Journal of Internal Medicine最新文献

{"title":"Amiodarone induced thyroid dysfunction: A high cumulative incidence in a nationwide cohort study in Iceland","authors":"Páll Guðjónsson,&nbsp;Ari J. Jóhannesson,&nbsp;Elías Eyþórsson,&nbsp;Karl Andersen","doi":"10.1111/joim.20115","DOIUrl":"10.1111/joim.20115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amiodarone induced thyroid dysfunction (AITD) is divided into amiodarone induced thyrotoxicosis (AIT) and amiodarone induced hypothyroidism (AIH). The prevalence of them varies from 1.2% to 12% for AIT and 12%–17% for AIH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To study the incidence and complications of AITD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The cohort comprised all euthyroid patients who filled their first amiodarone prescription in Iceland in 2014, 262 persons. Data were gathered with chart review, and diagnosis confirmed with thyroid function tests. The cumulative incidence accounting for death as a competing risk was estimated for AIT, AIH, and AITD with three separate Fine-Gray models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overall incidence of AIT, AIH, and AITD was 9.2% (95% CI: 5.6%–12.7%), 13.4% (95% CI: 9.2%–17.5%), and 22.5% (95% CI: 17.4%–27.6%), respectively, and the 5-year cumulative incidence in the same order was 19.0% (95% CI: 11.9%–25.5%), 21.8% (95% CI: 14.7%–28.2%), and 38.5% (95% CI: 30.4%–45.7%). The highest yearly incidence rate of AIT was 9.8% during the third treatment year, and for AIH, it was 9.8% during the first year of treatment. The complications of AIT were hypothyroidism (8%), thyroidectomy (8%), hospitalizations (36%), and death (4%). Most patients (91.7%) with AIH were placed on thyroid replacement therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Nearly 40% of patients taking amiodarone for 5 years acquire thyroid dysfunction, which is higher than previously described. Frequent monitoring of thyroid function should be considered during the high-risk periods of the first and third treatment years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"228-236"},"PeriodicalIF":9.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599000","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":"Overstated association between adolescent physical fitness and adulthood depression risk due to familial factors","authors":"Marcel Ballin,&nbsp;Örjan Ekblom,&nbsp;Anna Nordström,&nbsp;Viktor H. Ahlqvist,&nbsp;Peter Nordström","doi":"10.1111/joim.20109","DOIUrl":"10.1111/joim.20109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Examine the association between adolescent cardiorespiratory fitness and future risk of depression and dispensation of antidepressants, including the role of familial confounding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort study with sibling-comparisons based on Swedish men who participated in mandatory military conscription examinations from 1972 to 1995. The exposure was cardiorespiratory fitness estimated using a maximal ergometer bicycle test. The outcomes were depression diagnosis in specialized outpatient or inpatient care and dispensation of antidepressants until 31 December 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1,013,885 men (mean age 18.3 years), of which 410,198 were full siblings, were followed until a median age of 56.8 years, during which 47,283 were diagnosed with depression and 237,409 were dispensed antidepressants. In cohort analysis, the highest decile of fitness had lower risks of depression (adjusted hazard ratio [HR] 0.54, [95% confidence interval, 0.52, 0.57]) and antidepressants (HR 0.63; 0.62, 0.65) compared to the lowest decile, with differences in the standardized cumulative incidence by age 65 of −3.9% and −12.3%, respectively. In sibling-comparison analyses accounting for unobserved familial confounders, the associations attenuated for both depression (HR 0.67, 0.59–0.75; incidence difference −2.4%) and antidepressants (HR 0.76, 0.72–0.80; incidence difference −7.2%). Hypothetically shifting everyone to the highest decile of fitness was associated with a preventable fraction of 29.1% for depression and 17.8% for antidepressants in cohort analysis, which attenuated to 17.6% and 10.4% in sibling-comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High levels of adolescent cardiorespiratory fitness are associated with lower risks of future depression and antidepressants, but the associations might be overstated due to familial confounding.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"200-213"},"PeriodicalIF":9.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599001","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":"Soluble urokinase plasminogen activator receptor and interleukin-6 improves prediction of all-cause mortality and major adverse cardiovascular events in Type 1 diabetes","authors":"Hashmat Sayed Zohori Bahrami,&nbsp;Peter Godsk Jørgensen,&nbsp;Jens Dahlgaard Hove,&nbsp;Ulrik Dixen,&nbsp;Line Jee Hartmann Rasmussen,&nbsp;Jesper Eugen-Olsen,&nbsp;Peter Rossing,&nbsp;Magnus T. Jensen","doi":"10.1111/joim.20108","DOIUrl":"10.1111/joim.20108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 1 diabetes (T1D) increases premature mortality risk, with cardiovascular disease being the leading cause. Chronic inflammation may play a role. Associations between inflammatory biomarkers and mortality are not well-known in T1D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated a prospective clinical cohort with T1D without known cardiovascular disease. The inflammatory biomarkers soluble-urokinase-plasminogen-activator-receptor (suPAR) and interleukin-6 (IL-6) were measured. Patients were stratified by elevated/low suPAR or IL-6, or simultaneously elevated suPAR and IL-6. Primary and secondary endpoints were all-cause mortality and major adverse cardiovascular events (MACE), respectively. Cox models were adjusted for 10 Steno T1 Risk Engine variables and inflammatory biomarkers. Net reclassification improvement (NRI) and C-statistics were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 962 participants (52% male, median age 50, median follow-up 13.1 years), mortality was higher in patients with elevated inflammation: 31% for elevated versus 9% for low suPAR; 30% for elevated versus 11% for low IL-6; and 50% for simultaneously elevated suPAR and IL-6 versus 5% for low suPAR and IL-6. In fully adjusted models, elevated inflammation was associated with mortality (hazard ratios [95% confidence intervals]: suPAR 2.0 [1.4–3.0, <i>p</i> &lt; 0.001], IL-6 1.8 [1.3–2.6; <i>p </i>= 0.001], and combined 4.0 [2.3–7.2, <i>p</i> &lt; 0.001]) and MACE (suPAR 1.9 [1.4–2.6, <i>p</i> &lt; 0.001], IL-6 1.4 [1.0–1.8, <i>p </i>= 0.034], and combined 2.6 [1.7–4.1, <i>p</i> &lt; 0.001]). Adding suPAR, IL-6, and their combination to the Steno T1 Risk Engine improved NRI for mortality by 61%, 53%, and 84%, respectively, whereas C-statistics improved from 0.808 to 0.829, 0.826, and 0.881, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>suPAR, IL-6, and especially their combination independently predicts all-cause mortality and MACE in T1D without known cardiovascular disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"188-199"},"PeriodicalIF":9.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574566","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":"Gaucher disease, state of the art and perspectives","authors":"Fabrice Camou,&nbsp;Marc G. Berger","doi":"10.1111/joim.20114","DOIUrl":"10.1111/joim.20114","url":null,"abstract":"<p>Knowledge about Gaucher disease (GD), considered a model for rare diseases, has considerably increased since its discovery. The pathophysiology of this lysosomal disorder is better known, and specific therapies that can control many aspects of the disease have been developed, particularly for the most common form, Type 1 GD. Yet, in part because of the rarity of GD, but also because of a lack of awareness by physicians, diagnostic delay too often leads to a belated management of patients having accumulated comorbidities. Gaucher cells, the most visible consequence of glucocerebrosidase deficiency, have been known for many years. However, the pathophysiological mechanisms underlying some major lesions, such as bone disease, predisposition to Parkinson's disease in Type 1 GD, or neurological involvement in Type 2 and Type 3 GD, remain poorly understood. Diagnostic, therapeutic, and follow-up issues associated with these symptoms remain critical to optimize the care of these patients. In this review, clinical characteristics, pathophysiology, diagnosis, treatment, and prognosis of GD are successively considered, highlighting for each of them the remaining challenges. Continued efforts to better understand pathophysiological mechanisms, use of the most modern methods such as artificial intelligence, international collaboration, and development of new therapeutic strategies seem essential for the future of this rare disease.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"155-172"},"PeriodicalIF":9.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558628","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":"Use of dipeptidyl peptidase-4 inhibitors is associated with lower risk of severe renal outcomes in pre-dialysis patients with Type 2 diabetes","authors":"Tung-Ying Hung,&nbsp;Tzu-Chieh Lin,&nbsp;Ying-Jay Liou,&nbsp;Tzu-Han Lin,&nbsp;Yu-Juei Hsu,&nbsp;Liang-Yu Lin,&nbsp;Meng-Ting Wang","doi":"10.1111/joim.20112","DOIUrl":"10.1111/joim.20112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Patients with diabetes and Stage 5 chronic kidney disease (CKD) not on dialysis are susceptible to renal replacement therapy and severe complications. Among limited antidiabetic options in this vulnerable population, dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4i) are widely used; however, supporting evidence is scant. This study assessed severe renal outcomes associated with DPP-4i in diabetic and pre-dialysis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employed an active-comparator and propensity score–based inverse probability of treatment weighting approach, using Taiwan's nationwide healthcare claims database from 2012 to 2020. We identified patients with diabetes and CKD stage 5 not on dialysis who received erythropoietin (erythropoietin-stimulating agent), a drug reimbursed for patients with an estimated glomerular filtration rate &lt;15 mL/min/1.73 m². The primary outcome was a composite of renal replacement therapy, renal death, and kidney-related hospitalization events, and secondary outcomes included each component of the composite and hypoglycemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 7271 diabetic and pre-dialysis patients with CKD stage 5, of whom 5028 received DPP-4i and 2243 received meglitinides. DPP-4i were associated with a 14% reduced risk of the renal composite outcome compared to meglitinides (weighted hazard ratio [HR], 0.86; 95% confidence interval, 0.81–0.92). Individual component analysis revealed that the decreased risk was confined to renal replacement therapy, with a 17% reduction. DPP-4i was related to a 41% decreased severe hypoglycemia risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In diabetic and pre-dialysis patients with CKD stage 5, DPP-4i are related to a lower risk of the renal composite outcome, primarily driven by lower renal dialysis risk, and a lower hypoglycemia risk compared with meglitinides.</p>\u0000 </section>\u0000 </div>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"214-227"},"PeriodicalIF":9.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558629","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":"Promoting function-oriented, primary care approaches to improve the management of cognitive impairment and dementia","authors":"Marco Canevelli","doi":"10.1111/joim.20116","DOIUrl":"10.1111/joim.20116","url":null,"abstract":"&lt;p&gt;Primary care is currently at the forefront of a profound reorienting of healthcare systems worldwide, aimed at enhancing the health and well-being of older persons for various compelling reasons. Due to population aging, primary care, including community-based healthcare, will serve as the initial point of contact for an increasing number of older adults facing common age-related conditions and declines in capacity. The current supply of many specialists and healthcare professionals, especially those with geriatric competencies, is inadequate to address the rising demand and health needs of large and rapidly growing aging populations [&lt;span&gt;1&lt;/span&gt;]. Additionally, primary care is increasingly recognized as the ideal setting to implement risk reduction strategies, including lifestyle changes, to mitigate modifiable risk factors for highly prevalent chronic diseases [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In this context, a perspective paper published in the Journal of Internal Medicine by a group of experts on Alzheimer's disease and related dementias (ADRD) in the United States outlines the opportunities, challenges, and potential solutions related to the early detection of cognitive impairment within primary care settings [&lt;span&gt;3&lt;/span&gt;]. ADRD is among the foremost causes of mortality, disability, and dependency globally, posing a serious threat to the sustainability of social and healthcare systems, especially in low-resource settings. Cognitive impairment frequently goes underdiagnosed or is identified only after significant delays. This situation limits access to preventive, therapeutic, and rehabilitative interventions, intensifies the burden on caregivers, and potentially increases the risk of adverse outcomes. In light of these considerations, the paper emphasizes the critical role of primary care in conducting early cognitive evaluations, promoting brain health, facilitating lifestyle modifications, addressing reversible factors contributing to cognitive decline, and enhancing health and safety outcomes for both at-risk individuals and those already affected [&lt;span&gt;3&lt;/span&gt;]. Practical solutions are also proposed to overcome existing barriers to detecting ADRD in primary care [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The paper by Fowler et al. reaffirms the centrality of primary care in the management of ADRD [&lt;span&gt;3&lt;/span&gt;]. However, primary care approaches to ADRD should ideally be nested within broader care models aimed at improving the overall health, functioning, and well-being of older adults. There is growing recognition that disease-oriented frameworks may fail to capture critical health aspects relevant to older persons and their carers [&lt;span&gt;4&lt;/span&gt;]. A primary focus on specific nosological conditions may result in healthcare systems that are poorly responsive to the multifaceted needs and priorities of older people and may inadvertently lead to misclassification, mistreatment, malpractice, and inequalities [&lt;span&gt;4, 5&lt;/span&gt;]. Furthermore, disease-centr","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"146-148"},"PeriodicalIF":9.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537595","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":"Community prevalence of advanced liver fibrosis in Type 2 diabetes—How big is the challenge?","authors":"Kushala W. M. Abeysekera,&nbsp;Paul N. Brennan","doi":"10.1111/joim.20113","DOIUrl":"10.1111/joim.20113","url":null,"abstract":"<p>Editorial</p><p>Current population estimates suggest over a third of adults in the world have hepatic steatosis, and the majority would meet criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) [<span>1</span>]. This was previously termed non-alcoholic fatty liver disease until an international multi-society consensus to change the name in 2023 [<span>2</span>] to facilitate a proactive diagnosis rather than being a diagnosis of exclusion.</p><p>However, only a small proportion of patients with MASLD will have a major adverse liver outcome in their lifetime, such as decompensated cirrhosis or developing a hepatocellular carcinoma (HCC). The major risk for adults with hepatic steatosis is a major adverse cardiovascular event (MACE), particularly myocardial infarction, with an increased lifetime odds of coronary artery disease rising by 33% compared to adults without steatosis [<span>3</span>].</p><p>The counterfactual is MASLD is a leading indication for liver transplantation across Europe and North America, in part due to the success of the Hepatitis C eradication programmes internationally. MASLD is also a rapidly rising cause of liver-related deaths in the WHO global burden of disease study, behind alcohol-related liver disease and viral hepatitis. Modelling of trajectories of liver disease–related deaths from seven international liver disease cohorts suggests MASLD related deaths will have doubled between 2015 and 2030 [<span>4</span>]. It is also driving the rise in HCC in non-cirrhotic liver disease across the western world, with one multicentre French cohort reporting 72% of non-cirrhotic HCC diagnoses were made incidentally over an 11-year period [<span>5</span>].</p><p>Crucially, fibrosis progression rates (FPRs) in MASLD are slow, and addressing cardiometabolic risk factors can halt—and even reverse—progression whilst improving all-cause morbidity and mortality from MACE. Importantly, fibrosis is the only histological feature which is known to determine the risk of liver-related events, with progressive stages of fibrosis conferring the highest risk of adverse outcomes [<span>6, 7</span>]. Therefore, identifying patients with MASLD with advanced fibrosis is pivotal in terms of risk stratification. Emerging data suggested that Type 2 diabetes (T2D) is one of the strongest potentiators of fibrogenesis, and FPRs in those with T2D are enhanced [<span>8</span>]. However, a substantial proportion of this evidence comes from clinical trials or those attending secondary care diabetes services; thus, real-world evidence, particularly from primary care settings, is to be welcomed.</p><p>In this context, Balkhed et al. provide valuable normative data when screening for MASLD amongst T2D patients in the primary care setting [<span>9</span>]. Steatosis prevalence in T2D has historically been reported at 50%–70% [<span>10</span>], and multiple societies such as the European Association for the Study of the Liver and the Ame","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"152-154"},"PeriodicalIF":9.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525727","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":"Advanced imaging of relapse in giant cell arteritis: The role of vascular adhesion protein-1 and [68Ga]Ga-DOTA-Siglec-9 positron emission tomography–computed tomography","authors":"Simon M. Petzinna,&nbsp;Jim Küppers,&nbsp;Benedikt Schemmer,&nbsp;Anna L. Kernder,&nbsp;Claus-Jürgen Bauer,&nbsp;Niklas T. Baerlecken,&nbsp;Denada Bruci,&nbsp;Pantelis Karakostas,&nbsp;Raúl N. Jamin,&nbsp;Maike S. Adamson,&nbsp;Anja Winklbauer,&nbsp;Rayk Behrendt,&nbsp;Markus Essler,&nbsp;Valentin S. Schäfer","doi":"10.1111/joim.20111","DOIUrl":"10.1111/joim.20111","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Giant cell arteritis (GCA) is an immune-mediated vasculitis primarily affecting medium- and large-sized vessels. Although positron emission tomography–computed tomography (PET/CT) with [&lt;sup&gt;18&lt;/sup&gt;F]fluorodeoxyglucose ([&lt;sup&gt;18&lt;/sup&gt;F]FDG) has proven useful for assessing disease activity, persistent tracer uptake due to vascular remodeling is found in up to 80% of patients in clinical remission [&lt;span&gt;1&lt;/span&gt;]. &lt;sup&gt;68&lt;/sup&gt;Ga-labeled sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) offers potentially higher specificity for active inflammation, as Siglec-9 functions as a ligand for vascular adhesion protein-1 (VAP-1) [&lt;span&gt;2&lt;/span&gt;]. In the vasculature, VAP-1 is expressed on vascular smooth muscle and endothelial cells, existing in both a membrane-bound and soluble form (sVAP-1), which is cleaved by matrix metalloproteinases (MMPs) [&lt;span&gt;3&lt;/span&gt;]. Proinflammatory cytokines (tumor necrosis factor alpha, interferon gamma, interleukin-1 beta) drive VAP-1 translocation to the cell surface, where it mediates leukocyte adhesion, migration, and inflammation [&lt;span&gt;1&lt;/span&gt;]. Recent findings suggest that [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-Siglec-9-PET/CT can detect vascular inflammation during GCA relapse [&lt;span&gt;3, 4&lt;/span&gt;]. This study is the first to assess the diagnostic value of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-Siglec-9 PET/CT in multiple patients with relapsing GCA and to explore the roles of Siglec-9 and VAP-1 in GCA pathogenesis (Fig. S1).&lt;/p&gt;&lt;p&gt;Patients with relapsing GCA, as confirmed by a board-certified rheumatologist, who previously fulfilled the classification criteria for GCA [&lt;span&gt;5&lt;/span&gt;], and age-/sex-matched healthy controls were prospectively enrolled. The patients with active GCA underwent [⁶⁸Ga]Ga-DOTA-Siglec-9-PET/CT following intravenous injection of 135.1 ± 31.7 MBq of tracer. Low-dose CT for attenuation correction and a whole-body PET scan were acquired 56.2 ± 8.3 min postinjection (Supporting Information Protocol). Maximum standardized uptake values (SUVmax) were obtained for the aorta and axillary, subclavian, brachial, thoracic, and abdominal arteries. Vascular ultrasound was conducted on the superficial temporal arteries and their branches, as well as the facial, axillary, carotid, and vertebral arteries as described before [&lt;span&gt;6&lt;/span&gt;]. Moreover, the OMERACT Giant Cell Arteritis Ultrasonography score was calculated. Levels of sVAP-1, MMP-2, MMP-3, and MMP-9 were determined by enzyme-linked immunosorbent assay, and Siglec-9 expression on selected peripheral blood mononuclear cells was analyzed by flow cytometry.&lt;/p&gt;&lt;p&gt;Eight patients with relapsing GCA and eight healthy controls were included. The corresponding demographic, clinical, laboratory, and imaging data are provided in Table S1. Tracer administration was well tolerated by all GCA patients. The [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-Siglec-9-PET/CT scan revealed localized, patient-specific increases in SUVmax, most prominently in the thoracic and abdominal","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 2","pages":"138-142"},"PeriodicalIF":9.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493242","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":"Cholecystokinin: Clinical aspects of the new biology","authors":"Jens F. Rehfeld","doi":"10.1111/joim.20110","DOIUrl":"10.1111/joim.20110","url":null,"abstract":"<p>Cholecystokinin (CCK) is a classic gut hormone that has been known for almost a century to regulate gallbladder emptying, pancreatic enzyme secretion, and gastrointestinal motor activity. In 1968, the CCK structure was identified by Viktor Mutt and Erik Jorpes from porcine gut extracts as a peptide of 33 amino acid residues. Based on that structure, physiological, immunochemical, molecular, and cell biological research has since expanded the insight into the biology of CCK remarkably. Thus, CCK was the first identified intestinal satiety signal to the brain. Moreover, the CCK gene is now known to be expressed in different molecular forms not only in the gut, but very much so in central and peripheral neurons, in addition to extra-intestinal endocrine cells, immune cells, cardiomyocytes, spermatogenic cells, and certain fat cells. Accordingly, CCK peptides function not only as hormones. They are also neurotransmitters, paracrine growth and satiation factors, anti-inflammatory cytokines, incretins, adipokins, myokines, potential fertility factors, and tumor markers. Consequently, CCK biology has now opened windows for insights into pathophysiology with diagnostic and therapeutic possibilities in metabolic disorders (obesity, eating disorders, and diabetes mellitus), gallbladder disease, neuropsychiatric diseases (cerebral tumors, memory, and anxiety disorders), cardiac diseases (prognosis in heart failure), neuroendocrine and pediatric tumors, as well as perhaps infertility.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 3","pages":"251-267"},"PeriodicalIF":9.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482721","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":"The TP53 tumor suppressor gene: From molecular biology to clinical investigations","authors":"Panagiotis Baliakas,&nbsp;Thierry Soussi","doi":"10.1111/joim.20106","DOIUrl":"10.1111/joim.20106","url":null,"abstract":"<p>Extensively studied over the past four decades, the <i>TP53</i> gene has emerged as a pivotal watchman in cellular defense and a key factor in cancer biology. <i>TP53</i> is the most frequently mutated gene in human malignancies, 50% of which carry alterations to it. Initially, the functions of p53 were thought to be restricted to cell-cycle arrest and apoptosis. With time, however, a growing number of functions have been discovered, illustrating p53's role as a master switch between any cellular stress and cellular or multicellular responses that contribute to its anti-tumor activity. Indeed, the peculiar landscape of <i>TP53</i> mutations and its high heterogeneity are linked both to the structure of the protein and its ubiquitous function in regulating cellular homeostasis. Mutations in p53 are associated with poor response to therapy and shorter survival in most cancer types, and the diagnosis of p53 mutations is currently used to improve case management in some types of leukemia and lymphoma. Although <i>TP53</i> has been defined as a tumor suppressor gene, overexpressed mutated p53 variants found in human tumors are defined as dominant oncogenes with a potential gain of function, which makes the gene a very attractive target for developing new cancer treatments. Beyond its role in cancer, our review also highlights TP53's significance in non-neoplastic conditions, such as bone marrow failure syndromes and certain developmental disorders, where chronic p53 activation plays a crucial role in cellular stress responses, demonstrating its broader biological importance.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"298 2","pages":"78-96"},"PeriodicalIF":9.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309353","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}