and mortality attributed to bacterial pneumonia, sepsis, and infective endocarditis.
Results
High BMI and low CRF in late adolescence were strongly associated with an increased risk of bacterial pneumonia, sepsis, and infective endocarditis in adulthood. The highest risk was seen among the obese for sepsis (hazard ratio [HR] 3.1 (2.7–3.5)), with elevated hazards observed already at high-normal BMI levels (22.5–25 kg/m2), compared with BMI 18.5–19.9. The risk of dying due to bacterial infections increased gradually with higher BMI. High, compared with low CRF, was associated with lower risk of contracting bacterial infections (0.78, 0.76–0.80), and dying from them (0.58, 0.51–0.65).
Conclusion
High BMI and low CRF in adolescence are associated with an increased risk of contracting and dying of severe bacterial infections later in life. Hence, addressing these preventable risk factors in youths may serve as an effective measure to improve their long-term health.
{"title":"High BMI and low cardiorespiratory fitness in adolescence are associated with increased risk of severe bacterial infections in adulthood","authors":"Birger Sourander, Kirsten Mehlig, Fredrik Olsen, Martin Lindgren, Ulrika Snygg-Martin, Magnus Gisslén, Annika Rosengren, Maria Åberg, Josefina Robertson","doi":"10.1111/joim.70043","DOIUrl":"10.1111/joim.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity and poor physical fitness in youth are established risk factors for future cardiovascular disease and cancer. However, their potential impact on the risk of severe bacterial infections later in life remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This register-based cohort study followed almost 1 million Swedish conscripts (mean age 18.3 years) over a period of three decades. Measured body mass index (BMI) and cardiorespiratory fitness (CRF) at conscription to military service served as exposure variables, whereas outcomes included morbidity and mortality attributed to bacterial pneumonia, sepsis, and infective endocarditis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High BMI and low CRF in late adolescence were strongly associated with an increased risk of bacterial pneumonia, sepsis, and infective endocarditis in adulthood. The highest risk was seen among the obese for sepsis (hazard ratio [HR] 3.1 (2.7–3.5)), with elevated hazards observed already at high-normal BMI levels (22.5–25 kg/m<sup>2</sup>), compared with BMI 18.5–19.9. The risk of dying due to bacterial infections increased gradually with higher BMI. High, compared with low CRF, was associated with lower risk of contracting bacterial infections (0.78, 0.76–0.80), and dying from them (0.58, 0.51–0.65).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>High BMI and low CRF in adolescence are associated with an increased risk of contracting and dying of severe bacterial infections later in life. Hence, addressing these preventable risk factors in youths may serve as an effective measure to improve their long-term health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 1","pages":"158-171"},"PeriodicalIF":9.2,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585534","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}
Maria Tydén, Gorav Batra, Bengt Fellström, Claes Held, Johan Lindbäck, Inga Soveri, Maria K. Svensson, Ralph Stewart, Harvey D. White, Lars Wallentin
Background
Renal dysfunction increases cardiovascular (CV) risk. We compared cystatin C-based estimated glomerular filtration rate (eGFRcys), creatinine-based eGFR (eGFRcr), and their ratio (eGFRcys/eGFRcr) in relation to major adverse cardiovascular events (MACE) and all-cause mortality in chronic coronary syndrome, assessing the added prognostic value of the eGFRratio.
Methods
In this post hoc analysis of 14,513 Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy trial patients, we investigated associations between baseline eGFRcys, eGFRcr, their ratio, and MACE and all-cause death using Cox regression models, unadjusted and adjusted for eGFRcys, eGFRcr, and their combination. Discrimination was assessed using Harrell's C-index; added value by the fraction of new information (FNI).
Results
Median age was 65 years; 82% were male. Median eGFRcys was 77 (interquartile range [IQR]: 61–94) and eGFRcr 79 (IQR: 65–91) mL/min/1.73 m2. Over 3.7 years, 1449 MACE and 1063 deaths occurred. Lower eGFR values and eGFRratio were associated with increased MACE risk, primarily driven by CV death. For eGFRcys 60 versus 90, the hazard ratio (HR) for MACE adjusted for eGFRcr was 1.77 (95% CI: 1.49–2.09, FNI 54%). In contrast, eGFRcr adjusted for eGFRcys showed no positive association (HR 0.82, 95% CI: 0.68–0.97, FNI 3%). A lower eGFRratio was linked to higher MACE risk (HR 1.99, 95% CI: 1.80–2.21), which remained after eGFRcr adjustment (HR 1.89, 95% CI: 1.70–2.10, FNI 54%) but was attenuated after eGFRcys adjustment (HR 1.29, 95% CI: 1.13–1.46, FNI 5%).
Conclusion
In chronic coronary syndrome, lower eGFRcys, eGFRcr, and eGFRratio were associated with higher MACE and mortality risk. eGFRcys had the strongest association; eGFRcr and eGFRratio added limited incremental value.
{"title":"Different eGFR markers and prediction of cardiovascular risk","authors":"Maria Tydén, Gorav Batra, Bengt Fellström, Claes Held, Johan Lindbäck, Inga Soveri, Maria K. Svensson, Ralph Stewart, Harvey D. White, Lars Wallentin","doi":"10.1111/joim.70050","DOIUrl":"10.1111/joim.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Renal dysfunction increases cardiovascular (CV) risk. We compared cystatin C-based estimated glomerular filtration rate (eGFRcys), creatinine-based eGFR (eGFRcr), and their ratio (eGFRcys/eGFRcr) in relation to major adverse cardiovascular events (MACE) and all-cause mortality in chronic coronary syndrome, assessing the added prognostic value of the eGFRratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this post hoc analysis of 14,513 Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy trial patients, we investigated associations between baseline eGFRcys, eGFRcr, their ratio, and MACE and all-cause death using Cox regression models, unadjusted and adjusted for eGFRcys, eGFRcr, and their combination. Discrimination was assessed using Harrell's <i>C</i>-index; added value by the fraction of new information (FNI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median age was 65 years; 82% were male. Median eGFRcys was 77 (interquartile range [IQR]: 61–94) and eGFRcr 79 (IQR: 65–91) mL/min/1.73 m<sup>2</sup>. Over 3.7 years, 1449 MACE and 1063 deaths occurred. Lower eGFR values and eGFRratio were associated with increased MACE risk, primarily driven by CV death. For eGFRcys 60 versus 90, the hazard ratio (HR) for MACE adjusted for eGFRcr was 1.77 (95% CI: 1.49–2.09, FNI 54%). In contrast, eGFRcr adjusted for eGFRcys showed no positive association (HR 0.82, 95% CI: 0.68–0.97, FNI 3%). A lower eGFRratio was linked to higher MACE risk (HR 1.99, 95% CI: 1.80–2.21), which remained after eGFRcr adjustment (HR 1.89, 95% CI: 1.70–2.10, FNI 54%) but was attenuated after eGFRcys adjustment (HR 1.29, 95% CI: 1.13–1.46, FNI 5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In chronic coronary syndrome, lower eGFRcys, eGFRcr, and eGFRratio were associated with higher MACE and mortality risk. eGFRcys had the strongest association; eGFRcr and eGFRratio added limited incremental value.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 1","pages":"143-157"},"PeriodicalIF":9.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572731","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}
Jasmin Elkin, Chris Schilling, Michael W. Hii, Peter F. Choong, Michelle Dowsey, Cade Shadbolt
{"title":"Diagnostic performance of a new framework for identifying obesity","authors":"Jasmin Elkin, Chris Schilling, Michael W. Hii, Peter F. Choong, Michelle Dowsey, Cade Shadbolt","doi":"10.1111/joim.70049","DOIUrl":"10.1111/joim.70049","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 1","pages":"172-175"},"PeriodicalIF":9.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572718","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}
Rasmus Mortensen, Cecilia S. Lindestam Arlehamn, Rhea N. Coler, Michael Y. Gerner, Delia Goletti, Deborah A. Lewinsohn, Robert L. Modlin, Munyaradzi Musvosvi, Jyothi Rengarajan, Kevin B. Urdahl, Gerhard Walzl, Samuel M. Behar, Daniel L. Barber, For the Collaboration for Tuberculosis Vaccine Discovery – Conventional T cells Research Community, Gates Foundation
Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality, and the development of a new, highly effective vaccine would have a tremendous beneficial impact on global health. Although conventional memory CD4 and CD8 T cells will likely be key mediators of long-lived, vaccine-elicited protection, a potent T cell–inducing vaccine against TB has been elusive. Protection by Mycobacterium tuberculosis (Mtb)-specific T cells is mediated primarily through their communication with Mtb-infected macrophages. Here, we discuss emerging evidence of multiple structural and immunoregulatory factors that limit effective T cell–macrophage interactions in TB granulomas, posing a unique challenge to vaccine-induced protection. Developing new TB vaccination strategies will require a better understanding of the crosstalk between T cells and infected pulmonary macrophages and strategies to enhance these interactions.
{"title":"T cell–macrophage interactions in tuberculosis: What we've got here is failure to communicate","authors":"Rasmus Mortensen, Cecilia S. Lindestam Arlehamn, Rhea N. Coler, Michael Y. Gerner, Delia Goletti, Deborah A. Lewinsohn, Robert L. Modlin, Munyaradzi Musvosvi, Jyothi Rengarajan, Kevin B. Urdahl, Gerhard Walzl, Samuel M. Behar, Daniel L. Barber, For the Collaboration for Tuberculosis Vaccine Discovery – Conventional T cells Research Community, Gates Foundation","doi":"10.1111/joim.70028","DOIUrl":"10.1111/joim.70028","url":null,"abstract":"<p>Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality, and the development of a new, highly effective vaccine would have a tremendous beneficial impact on global health. Although conventional memory CD4 and CD8 T cells will likely be key mediators of long-lived, vaccine-elicited protection, a potent T cell–inducing vaccine against TB has been elusive. Protection by <i>Mycobacterium tuberculosis</i> (Mtb)-specific T cells is mediated primarily through their communication with Mtb-infected macrophages. Here, we discuss emerging evidence of multiple structural and immunoregulatory factors that limit effective T cell–macrophage interactions in TB granulomas, posing a unique challenge to vaccine-induced protection. Developing new TB vaccination strategies will require a better understanding of the crosstalk between T cells and infected pulmonary macrophages and strategies to enhance these interactions.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 1","pages":"44-65"},"PeriodicalIF":9.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572645","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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