European Journal of Clinical Investigation最新文献

{"title":"Environmental and dietary triggers of hyperuricemia in chronic kidney disease: A cardiovascular perspective","authors":"Mohammed AbuBaha,&nbsp;Anwar Zahran,&nbsp;Ahmad Nouri,&nbsp;Mohammad Bdair,&nbsp;Husam Hamshary,&nbsp;Hasan Fuqha,&nbsp;Bara Abubaha,&nbsp;Fathalla Noori,&nbsp;Ayman Khaled,&nbsp;Ameer Awashra,&nbsp;Abdalhakim Shubietah","doi":"10.1111/eci.70197","DOIUrl":"10.1111/eci.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hyperuricemia—defined as serum urate above 6.8 mg/dL—is increasingly recognized as a risk marker and amplifier of chronic kidney disease (CKD) progression and cardiovascular disease (CVD), rather than merely a precursor to gout. In CKD, impaired renal urate clearance is exacerbated by environmental toxins, including airborne pollutants and heavy metals (lead, cadmium, arsenic), which disrupt tubular function and downregulate urate transporters (ABCG2, OAT1/3, URAT1). Dietary factors such as high-purine foods, fructose-rich beverages, and alcohol promote urate overproduction and reduce excretion, whereas DASH and Mediterranean dietary patterns are associated with lower serum urate and reduced cardiovascular risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review synthesizes current evidence from PubMed, Scopus, and Google Scholar on hyperuricemia in CKD, with a focus on environmental and dietary triggers and their cardiovascular implications. Priority was given to high-level evidence, including systematic reviews, meta-analyses, randomized controlled trials, and large cohort studies, alongside mechanistic and preclinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mechanistically, uric acid promotes systemic inflammation, endothelial dysfunction, and oxidative stress via xanthine oxidase, contributing to microvascular and macrovascular injury. Genetic polymorphisms in urate transporters modulate susceptibility but represent non-modifiable risk factors. Observational studies consistently link elevated serum urate with adverse CKD and CVD outcomes; however, randomized trials of xanthine oxidase inhibitors have yielded conflicting results regarding clinical benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An integrated approach is required to manage hyperuricemia in CKD. Lifestyle strategies, including reducing dietary fructose, limiting alcohol, and adopting plant-forward diets, may lower serum urate, while mitigating environmental exposures may help preserve renal function. Pharmacotherapy should be individualized based on comorbidities and risk profiles. Despite supportive mechanistic and observational evidence, randomized trials remain inconclusive, highlighting the need for further research to clarify the cardiovascular impact of urate-lowering therapies and their role in CKD populations. A comprehensive, multidisciplinary approach may help reduce risk factors associated with CKD progression and cardiovascular disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CMR-derived skeletal muscle T1 time and extracellular volume as novel diagnostic markers for cardiac amyloidosis","authors":"Christina Kronberger,&nbsp;Katharina Mascherbauer,&nbsp;Michael Poledniczek,&nbsp;Lena Marie Schmid,&nbsp;Carolina Donà,&nbsp;Matthias Koschutnik,&nbsp;Laura Lunzer,&nbsp;René Rettl,&nbsp;Franz Duca,&nbsp;Christina Binder,&nbsp;Christian Nitsche,&nbsp;Nikita Ermolaev,&nbsp;Gözde Celebi,&nbsp;Varius Dannenberg,&nbsp;Dietrich Beitzke,&nbsp;Roza Badr Eslam,&nbsp;Jutta Bergler-Klein,&nbsp;Julia Mascherbauer,&nbsp;Johannes Kastner,&nbsp;Christian Hengstenberg,&nbsp;Andreas Anselm Kammerlander","doi":"10.1111/eci.70191","DOIUrl":"10.1111/eci.70191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cardiac amyloidosis (CA) is a progressive cardiomyopathy caused by amyloid deposition, leading to heart failure and increased mortality. Cardiac magnetic resonance (CMR) identifies myocardial involvement via elevated native T1 relaxation time and extracellular volume (ECV). Although amyloid infiltration has also been observed in thoracic skeletal muscle, the diagnostic and prognostic relevance of thoracic skeletal muscle T1 time and ECV remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To compare native thoracic skeletal muscle T1 time and ECV between CA patients and controls and assess their diagnostic and prognostic value.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a prospective CMR registry, consecutive CA patients and controls underwent CMR with T1-mapping. Native and post-contrast T1 relaxation time and ECV were quantified in myocardium and thoracic skeletal muscles. Diagnostic performance was evaluated using ROC analysis and associations with mortality were assessed using Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1976 participants (267 CA, 1709 controls), CA patients showed significantly higher native myocardial T1 time and ECV, as well as elevated native thoracic skeletal muscle T1 time (919.4 vs. 868.5 ms, <i>p</i> &lt; 0.001) and ECV (16.4 vs. 12.9%, p &lt; 0.001). Native thoracic skeletal muscle T1 time demonstrated moderate diagnostic performance for CA (AUC = 0.70), with an optimal cutoff of 895 ms yielding a sensitivity of 61% and specificity of 59%. Higher native thoracic skeletal muscle T1 time predicted increased mortality (HR = 1.65 per 100 ms, <i>p</i> &lt; 0.001), and this association remained significant after adjusting for age, sex and ventricular function (HR = 1.21 per 100 ms, <i>p</i> = 0.008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Native skeletal muscle T1 relaxation time and ECV indicate systemic amyloid involvement and provide additional diagnostic and prognostic information beyond myocardial assessment, potentially supporting improved detection and risk stratification in CA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring heart rate variability as a biomarker for frailty: A narrative review","authors":"Luca Tagliafico,&nbsp;Silvia Ottaviani,&nbsp;Riccardo Balzano,&nbsp;Stefania Peruzzo,&nbsp;Alessio Nencioni,&nbsp;Fiammetta Monacelli","doi":"10.1111/eci.70194","DOIUrl":"10.1111/eci.70194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Frailty is defined as a state of increased vulnerability to stressors resulting from reduced physiological homeostasis. The need to identify biomarkers capable of offering insight into the biological underpinnings of frailty and supporting early detection, diagnosis, and prognostic evaluation has grown in recent years. Heart rate variability (HRV), defined as the temporal variability between consecutive R waves of the electrocardiogram (R-R intervals), has emerged as a promising physiological biomarker in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a narrative review of studies to synthesize evidence on HRV and frailty, examining analytical domains of HRV and situating findings within the current biomarker framework. Relevant literature was assessed across time-domain, frequency-domain, geometric and non-linear measures of HRV, together with reported associations involving clinical, functional and cognitive outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Within the landscape of frailty biomarkers, HRV provides a non-invasive index of autonomic nervous system function. Reduced HRV has been associated with frailty status, diminished physiological reserve, adverse clinical outcomes, and cognitive decline, with particularly notable findings when assessed during physiological challenges rather than at rest. It should be noted, however, that the literature is heterogeneous and methodologically inconsistent, especially regarding recording duration and the specific HRV parameters analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HRV is a highly promising physiological biomarker in the context of frailty, but further research is needed to clarify several aspects of its role. Its potential integration with other biomarkers may help confirm its validity and could contribute to identifying biomarker clusters relevant to personalized approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic esophagitis: From pathophysiology to diagnosis, monitoring and treatment","authors":"Luisa Bertin,&nbsp;Emma Sirinic,&nbsp;Matteo Ghisa,&nbsp;Tarek Arraf,&nbsp;Amir Mari,&nbsp;Amir Farah,&nbsp;Javier Chahuán,&nbsp;Federico Caldart,&nbsp;Edoardo Vincenzo Savarino","doi":"10.1111/eci.70192","DOIUrl":"10.1111/eci.70192","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disorder of the oesophagus that has transformed from a rarely recognized condition to one of the most common causes of dysphagia and food impaction in children and young adults. This review provides a comprehensive, clinically oriented overview of EoE for the practicing clinician.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a narrative review focusing on systematic reviews, meta-analyses, randomized controlled trials and international guidelines published through 2025.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EoE pathogenesis involves genetic susceptibility, environmental triggers, epithelial barrier dysfunction and type 2 immune activation. Diagnosis requires clinical symptoms, endoscopic findings and histologic confirmation of ≥15 eosinophils per high-power field. Treatment options include proton pump inhibitors (histologic remission ~45%), swallowed topical corticosteroids (~80%–93%), dietary elimination strategies (~60%) and dupilumab (~60%). Without treatment, EoE progresses from inflammatory to fibrostenotic disease, with stricture risk increasing approximately 5% per year of undiagnosed disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>EoE management requires integration of clinical, endoscopic and histologic assessments. Current treatments effectively induce remission in most patients. Future priorities include developing non-invasive monitoring tools and identifying predictors of treatment response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYH11 variants in thoracic aortic aneurysm pathophysiology: From bench to bedside","authors":"Aria Atash,&nbsp;Barend M. E. Mees,&nbsp;Maarten J. Cramer,&nbsp;Annette F. Baas,&nbsp;Leon J. Schurgers,&nbsp;Pieter A. Doevendans,&nbsp;Francesca Stillitano","doi":"10.1111/eci.70196","DOIUrl":"10.1111/eci.70196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Thoracic aortic aneurysms and dissections (TAAD) are life-threatening vascular disorders affecting the medial layer of the aortic wall, associated with high mortality when a rupture or dissection occurs. Though numerous genes are associated with familial TAAD (FTAAD), pathogenic variants in <i>MYH11</i>, encoding smooth muscle cell specific myosin heavy chain (SM-MHC), represent a rare but interesting subgroup as many gaps remain in the knowledge of disease mechanisms, phenotype presentation and gene–environmental interactions. No reliable therapy exists in halting aneurysm growth in affected individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Scope of Review</h3>\u0000 \u0000 <p>This review aims to summarize current evidence on disease pathophysiological mechanisms. Furthermore, phenotypic variability, extrathoracic vascular involvement and the possibility of future curative gene therapy options are evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Most reported pathogenic <i>MYH11</i> variants are missense or splice-site variants that disrupt the C-terminal coiled-coil dimerization and therefore thick filament assembly. Evidence from mouse models, patient-derived cells and limited human ex vivo tissue studies shows that these variants are associated with impaired thick filament organization, reduced force generation and disruption of the elastin-contractile unit, with subsequent alterations in ECM remodelling. However, the precise causal sequence in human disease has not yet been established. Clinically, <i>MYH11-</i>associated disease is associated with FTAAD and patent ductus arteriosus (PDA). Reduced penetrance, variable expression of disease and unknown potential gene–environment interactions complicate risk prediction and clinical counselling of affected individuals. Emerging RNA-therapy strategies aimed at allele-specific correction of genetic disease offer interesting future therapeutic targets, although vascular delivery and long-term safety remain challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>MYH11</i> should be viewed as a clinically meaningful gene that is associated with TAAD and PDA. Current limited evidence shows that the phenotype is characterized by contractile dysfunction, increased aortic stiffness and potential susceptibility to hemodynamic stress. Future work should investigate translatable mechanistic studies, larger registries for genotype–phenotype correlations and evaluation of targeted gene therapy approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nomogram for predicting in-hospital death in a multinational cohort of patients with takotsubo syndrome","authors":"Yuyi Chen,&nbsp;Amanda Chang,&nbsp;Fangyuan Cheng,&nbsp;Davide Di Vece,&nbsp;Michael Würdinger,&nbsp;Philipp Theil,&nbsp;Tou Kun Chong,&nbsp;Christian Templin,&nbsp;Jian Chen,&nbsp;Xiaodong Wu,&nbsp;Kan Liu","doi":"10.1111/eci.70190","DOIUrl":"10.1111/eci.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An effective risk stratification model on hospitalized patients with takotsubo syndrome (TTS) helps guide treatment to mitigate adverse events and improve prognosis. We aimed to develop a nomogram for predicting in-hospital death in a multinational cohort of TTS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 829 TTS patients from AmSC Research Network, InterTAK registry and ChiTTS registry, classified into the training (<i>n</i> = 578), test (<i>n</i> = 145) and external validation (<i>n</i> = 106) cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Body mass index (BMI), chronic kidney disease (CKD), neurologic disorders, cardiogenic shock, low systolic blood pressure (SBP, &lt;122 mmHg) and abnormal white blood cell (WBC, ≥11.3 × 10⁹/L) were independent positive predictors, while chest pain was an independent negative predictor of in-hospital death. A nomogram was constructed to predict in-hospital death in TTS patients based on these seven independent variables, which showed that the area under the curves (AUCs) in the training and test cohorts were .854 (95% CI: .805–.904, <i>p</i> &lt; .001) and .836 (95% CI: .737–.934, <i>p</i> &lt; .001), respectively. The calibration curves showed good consistency between the prediction of the nomogram and the actual observation in both the training and test cohorts. Decision curve analyses indicated that the use of the nomogram to predict in-hospital death in TTS patients could provide better net benefit than the ‘treat all’ or ‘treat none’ strategies when the threshold probability ranged from 2% to 75% in the training cohort and from 2% to 72% in the test cohort. The nomogram was further validated, with AUC of .838 (95% CI: .663–1.000, <i>p</i> = .003) in the external validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The nomogram, composed of BMI, CKD, neurologic disorders, chest pain, cardiogenic shock, low SBP and abnormal WBC, helps predict in-hospital death in TTS patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13022065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential far-reaching metabolic consequences of cholecystectomy","authors":"Mohamad Khalil,&nbsp;Georgy Baffy,&nbsp;Jerlin Stephy JohnBritto,&nbsp;Emilie Mitten,&nbsp;Agostino Di Ciaula,&nbsp;Piero Portincasa","doi":"10.1111/eci.70198","DOIUrl":"10.1111/eci.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cholecystectomy is one of the most commonly performed abdominal surgical procedures and is considered the gold standard for symptomatic gallstone disease. Removing the gallbladder, however, is not a neutral process. The gallbladder stores and concentrates diluted cholesterol- and bile acid-enriched hepatic bile and is dynamically involved in the daily enterohepatic circulation of bile acids, with critical local and systemic metabolic effects via agonism of nuclear and membrane-associated receptors such as FXR and GPBAR1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a narrative review to discuss the mechanisms driving cholecystectomy-associated dysmetabolism and disruption of the gut-liver axis. We reviewed studies that connect cholecystectomy to bile acid-mediated metabolic effects and examine the pathophysiological processes possibly involved in this scenario.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Experimental and human evidence highlights that cholecystectomy may be linked to several metabolic disorders, also increasing the risk of colorectal cancer. After cholecystectomy, the reservoir and concentrating function of the gallbladder are absent and bile enters the intestine directly. This new anatomical and functional configuration represents a major change in the entero-hepatic circulation of primary and secondary bile acids and in their signalling functions, with altered effects on metabolic receptors and on the gut microbiome. Post-cholecystectomy gut dysbiosis may lead to reduced microbial diversity and diminished capacity to generate beneficial short-chain fatty acids, promoting a pro-inflammatory milieu and altered metabolic homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Cholecystectomy can predispose to metabolic changes leading to type 2 diabetes mellitus, obesity, metabolic dysfunction-associated steatotic liver disease and cardiovascular diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver disease in management and outcomes of European and Asian patients with atrial fibrillation: A report from two observational prospective registries","authors":"Davide Antonio Mei,&nbsp;Tommaso Bucci,&nbsp;Giulio Francesco Romiti,&nbsp;Bernadette Corica,&nbsp;Alena Shantsila,&nbsp;Hung-Fat Tse,&nbsp;Giuseppe Boriani,&nbsp;Tze-Fan Chao,&nbsp;Marco Proietti,&nbsp;Gregory Y. H. Lip","doi":"10.1111/eci.70193","DOIUrl":"10.1111/eci.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In patients with atrial fibrillation (AF), the impact of liver disease (LD) on oral anticoagulant (OAC) prescription and outcomes remains unclear, as well as possible differences between European and Asian populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To examine the impact of LD on OAC prescriptions and risks of adverse outcomes in a large cohort of European and Asian AF patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AF patients were derived from two large observational registries held in Europe and Asia. OAC prescription and risk of outcomes were analysed according to LD at baseline. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Logistic regression assessed associations with OAC prescription, and Cox regression analyses evaluated risks of outcomes. Interaction analyses were performed between European and Asian patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 15,681 patients (mean age 68.4 ± 10.7 years; 37.1% female), 517 (3.3%) had LD. The OAC prescription rate was similar among European and Asian individuals (6.8% vs. 82.9%, <i>p</i> = .113). After adjustments, LD was associated with lower OAC prescription (OR .67, 95% CI .53–.84), with a greater reduction in European than in Asian patients (<i>p</i>_int = .015). LD was associated with a higher risk of the composite outcome (HR 1.42, 95% CI 1.11–1.81) and MACEs (HR 1.47, 95% CI 1.07–2.02), with no significant European versus Asian differences (<i>p</i>_int = .631). Among LD patients, those not prescribed OAC had a higher MACE risk compared with those prescribed OAC (<i>p</i>_int = .050), with no differences in major bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In AF, LD is associated with reduced OAC prescription, especially in Europe, and a higher risk of adverse outcomes, particularly in patients not receiving OAC, with no significant differences between European and Asian cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious seeds of valve calcification: Exploring the bacterial hypothesis in the pathogenesis of calcific aortic valve disease","authors":"Antonella Forlino,&nbsp;Paola Giordani,&nbsp;Cristina Merla,&nbsp;Silvia Roda,&nbsp;Roberta Besio,&nbsp;Abeer Ahmed Qaed Ahmed,&nbsp;Angela Kuka,&nbsp;Irene Mileto,&nbsp;Greta Petazzoni,&nbsp;Marta Corbella,&nbsp;Patrizia Cambieri,&nbsp;Baldanti Fausto,&nbsp;Annalisa De Silvestri,&nbsp;Totaro Pasquale,&nbsp;Filippo Amoroso,&nbsp;Pelenghi Stefano,&nbsp;Maraschi Federica,&nbsp;Eloisa Arbustini,&nbsp;Viviana Vilardo,&nbsp;Alexandra Smirnova,&nbsp;Raffaele Bruno,&nbsp;Seminari Elena","doi":"10.1111/eci.70188","DOIUrl":"10.1111/eci.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Calcific aortic valve disease (CAVD) is a multifactorial condition characterized by progressive leaflet calcification with a potential role for bacterial colonization in its pathogenesis. This study investigates clinical, microbiological and molecular features of calcified versus non-calcified aortic regurgitation (AR) valves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a prospective, observational study, whose primary objective was to compare the occurrence of bacterial detection between CAVD and AR. The secondary objectives included the evaluation of bone-related calcification markers in valves from CAVD and AR patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 31 CAVD and 8 AR valves, yielding 111 leaflets (84 calcified, 27 non-calcified). Light microscopy of CAVD leaflets revealed near-complete disruption of the three-layered valve architecture, with calcified masses extending through the leaflets, sparse cellularity and focal micro-angiogenesis; no bacteria were detected by GRAM, PAS or TEM. Enrichment culture detected low-virulence bacteria in 5.95% of CAVD and 4.16% of AR leaflets; 16S rRNA PCR was positive in 22.5% of CAVD and 12.5% of AR cases, with <i>Staphylococcus</i> and <i>Streptococcus</i> spp. predominating. Calcium content was significantly higher in CAVD leaflets (<i>p</i> = .001) and correlated with dyslipidemia (<i>p</i> = .02). Osterix expression was higher in valves with positive microbiological findings (<i>p</i> &lt; .0001), while ALP was increased in CAVD and bicuspid valves regardless of microbial status. Valve interstitial cells from CAVD exhibited spontaneous in vitro calcification, unlike controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The early osteogenic marker osterix was found to be upregulated in patients whose valves tested positive for microbial DNA, suggesting a potential role for bacteria in driving cellular differentiation towards an osteoblastic phenotype in CAVD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-reported outcomes in internal medicine: Methodological considerations for valid measurement and interpretation","authors":"Carmine Zoccali,&nbsp;Giovanni Tripepi","doi":"10.1111/eci.70189","DOIUrl":"10.1111/eci.70189","url":null,"abstract":"<p>Patient-reported outcome measures (PROMs) have become essential in contemporary internal medicine, where chronic, multisystem diseases and comorbidities make traditional biomedical endpoints insufficient as sole indicators of therapeutic benefit. PROMs capture symptom burden, functional capacity, emotional well-being, social participation and overall quality of life, thereby complementing laboratory indices, imaging findings and clinician-rated scales. Their growing use in regulatory evaluation, health technology assessment and value-based care underscores the need for rigorous methodology in their development, validation and interpretation. This review outlines key conceptual and practical issues that must be addressed for PROMs to provide valid, interpretable and clinically meaningful information. It emphasizes the central importance of a clearly articulated conceptual framework grounded in literature, clinical expertise and qualitative research with patients. It summarizes best practices in item generation and refinement, scaling and response options and the assessment of psychometric properties, including reliability, validity, responsiveness and interpretability. Particular attention is given to cross-cultural adaptation, differential item functioning and longitudinal measurement, which are crucial in heterogeneous internal medicine populations. The review also addresses the integration of PROMs into clinical trials and routine care, focusing on issues of feasibility, respondent burden, missing data and the translation of score changes into clinically actionable decisions. By clarifying these methodological foundations, it aims to support clinicians, investigators and policymakers in choosing, implementing and interpreting PROMs so that they genuinely reflect patients' experiences and priorities and thereby advance the practice of patient-centered internal medicine.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}