European Journal of Clinical Investigation最新文献

{"title":"An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study","authors":"Ferdinando D'Amico,&nbsp;Luca Massimino,&nbsp;Giulia Palmieri,&nbsp;Arianna Dal Buono,&nbsp;Roberto Gabbiadini,&nbsp;Benedicte Caron,&nbsp;Paula Moreira,&nbsp;Isabel Silva,&nbsp;Maia Bosca-Watts,&nbsp;Tommaso Innocenti,&nbsp;Gabriele Dragoni,&nbsp;Cristina Bezzio,&nbsp;Alessandra Zilli,&nbsp;Federica Furfaro,&nbsp;Simone Saibeni,&nbsp;María Chaparro,&nbsp;María José García,&nbsp;George Michalopoulos,&nbsp;Nikos Viazis,&nbsp;Gerassimos J. Mantzaris,&nbsp;Pierre Ellul,&nbsp;Javier P. Gisbert,&nbsp;Fernando Magro,&nbsp;Laurent Peyrin-Biroulet,&nbsp;Alessandro Armuzzi,&nbsp;Federica Ungaro,&nbsp;Silvio Danese,&nbsp;Gionata Fiorino,&nbsp;Mariangela Allocca","doi":"10.1111/eci.14283","DOIUrl":"10.1111/eci.14283","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR &lt;1 × 10⁻¹⁰) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558417","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":"The glucagon-like peptide-1 receptor agonist semaglutide in diabetic kidney disease: A new kid on the block to afford maximal kidney protection","authors":"Panagiotis I. Georgianos,&nbsp;Konstantinos Leivaditis,&nbsp;Vassilios Liakopoulos","doi":"10.1111/eci.14284","DOIUrl":"10.1111/eci.14284","url":null,"abstract":"&lt;p&gt;Chronic kidney disease (CKD) is the most common complication of type 2 diabetes (T2D).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The co-existence of CKD and T2D is associated with a substantially higher risk for adverse cardiovascular outcomes and faster deterioration of kidney function.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For almost two decades, the only available pharmacological interventions to mitigate this excess cardiorenal risk included the optimization of blood glucose levels towards an individualized glycaemic target, the adequate blood pressure control and the use of an agent blocking the renin–angiotensin system (RAS) at maximum or maximally tolerated doses.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Fortunately, this disappointing picture has been modified after the discovery of novel therapies that afford additive cardiorenal protective benefits.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In a triad of landmark trials conducted specifically in CKD patients who were already treated with a RAS blocker, sodium-glucose co-transporter type 2 (SGLT-2) inhibitors provoked an impressive placebo-subtracted reduction in the risk of kidney failure and death from kidney or cardiovascular causes.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Similarly, in a large phase 3 clinical trial programme involving 13,026 patients with T2D and a broad spectrum of CKD, the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone improved the composite kidney and cardiovascular outcomes relative to placebo.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Once again, these additive effects were demonstrated in patients receiving optimized background therapy with maximally tolerated doses of a RAS blocker before randomization.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; On this scientific basis, both SGLT-2 inhibitors and finerenone have been included as recommended pharmacological interventions for patients with CKD associated with T2D in recently released guidelines.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; However, the residual cardiorenal risk of these patients remains an unresolved issue, generating the need for additional effective therapies.&lt;/p&gt;&lt;p&gt;In this Commentary, we discuss the kidney protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with diabetic kidney disease, providing a critical evaluation of the results of the FLOW (Evaluate Renal Function with Semaglutide Once Weekly) trial.&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;GLP-1RAs are established and guideline-directed therapies for the improvement of glycaemic control and weight loss in patients with T2D.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; Some agents that belong to this novel antidiabetic drug class also mitigate the risk for major adverse cardiovascular events in patients with T2D and established cardiovascular disease or in people with T2D and multiple cardiovascular risk factors.&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; However, until recently, the potential kidney protective effects of GLP-1RAs were based mainly on indirect evidence from secondary exploratory analyses of cardiovascular outcome or glycaemic","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558418","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":"The association between bilirubin concentrations and inflammatory bowel disease: Insights from a systematic review and meta-analysis","authors":"Stefano Zoroddu,&nbsp;Biagio Di Lorenzo,&nbsp;Panagiotis Paliogiannis,&nbsp;Arduino A. Mangoni,&nbsp;Ciriaco Carru,&nbsp;Angelo Zinellu","doi":"10.1111/eci.14281","DOIUrl":"10.1111/eci.14281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), poses a significant challenge to health care systems because of its chronic nature and increasing global prevalence. Effective management of IBD requires accurate diagnostic tools and biomarkers. This systematic review and meta-analysis aimed to evaluate the relationship between bilirubin concentrations and IBD activity and outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive search of electronic databases identified 11 studies that included 2606 subjects with IBD and 3607 healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bilirubin concentrations were significantly lower in subjects with IBD when compared to controls (SMD = −0.96, 95% CI −1.21 to −0.70; <i>p</i> &lt; .001). Although substantial heterogeneity was observed, sensitivity analysis confirmed the robustness of the results. Publication bias was detected, but subgroup analyses did not significantly alter the results. Meta-regression showed that age was a significant factor influencing the association between bilirubin concentrations and IBD. Subgroup analyses showed a more pronounced reduction in bilirubin concentrations in subjects with CD than those with UC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study supports the potential utility of bilirubin as a biomarker in IBD, emphasizing the need for further research to validate its clinical significance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544654","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":"Which is the best glomerular filtration marker: Creatinine, cystatin C or both?","authors":"Thomas Stehlé,&nbsp;Pierre Delanaye","doi":"10.1111/eci.14278","DOIUrl":"10.1111/eci.14278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The glomerular filtration rate (GFR) is estimated by the serum or plasma concentration of creatinine and/or cystatin C using equations that include demographic data. The equations worldwide most widely used are those of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) consortium and updated in 2021 to remove the Afro-American racial correction factor. In 2021 and then in 2023, the European Kidney Function Consortium also developed equations based on creatinine and cystatin C, usable across the full age spectrum, and constructed by including the <i>Q</i> value (i.e. the median creatinine or cystatin C in healthy men and women, which is customizable for specific populations).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The aim of this narrative review is to examine the strengths and weaknesses of each biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both biomarkers have non-GFR determinants, namely muscle mass, protein intake and tubular secretion for creatinine; dysthyroidism and systemic corticosteroids for cystatin C, as well as other more debated determinants (diabetes, obesity, proteinuria, inflammatory syndrome). These non-GFR determinants are the reason why no equation based on a single endogenous biomarker has an accuracy within 30% greater than 90% over the entire age spectrum (in at least one patient in 10, estimated GFR is at least 30% higher or at least 30% lower than the measured GFR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Equations combining the two biomarkers provide a better estimate of GFR, particularly in the subgroup of patients whose estimates based on each of the biomarkers are highly discordant. These patients must also be identified as being at increased risk of morbidity, particularly cardiovascular, and mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467031","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":"Stroke outcomes following cardiac and aortic surgery are improved by the involvement of a stroke team","authors":"Amer Harky,&nbsp;Vanessa Jane Chow,&nbsp;Calum Voller,&nbsp;Kartik Goyal,&nbsp;Matthew Shaw,&nbsp;Anurodh Bhawnani,&nbsp;Ayman Kenawy,&nbsp;Ian Wilson,&nbsp;Gregory Y. H. Lip,&nbsp;Mark Field,&nbsp;Manoj Kuduvalli","doi":"10.1111/eci.14275","DOIUrl":"10.1111/eci.14275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Post-cardiac and aortic surgery stroke is often underreported. We detail our single-centre experience the following introduction of comprehensive consultant-led daily stroke service, to demonstrate the efficacy of a stroke team in recovery from stroke following cardiac and aortic surgeries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective, single-centre observational cohort study analysed consecutive patients undergoing cardiac and aortic surgery at our institution from August 2014 to December 2020. Main outcomes included stroke rate, predictors of stroke, and neurological deficit resolution or persistence at discharge and clinic follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 12,135 procedures were carried out in the reference period. Among these, 436 (3.6%) suffered a stroke. Overall survival to discharge and follow-up were 86.0% and 84.0% respectively. Independent risk factors for post-operative stroke included advanced age (OR 1.033, 95% CI [1.023, 1.044], <i>p</i> &lt; .001), female sex (OR 1.491, 95% [1.212, 1.827], <i>p</i> &lt; .001), history of previous cardiac surgeries (OR 1.670, 95% CI [1.239, 2.218], <i>p</i> &lt; .001), simultaneous coronary artery bypass graft + valve procedures (OR 1.825, 95% CI [1.382, 2.382], <i>p</i> &lt; .001) and CPB time longer than 240 min (OR 3.384, 95% CI [2.413, 4.705], <i>p</i> &lt; .001). Stroke patients managed by the multidisciplinary team demonstrated significantly higher rates of survival at discharge (87.3% vs. 61.9%, <i>p</i> = .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Perioperative stroke can be debilitating immediately long term. The involvement of specialist stroke teams plays a key role in reducing the long-term burden and mortality of this condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467030","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":"Association of MASLD with the risk of extrahepatic cancers: A systematic review and meta-analysis of 18 cohort studies","authors":"Ben-Gang Zhou,&nbsp;Xin Jiang,&nbsp;Qiang She,&nbsp;Yan-Bing Ding","doi":"10.1111/eci.14276","DOIUrl":"10.1111/eci.14276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Numerous recent studies have explored the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of various extrahepatic cancers. However, the conclusions were inconclusive. The aim of this study was to clarify this relationship by conducting a robust meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Systematic searches were conducted on PubMed, Embase and Web of Science databases to identify relevant cohort studies published prior to February 2024. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were combined using a random-effects model in this meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighteen cohort studies (approximately 16.7 million participants) were finally included in this meta-analysis. MASLD was linked to a higher risk of extrahepatic cancers, such as gastric (<i>n</i> = 10, HR = 1.47, 95% CI: 1.07–2.01), colorectal (<i>n</i> = 13, HR = 1.33, 95% CI: 1.16–1.53), pancreatic (<i>n</i> = 8, HR = 1.41, 95% CI: 1.11–1.79), biliary tract (<i>n</i> = 5, HR = 1.27, 95% CI: 1.18–1.37), thyroid (<i>n</i> = 6, HR = 1.46, 95% CI: 1.02–2.09), urinary system (<i>n</i> = 10, HR = 1.45, 95% CI: 1.25–1.69), breast (<i>n</i> = 11, HR = 1.17, 95% CI: 1.08–1.26) and female genital organ cancers (<i>n</i> = 10, HR = 1.36, 95% CI: 1.11–1.66). However, there was no statistically significant association between MASLD and the risk of head and neck (<i>n</i> = 6, HR = 1.03, 95% CI: 99–1.07), oesophageal (<i>n</i> = 9, HR = 1.26, 95% CI: 0.86–1.86), lung (<i>n</i> = 9, HR = 1.01, 95% CI: 0.92–1.10), prostate (<i>n</i> = 9, HR = 1.06, 95% CI: 0.94–1.19) or small intestine cancer (<i>n</i> = 2, HR = 1.75, 95% CI: 1.00–3.06).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This latest large-scale meta-analysis indicated that MASLD was associated with an increased risk of various extrahepatic cancers, such as gastric, colorectal, pancreatic, biliary duct, thyroid, urinary system, breast, skin and female genital cancers. Further research is needed to investigate the mechanisms underlying these associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467026","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":"Metabolic profiling of tryptophan pathways: Implications for obesity and metabolic dysfunction-associated steatotic liver disease","authors":"Carmen Arto,&nbsp;Elena Cristina Rusu,&nbsp;Helena Clavero-Mestres,&nbsp;Andrea Barrientos-Riosalido,&nbsp;Laia Bertran,&nbsp;Razieh Mahmoudian,&nbsp;Carmen Aguilar,&nbsp;David Riesco,&nbsp;Javier Ugarte Chicote,&nbsp;David Parada,&nbsp;Salomé Martínez,&nbsp;Fàtima Sabench,&nbsp;Cristóbal Richart,&nbsp;Teresa Auguet","doi":"10.1111/eci.14279","DOIUrl":"10.1111/eci.14279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The rise in obesity highlights the need for improved therapeutic strategies, particularly in addressing metabolic dysfunction-associated steatotic liver disease (MASLD). We aim to assess the role of tryptophan metabolic pathways in the pathogenesis of obesity and in the different histological stages of MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We used ultra-high performance liquid chromatography to quantify circulating levels of 15 tryptophan-related metabolites from the kynurenine, indole and serotonin pathways. A cohort of 76 subjects was analysed, comprising 18 subjects with normal weight and 58 with morbid obesity, these last being subclassified into normal liver (NL), simple steatosis (SS) and metabolic dysfunction-associated steatohepatitis (MASH). Then, we conducted gene expression analysis of hepatic IDO-1 and kynyrenine-3-monooxygenase (KMO).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Key findings in obesity revealed a distinct metabolic signature characterized by a higher concentration of different kynurenine-related metabolites, a decrease in indole-3-acetic acid and indole-3-propionic acid, and an alteration in the serotonin pathway. Elevated tryptophan levels were associated with MASLD presence (37.659 (32.577–39.823) μM of tryptophan in NL subjects; 41.522 (38.803–45.276) μM in patients with MASLD). Overall, pathway fluxes demonstrated an induction of tryptophan catabolism via the serotonin pathway in SS subjects and into the kynurenine pathway in MASH. We found decreased IDO-1 and KMO hepatic expression in NL compared to SS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We identified a distinctive metabolic signature in obesity marked by changes in tryptophan catabolic pathways, discernible through altered metabolite profiles. We observed stage-specific alterations in tryptophan catabolism fluxes in MASLD, highlighting the potential utility of targeting these pathways in therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467028","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":"Omega-3 polyunsaturated fatty acids and pulmonary arterial hypertension: Insights and perspectives","authors":"Marika Massaro,&nbsp;Stefano Quarta,&nbsp;Nadia Calabriso,&nbsp;Maria Annunziata Carluccio,&nbsp;Egeria Scoditti,&nbsp;Peter Mancuso,&nbsp;Raffaele De Caterina,&nbsp;Rosalinda Madonna","doi":"10.1111/eci.14277","DOIUrl":"10.1111/eci.14277","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467029","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":"Batch-dependent safety of COVID-19 vaccines in the Czech Republic and comparison with data from Denmark","authors":"Tomáš Fürst,&nbsp;Petr Šourek,&nbsp;Zuzana Krátká,&nbsp;Jaroslav Janošek","doi":"10.1111/eci.14271","DOIUrl":"10.1111/eci.14271","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467027","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":"A novel framework to assess haematology and oncology registration trials: The THEOREMM project","authors":"Timothée Olivier,&nbsp;Alyson Haslam,&nbsp;Patricia Burke,&nbsp;Isabelle Boutron,&nbsp;Florian Naudet,&nbsp;John P. A. Ioannidis,&nbsp;Vinay Prasad","doi":"10.1111/eci.14267","DOIUrl":"10.1111/eci.14267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Methodological limitations affect a significant number of oncology and haematology trials, raising concerns about the applicability of their results. For example, a suboptimal control arm or limited access to best care upon progression may skew the trial results toward a benefit in the experimental arm. Beyond the fact that such limitations do not prevent drugs reaching the market, other assessment tools, such as those developed by professional societies—ESMO-MCBS and ASCO Value Framework—do not integrate these important shortcomings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We propose creating a novel framework with the scope of assessing registration cancer clinical trials in haematology and oncology (randomized or single arm)—that is trials leading to a marketing authorization. The main steps of the methods are (1) assembling a scientific board; (2) defining the scope, goal and methods through pre-specified, pre-registered and protocolized methodology; (3) preregistration of the protocol; (4) conducting a scoping review of limitations and biases affecting oncology trials and assessing existing scores or methods; (5) developing a list of features to be included and assessed within the framework; (6) assessing each feature through a questionnaire sent to highly cited haematologists and oncologists involved in clinical trials; and (7) finalizing the first version of framework.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Not applicable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our proposal emerged in response to the lack of consideration for key limitations in current trial assessments. The goal is to create a framework specifically designed to assess single trials leading to marketing authorization in the field of oncology and haematogy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456086","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}