European Journal of Internal Medicine最新文献

{"title":"Cluster analysis for clinical, radiological, and histopathological profiling in chronic pulmonary graft-versus-host disease.","authors":"Sara Piciucchi, Marco Chilosi, Giuseppe Alfano, Simone Petrarulo, Roland Barbante, Emanuela Giampalma, Claudia Ravaglia, Pier Luigi Zinzani, Venerino Poletti","doi":"10.1016/j.ejim.2025.07.011","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.011","url":null,"abstract":"<p><strong>Background: </strong>Chronic pulmonary graft-versus-host disease (Pc-GVHD) is a late non-infectious complication of allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the study is to determine whether the application of the International Society for Heart and Lung Transplantation (ISHLT) criteria for chronic STUDY DESIGN AND METHODS: We conducted a retrospective observational study involving patients with hematological disorders who developed late-onset, non-infectious respiratory complications following hematopoietic stem cell transplantation (HSCT). Eligibility criteria were adapted from the guidelines of the International Society for Heart and Lung Transplantation (ISHLT). Chest CT scans were assessed for features indicative of airway disease, interstitial lung disease, and organizing pneumonia-like changes. Cluster analysis was performed using Gower distance.</p><p><strong>Results: </strong>Of the 60 patients initially enrolled, 40 met the inclusion criteria (mean age: 45 years; range: 19-71; 47.5 % male). Pulmonary function tests demonstrated an obstructive pattern in 40 % and a restrictive pattern in 60 % of cases. Chest CT imaging identified airway abnormalities in 60 % and fibrotic-interstitial changes in 30 % of patients. Among the 12 patients with available lung histology, centrilobular pathology was observed, including bronchiolitis obliterans, organizing pneumonia, and peribronchiolar or interstitial fibrosis. Fibrotic changes were more commonly observed in patients with restrictive physiology. Cluster analysis identified two distinct phenotypic groups (silhouette index: 0.4611). Cluster 1 (n = 16) was characterized by obstructive physiology, airway-predominant disease, and limited parenchymal fibrosis. Cluster 2 (n = 24) exhibited restrictive physiology, extensive fibrotic interstitial involvement, and coexisting airway disease. Patients in the restrictive group tended to be younger at the time of HSCT and showed more severe fibrotic changes on both imaging and histology (p < 0.05). Features consistent with organizing pneumonia were similarly distributed between the two clusters.</p><p><strong>Conclusions: </strong>Our findings suggest a substantial overlap between airway and interstitial lung disease phenotypes in late-onset Pc-GVHD, supporting a continuum within its pulmonary manifestations and potentially refining disease classification and management.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745790","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":"Recurrent bilateral infrapatellar subcutaneous nodules: what is the diagnosis?","authors":"Rodrigo Villaseñor-Echavarri, Yann Charli-Joseph, Gabriela Sánchez-Cárdenas","doi":"10.1016/j.ejim.2025.07.029","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.029","url":null,"abstract":"","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745792","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":"Fever and eye swelling in a teenager.","authors":"Haruhiko Fukuchi, Kazuya Nagasaki","doi":"10.1016/j.ejim.2025.07.026","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.026","url":null,"abstract":"","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745791","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":"Oral semaglutide in HFpEF: Real-world evidence and causal considerations.","authors":"Victoria Catalán, Gema Frühbeck, Javier Gómez-Ambrosi","doi":"10.1016/j.ejim.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.024","url":null,"abstract":"","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735053","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":"Crystal clear - part I: The role of uric acid in cardiorenal disease.","authors":"Claudio Borghi, Federica Fogacci, Arrigo Fg Cicero","doi":"10.1016/j.ejim.2025.07.028","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.028","url":null,"abstract":"<p><p>This review opens a two-part series by exploring the evolutionary origins, vascular implications, renal pathophysiology, and prognosis related to serum uric acid (SUA). We begin by examining the ancestral loss of uricase in hominoids, which conferred elevated SUA-initially advantageous for sodium retention and antioxidant defense, yet maladaptive in today's purine- and fructose-abundant diet. UA thus re-emerges as a biologically active molecule, exhibiting both protective antioxidant effects and harmful pro-inflammatory actions. We then delineate SUA's vascular effects: it drives oxidative stress, endothelial dysfunction, and metabolic signaling disruption, magnified in chronic kidney disease (CKD) by impaired clearance and systemic inflammation. Elevated SUA is independently linked to renal function decline, as shown in prospective cohorts across diverse populations. We also evaluate urate-lowering therapies (ULT), discussing mixed evidence of benefit on kidney outcomes and emphasizing the need for more precise risk targeting. Finally, we outline strong associations between hyperuricemia and increased all-cause and cardiovascular mortality, particularly in high-risk groups (CKD, heart failure, diabetes, gout). Taken together, this first installment highlights the importance of stratified treatment strategies in hyperuricemia, suggesting that future trials should focus on interventions tailored to specific clinical phenotypes, avoiding unnecessary UA reduction in low-risk populations.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735052","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":"sTREM2 evaluation in women with metabolic dysfunction-associated steatotic liver disease: Advancing diagnostic approaches for early MASH.","authors":"Razieh Mahmoudian, Helena Clavero-Mestres, Elena Cristina Rusu, Vicente Arredondo-Prats, Carmen Aguilar, Javier U Chicote, Salomé Martinez, David Riesco, Èlia Bartra, Anna Trinidad Borras, Fàtima Sabench, Teresa Auguet","doi":"10.1016/j.ejim.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.014","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. Some patients progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and fibrosis. MASH diagnosis still depends on invasive liver biopsy, as accurate and validated noninvasive biomarkers are lacking. We aim to investigate the potential of sTREM2 as a noninvasive diagnostic marker for detecting early MASH.</p><p><strong>Methods: </strong>This study involved 68 Caucasian women with severe-morbid obesity undergoing bariatric surgery, during which liver biopsies and fasting blood samples were collected. Soluble TREM2 levels in plasma were measured by ELISA, while hepatic TREM2 gene expression was analyzed via qPCR. Macrophage infiltration in liver tissue was assessed through CD68 immunohistochemistry.</p><p><strong>Results: </strong>Serum sTREM2 levels were significantly higher in patients with MASH compared to those with NL (normal liver) and SS (simple steatosis), and ROC analysis demonstrated strong diagnostic performance for identifying early MASH (AUC=0.89). sTREM2 levels increased progressively with steatosis grade, lobular inflammation, and NAS score. Similarly, hepatic TREM2 mRNA expression was significantly elevated in MASH and correlated with histological severity, including steatosis, ballooning, and inflammation. CD68+ macrophage infiltration was significantly higher in MASH, and strong correlations were observed between sTREM2, TREM2 expression, CD68+ cells, and MASLD-related biochemical and histological features.</p><p><strong>Conclusions: </strong>Our findings show that sTREM2 is elevated in early MASH, correlates with hepatic TREM2 expression and macrophage infiltration, and reflects key histological and biochemical features of disease progression. These results support sTREM2 as a promising non-invasive serum biomarker for identifying reversible stages of MASH.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735054","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":"Whether an optimal strategy exists for VTE prevention in critically ill patients: Insights from guidelines and randomized controlled trials.","authors":"Di Wei, Sinan Ma, Weijia Huang, Ting Yang, Keyu Chen, Baoni Sun, Xinye Li, Li Zhang, Yan Wang","doi":"10.1016/j.ejim.2025.07.022","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.022","url":null,"abstract":"<p><strong>Background: </strong>Critically ill patients face challenges in venous thromboembolism (VTE) prevention, with limited consensus on the efficacy of different anticoagulants and prevention methods. This study aims to systematically evaluate the quality of existing clinical practice guidelines (CPGs) and the efficacy and safety of various anticoagulation regimens for VTE prevention in such patients.</p><p><strong>Methods: </strong>CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and Reporting Items for Practice Guidelines in Healthcare (RIGHT) tools. A network comparison was conducted to evaluate the efficacy and safety of distinct low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) for thromboprophylaxis.</p><p><strong>Results: </strong>Seventeen CPGs and 12 randomized controlled trials (7636 patients) were systematically reviewed. The scores for \"stakeholder involvement\" (58.8%) and \"applicability\" (60.7%) were relatively low in AGREE II. The RIGHT checklist identified insufficient reporting in \"review and quality assurance\" (44.1%) and \"evidence\" (57.1%). Four CPGs (NICE2019, ACCP2012, ASH2018, and ASH2019) demonstrated high clinical applicability. Network analysis revealed no significant differences among separate LMWHs (bemiparin, enoxaparin, nadroparin, dalteparin) or between different LMWHs and UFH in reducing deep vein thrombosis (DVT), pulmonary embolism, or VTE. However, pooled LMWHs analysis demonstrated a significant reduction only in DVT compared to UFH (odds ratio 0.71, 95% credible interval: 0.42-0.99).</p><p><strong>Conclusions: </strong>Although the 17 CPGs propose various strategies for VTE prevention, substantial differences exist in their quality and clinical applicability. Existing clinical evidence fails to demonstrate superior prophylactic efficacy among VTE prevention strategies in critically ill patients.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719013","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":"Lipoprotein (a): A new target for pharmacological research and an option for treatment.","authors":"Angela Pirillo, Alberico L Catapano","doi":"10.1016/j.ejim.2025.07.021","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.021","url":null,"abstract":"<p><p>Lipoprotein(a) [Lp(a)] is increasingly recognised as a crucial and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), calcific aortic valve stenosis (AVS), and possibly heart failure and peripheral artery disease. Lp(a) consists of an LDL-like particle covalently bound to apolipoprotein(a) [apo(a)], a highly polymorphic protein encoded by the LPA gene. The Lp(a) level in plasma is predominantly genetically determined and remains stable throughout life, relatively unaffected by lifestyle, comorbidities or standard lipid-lowering therapies. Elevated Lp(a) levels are associated with a higher risk of ASCVD, particularly in individuals with familial hypercholesterolaemia or smaller apo(a) isoforms. Despite its clinical relevance, Lp(a) is rarely measured in daily clinical practice, although most guidelines recommend at least one lifetime measurement. Novel RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran, zerlasiran)-have shown the potential to reduce Lp(a) levels by >80 %. The small oral molecule muvalaplin also shows promise in inhibiting Lp(a) formation. Large-scale clinical trials are underway to assess the effects of Lp(a)-lowering therapies on cardiovascular outcomes. Measurement of Lp(a) and characterisation of the isoforms remain a challenge, and standardisation of assays is still a matter of debate. As new therapeutic options are developed that specifically target Lp(a), the inclusion of Lp(a) in cardiovascular risk assessment could improve stratification and lead to targeted interventions, particularly in high-risk populations. The growing body of genetic, epidemiological and clinical evidence makes Lp(a) a critical target in cardiovascular research and therapy.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719011","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":"Performance of enhanced liver fibrosis test and indirect serum fibrosis markers for exclusion of advanced liver fibrosis in alpha-1 antitrypsin deficiency.","authors":"Naomi N Kappe, Malin Fromme, Jan Stolk, Ilaria Ferrarotti, Pavel Strnad, Bart van Hoek","doi":"10.1016/j.ejim.2025.07.019","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.019","url":null,"abstract":"<p><strong>Introduction: </strong>Alpha-1 antitrypsin deficiency (AATD) (Pi*ZZ) can cause advanced liver fibrosis and cirrhosis in a subset of patients. Transient elastography (TE) to determine degree of fibrosis has been validated in AATD, but is sometimes unavailable. Serum markers of liver fibrosis have not been tested extensively in AATD. Aim was to determine performance of serum markers to exclude significant or advanced fibrosis in Pi*ZZ patients.</p><p><strong>Methods: </strong>In two cohorts of total 362 Pi*ZZ patients with sera and TE from Leiden and Aachen 2015-2023 enhanced liver fibrosis test (ELF), Aspartate aminotransferase to Platelet Ratio Index (APRI), and fibrosis-4 index (FIB-4) were determined retrospectively, and performance for the evaluation of fibrosis status was assessed using TE as gold standard, calculating area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) for excluding significant or advanced fibrosis.</p><p><strong>Results: </strong>AUROC of APRI was highest for significant and advanced fibrosis in both cohorts (Leiden: 0.854 (95 % CI 0.749-0.958), Aachen: 0.684 (95 % CI 0.605-0.763)), followed by FIB-4. ELF had the lowest AUROC for significant fibrosis. For advanced fibrosis AUROC for ELF was slightly higher than for FIB-4. APRI <0.41 demonstrated the best overall diagnostic performance in excluding advanced fibrosis with NPV of 97 %. The limited number of liver-related clinical endpoints within 4 years were predicted by APRI and FIB-4.</p><p><strong>Conclusion: </strong>In Pi*ZZ AATD patients APRI below 0.41 or FIB-4 below 1.79 excludes advanced fibrosis/cirrhosis if TE in unavailable, ELF had no additional value. TE remains the preferred method for staging fibrosis in AATD.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719012","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":"Effect of sodium-glucose cotransporter-2 inhibitors on skeletal muscle.","authors":"Claudia Stöllberger, Josef Finsterer, Birke Schneider","doi":"10.1016/j.ejim.2025.07.016","DOIUrl":"https://doi.org/10.1016/j.ejim.2025.07.016","url":null,"abstract":"<p><p>Empagliflozin and dapagliflozin, frequently prescribed Sodium-Glucose- Cotransporter2-inhibitors (SGLT2i), are now also recommended for nondiabetic patients with heart failure (HF). Since concerns exist about myopathy and sarcopenia as adverse effects of SGLT2i, the review summarizes effects of dapagliflozin and empagliflozin on skeletal muscle. PubMed was searched for \"SGLT2\" OR \"SGLT2 inhibitors\" OR \"SGLT2i\" OR \"dapagliflozin\" OR \"empagliflozin\" AND \"myopathy\" OR \"sarcopenia\" OR \"skeletal muscle\" OR \"muscle loss\" OR \"muscle weakness\" OR \"muscle wasting\" OR \"myotoxicity\" OR \"muscle atrophy\" OR \"rhabdomyolysis\". Excluded were reviews, editorials, study protocols, letters to the editor, in vitro and in vivo studies. Myopathy/rhabdomyolysis were reported in 5 patients, 3 with concomitant statins, whereas 3 clinical/pharmacovigilance studies found no increased myopathy/rhabdomyolysis-risk with a SGLT2i-statin-combination. SGLT2i-associated sarcopenia was studied in small cohorts (<100 patients in 65 % of the studies), with diabetes-mellitus (68 %) and Japanese (53 %). Observation time was >6 months in only 32 % of the studies, HF-patients were included in 26 %. Controversial data are reported for muscle-mass, which decreased in 15 and remained unchanged in 6 studies. Physical-performance-tests remained unchanged under SGLT2i. Muscle-biopsies found SGLT2i-assosciated metabolic changes and myofiber-atrophy, but no correlation with functional tests were reported. Exercise or dietary measures did not influence SGLT2i-associated loss of muscle-mass. Two pharmacovigilance studies identified SGLT2i as risk factors for sarcopenia. Data on SGLT2i-associated effects on skeletal muscle are limited and controversial. There is an urgent need for research, especially in nondiabetic, non-Japanese and HF-patients. Since sarcopenia develops over time, observation periods of >12 months are necessary.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709666","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}