European Journal of Clinical Investigation最新文献

{"title":"Biases and debiasing in policy decision-making.","authors":"Michaéla C Schippers, Kasper P Kepp, John P A Ioannidis","doi":"10.1111/eci.70064","DOIUrl":"https://doi.org/10.1111/eci.70064","url":null,"abstract":"<p><p>Policy decision-making should use the best evidence obtained with the most rigorous and reproducible science and should be applied with minimal bias to maximize positive outcomes. This is particularly important in public health and other major decisions. Reality, however, is usually far from this ideal. The quality and use of scientific evidence to address wicked problems and sticky crises have been the focus of intense debate. Policymakers often succumb to fallacies, leading to suboptimal decision-making and maladaptive practices. We map the key biases involved at three different, but communicating, domains: the scientific evidence itself, the policymakers and the citizens. Biases may be classified along two axes pertaining to the perception of the risk and the perception of the effectiveness of the intervention: minimizing risk (e.g. crisis denial), maximizing risk (e.g. moral panic), minimizing intervention effectiveness (e.g. anti-medicine, anti-government) and maximizing effectiveness (e.g. drug lobbyism). We discuss common cognitive biases, including normalcy bias, ostrich effect, negativity bias, Just World Fallacy, false consensus effect, action bias and death spiral effect. Furthermore, we present an overview of potential debiasing processes and tools. Debiasing may help enhance the quality of implementations and trust in institutions, to the benefit of both science and society at large.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70064"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988268","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":"Pregnancy-specific glycoprotein 1 promotes wound closure in animal models.","authors":"Tom Moore, John M Williams, Kathy Barriscale Walsh, Derek Whelan, James Clover","doi":"10.1111/eci.70056","DOIUrl":"https://doi.org/10.1111/eci.70056","url":null,"abstract":"<p><p>Recombinant human PSG1 administered intradermally at wound margins enhances skin wound healing in the mouse and pig, including in an acute diabetic mouse model. A highly significant effect on wound re-epithelialisation was observed in the pig, and PSG1 treatment of the human HaCaT keratinocyte cell line regulated wound healing-associated genes and enhanced scratch wound closure in cell monolayers in vitro. Clinical use of PSG1 might enhance closure of incisional and traumatic wounds and enhance re-epithelialisation of burn injuries.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70056"},"PeriodicalIF":4.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991730","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":"Bosutinib mitigates inflammation in experimental sepsis.","authors":"C M C Cunha, V H P Abreu, V Estato, G M V Soares, B P T Moraes, G P Oliveira, J D Silva, P L Silva, R Immler, P R Rocco, M Sperandio, A R Silva, P T Bozza, H C Castro-Faria-Neto, C F Gonçalves-de-Albuquerque","doi":"10.1111/eci.70055","DOIUrl":"https://doi.org/10.1111/eci.70055","url":null,"abstract":"<p><strong>Background: </strong>Sepsis, a leading cause of death globally, lacks targeted and effective treatment. Its pathophysiology involves unbalanced inflammation, marked by a high release of inflammatory mediators, leukocyte recruitment, vascular changes and dysfunction of the nervous and respiratory systems. Src family tyrosine kinases (SFK) play a critical role in immune responses, and their inhibition can modulate excessive inflammation. This study investigates the potential of bosutinib, an SFK inhibitor, as a treatment for sepsis.</p><p><strong>Methods: </strong>Clinical signs, survival rates, systemic and neuronal inflammatory responses, cell recruitment, lung function and cerebral microcirculation were analysed in mice treated with bosutinib (3 mg/kg) or DMSO/saline followed by cecal ligation and puncture (CLP)-induced sepsis.</p><p><strong>Results: </strong>Bosutinib treatment reduced the severity of sepsis, improved survival rates and reduced the levels of pro-inflammatory cytokines and chemokines in peritoneal lavage, plasma and brain tissue. It also reduced cellular infiltration and bacterial growth at the infection site and protected lung function by reducing diffuse alveolar damage. Using intravital microscopy and laser speckle techniques, bosutinib improved capillary density and blood perfusion and reduced leukocyte recruitment and adhesion in the cerebral microcirculation of septic animals.</p><p><strong>Conclusions: </strong>Bosutinib pretreatment attenuated dysregulated inflammatory responses and neurovascular changes in experimental sepsis.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70055"},"PeriodicalIF":4.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980589","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":"Extracellular matrix mechanical cues (dys)regulate metabolic redox homeostasis due to impaired autophagic flux.","authors":"Heloísa Gerardo, Tânia Lourenço, Júlio Torres, Manuela Ferreira, Célia Aveleira, Susana Simões, Lino Ferreira, Cláudia Cavadas, Paulo J Oliveira, José Teixeira, Mário Grãos","doi":"10.1111/eci.70051","DOIUrl":"https://doi.org/10.1111/eci.70051","url":null,"abstract":"<p><strong>Background: </strong>Extracellular matrix (ECM) stiffness is increasingly recognized as a critical regulator of cellular behaviour, governing processes such as proliferation, differentiation, and metabolism. Neurodegenerative diseases are characterized by mitochondrial dysfunction, oxidative stress, impaired autophagy, and progressive softening of the brain tissue, yet research into how mechanical cues influence cellular metabolism in this context remains scarce.</p><p><strong>Materials and methods: </strong>In this study, we evaluated the long-term effects of brain-compliant, soft ECM on mitochondrial bioenergetics, redox balance, and autophagic capacity in human neuroblastoma (SH-SY5Y) and mouse hippocampal (HT22) cell lines, as well as primary mouse neurons.</p><p><strong>Results: </strong>We observed that prolonged exposure to soft ECM does not impact cell proliferative capacity of neuronal cells but results in mitochondrial bioenergetic dysfunction, redox imbalance, and disrupted autophagic flux. These findings were consistently validated across both human and mouse neuronal cells. Our data indicate a decreased maximal autophagic capacity in cells exposed to long-term soft ECM, potentially due to an imbalance in autophagosome formation and degradation, as demonstrated by decreased LC3 II levels following chloroquine-induced autophagic flux inhibition. This impairment in autophagy was coupled with increased cellular oxidative stress, further indicating metabolic alterations.</p><p><strong>Conclusions: </strong>These findings emphasize the critical role of ECM stiffness in regulating neuronal cell metabolism and suggest that prolonged exposure to soft ECM may mimic key aspects of neurodegenerative disease pathology, thereby enhancing the physiological relevance of in vitro models. This study underscores the necessity for further research into ECM mechanics as a contributing factor in neurodegenerative disease progression and as a potential target for therapeutic strategies.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70051"},"PeriodicalIF":4.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964911","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":"Cancer and cardiovascular diseases: A deadly combination.","authors":"Aldo Bonaventura, Luca Liberale, Federico Carbone, Fabrizio Montecucco","doi":"10.1111/eci.70060","DOIUrl":"https://doi.org/10.1111/eci.70060","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70060"},"PeriodicalIF":4.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959916","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":"Effects of 4-month treatment with glycocalyx dietary supplement on endothelial glycocalyx and vascular function after COVID-19 infection.","authors":"George Pavlidis, Aikaterini Kountouri, Konstantinos Katogiannis, John Thymis, Panagiota Efstathia Nikolaou, Christina Chania, John Karalis, Gabriella Kostelli, Eleni Michalopoulou, Eleni Katsanaki, John Parissis, Hans Vink, Robert Long, Sotirios Tsiodras, Vaia Lambadiari, Ignatios Ikonomidis","doi":"10.1111/eci.70058","DOIUrl":"https://doi.org/10.1111/eci.70058","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19) has been associated with impaired endothelial and vascular function. We investigated whether intervention with glycocalyx dietary supplement (GDS), containing glucosamine sulfate and fucoidan, improves endothelial glycocalyx and vascular function after COVID-19 infection.</p><p><strong>Methods: </strong>Fifty-seven convalescent patients 14 days after mild-to-moderate COVID-19 infection managed in an outpatient setting were randomized to receive GDS (n = 29) or placebo (n = 28) for 4 consecutive months. We measured at baseline and at 4 months: (a) perfused boundary region (PBR) of the sublingual microvessels with a diameter range of 4-25 μm, as a marker of endothelial glycocalyx integrity, (b) pulse wave velocity and augmentation index, (c) coronary flow reserve using Doppler echocardiography, and (d) malondialdehyde and protein carbonyls as oxidative stress markers.</p><p><strong>Results: </strong>Four months after treatment, patients who received GDS showed a greater reduction in PBR 4-25 μm (-6.8% vs. -1.3%), pulse wave velocity (-13.2% vs. -3%), augmentation index (-28.5% vs. -2.5%), malondialdehyde (-26% vs. -2.9%), protein carbonyls (-31.3% vs. -1%) and a greater increase in coronary flow reserve (12.9% vs. 1.6%) compared to placebo (p < .05). In the GDS group, the reduction in PBR 4-25 μm was associated with the corresponding decrease in pulse wave velocity (r = .31, p = .047), malondialdehyde, and protein carbonyls, as well as with the increase in coronary flow reserve (r = -.59, p = .008) at follow-up. Post-treatment, none of the patients under GDS reported post-COVID symptoms compared to 21.4% of the patients under placebo.</p><p><strong>Conclusion: </strong>Four-month treatment with GDS may improve endothelial glycocalyx and vascular function after COVID-19 infection.</p><p><strong>Clinical trial registration: </strong>URL: https://www.</p><p><strong>Clinicaltrials: </strong>gov. Unique identifier: NCT05185934.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70058"},"PeriodicalIF":4.4,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991516","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":"The evolving role of positron emission tomography in precision prostate cancer biopsy.","authors":"Alessio Imperiale, Valentina Berti, Roberto Luigi Cazzato, Darejan Mamulashvili Bessac, Alice Ressault, Luca Vaggelli, Mehdi Helali, Camilo Garcia, Hervé Lang, Desirée Deandreis, Luc Mertz, Afshin Gangi","doi":"10.1111/eci.70062","DOIUrl":"https://doi.org/10.1111/eci.70062","url":null,"abstract":"<p><p>Prostate cancer is one of the most common cancers among men, and accurate detection and diagnosis are crucial for effective treatment planning. Diagnostic prostate biopsy plays a pivotal role in the detection and characterization of prostate cancer. Recent advancements in molecular imaging, particularly with Positron Emission Tomography (PET) using radiolabelled Prostate-Specific Membrane Antigen (PSMA) tracers, have shown significant improvements in enhancing prostate cancer detection. PSMA PET, when combined with magnetic resonance imaging (MRI) in hybrid PET/MRI systems, provides improved sensitivity and specificity, enabling more precise localization of clinically significant prostate cancer (csPCa) lesions. This narrative review explores the evolving role of PET/CT and PET/MRI-guided prostate biopsy. We examine the integration of PET with MRI for the detection of prostate cancer, highlighting key studies that have demonstrated improved diagnostic outcomes. Additionally, we discuss the current limitations, including the high costs and longer scan times associated with PET/MRI, as well as the challenges in data interpretation. The review also considers emerging technologies, such as promising molecular probes for prostate PET imaging, such as gastrin-releasing peptide receptor (GRPR) and fibroblast activation protein inhibitor (FAPI). Finally, the present work provides the clinician with a comprehensive yet concise up-to-date review of the literature to easily evaluate the possibilities currently offered by hybrid imaging technologies of personalized imaging-guided biopsy for prostate cancer patients.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70062"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988284","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":"SGLT-2 inhibitors for cardiac amyloidosis: Hype or hope?","authors":"Flavio Tangianu, Eleonora Nicolini, Francesco Dentali, Aldo Bonaventura","doi":"10.1111/eci.70063","DOIUrl":"https://doi.org/10.1111/eci.70063","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70063"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984564","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":"The contribution of prolactin in the occurrence of premature cardiovascular disease predominantly through modulating the inflammatory cascade.","authors":"Lisa Kamperdijk, Nikol Shkarpa, Marcel Th B Twickler","doi":"10.1111/eci.70042","DOIUrl":"https://doi.org/10.1111/eci.70042","url":null,"abstract":"<p><p>Cardiovascular disease, mainly coronary atherothrombosis, is an essential contributor to all-cause mortality, accounting for approximately 30% of all global deaths. Imbalances in hormone profiles may play a role in the evolution of atherothrombosis. In the last decade, our clinical research focused on the hormone prolactin (PRL) and its contribution to premature cardiovascular disease. In this narrative review, we aimed to give current insights into how PRL could modulate the inflammatory cascade within the microenvironment of the atherosclerotic plaque, which could lead to increased cardiovascular morbidity and mortality.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70042"},"PeriodicalIF":4.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998936","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":"Prediction of major outcomes in patients with malignant hypertension using machine learning: A report from the West Birmingham malignant hypertension registry.","authors":"Antonios A Argyris, Hironori Ishiguchi, Yang Chen, Yalin Zheng, Alena Shantsila, Eduard Shantsila, D Gareth Beevers, Gregory Y H Lip","doi":"10.1111/eci.70052","DOIUrl":"https://doi.org/10.1111/eci.70052","url":null,"abstract":"<p><strong>Background: </strong>Malignant hypertension (MHT) is a rare, yet severe condition with high morbidity and mortality. We aimed to assess the potential of machine learning (ML) algorithms in forecasting prognostic outcomes in MHT patients.</p><p><strong>Methods: </strong>Data from the West Birmingham MHT Registry were used. We evaluated the efficacy of 9 ML algorithms, CatBoost, Decision Tree (DT), Light-Gradient Boosting Machine (LightGBM), K-Nearest Neighbours (KNN), Logistic Regression (LR), Multi-Layer Perceptron (MLP), Random Forest (RF), Support Vector Machine (SVM) and XGBoost in predicting a composite outcome of all-cause mortality/dialysis. Evaluation metrics included the area under the receiver operating characteristic curve (AUC) and F1 score. SHapley Additive exPlanations values were employed to quantify the importance of each feature.</p><p><strong>Results: </strong>The cohort comprised 385 individuals with MHT (mean age 48 ± 13 years, 66% male). During a median follow-up of 11 (interquartile range: 3-18) years, 282 patients (73%) experienced the composite outcome. Among 24 demographic and clinical variables, 16 were selected into the ML models. The SVM, LR, and MLP models exhibited robust predictive performance, achieving AUCs of .81 (95% CI: .70-.90), .82 (95% CI: .71-.92) and .81 (95% CI: .71-.90), respectively. Furthermore, these models demonstrated high F1 scores (SVM: .75, LR: .80. MLP: .75). Age, smoking, follow-up systolic blood pressure, and baseline creatinine were commonly identified as primary prognostic features in both SVM and LR models.</p><p><strong>Conclusions: </strong>The application of ML algorithms facilitates effective prediction of prognostic outcomes in MHT patients, illustrating their potential utility in clinical decision-making through more targeted risk stratification and individualised patient care.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70052"},"PeriodicalIF":4.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981234","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}