European Journal of Clinical Investigation最新文献

{"title":"Vascular endothelial growth factor in inflammatory bowel disease: A systematic review and meta-analysis.","authors":"Stefano Zoroddu, Biagio Di Lorenzo, Panagiotis Paliogiannis, Arduino A Mangoni, Ciriaco Carru, Angelo Zinellu","doi":"10.1111/eci.14361","DOIUrl":"https://doi.org/10.1111/eci.14361","url":null,"abstract":"<p><strong>Aim: </strong>Vascular endothelial growth factor (VEGF) is linked to inflammation and angiogenesis, indicating a possible role in inflammatory bowel disease (IBD) and its main clinical manifestations, Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and meta-analysis investigated studies assessing circulating VEGF concentrations in IBD patients and healthy controls, considering the effect of IBD type, sample type and geographical location.</p><p><strong>Methods: </strong>A systematic search identified 18 studies (28 group comparators) investigating 1741 IBD patients and 1291 controls. Data were extracted and analysed using standardized mean differences (SMD) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>VEGF concentrations were significantly higher in IBD patients (SMD = .71, 95% CI .38 to 1.04; p < .001). UC patients showed higher VEGF concentrations than CD patients. Serum samples indicated significant VEGF elevations, unlike plasma samples. Significant VEGF increases were observed in studies conducted in Western Europe and Asia, but not in Eastern Europe. No significant differences were found between active and inactive disease.</p><p><strong>Conclusions: </strong>VEGF concentrations are elevated in IBD patients, with variations by disease type, sample type and geography. However, VEGF is not a reliable marker of disease activity. Future research should standardize methods and explore regional influences to enhance VEGF's clinical utility as a biomarker of IBD.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14361"},"PeriodicalIF":4.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638705","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":"Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients.","authors":"Josef E Gillson, Sooin Byeon, Angela Chou, Sarah Maloney, Nick Pavlakis, Stephen J Clarke, David L Chan, Connie I Diakos, Anthony J Gill, Jaswinder S Samra, Anubhav Mittal, Sumit Sahni","doi":"10.1111/eci.14341","DOIUrl":"https://doi.org/10.1111/eci.14341","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients.</p><p><strong>Methods: </strong>This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival.</p><p><strong>Results: </strong>Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months).</p><p><strong>Conclusion: </strong>A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14341"},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564113","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":"Adiponectin as a biomarker in liver cirrhosis—A systematic review and meta-analysis","authors":"Abdulrahman Ismaiel,&nbsp;Vera Ciornolutchii,&nbsp;Thelva Esposito Herrera,&nbsp;Mohamed Ismaiel,&nbsp;Daniel-Corneliu Leucuta,&nbsp;Stefan-Lucian Popa,&nbsp;Dan L. Dumitrascu","doi":"10.1111/eci.14328","DOIUrl":"10.1111/eci.14328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Adiponectin, a key adipokine, shows promise as a non-invasive biomarker for liver cirrhosis by reflecting inflammation and metabolic changes, but conflicting findings highlight the need for a systematic review and meta-analysis to clarify its role. Our study aimed to evaluate adiponectin levels across various stages of liver cirrhosis, compare them with other chronic liver diseases (CLD) and hepatocellular carcinoma (HCC), and assess its potential as a diagnostic and prognostic biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our systematic search was conducted on September 2023 using PubMed, EMBASE and Scopus, searching for observational studies evaluating serum and plasma adiponectin levels in liver cirrhosis. Inclusion and exclusion criteria were applied, and study quality was assessed using the Newcastle-Ottawa Scale. To evaluate the overall effect size, we utilized a random-effects model along with a mean difference (MD) analysis. The principal summary outcome was the MD in adiponectin levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 16 articles involving 2617 subjects in our qualitative and quantitative synthesis. We found significantly higher adiponectin levels in liver cirrhosis patients (8.181 [95% CI 3.676, 12.686]), especially in Child-Pugh B individuals (13.294 [95% CI 4.955, 21.634]), compared to controls. Child-Pugh A patients did not show significant differences compared to controls. In addition, adiponectin levels were significantly elevated in primary biliary cholangitis (PBC) patients compared to controls (8.669 [95% CI .291, 17.047]), as well as in liver cirrhosis compared to other CLD patients (4.805 [95% CI 1.247, 8.363]), including non-alcoholic fatty liver disease (NAFLD) (8.532 [95% CI 3.422, 13.641]), but not viral hepatitis. No significant MD was observed between liver cirrhosis and HCC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adiponectin levels are significantly elevated in liver cirrhosis, especially in advanced stages, potentially serving as a biomarker for advanced cirrhosis. Adiponectin also differentiates cirrhosis from other CLD, including NAFLD. However, its role in distinguishing cirrhosis from viral hepatitis and HCC is limited.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564094","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":"Modification, validation and comparison of Naples prognostic score to determine in-hospital mortality in ST-segment elevation myocardial infarction","authors":"Omer Genc,&nbsp;Abdullah Yildirim,&nbsp;Aslan Erdogan,&nbsp;Ersin Ibisoglu,&nbsp;Yeliz Guler,&nbsp;Gazi Capar,&nbsp;M. Mert Goksu,&nbsp;Huseyin Akgun,&nbsp;Gamze Acar,&nbsp;G. Cansu Ozdogan,&nbsp;Gunseli Uredi,&nbsp;Furkan Sen,&nbsp;Ufuk S. Halil,&nbsp;Fahri Er,&nbsp;Murside Genc,&nbsp;Eyup Ozkan,&nbsp;Ahmet Guler,&nbsp;Ibrahim H. Kurt","doi":"10.1111/eci.14332","DOIUrl":"10.1111/eci.14332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The relationship between inflammatory status and poor outcomes in acute coronary syndromes is a significant area of current research. This study investigates the association between in-hospital mortality and the modified Naples prognostic score (mNPS) as well as other inflammatory biomarkers in STEMI patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-centre, cross-sectional study included 2576 consecutive STEMI patients who underwent primary percutaneous coronary intervention between January 2022 and November 2023. Participants were randomly divided into derivation and validation cohorts in a 6:4 ratio. The following inflammatory indices were calculated: pan-immune-inflammation value (PIV), systemic immune-inflammation-index (SII), systemic inflammation-response index (SIRI) and conventional NPS. The mNPS was derived by integrating hs-CRP into the conventional NPS. The performance of these indices in determining in-hospital mortality was assessed using regression, calibration, discrimination, reclassification and decision curve analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inflammatory biomarkers, including PIV, SII, SIRI, NPS and mNPS, were significantly higher in patients who died during in-hospital follow-up compared to those discharged alive in both the derivation and validation cohorts. Multivariable logistic regression analyses were performed separately for the derivation and validation cohorts. In the derivation cohort, mNPS was associated with in-hospital mortality (aOR = 1.490, <i>p</i> &lt; .001). Similarly, in the validation cohort, mNPS was associated with in-hospital mortality (aOR = 2.023, <i>p</i> &lt; .001). mNPS demonstrated better discriminative and reclassification power than other inflammatory markers (<i>p</i> &lt; .05 for all). Additionally, regression models incorporating mNPS were well-calibrated and showed net clinical benefit in both cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>mNPS may be a stronger predictor of in-hospital mortality in STEMI patients compared to the conventional scheme and other inflammatory indices.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461197","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":"Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry","authors":"Barbara E. Stähli,&nbsp;Matthias Schindler,&nbsp;Victor Schweiger,&nbsp;Victoria L. Cammann,&nbsp;Konrad A. Szawan,&nbsp;David Niederseer,&nbsp;Michael Würdinger,&nbsp;Alexander Schönberger,&nbsp;Maximilian Schönberger,&nbsp;Iva Koleva,&nbsp;Julien C. Mercier,&nbsp;Vanya Petkova,&nbsp;Silvia Mayer,&nbsp;Rodolfo Citro,&nbsp;Carmine Vecchione,&nbsp;Eduardo Bossone,&nbsp;Sebastiano Gili,&nbsp;Michael Neuhaus,&nbsp;Jennifer Franke,&nbsp;Benjamin Meder,&nbsp;Miłosz Jaguszewski,&nbsp;Michel Noutsias,&nbsp;Maike Knorr,&nbsp;Thomas Jansen,&nbsp;Fabrizio D’Ascenzo,&nbsp;Wolfgang Dichtl,&nbsp;Dirk von Lewinski,&nbsp;Christof Burgdorf,&nbsp;Behrouz Kherad,&nbsp;Carsten Tschöpe,&nbsp;Annahita Sarcon,&nbsp;Jerold Shinbane,&nbsp;Lawrence Rajan,&nbsp;Guido Michels,&nbsp;Roman Pfister,&nbsp;Alessandro Cuneo,&nbsp;Claudius Jacobshagen,&nbsp;Mahir Karakas,&nbsp;Wolfgang Koenig,&nbsp;Alexander Pott,&nbsp;Philippe Meyer,&nbsp;Marco Roffi,&nbsp;Adrian Banning,&nbsp;Mathias Wolfrum,&nbsp;Florim Cuculi,&nbsp;Richard Kobza,&nbsp;Thomas A. Fischer,&nbsp;Tuija Vasankari,&nbsp;K. E. Juhani Airaksinen,&nbsp;L. Christian Napp,&nbsp;Rafal Dworakowski,&nbsp;Philip MacCarthy,&nbsp;Christoph Kaiser,&nbsp;Stefan Osswald,&nbsp;Leonarda Galiuto,&nbsp;Christina Chan,&nbsp;Paul Bridgman,&nbsp;Daniel Beug,&nbsp;Clément Delmas,&nbsp;Olivier Lairez,&nbsp;Ekaterina Gilyarova,&nbsp;Alexandra Shilova,&nbsp;Mikhail Gilyarov,&nbsp;Ibrahim El-Battrawy,&nbsp;Ibrahim Akin,&nbsp;Karolina Poledniková,&nbsp;Petr Toušek,&nbsp;David E. Winchester,&nbsp;Michael Massoomi,&nbsp;Jan Galuszka,&nbsp;Christian Ukena,&nbsp;Gregor Poglajen,&nbsp;Pedro Carrilho-Ferreira,&nbsp;Christian Hauck,&nbsp;Carla Paolini,&nbsp;Claudio Bilato,&nbsp;Yoshio Kobayashi,&nbsp;Ken Kato,&nbsp;Iwao Ishibashi,&nbsp;Toshiharu Himi,&nbsp;Jehangir Din,&nbsp;Ali Al-Shammari,&nbsp;Abhiram Prasad,&nbsp;Charanjit S. Rihal,&nbsp;Kan Liu,&nbsp;P. Christian Schulze,&nbsp;Matteo Bianco,&nbsp;Lucas Jörg,&nbsp;Hans Rickli,&nbsp;Gonçalo Pestana,&nbsp;Thanh H. Nguyen,&nbsp;Michael Böhm,&nbsp;Lars S. Maier,&nbsp;Fausto J. Pinto,&nbsp;Petr Widimský,&nbsp;Stephan B. Felix,&nbsp;Ruediger C. Braun-Dullaeus,&nbsp;Wolfgang Rottbauer,&nbsp;Gerd Hasenfuß,&nbsp;Burkert M. Pieske,&nbsp;Heribert Schunkert,&nbsp;Monika Budnik,&nbsp;Grzegorz Opolski,&nbsp;Holger Thiele,&nbsp;Johann Bauersachs,&nbsp;John D. Horowitz,&nbsp;Carlo Di Mario,&nbsp;William Kong,&nbsp;Mayank Dalakoti,&nbsp;Yoichi Imori,&nbsp;Luca Liberale,&nbsp;Fabrizio Montecucco,&nbsp;Thomas Münzel,&nbsp;Filippo Crea,&nbsp;Thomas F. Lüscher,&nbsp;Jeroen J. Bax,&nbsp;Frank Ruschitzka,&nbsp;Jelena R. Ghadri,&nbsp;Davide Di Vece,&nbsp;Christian Templin","doi":"10.1111/eci.14317","DOIUrl":"10.1111/eci.14317","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 2′938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18–2.12, <i>p</i> =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21–2.03, <i>p</i> =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22–2.11, <i>p</i> =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17–1.89, <i>p</i> =.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461194","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":"Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease","authors":"Mehmet Kanbay,&nbsp;Sidar Copur,&nbsp;Mustafa Guldan,&nbsp;Lasin Ozbek,&nbsp;Francesca Mallamaci,&nbsp;Carmine Zoccali","doi":"10.1111/eci.14330","DOIUrl":"10.1111/eci.14330","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>Glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors are two novel classes of glucose-lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon-like peptide-1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well-established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461196","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":"Modulation of mitochondrial permeability transition pores in reperfusion injury: Mechanisms and therapeutic approaches","authors":"Giampaolo Morciano,&nbsp;Paolo Pinton","doi":"10.1111/eci.14331","DOIUrl":"10.1111/eci.14331","url":null,"abstract":"<p>Ischemia/reperfusion injury is attracting continuous interest in science for two reasons: because it affects several clinical conditions and because it has been identified, albeit in broad terms, the molecular entity becoming activated by the reperfusion damage paradoxes. Indeed, calcium, oxygen-dependent oxidative stress and pH would activate conformational changes in the mitochondrial cristae embedded F₁/F_O ATP synthase, allowing the formation of pores in the inner mitochondrial membrane thus increasing its permeability. This is a key determinant for mitochondrial stress, cell death and tissue dysfunction. Targeting each of these factors has never contributed to improved clinical outcome of the patients affected by reperfusion damage; now, the focus on the PTP opening could represent the closest target to solve this pathway made by extensive cell death when the tissues become revascularized. In this review, we summarized last knowledge about the structure, the modulation and the therapeutic targeting of the PTP, focusing on ATP synthase and cardiac ischemia/reperfusion.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389104","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 newly developed, easy-to-use prehospital drug-derived score compared with three conventional scores: A prospective multicenter study","authors":"Jesús Jurado-Palomo,&nbsp;José Luis Martin-Conty,&nbsp;Begoña Polonio-López,&nbsp;Juan J. Bernal-Jiménez,&nbsp;Rosa Conty-Serrano,&nbsp;Michele Dileone,&nbsp;Miguel A. Castro Villamor,&nbsp;Carlos del Pozo Vegas,&nbsp;Raúl López-Izquierdo,&nbsp;Cristina Rivera-Picón,&nbsp;Francisco Martín-Rodríguez,&nbsp;Ancor Sanz-García","doi":"10.1111/eci.14329","DOIUrl":"10.1111/eci.14329","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time-consuming and therefore difficult to use in an emergency setting. For early decision-making, an easy-to-use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug-derived score (PDDS) for 2-day mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective, multicenter, ambulance-based cohort study was conducted in adults with undifferentiated acute diseases treated by EMS and transferred to the emergency department. Demographic data, prehospital diagnosis data, prehospital medication and variables for the calculation of the National Early Warning Score 2 (NEWS2), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) were collected. The PDDS was developed and validated, establishing three levels of risk of 2-day mortality. The predictive capability of each score was determined by the area under the curve of the receiver operating characteristic curve (AUROC) and compared using the Delong's test (<i>p</i>-value).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 6401 patients were included. The PDDS included age and the use of norepinephrine, analgesics, neuromuscular blocking agents, diuretics, antihypertensive agents, tranexamic acid, and bicarbonate. The AUROC of PDDS was .86 (95% CI: .816–.903) versus NEWS2 .866 (95% CI: .822–.911), <i>p</i> = .828; versus REMS .885 (95% CI: .845–.924), <i>p</i> = .311; versus RAPS .886 (95% CI: .846–.926), <i>p</i> = .335, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The newly developed easy-to-use prehospital drug-derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380338","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":"ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function","authors":"Valerie Dicenta-Baunach,&nbsp;Zoi Laspa,&nbsp;David Schaale,&nbsp;Manuel Sigle,&nbsp;Alp Bayrak,&nbsp;Tatsiana Castor,&nbsp;Thanigaimalai Pillaiyar,&nbsp;Stefan Laufer,&nbsp;Meinrad Paul Gawaz,&nbsp;Anne-Katrin Rohlfing","doi":"10.1111/eci.14327","DOIUrl":"10.1111/eci.14327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Platelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardiovascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signalling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Using a proximity ligation assay (PLA, Duolink®) to screen for CXCR4/ACKR3 heterodimerization inducing compounds, we found that ACKR3 agonism but not conventional platelet agonists or endogen ligands lead to heterodimer formation. To further characterize the formation of ACKR3/CXCR4 heterodimers, we studied the CXCL12-dependent platelet activation via CXCR4. Both, CXCL12-dependent platelet aggregation and collagen-dependent ex vivo thrombus formation were significantly downregulated by ACKR3 agonism. Moreover, platelet intracellular calcium and Akt signalling were increased by CXCL12 and again suppressed by ACKR3-specific agonists. Previously, CXCL12 was shown to decrease platelet cAMP levels via CXCR4. Treatment with a specific ACKR3 agonist counteracted this CXCL12/CXCR4-dependent cAMP decrease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results reveal that the formation of platelet ACKR3/CXCR4 heterodimers is dependent on ACKR3 rather than CXCR4. Furthermore, ACKR3 agonism induced heterodimerization is associated with mitigating CXCL12/CXCR4-dependent platelet activation possibly by modulating CXCR4-dependent G protein signalling. Our results indicate possible ACKR3 agonist functions and reinforce the potential therapeutic applications of ACKR3 agonists.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380339","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":"Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors","authors":"Antonio Gallo,&nbsp;Wilfried Le Goff,&nbsp;Raul D. Santos,&nbsp;Isabella Fichtner,&nbsp;Stefano Carugo,&nbsp;Alberto Corsini,&nbsp;Cesare Sirtori,&nbsp;Massimiliano Ruscica","doi":"10.1111/eci.14326","DOIUrl":"10.1111/eci.14326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380340","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}