Journal of Internal Medicine最新文献

{"title":"Social jet lag is associated with incident cardiovascular disease independent of sleep duration and cardiac genetic risk","authors":"Neeraj Kumar,&nbsp;Sairam Krishnamurthy","doi":"10.1111/joim.70133","DOIUrl":"10.1111/joim.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, yet many events occur in individuals not fully explained by traditional clinical and lifestyle factors. Social jet lag reflects misalignment between biological timing and socially imposed sleep schedules and may represent an overlooked behavioral circadian cardiovascular risk factor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine whether accelerometer-derived social jet lag is independently associated with incident CVD beyond established clinical factors, sleep-related characteristics, and cardiac genetic risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sleep timing was assessed using wrist accelerometry in 51,562 UK Biobank participants. Social jet lag was defined as the absolute difference between weekday and weekend mid-sleep timing. Participants were prospectively followed for incident CVD, including myocardial infarction, ischemic heart disease, heart failure, stroke, and atrial fibrillation (3853 events).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher social jet lag was associated with increased CVD incidence after multivariable adjustment. Each standard deviation increase in social jet lag increased composite CVD risk (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.09, <i>p</i> = 0.0015). Individuals with ≥2 h of social jet lag had greater CVD risk (HR 1.30, 95% CI 1.11–1.54, <i>p</i> = 0.0014). Associations were strongest for myocardial infarction, ischemic heart disease, and heart failure. Severe social jet lag remained associated with CVD even among individuals with normal sleep duration, whereas sleep duration itself was not independently associated with risk. Social jet lag also remained independently associated with CVD after accounting for cardiac genetic risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Social jet lag was associated with incident CVD independent of sleep duration and cardiac genetic susceptibility, supporting a role for circadian misalignment in cardiovascular pathophysiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"360-378"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366218","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}

{"title":"Targeting progressive multiple sclerosis: Toward mechanism-informed precision medicine","authors":"Fredrik Piehl,&nbsp;Gonçalo Castelo-Branco,&nbsp;Maja Jagodic,&nbsp;Tomas Olsson","doi":"10.1111/joim.70125","DOIUrl":"10.1111/joim.70125","url":null,"abstract":"<p>Multiple sclerosis has undergone a therapeutic revolution over the past three decades. Randomized clinical trials and real-world data demonstrate that modern disease-modifying therapies substantially reduce relapse rates and acute inflammatory activity detected by magnetic resonance imaging (MRI). However, disability accumulation increasingly occurs independent of relapse activity, highlighting progression biology as the principal unmet need. Converging epidemiological and molecular evidence supports a pivotal role for Epstein–Barr virus (EBV) infection in disease initiation, whereas later stages appear dominated by brain-intrinsic mechanisms, including compartmentalized inflammation, microglial activation, failure of remyelination and accelerated biological ageing. Population-based cohorts demonstrate that early high-efficacy therapy improves long-term outcomes, yet the risk of progression rises markedly after midlife despite effective relapse suppression. Emerging biomarkers, such as serum neurofilament light chain, glial fibrillary acidic protein, paramagnetic rim lesions and advanced quantitative MRI metrics, now enable more granular monitoring of progressive pathology. Integration of imaging, fluid biomarkers, genetics and machine learning offers opportunities for individualized benefit–risk stratification. Brain-penetrant Bruton's tyrosine kinase inhibitors, CD40 ligand-targeting biologics, refined B-cell-depleting strategies and emerging chimeric antigen receptor T-cell therapies represent promising approaches to target different aspects of compartmentalized inflammation and smoldering disease biology. Future management will require mechanism-informed treatment algorithms that align therapeutic choice with dominant disease drivers while incorporating comorbidity management, de-escalation strategies and potential EBV-targeted preventive approaches to optimize outcomes across the entire disease course.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"238-257"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547239","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}

{"title":"Regarding: Myasthenia gravis following the initiation of statin therapy","authors":"Sha Zeng,&nbsp;ZhengRong Shi","doi":"10.1111/joim.70122","DOIUrl":"10.1111/joim.70122","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"382-383"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194404","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}

{"title":"Fabricated references are twice as common in medRxiv preprints as in peer-reviewed articles","authors":"Maxim Topaz,&nbsp;Zhihong Zhang,&nbsp;Pallavi Gupta,&nbsp;Nir Roguin,&nbsp;Laura-Maria Peltonen","doi":"10.1111/joim.70139","DOIUrl":"10.1111/joim.70139","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"379-381"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434682","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}

{"title":"Age-stratified effectiveness of a nurse-led heart failure programme: A population-based study","authors":"Blanca Torres-Cardús,&nbsp;Emili Vela-Vallespín,&nbsp;David Monterde,&nbsp;Gerard Carot-Sans,&nbsp;Jordi Piera-Jiménez,&nbsp;Júlia Folguera,&nbsp;Laia Alcober-Morte,&nbsp;Raúl Ramos-Polo,&nbsp;Encarnación Hidalgo-Quirós,&nbsp;Núria José-Bazán,&nbsp;Sergi Yun Viladomat,&nbsp;Pedro Moliner,&nbsp;Santiago Jiménez-Marrero,&nbsp;Alberto Garay Melero,&nbsp;Alexandra Pons Riverola,&nbsp;Lídia Alcoberro Torres,&nbsp;Herminio Morillas,&nbsp;Betlem Salvador-González,&nbsp;Sílvia Jovells-Vaqué,&nbsp;Mireia Andrés Villareal,&nbsp;Cristina Enjuanes,&nbsp;Josep Comin-Colet","doi":"10.1111/joim.70136","DOIUrl":"10.1111/joim.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Old age is associated with poor outcomes in patients with heart failure (HF). This study aimed to assess the impact of age on the effectiveness of a new integrated, transition-based nurse-led HF programme in a healthcare area with 209,255 inhabitants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a population-based evaluation of all patients discharged from the hospital with International Classification of Diseases, ninth revision, Clinical Modification code for HF as the primary diagnosis in Catalonia between 2015 and 2019. We compared outcomes between patients exposed to the new HF programme with the rest of Catalonia, stratified by age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 77,554 patients with HF were classified into three groups: 15–74, 75–84 and &gt;84 years. In the Bellvitge University Hospital (HUB)-Delta area (3396 HF patients), comparison of the pre-implementation and consolidation periods of the programme showed a decrease in clinically related hospitalisation in the youngest group (hazard ratio [HR] 0.87; confidence interval [CI] 0.84–0.91, <i>p </i>&lt; 0.001), the middle-age group (HR 0.90; CI 0.87–0.93, <i>p</i> &lt; 0.001) and the oldest group (HR 0.83; CI 0.83–0.89; <i>p </i>&lt; 0.001). Similar results were observed for all-cause mortality and readmission. Compared with HF care in the rest of Catalonia, the new programme resulted in a significant reduction in all-cause mortality across all age groups and all-cause hospitalisations among the young and middle-aged groups during the programme's transition and consolidation periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Implementation of the new HF programme within a universal-coverage healthcare system was associated with significant reductions in all-cause clinically related hospitalisations and HF readmissions across all age groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"345-359"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429436","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}

{"title":"Continue or discontinue antihypertensive medication in hospitalized patients—The coin has two sides","authors":"Peter Bárány","doi":"10.1111/joim.70107","DOIUrl":"10.1111/joim.70107","url":null,"abstract":"&lt;p&gt;Despite progress in controlling hypertension globally, it is still the leading risk factor for early death and poor health [&lt;span&gt;1&lt;/span&gt;]. Effective antihypertensive treatment reduces cardiovascular morbidity and mortality and prevents progression of diabetic complications, heart failure, and chronic kidney disease. However, WHO estimates that only 23% of adults with hypertension worldwide have it under control.&lt;/p&gt;&lt;p&gt;Based on randomized controlled studies, recent guidelines recommend a blood pressure goal of less than 130/80 mm Hg in patients with cardiovascular disease, diabetes mellitus, and chronic kidney disease [&lt;span&gt;2&lt;/span&gt;]. Especially in elderly patients, achieving such a strict blood pressure target carries a risk of hypotension, syncope, and acute kidney injury (AKI) episodes [&lt;span&gt;3&lt;/span&gt;]. Hypotension and hemodynamic instability during acute illness are common events leading to temporary withholding of antihypertensive medication.&lt;/p&gt;&lt;p&gt;Aspects of inhospital management of patients with hypertension have been studied and debated recently. A meta-analysis found a decreased risk of perioperative hypotension when renin-angiotensin-aldosterone system inhibitors (RAASi) were discontinued up to 10–48 h before surgery [&lt;span&gt;4&lt;/span&gt;]. The risk of postoperative atrial fibrillation increased, but no effect on mortality was observed. In hospitalized patients with elevated blood pressure, it is necessary to distinguish between asymptomatic hypertension and emergencies with target-organ damage requiring immediate intervention [&lt;span&gt;5&lt;/span&gt;]. Patients with asymptomatic hypertension should continue their medications but intensified treatment of inpatients, with often transient increase in blood pressure, should be avoided.&lt;/p&gt;&lt;p&gt;In the large propensity score–matched cohort study of stable hospitalized patients with hypertension by Ribak et al in this issue of &lt;i&gt;Journal of Internal Medicine&lt;/i&gt; [&lt;span&gt;6&lt;/span&gt;], clinical outcomes associated with discontinuation of antihypertensive therapy were evaluated. Exclusion criteria included patients admitted with AKI or hypotension as well as patients in the ICU and cardiology wards.&lt;/p&gt;&lt;p&gt;Overall, 28.4% of the whole cohort of hypertensive patients discontinued one or more prescribed antihypertensive medications. Discontinuation of diuretics was most common, followed by RAASi, whereas 85.9% of patients on beta-blockers continued treatment. Stopping beta-blockers abruptly preoperatively is not recommended in cardiology guidelines because it may lead to rebound tachycardia and hypertension [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Consistent in most subgroups, the main findings were increased inhospital and 90-day mortality when antihypertensive therapy was discontinued. Discontinuation in patients admitted to internal medicine wards and patients with infections was associated with higher rates of AKI, whereas withholding antihypertensives in surgical patients was linked to increased risk of myocardial injury. No b","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"218-219"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969150","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}

{"title":"Authors’ reply: Myasthenia gravis following the initiation of statin therapy","authors":"Vincent Ka Chun Yan,&nbsp;Wanchun Xu,&nbsp;Yuta Taniguchi,&nbsp;Kwun Kei Fung,&nbsp;Koon Ho Chan,&nbsp;Gary Kui Kai Lau,&nbsp;Celine Sze Ling Chui,&nbsp;Francisco Tsz Tsun Lai,&nbsp;Xue Li,&nbsp;Masao Iwagami,&nbsp;Rie Masuda,&nbsp;Nanako Tamiya,&nbsp;Sreemanee Raaj Dorajoo,&nbsp;Jing Wei Neo,&nbsp;Esther Wai Yin Chan,&nbsp;Ian Chi Kei Wong,&nbsp;Eric Yuk Fai Wan","doi":"10.1111/joim.70123","DOIUrl":"10.1111/joim.70123","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;We thank Zeng and Shi for their thoughtful letter [&lt;span&gt;1&lt;/span&gt;] and for the opportunity to address some common concerns that may be raised regarding our study on statin initiation and myasthenia gravis (MG) [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;First, it is indeed possible that statin-induced muscle-related adverse events may prompt further clinical investigations, thereby increasing the likelihood of an MG diagnosis being made, rather than statins being a direct cause of MG. Furthermore, we also conducted sensitivity analysis, which aimed to evaluate if the unmasking of preexisting undiagnosed MG after statin initiation could have influenced our findings, and the results were consistent with our main analysis. These suggest that our findings are unlikely to be fully explained by diagnostic detection bias alone. Future studies where detailed information on diagnostic markers, such as anti-acetylcholine receptor antibody levels, are available would enable better differentiation between true MG and other muscle-related adverse events.&lt;/p&gt;&lt;p&gt;Second, heterogeneity is indeed a common challenge for multinational studies, especially those involving different ethnicities. As discussed in our study, differences in healthcare systems, database coverage, and case ascertainment across different countries could limit the generalisability of our findings. Although the Japanese cohort showed no significant risk increase, it should be noted that as an insurer-based claims database, JMDC database tends to include younger and employed individuals. The use of only low-to-moderate intensity statins in the Japanese cohort could have also reduced the overall risk of MG as our study showed such risk tended to be dose-dependent. We encouraged readers to consider the presented results from individual sites in addition to the summary IRRs to gain a more comprehensive picture.&lt;/p&gt;&lt;p&gt;Third, we would like to reemphasize that MG is rare as an adverse event, and thus the potential benefits of statin therapy are expected to outweigh the associated risks. Our findings suggest the importance of considering the possibility of new-onset MG after initiating statin therapy, especially among individuals receiving high-intensity statin regimens who present with persistent muscular symptoms that do not resolve after discontinuation of statin therapy for suspected statin-induced myopathy.&lt;/p&gt;&lt;p&gt;Finally, as with all retrospective observational studies, readers are encouraged not to infer the findings as establishing causation. Having said so, SCCS provides one of the best methodological frameworks for pharmacovigilance studies and has proved useful in, for example, the detection of adverse events for vaccines. We hope our findings offer real-world evidence that improves medication safety, in the absence of high-quality data from randomized studies that could capture such safety signals.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Vincent Ka Chun Yan&lt;/b&gt;: Writing—original draft; methodology; writing—review and ed","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"384-386"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215925","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}

{"title":"Long-term outcomes in patients with postural orthostatic tachycardia syndrome with an average follow-up of over 20 years","authors":"Kate M. Bourne,&nbsp;Alfredo Gamboa,&nbsp;Bonnie Black,&nbsp;Juliette Hall,&nbsp;Italo Biaggioni,&nbsp;Cyndya A. Shibao,&nbsp;André Diedrich,&nbsp;Amanda Peltier,&nbsp;Giris Jacob,&nbsp;Luis Okamoto,&nbsp;Robert S. Sheldon,&nbsp;Satish R. Raj","doi":"10.1111/joim.70104","DOIUrl":"10.1111/joim.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Postural orthostatic tachycardia syndrome (POTS) is a chronic form of orthostatic intolerance that primarily affects female patients. There are scarce data evaluating the long-term outcomes in POTS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study sought to evaluate the long-term impacts of POTS over multiple decades in adult patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Past research participants at the VUMC Autonomic Dysfunction Center Research Unit (symptomatic ≥10 years) were recruited to participate in the study. A custom survey was administered at one time point. Participants were grouped as IMPROVED or NOT IMPROVED based on symptom course over time. Continuous data are reported as median (25th, 75th).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with POTS (<i>n</i> = 44; 98% female) were included in the analysis (62% response rate). Patient age at the time of survey was 48 (38, 54) years, with 23 (15, 27) years from POTS symptom onset, and 17 (12, 24) years from POTS diagnosis. Since diagnosis, symptoms completely resolved in 2%, improved in 46%, worsened in 25%, were unchanged in 11%, and demonstrated a variable symptom course in 16%. Patients who were NOT IMPROVED were more likely than those IMPROVED to have neuropathy, gastroparesis, and overactive bladder symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In a cohort of adult patients with POTS who received care at a national referral center for autonomic disorders, almost half reported their POTS symptoms as improved 10 or more years after symptom onset. Most patients with POTS experienced ongoing symptoms for many years after diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"299-311"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969127","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}

{"title":"Brain pathology in relation to somatic diseases: Exploring the body–brain crosstalk","authors":"G. Grande,&nbsp;M. Valletta,&nbsp;F. Gasparini,&nbsp;D. L. Vetrano,&nbsp;M. Canevelli,&nbsp;J. R. Bacci,&nbsp;C. Qiu,&nbsp;A. Marengoni,&nbsp;M. Toccaceli Blasi,&nbsp;H. Xu,&nbsp;L. Fratiglioni,&nbsp;M. M. Mielke","doi":"10.1111/joim.70119","DOIUrl":"10.1111/joim.70119","url":null,"abstract":"<p>Several somatic diseases have been consistently linked with an increased dementia risk. However, the underlying neuropathological substrates remain poorly characterized. This narrative review aims to summarize evidence on the association between common age-related somatic conditions (i.e., heart diseases, type 2 diabetes, kidney disease, liver diseases, lung disease, and anemia) and neuropathological findings, encompassing both Alzheimer's disease (AD)-related pathology (amyloid and tau deposition) and non-AD co-pathologies (i.e., neuronal loss, neuroinflammation, cerebrovascular lesions, and non-AD proteinopathies). We conducted a PubMed search for human studies examining these associations using postmortem data, brain imaging, or cerebrospinal fluid biomarkers. Evidence was qualitatively synthesized and graded according to its strength. Strong and consistent associations were observed between most examined somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, evidence associating these conditions with amyloid and tau pathology was limited and inconsistent. No studies systematically examined neuroinflammation or non-AD proteinopathies in relation to somatic diseases. Together, the available evidence suggests that somatic diseases are unlikely to primarily drive AD pathology but instead contribute to brain damage through a combination of non-AD processes, particularly cerebrovascular injury and diffuse neuronal loss. These findings highlight the need to increase our knowledge of “mixed dementia” and move beyond a purely brain-centric view of dementia, especially in older adults with complex clinical profiles.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"223-237"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147629","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}

{"title":"Anti-inflammatory agents in atherosclerosis—and a need for reform: Extraordinary claims require extraordinary evidence","authors":"Kevin Jon Williams","doi":"10.1111/joim.70128","DOIUrl":"10.1111/joim.70128","url":null,"abstract":"<p>Since 1858, human atherosclerotic plaques have been shown to contain immune cells. But are these cells suitable therapeutic targets? Dozens of clinical trials of anti-inflammatory agents other than colchicine have been performed in patients with clinically evident atherosclerosis. None of these trials led any regulatory body in any jurisdiction to allow a cardiovascular indication for any of these agents. This discouraging work provides a background to evaluate new data on colchicine. In 2024–2025, new clinical trials of colchicine in patients with atherosclerosis showed benefit, no benefit, or harm. In 2025–2026, over a dozen meta-analyses so far have appeared, drawing on ∼34 trials, but do not agree with each other. One of these meta-analyses, Xie et al.’s in the <i>Journal of Internal Medicine</i>, provides a compelling graphical display of the pre-specified primary outcomes of six long-term clinical trials as they were published over time. The pattern of early positive trials, then newer negative (null) trials, suggests regression to the truth. Jeon and Cho et al.’s population-wide study in the <i>Journal of Internal Medicine</i> of patients with Type 2 diabetes and gout found no benefit from colchicine over nonsteroidal anti-inflammatory drugs on major adverse cardiovascular events. This information suggests several areas for reform of research on inflammation in atherosclerosis. Fully informed consent should require that clinical trials of anti-inflammatory agents in atherosclerotic arterial disease must disclose to trial participants the failures of this approach in over 50 clinical trials to date, spanning decades. Additionally, the field might reconsider its commitment to the Big Idea that inflammation must be a definitive therapeutic target in atherosclerosis. The track record so far for inflammation inhibition in atherosclerosis is extensive and disappointing—a fact that merits wider discussion. Therapeutic successes from targeting cholesterol-rich, apolipoprotein-B-containing lipoproteins—the proven causative agents of this disease—provide extraordinary evidence. Current data for colchicine and other anti-inflammatory therapies do not.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"300 3","pages":"258-283"},"PeriodicalIF":7.6,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429504","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}