Journal of Internal Medicine最新文献

{"title":"High cholesterol absorption efficiency enhances proatherogenic properties of low-density lipoprotein particles.","authors":"Katariina Öörni, Lauri Äikäs, Maija Ruuth, Feven Tigistu-Sahle, Reijo Käkelä, Ingmar Wester, Helena Gylling, Piia Simonen","doi":"10.1111/joim.70085","DOIUrl":"10.1111/joim.70085","url":null,"abstract":"<p><strong>Background and aims: </strong>High cholesterol absorption efficiency is determined by genetic variation in small intestinal sterol transporters and affects one-third of individuals. Their risk for atherosclerotic cardiovascular disease (ASCVD) is increased compared with low cholesterol absorbers, despite similar serum lipid concentrations. We investigated the association of cholesterol absorption efficiency with proatherogenic properties of low-density lipoproteins (LDLs).</p><p><strong>Methods: </strong>The study cohort consisted of 90 middle-aged participants, 56 females and 34 males, without lipid-lowering therapy or ASCVD. They were divided into low (n = 45) and high (n = 45) cholesterol absorbers by the median value of serum cholestanol to cholesterol ratio. LDL aggregation susceptibility and binding of lipoproteins to proteoglycans were determined as biomarkers of lipoprotein atherogenicity. Nuclear magnetic resonance spectroscopy, mass spectrometry, and gas-liquid chromatography were used to determine lipoprotein subclass profile, LDL lipidome, and serum concentrations of cholesterol and noncholesterol sterols, respectively.</p><p><strong>Results: </strong>Age, dietary cholesterol, and serum total cholesterol or lipoprotein cholesterol levels did not differ between the groups. In the high absorbers, LDL particles were larger, and LDL aggregation susceptibility and the binding of lipoproteins to proteoglycans were increased in the low absorbers. Of LDL surface lipids, sphingomyelin 42:3;O2, and phosphatidylcholine (PC) 32:0 correlated positively, whereas PC 32:1 correlated negatively with serum cholestanol levels. These LDL surface lipids were also associated with increased LDL aggregation susceptibility and proteoglycan-binding.</p><p><strong>Conclusions: </strong>The present findings suggest that increased proatherogenic properties in high cholesterol absorbers may contribute to increased ASCVD risk.</p><p><strong>Registration: </strong>https://clinicaltrials.gov/study/NCT01315964.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"711-725"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607686","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":"Immune endotypes in tuberculosis: Keys to decoding disease complexity.","authors":"Shamila D Alipoor, Julia Guthrie, Lina Davies Forsman, Andrew R Di Nardo, Susanna Brighenti","doi":"10.1111/joim.70092","DOIUrl":"10.1111/joim.70092","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a major global health challenge, with multi-drug antibiotic regimens as the current standard of care. While effective at killing Mycobacterium tuberculosis, these treatments do not resolve persistent inflammation, prevent lung damage, or reverse immune dysregulation that contribute to poor outcomes and disease recurrence. Precision medicine offers a promising alternative but requires deeper insight into disease mechanisms to enable tailored interventions. This comprehensive review introduces the concept of immune endotyping to define the underlying disease mechanisms as tools to decode clinical and immunological heterogeneity in TB. TB displays a wide spectrum of clinical phenotypes, from latent or asymptomatic infection to mild or severe disease with characteristic non-cavitary or cavitary lung pathology. Instead, distinct immune endotypes capture the diverse biological pathways that shape disease progression and treatment response. Similar clinical presentations may arise from different immune dysfunctions, underscoring the need to move beyond broad phenotypic classifications. Advances in multi-omics and computational analyses uncover immune signatures that enable stratification for host-directed therapies (HDTs) targeting hyperinflammation, immunosuppression, coagulopathy or metabolic exhaustion. Integrating clinical, radiological, and immunological data through multimodal profiling is essential for developing personalized interventions. We also explore how endotyping has transformed treatment in other diseases, offering valuable insights for TB. Additionally, we present examples of how putative immune endotypes may be targeted with appropriate HDTs. In summary, this review underscores the potential of immune endotypes to advance precision medicine in TB, moving beyond one-size-fits-all treatment to improve outcomes, especially in severe and drug-resistant cases.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"670-693"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607713","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":"Correction to \"Identifying subjects at risk of liver cirrhosis via a range of thresholds for common fibrosis markers: A Welsh general population-based cohort study\".","authors":"","doi":"10.1111/joim.70090","DOIUrl":"10.1111/joim.70090","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"781"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571393","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":"Poor long-term cardiovascular risk factor management after acute coronary syndrome: An observational cohort study.","authors":"Jessica Schubert, Maria K Svensson, Margret Leosdottir, Bertil Lindahl, Håkan Melhus, Elin Täufer Cederlöf, Nina Johnston, Thomas Cars, Emil Hagström","doi":"10.1111/joim.70086","DOIUrl":"10.1111/joim.70086","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular risk factor control reduces the risk of recurrent events after acute coronary syndrome (ACS). Long-term post-ACS management is poorly studied.</p><p><strong>Objectives: </strong>To assess frequency of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) monitoring and target achievement during 3 years post-ACS.</p><p><strong>Methods: </strong>Data from all patients hospitalized for ACS in Uppsala between 2012 and 2020 were obtained from electronic health records (EHRs). The probability of measurement and target achievement was estimated with adjusted regression models. Associations were assessed for sex, participation in cardiac rehabilitation (CR), presence of diabetes with nurse-led follow-up and documentation of an ICD-10 code for chronic ischaemic heart disease in the EHR.</p><p><strong>Results: </strong>Among 6083 patients (median age 73 years, 34% female), follow-up data were available for 72% in year 1, 56% in year 2 and 44% in year 3. Year 3 LDL-C was not measured in 48% of patients, and 19% were at target (<1.8 mmol/L). For SBP, 16% lacked a measurement, and 50% were at target (<140 mmHg). Female sex was associated with lower probability of having LDL-C measured or having LDL-C or SBP at target. CR participation, structured diabetes follow-up or having a chronic ischaemic heart disease code in the EHR was associated with a higher probability of LDL-C and SBP measurements at 2 and 3 years.</p><p><strong>Conclusions: </strong>Lack of measurement and low risk factor achievement highlight missed opportunities in secondary prevention. Female sex, lack of structured follow-up and the absence of diagnostic labelling were associated with less frequent monitoring and poorer risk factor control.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"726-740"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483957","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":"Individualized management of primary hyperparathyroidism.","authors":"Jens Bollerslev, Filomena Cetani, Neil Gittoes, Lars Rolighed","doi":"10.1111/joim.70089","DOIUrl":"10.1111/joim.70089","url":null,"abstract":"<p><p>Primary hyperparathyroidism (PHPT) is a common endocrine disease that typically presents in peri- and postmenopausal women. PHPT is due to a single parathyroid adenoma in most cases, which leads to stable hypercalcemia over years. Nowadays, the diagnosis is often coincidental, reached by chance in subjects without specific symptoms-asymptomatic PHPT. However, the patients might have subtle disease-related manifestations. Management standards have been reviewed through international workshops over more than three decades, leading to absolute and relative indications for parathyroidectomy (PTX), the only curative treatment. The alternative to PTX is observation without intervention in asymptomatic patients without organ manifestations and only mildly elevated calcium levels (mild PHPT). On the basis of recent literature, our aim is to challenge current recommendations for managing PHPT with focus on mild asymptomatic disease, integrating informed patient preferences. Considering the changing patient demography with increasing life expectancy, more sensitive visualization procedures, improved surgical techniques, and new data on PHPT-related morbidity, we test some of the established indications for PTX, particularly age as an isolated criterion, and the validity of a circulating calcium \"threshold\" for considering PTX. Additionally, bone mineral density (BMD) decreases for at least a decade with observation in contrast to PTX, where BMD normalizes after surgery and remains stable in the axial compartments for years. Therefore, skeletal-related thresholds for PTX also deserve review. In conclusion, we suggest integrating more clinical outcomes and wider perspectives in decision-making for the management of mild PHPT, taking patient preferences into consideration, and focusing on informed and shared decision-making.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"650-669"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621167","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":"Depression following the initiation of glucagon-like-peptide-1 receptor agonist therapy: A multinational self-controlled case series study.","authors":"Vincent Ka Chun Yan, Zi-Yang Peng, Vincent Kai Chung Wong, Ian Chi Kei Wong, Esther Wai Yin Chan, Huang-Tz Ou, Eric Yuk Fai Wan","doi":"10.1111/joim.70098","DOIUrl":"10.1111/joim.70098","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"776-780"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687474","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":"Factors associated with potentially inappropriate medication use, medication underuse and overuse in older adults in the German National Cohort.","authors":"Miriam Degen, Ulrike Haug, Oliver H F Scholle, Yaw Awuku-Larbi, Sigrid Carlsson, Nina Ebert, Volker Harth, Anja M Hauri, Margit Heier, Anne Herrmann, Michael Leitzmann, Jakob Linseisen, Claudia Meinke-Franze, Nadia Obi, Phil Pendt, Thomas Reinhold, Barbara Thorand, Hermann Brenner, Ben Schöttker","doi":"10.1111/joim.70097","DOIUrl":"10.1111/joim.70097","url":null,"abstract":"<p><strong>Background: </strong>Effectively identifying individuals exposed to drug underuse, overuse and potentially inappropriate medication (PIM) in older adults is essential for minimizing preventable drug-related harms.</p><p><strong>Methods: </strong>We analysed data from 54,296 individuals aged 60-74 years from the German National Cohort (NAKO). We assessed the frequency of PIM, untreated conditions (medication and vaccination underuse) and medications without indication (overuse) utilizing the Fit fOR The Aged (FORTA) list. Factors associated with PIM, medication overuse and underuse were identified by multivariable logistic regression models.</p><p><strong>Results: </strong>The frequency of PIM, underuse and overuse of medications was 26.1%, 19.1% and 23.6%, respectively. In participants with available vaccination information, 90.6% and 62.7% did not have the recommended pneumococcal and annual influenza virus vaccinations, respectively. Parkinson's disease, arterial hypertension, epilepsy and depression were strongly associated with PIM use, with 16.2-, 4.5-, 4.3- and 2.1-fold increased odds, respectively. Osteoporosis, atrial fibrillation, Parkinson's disease and chronic obstructive pulmonary disease were identified as particularly strongly associated with underuse, with 9.5-, 6.1-, 2.6- and 2.0-fold increased odds, respectively. Depression and epilepsy were the most prominent factors associated with overuse (1.6- and 1.5-fold increased odds).</p><p><strong>Conclusion: </strong>PIM and medication overuse, as well as drug and vaccine underuse, are very common among older German individuals. Comprehensive medication reviews are needed to improve medication quality. This work identifies people with specific characteristics who would benefit the most and could be prioritized for medication reviews.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"754-775"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653514","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":"Co-pathologies and biological processes beyond amyloid-beta and tau in people with Alzheimer's disease: Evidence from clinical cohort studies.","authors":"Daniel Ferreira, Tomasz Chmiela, Maria Eriksdotter, Clifford R Jack, Grégoria Kalpouzos, Anna Marseglia, Patrizia Mecocci, Agneta Nordberg, Dorota Religa, Eric Westman","doi":"10.1111/joim.70096","DOIUrl":"10.1111/joim.70096","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is neuropathologically defined by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. However, co-pathologies and other pathobiological processes are involved in the pathogenesis of AD, contributing to neurodegeneration and clinical symptoms. The most common co-pathologies in people with AD are alpha-synucleinopathy, vascular brain injury and transactive response DNA-binding protein of 43 kDa-related pathology. Neuroinflammation, iron accumulation, cholinergic dysfunction and cellular senescence are recognized pathobiological processes beyond Aβ- and tau-related pathology. However, the exact mechanisms by which these co-pathologies and pathobiological processes contribute to the neurodegeneration and clinical symptoms in people with AD remain unclear. The individual combination of these co-pathologies and pathobiological processes increases phenotypical heterogeneity in people with AD. This highlights the unmet need to advance their current understanding, and the field strives to develop accurate biomarkers for personalized assessment and investigation. Elucidating this biologic-clinical complexity and heterogeneity is crucial for increasing our current understanding of AD, with implications for diagnosis, prognosis and therapeutics.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"694-710"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687512","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":"Flare risk after oral glucocorticoid bridging with methotrexate or intra-articular bridging with triple therapy in early rheumatoid arthritis.","authors":"Kristina Lend, Jos W R Twisk, Frieda A Koopman, Anna Rudin, Merete Lund Hetland, Till Uhlig, Dan C Nordström, Michael T Nurmohamed, Bjorn Gudbjornsson, Kim Hørslev-Petersen, Marte Schrumpf Heiberg, Tuulikki Sokka-Isler, Gerdur Grondal, Espen A Haavardsholm, Mikkel Østergaard, Jon Lampa, Ronald van Vollenhoven","doi":"10.1111/joim.70094","DOIUrl":"10.1111/joim.70094","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate, in early rheumatoid arthritis, whether bridging with glucocorticoids (GCs) is associated with an increased risk of flare following GC tapering and withdrawal.</p><p><strong>Methods: </strong>A total of 810 NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) patients were included in this post hoc analysis: all received methotrexate (MTX), in addition to which 135 patients received oral GC bridging therapy ('oral GC group'); 80 received intra-articular (IA) GC bridging therapy, sulfasalazine and hydroxychloroquine ('injection GC group'); and 595 received one of three (certolizumab pegol, abatacept and tocilizumab) biologic disease-modifying antirheumatic drugs (bDMARDs), hereafter the ('bDMARD group'). Clinical disease activity index (CDAI) flares (≥4.5 increase in CDAI score) were assessed longitudinally.</p><p><strong>Results: </strong>Up to 48 weeks, flare occurred at least once in 43% of oral GC, 24% of injection GC and 28% of bDMARD patients. Over-time relative risk (RR) was higher with oral GC bridging (adjusted RR, 1.54; 95% CI, 1.16-2.03) but similar with injection GC bridging (adjusted RR 0.93; 95% CI, 0.54-1.55) versus bDMARD. Flare rates were numerically higher in the oral GC versus bDMARD group at all time points (12, 24, 32, 40 and 48 weeks), with a significant difference at w.40, the visit after protocol-defined GC discontinuation; at this visit 27% of patients who discontinued GC experienced flare; 29% among those in remission; 33% remained on low-dose prednisolone at 48 weeks.</p><p><strong>Conclusion: </strong>Discontinuation of oral GC bridging therapy on background MTX is associated with increased flare risk, even among patients in remission. Flare rates with IA GC bridging plus triple therapy did not differ from the bDMARD group.</p><p><strong>Trial registration number: </strong>EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":"741-753"},"PeriodicalIF":9.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626725","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":"An update on drug-induced liver injury-What's new?","authors":"Einar S Björnsson, Raul J Andrade","doi":"10.1111/joim.70111","DOIUrl":"https://doi.org/10.1111/joim.70111","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is an important medical condition. Recently, development of novel causality assessment tools has improved the diagnostic accuracy of idiosyncratic DILI, particularly RECAM (Revised Electronic Version of Roussel Uclaf Causality Assessment [RUCAM]). RECAM was found to be better than RUCAM in difficult cases and increased the precision of the DILI diagnosis but needs further refinement. In recent years, there has been an increased incidence of DILI with drugs, such as oncological drugs and herbal and dietary supplements (HDSs). DILI is commonly associated with checkpoint-induced liver injury. Treatment with corticosteroids has been the standard of care in this type of liver injury, but its use is controversial and potentially harmful. With the help of liver biopsy, 60% of subjects can avoid corticosteroids. In recent years, a number of dietary supplements have been found to lead to DILI, such as turmeric, Garcinia cambogia, kratom and ashwagandha. HLA-B*35:01 has been identified as a risk factor for green tea extract-induced liver injury. International collaborative efforts have tried to find candidate biomarkers, but no biomarker has yet demonstrated superior performance to standard liver tests. FDA has recently approved the use of serum glutamate dehydrogenase (GLDH) as a biomarker to distinguish liver injury from muscle injury. Serum GLDH should be used alongside standard liver injury monitoring in patients without pre-existing liver disease. In the current review, recent findings in DILI are presented on diagnostic strategies, new agents such as checkpoint inhibitors and HDSs leading to DILI, biomarkers and new therapies.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831581","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}