Journal of Internal Medicine最新文献

{"title":"The novel ITPR1 p.Phe2566Ser variant impairs IP3R1-mediated Ca2+ release and is associated with ataxia and miosis","authors":"Josephine Wincent, Songbai Zhang, Andrew Nolan, Shigeaki Kanatani, Frida Nordin, Malin Kvarnung, Per Uhlén, Martin Paucar, Ilse Eidhof","doi":"10.1111/joim.70081","DOIUrl":"10.1111/joim.70081","url":null,"abstract":"<p>Dear Editor,</p><p>Pathogenic variants in the <i>ITPR1</i> gene, which encodes the inositol 1,4,5-trisphosphate receptor type 1 (IP<sub>3</sub>R1) — a critical intracellular calcium (Ca<sup>2+</sup>) release channel — βare known to cause a spectrum of neurological disorders. These include spinocerebellar ataxia types 15 and 29 (SCA15, SCA29), Gillespie syndrome, and pontine/cerebellar hypoplasia. IP<sub>3</sub>R1 is highly expressed in cerebellar Purkinje cells, where it regulates inositol 1,4,5-trisphosphate (IP<sub>3</sub>)-evoked endoplasmic reticulum (ER) Ca<sup>2+</sup> release [<span>1</span>]. Although ataxia is a hallmark of <i>ITPR1</i>-related disease and aniridia or iris hypoplasia is characteristic of Gillespie syndrome, the co-occurrence of ataxia and miosis has been documented only in two cases [<span>2, 3</span>]. The mechanistic basis of this ultrarare presentation is largely elusive. Here, we report a third family with congenital ataxia and miosis, carrying a novel heterozygous <i>ITPR1</i> missense variant.</p><p>The index patient was diagnosed with ataxia and miosis in infancy. There was no follow-up until age 59 when a brain MRI showed mild white matter abnormalities, but no cerebellar atrophy. Upon examination at ages 60 and 62, she displayed mild non-progressive axial ataxia (SARA score 5.5), mirror movements (MM), broken pursuit, and miosis (Fig. 1a) with slow dark adaptation. OCT showed marked thinning of the iris (Fig. 1b). She did not have pyramidal symptoms or areflexia. The patient's mother, two children, and two grandchildren had ataxia, and four of them had miosis (Fig. 1c, Table S1). Unlike previously reported ataxia–miosis cases [<span>2, 3</span>], none exhibited intellectual disability or dysmorphism (Tables S1 and S2). The iris phenotype of the index, however, closely resembled that described by Chesneau et al. [<span>3</span>], with a thin dilator muscle without iris transillumination, distinguishing it from congenital microcoria [<span>4</span>]. Detailed clinical information can be found in the Supporting Information.</p><p>Genetic investigation identified the very rare heterozygous <i>ITPR1</i> variant c.7697T>C (NM_002222.7, p.Phe2566Ser) with a CADD score of 32, which was reported once in the general population (gnomAD v4.1.0), conserved across species, and co-segregated with disease. No pathogenic variants were identified in genes associated with MM.</p><p>The p.Phe2566Ser variant resided within the IP<sub>3</sub>R1 linker (LNK) domain, distinguishing it from the β-TF1 suppressor-domain variants previously associated with ataxia–miosis (Fig. 1d). Using cryo-EM structures of rat IP<sub>3</sub>R1 [<span>5</span>], we found that the homologous residue of Phe2566 (Phe2621) participates in IP<sub>3</sub>R1 state-dependent rearrangements (Figs. S2–S4). In the active IP<sub>3</sub>R1, Phe2621 formed many hydrophobic contacts, particularly with His2631 within a Zn<sup>2+</sup>-binding motif implicated in st","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 5","pages":"643-648"},"PeriodicalIF":9.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147315885","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":"High cholesterol absorption efficiency interferes with bile acid metabolism and cholesterol elimination from the body","authors":"Piia Simonen,&nbsp;Ingmar Wester,&nbsp;Jyri Lommi,&nbsp;Juha Sinisalo,&nbsp;Helena Gylling","doi":"10.1111/joim.70031","DOIUrl":"10.1111/joim.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Elevated low-density lipoprotein (LDL) cholesterol causes atherosclerotic cardiovascular diseases. Variables of whole-body cholesterol metabolism, for example, high cholesterol absorption efficiency, might also be atherogenic, whereas the role of bile acids is controversial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This post hoc study concerns the impact of cholesterol absorption on bile acid metabolism. The hypothesis was that cholesterol absorption efficiency interferes with bile acid metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cholesterol metabolism was studied using absolute and relative methods. Elimination of cholesterol from the body as bile acids and neutral sterols was assessed from 24-h faecal collections and analysed by gas–liquid chromatography. Cholesterol absorption efficiency was evaluated by a peroral continuous dual-isotope feeding method, and cholesterol synthesis by a sterol-balance technique. The relative methods included analyses of serum biomarkers of cholesterol absorption efficiency and cholesterol synthesis by gas–liquid chromatography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Faecal bile acids, neutral sterols and cholesterol synthesis were lower in high- versus low-cholesterol absorbers. Elimination of cholesterol from the body as bile acids and neutral sterols was reduced in high- versus low-cholesterol absorbers. Serum and LDL cholesterol levels did not differ in low- versus high-cholesterol absorbers. Absolute and relative methods of cholesterol metabolism correlated with each other, suggesting that the results can be considered valid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In high-cholesterol absorbers, poor elimination of cholesterol from the body as bile acids and neutral sterols may indicate an increased risk of atherosclerosis. It can be prevented by decreasing cholesterol absorption and increasing reverse cholesterol transport by dietary means combined with ezetimibe and statin treatment, when needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 5","pages":"628-638"},"PeriodicalIF":9.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335963","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":"Collagen and microvascular alterations contribute to neuromuscular degeneration and disease progression in chronic intestinal pseudo-obstruction","authors":"Elisa Boschetti,&nbsp;Irene Neri,&nbsp;Leonardo Caporali,&nbsp;Elena Bonora,&nbsp;Carolina Malagelada,&nbsp;Claudio Fiorini,&nbsp;Danara Ormanbekova,&nbsp;Alessandro Berghella,&nbsp;Roberto D'Angelo,&nbsp;Rita Rinaldi,&nbsp;Cristiana Caliceti,&nbsp;Anna Costanzini,&nbsp;Mirella Falconi,&nbsp;Vincenzo Stanghellini,&nbsp;Stefano Ratti,&nbsp;Lucia Manzoli,&nbsp;Valerio Carelli,&nbsp;Roberto De Giorgio","doi":"10.1111/joim.70078","DOIUrl":"10.1111/joim.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic intestinal pseudo-obstruction (CIPO) is a severe gastrointestinal motility disorder that may be idiopathic or associated with systemic disease. In idiopathic cases, the pathophysiological mechanisms remain poorly defined. Although mutations in angiogenic factors have been reported in mitochondrial forms of CIPO, their role in non-mitochondrial cases is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate genetic and molecular contributors to CIPO, with a specific focus on intestinal microvasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Jejunal samples from patients with CIPO were analysed by whole exome sequencing (WES) and mitochondrial DNA (mtDNA) profiling. Morphometric and immunohistochemical studies assessed collagen remodelling, vascular architecture, neuromuscular integrity and hypoxia. Expression of angiogenic factors, including thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF), was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WES did not identify known CIPO-causing variants, but rare mutations in collagen-related genes were detected in a subset of patients. Tissue analysis revealed higher fibrosis, vascular remodelling with a predominance of very small vessels, thinning of the longitudinal muscle and neuronal loss. TP and VEGF expression were significantly reduced, whereas hypoxia-inducible factor-1α (HIF-1α) was markedly upregulated. mtDNA integrity and copy number were preserved, whereas haplogroup J was overrepresented. Multivariate analysis linked these alterations to a higher frequency of sub-occlusive episodes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vascular dysfunction and collagen abnormalities emerge as key contributors to neuromuscular degeneration in CIPO. These findings provide novel mechanistic insights into disease pathophysiology and support further exploration of vascular-targeted therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 5","pages":"587-603"},"PeriodicalIF":9.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300429","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":"Increased intervals in enzyme replacement therapy for stable type 1 Gaucher disease: A non-inferiority sequential trial emulation","authors":"Maxime Beydon,&nbsp;Jérôme Stirnemann,&nbsp;Karima Yousfi,&nbsp;Samira Zebiche,&nbsp;Dalil Hamroun,&nbsp;Anaïs Brassier,&nbsp;Samia Pichard,&nbsp;Laure Swiader,&nbsp;Thierry Billette de Villemeur,&nbsp;Bénédicte Héron,&nbsp;Florence Dalbies,&nbsp;Bérengère Cador,&nbsp;Anne-Sophie Guemann,&nbsp;Francis Gaches,&nbsp;Bénédicte Hivert,&nbsp;Vanessa Leguy-Seguin,&nbsp;Agathe Masseau,&nbsp;Yves-Marie Pers,&nbsp;Magali Pettazzoni,&nbsp;Soumeya Bekri,&nbsp;Catherine Caillaud,&nbsp;Edouard Le Guillou,&nbsp;Marie Szymanowski,&nbsp;Leonardo Astudillo,&nbsp;Wladimir Mauhin,&nbsp;Yann Nadjar,&nbsp;Christine Serratrice,&nbsp;Marc G. Berger,&nbsp;Fabrice Camou,&nbsp;Nadia Belmatoug,&nbsp;Yann Nguyen,&nbsp;the French Evaluation of Gaucher Disease Treatment Committee","doi":"10.1111/joim.70079","DOIUrl":"10.1111/joim.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the efficacy and safety of extended interval (Q3–4W) enzyme replacement therapy (ERT) versus standard biweekly (Q2W) ERT in clinically stable type 1 Gaucher disease (GD) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We emulated a target trial with a sequential trial design, using data from the French Gaucher Disease Registry. Eligible patients were treated for ≥2 years biweekly without clinical events. Every 3 months, switchers to Q3–4W were matched to Q2W patients by age, sex, referral center follow-up, disease history (bone events, anemia, thrombocytopenia, splenectomy, and hepatosplenomegaly), and dose of ERT. The primary outcome was a composite of GD-related events (bone events, anemia, and thrombocytopenia). A 10% non-inferiority margin was prespecified. Secondary outcomes were biomarker changes and economic analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 280 eligible GD patients, 63 switched to Q3–4W and were matched to a total of 215 Q2W patients, followed for an average of 6.3 years. No significant difference in the risk of clinical events was observed between groups (hazard ratio: 0.98 [95% confidence intervals (CI): 0.54–1.51]). During follow-up, absolute risk difference remained below the 10% non-inferiority threshold at all timepoints. Biomarkers remained stable or slightly decreased in the Q3–4W group. The dosing interval extension led to an average reduction of 55 infusions per patient, corresponding to approximately €450,000 saved per patient over 6 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In stable GD1 patients, extending ERT administration to every 3–4 weeks was non-inferior to the standard biweekly regimen, supporting personalized spacing strategies that may improve quality of life and reduce healthcare costs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 5","pages":"604-614"},"PeriodicalIF":9.2,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147315866","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":"Stopping or continuing chronic antihypertensive therapy during hospitalization.","authors":"Ziv Ribak, Jacob David Miller, Nitzan Burrack, Victor Novack, Ran Abuhasira","doi":"10.1111/joim.70093","DOIUrl":"https://doi.org/10.1111/joim.70093","url":null,"abstract":"<p><strong>Background: </strong>Elevated blood pressure is common among hospitalized patients, but the effects of withholding chronic antihypertensive therapy during hospitalization remain unclear.</p><p><strong>Objectives: </strong>To assess the association between continuation versus discontinuation of chronic antihypertensive medications during hospitalization and short- and long-term outcomes.</p><p><strong>Methods: </strong>This retrospective propensity score-matched cohort study included adults (≥18 years) with chronic hypertension hospitalized in eight Clalit Health Services hospitals in Israel from January 2014 to May 2024. Eligible patients had received at least one antihypertensive medication continuously for 6 months before admission. Discontinuation was defined as omission of ≥1 chronic medication during hospitalization. Outcomes included in-hospital and 90-day acute kidney injury (AKI), myocardial injury, stroke, and all-cause mortality.</p><p><strong>Results: </strong>After 1:1 propensity matching, 82,230 patients were analyzed (50,070 internal medicine; 32,160 surgical). In internal medicine departments, discontinuation was associated with higher risk of in-hospital AKI (OR, 1.23; 95% CI, 1.16-1.30), 90-day AKI (OR, 1.19; 95% CI, 1.14-1.24), in-hospital mortality (OR, 2.69; 95% CI, 2.47-2.94), and 90-day mortality (OR, 1.81; 95% CI, 1.72-1.90). In surgical departments, discontinuation was linked to in-hospital myocardial injury (OR, 1.26; 95% CI, 1.10-1.44) but not AKI. Results were consistent across subgroups, including infection-related admissions.</p><p><strong>Conclusions: </strong>Discontinuing chronic antihypertensive therapy during hospitalization was associated with increased risks of AKI and mortality. These findings suggest that withholding antihypertensive therapy is unlikely to confer benefit and may be harmful.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607513","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":"Global kidney health: Are we failing the silent pandemic?","authors":"Taewon Yi, Daniel V O'Hara, Adeera Levin","doi":"10.1111/joim.70088","DOIUrl":"https://doi.org/10.1111/joim.70088","url":null,"abstract":"<p><p>Chronic kidney disease (CKD), although not infectious, has a sharply rising global incidence, alarming rates of death and disability, and the potential to disrupt health systems and economies. Thus, it demands the urgency and global attention of past pandemics. Over 850 million people are affected, disproportionately impacting people in low- and middle-income countries. Although CKD can be detected with simple and cost-effective testing, it is a silent condition, often remaining asymptomatic until it has progressed to advanced stages where effective treatment options are limited. Early detection relies on systematic population-level screening, especially among individuals with comorbidities. The global response to CKD has remained largely silent: There is limited evidence of prioritization within health agendas and inadequate infrastructure for screening, surveillance, and treatment. Coordinated global action is required to halt this silent \"pandemic,\" especially given advances in care and policy: New effective disease modifying therapies may lead to remission of CKD for many individuals, and the 2025 World Health Organization's adoption of the Kidney Health Resolution at the 78th World Health Assembly prioritizes kidney health to reduce the burden of noncommunicable diseases through promoting early screening, strengthening disease prevention, and improving access to care. In this review, we examine the failure to address the escalating CKD \"pandemic\" and explore how the use of low-cost and cost-effective screening tools, such as simple urine dipstick testing, and applying lessons learned from the COVID-19 pandemic are critical to further reframing CKD as a public health emergency and prioritizing kidney health on the global agenda.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607651","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":"Potassium binders and continuation of renin-angiotensin system inhibitors/mineralocorticoid receptor antagonist in chronic kidney disease and heart failure (the DEMONSTRATE database).","authors":"Hans Furuland, Anders Olof Larsson, Milica Uhde, Kristel Parv, Matilda Almstedt, Thomas Cars, Maria K Svensson","doi":"10.1111/joim.70087","DOIUrl":"https://doi.org/10.1111/joim.70087","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperkalaemia is a serious complication in patients with chronic kidney disease (CKD) and heart failure (HF), often leading to the discontinuation of renin-angiotensin-aldosterone system inhibitors (RAASi; renin-angiotensin system inhibitors [RASi] and mineralocorticoid receptor antagonists [MRAs]) despite their cardiorenal benefits. Although potassium binders, especially second-generation potassium binders, reduce the risk of hyperkalaemia in clinical trials, real-world evidence on whether they enable RAASi continuation and influence clinical outcomes remains scarce.</p><p><strong>Methods: </strong>This observational, population-based cohort study used Swedish healthcare data from the DEMONSTRATE database to identify adults with non-dialysis (ND) CKD and/or HF who initiated potassium binders (2018-2022). Patients were stratified by potassium binder generation. RASi and MRA treatment changes were assessed at 6 months, and clinical outcomes (all-cause mortality, hospitalization and three-point major adverse cardiovascular events [3P-MACE]) were evaluated over a 3-year follow-up using propensity-score-weighted Kaplan-Meier analyses.</p><p><strong>Results: </strong>Of 7913 potassium binder episodes (6232 patients), 7.1% used second-generation binders. These episodes were associated with increased RAASi persistence at 6 months: 76.9% and 57.5% of second-generation users maintained RASi and MRA therapy, respectively, compared with 66.4% and 47.8% in the first-generation group. Patients who maintained RASi had lower observed all-cause mortality and hospitalization rates, but no difference in incidence of 3P-MACE was found.</p><p><strong>Conclusion: </strong>Second-generation potassium binders were associated with higher RAASi persistence than first-generation binders. RASi persistence was associated with lower observed rates of all-cause mortality and hospitalization, with no clear differences in 3P-MACE. These findings suggest that potassium binders may enable sustained RAASi use in patients with ND-CKD and/or HF.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508193","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":"Microscopic colitis and primary sclerosing cholangitis are bidirectionally associated: A nationwide matched cohort and case-control study.","authors":"David Bergman, Anders Forss, Jiangwei Sun, Fahim Ebrahimi, Björn Lindkvist, Charlotte Hedin, Hannes Hagström, Annika Bergquist, Jialu Yao, Jonas F Ludvigsson","doi":"10.1111/joim.70084","DOIUrl":"https://doi.org/10.1111/joim.70084","url":null,"abstract":"<p><strong>Background: </strong>Microscopic colitis (MC) is an inflammatory disease of the colon. Although there is a known association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), evidence linking MC and PSC remains scarce. We aimed to investigate the bidirectional association between MC and PSC.</p><p><strong>Methods: </strong>Leveraging the nationwide Swedish histopathology cohort Epidemiology Strengthened by histoPathology Reports in Sweden, we conducted a matched cohort study (2002-2023, follow-up until 2024) and a case-control study (1987-2023). Patients with IBD were excluded. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox regression and adjusted odds ratios (aORs) using conditional logistic regression.</p><p><strong>Results: </strong>The cohort study included 21,340 patients with biopsy-confirmed MC and 101,707 matched reference individuals (matched by age, sex, birth year and county). Over a median follow-up of 7 years, PSC was diagnosed in 21 patients with MC and 15 reference individuals, corresponding to incidence rates of 11.9 (95% CI = 7.8-18.3) and 1.7 (95% CI = 1.0-2.8) per 100,000 person-years, yielding an aHR of 7.17 (95% CI = 3.69-13.9). The case-control study included 22,729 MC cases and 108,467 matched controls. Prior PSC was more frequent among MC cases (19/22,729; 0.08%) than controls (12/108,467; 0.01%), yielding an aOR of 7.26 (95% CI = 3.50-15.1). Our findings remained robust across multiple sensitivity analyses, including sibling-controlled analyses.</p><p><strong>Conclusion: </strong>This nationwide study reveals a bidirectional association between MC and PSC. Although absolute risks are low, these findings suggest that MC may have diagnostic relevance in suspected PSC cases, and vice versa. Physicians treating MC patients should be alert to signs and symptoms of PSC.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497072","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":"Persistent and emerging cancer risks after migration: Evidence from North and South Korean cohorts.","authors":"Junshik Hong, Kyeong Jin Kim, Jimi Choi, Jung A Kim, Kyoung Jin Kim, Yo Han Lee, Sang Min Park, Sung In Jang, Jung Myun Lee, Ju Hyang Lee, Mun Jeong Choi, Young-Hoon Kim, Sin Gon Kim","doi":"10.1111/joim.70082","DOIUrl":"https://doi.org/10.1111/joim.70082","url":null,"abstract":"<p><strong>Background: </strong>North Korean defectors in South Korea offer a rare natural model to trace cancer risk evolution after rapid environmental transition, given shared genetics but markedly contrasting early life exposures with South Korean residents.</p><p><strong>Methods: </strong>Using the Korean National Health Insurance database, we constructed a nationwide matched cohort of 25,798 North Korean defectors and 1,276,601 South Korean residents (1:50 frequency matching by sex, age, and index year). We compared overall and site-specific cancer risks and examined time-varying hazard ratios (HRs) since resettlement.</p><p><strong>Results: </strong>Overall cancer risk was higher among defectors (HR 1.13; 95% confidence interval, 1.07-1.18), particularly in men (HR 1.31). Liver (HR 2.53), uterine cervical (HR 2.10), and lung cancer (HR 1.69) were markedly elevated, reflecting infection- and deprivation-related legacies. In contrast, cancers more prevalent in developed countries, notably breast (HR 0.48) and colorectal (HR 0.71), were initially lower. However, HRs began to rise over time, especially for breast cancer, indicating a trend toward convergence with host-population patterns.</p><p><strong>Conclusion: </strong>The cancer profile of North Korean defectors demonstrates a dual burden: persistent risks from infection-related cancers rooted in pre-defection exposures and growing vulnerability to lifestyle-related cancers after resettlement. These findings highlight the importance of dual-track prevention strategies that address both legacy and emerging cancer risks in rapidly transitioning populations.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429473","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":"Correction to “Soluble urokinase plasminogen activator receptor and interleukin-6 improve prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes”","authors":"","doi":"10.1111/joim.70065","DOIUrl":"10.1111/joim.70065","url":null,"abstract":"<p>Bahrami HSZ, Jørgensen PG, Hove JD, Dixen U, Rasmussen LJH, Eugen-Olsen J, et al. Soluble urokinase plasminogen activator receptor and interleukin-6 improves prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes. <i>J Intern Med</i>. 2025;<b>298</b>(3):188–199. https://doi.org/10.1111/joim.20108.</p><p>In the article, there were errors in Figures 2 and 3, Table 1, Results Section and supporting information Tables S2, S3, S4 and S6.</p><p>In Figure 2, right panel, 2^nd row, the P value for Model 4.2 should be 0.010 instead of 0.009.</p><p>In Figure 3, right panel, 2^nd row, the P value of Model 4.2 should be 0.095 instead of 0.086.</p><p>The corrected Figures 2 and 3 are below:</p><p>In the Results section, under “Prognostic value of suPAR and IL-6”, 2^nd paragraph and second sentence.</p><p>The sentence was incorrect.</p><p>The associations persisted when additionally adjusting for the other inflammatory biomarkers, suggesting independent effects of suPAR and IL-6; suPAR: HR 2.0 (1.3–3.0, <i>p</i> = 0.001), IL-6: HR 1.7 (1.1–2.4, <i>p</i> = 0.009) (Fig. 2). The results were similar with MACE as outcome (Model 4), suPAR: HR 1.9 (CI 1.4–2.6, p &lt; 0.001), IL-6: HR 1.3 (1.0–1.8, <i>p</i> = 0.086) (Fig. 3).</p><p>The correct sentence should be:</p><p>The associations persisted when additionally adjusting for the other inflammatory biomarkers, suggesting independent effects of suPAR and IL-6; suPAR: HR 2.0 (1.3–3.0, <i>p</i> = 0.001), IL-6: HR 1.7 (1.1–2.4, <i>p</i> = 0.010) (Fig. 2). The results were similar with MACE as outcome (Model 4), suPAR: HR 1.9 (CI 1.4–2.6, p &lt; 0.001), IL-6: HR 1.3 (1.0–1.8, <i>p</i> = 0.095) (Fig. 3).</p><p>In Table 1, the values in the following section were incorrect:\u0000\u0000 </p><p>The corrected values are as follows:\u0000\u0000 </p><p>In supporting information, supplemental Tables 2, 3, 4 and 6 contained errors and have been corrected in the online version.</p><p>The authors confirm that these corrections do not alter the study's main findings, interpretations, or conclusions.</p><p>We apologize for these errors.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"299 4","pages":"534-536"},"PeriodicalIF":9.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984289","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}