Sofia-Panagiota Giannakopoulou, Smaragdi Antonopoulou, Fotios Barkas, Evangelos Liberopoulos, Christina Chrysohoou, Petros P Sfikakis, Christos Pitsavos, Costas Tsioufis, Demosthenes Panagiotakos
{"title":"Concordance-discordance between apolipoprotein B and lipid biomarkers in predicting 20-year atherosclerotic cardiovascular disease risk: The ATTICA study (2002-2022).","authors":"Sofia-Panagiota Giannakopoulou, Smaragdi Antonopoulou, Fotios Barkas, Evangelos Liberopoulos, Christina Chrysohoou, Petros P Sfikakis, Christos Pitsavos, Costas Tsioufis, Demosthenes Panagiotakos","doi":"10.1111/eci.70077","DOIUrl":"https://doi.org/10.1111/eci.70077","url":null,"abstract":"<p><strong>Background: </strong>A strong correlation exists between low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B100 (apoB). However, evidence suggests that LDL-C and non-HDL-C may underestimate apoB, potentially obscuring residual cardiovascular risk. Furthermore, interactions between apoB and lipoprotein(a) are implicated in atherogenesis. This study sought to determine whether discordance between apoB, LDL-C, non-HDL-C, or lipoprotein(a) is associated with 20-year atherosclerotic cardiovascular disease (ASCVD) risk within a cohort of apparently healthy adults.</p><p><strong>Methods: </strong>A cohort of 3042 CVD-free adults residing in greater Athens, Greece, was recruited in 2002. A 20-year follow-up was conducted in 2022, comprising n = 2169 participants, of which n = 1988 had complete data for cardiovascular disease incidence. Discordance between biomarkers was defined based on recommended lipid thresholds. Cox proportional hazards models were used to assess the association between discordant/concordant biomarker pairs and 20-year ASCVD risk.</p><p><strong>Results: </strong>ApoB strongly correlated with LDL-C and non-HDL-C, though concordance was limited. Increased 20-year ASCVD cumulative incidence with elevated apoB levels, beyond LDL-C, non-HDL-C, and lipoprotein(a). Discordance analysis revealed that elevated apoB independently predicted increased 20-year ASCVD risk, regardless of non-HDL-C and lipoprotein(a). However, this effect was observed only on concomitantly elevated LDL-C levels. Incorporating apoB into the assessment of traditional modifiable risk factors elucidated part of the previously residual 20-year ASCVD risk, especially in individuals with elevated LDL-C, non-HDL-C, or lipoprotein(a) levels.</p><p><strong>Conclusions: </strong>ApoB may be a superior biomarker for assessing long-term ASCVD risk, indicating that apoB-containing lipoprotein particle number, rather than cholesterol content, is a more robust predictor of ASCVD risk.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70077"},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093243","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}
Alberto Cordero, Rosa Fernandez Olmo, José R González-Juanatey, Leticia A Fernández-Freira, Sergio Manzano, Clara Bonanad, Gustavo Cortez, Armando Oterino, Belen Alvarez-Alvarez, Pedro J Flores Blanco, Jose M Castellano, Deepak L Bhatt
{"title":"Differential effect of triglycerides on the prognosis of patients with a first versus recurrent acute coronary syndrome.","authors":"Alberto Cordero, Rosa Fernandez Olmo, José R González-Juanatey, Leticia A Fernández-Freira, Sergio Manzano, Clara Bonanad, Gustavo Cortez, Armando Oterino, Belen Alvarez-Alvarez, Pedro J Flores Blanco, Jose M Castellano, Deepak L Bhatt","doi":"10.1111/eci.70072","DOIUrl":"https://doi.org/10.1111/eci.70072","url":null,"abstract":"<p><strong>Background: </strong>There is divergent evidence of triglycerides on cardiovascular prevention that might be explained by confounding factors.</p><p><strong>Methods: </strong>We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 8 hospitals from Spain. Triglycerides were measured during the hospitalization, and mortality and major adverse cardiovascular events (MACE) were analysed through follow-up.</p><p><strong>Results: </strong>We included 14,483 patients discharged after an ACS. Median triglycerides level was 120.5 (interquartile range [IQRS] 90-197) mg/dL and was slightly higher in patients with recurrent ACS (135 IQR 98-186 vs. 129 IQR 95-175; p < .01). Through the follow-up, 34.7% of the patients experienced a first MACE rate and 15.0% died. Multivariate analysis identified that triglycerides levels were associated with a higher risk of MACE (HR 1.01 95% CI 1.00-1.02, p = .021) but not with all-cause mortality (HR: 1.00 95% .99-1.02, p = .17). A significant interaction (p = .01) was observed for triglycerides and previous ACS for both endpoints and, therefore, analyses were performed separately. Triglycerides were only associated with a higher risk of MACE in patients with recurrent ACS (HR 1.03 95% CI 1.01-1.05, p = .012) and a higher risk of death in patients with a first ACS (HR 1.02 95% CI 1.01-1.04, p = .02).</p><p><strong>Conclusions: </strong>Previous ACS modifies the risk of triglycerides on MACE and mortality in patients discharged after an ACS. Triglycerides might be considered a target for treatment in patients after a first or recurrent ACS, although the expected benefit on outcomes might be different.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70072"},"PeriodicalIF":4.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075924","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}
Laura Salmón-Gómez, Victoria Catalán, Beatriz Ramírez, Maite Aguas-Ayesa, Amaia Rodríguez, Sara Becerril, Víctor Valentí, Rafael Moncada, Carolina M Perdomo, Camilo Silva, Javier Escalada, Gema Frühbeck, Javier Gómez-Ambrosi
{"title":"Differential effects of bariatric surgery on circulating GDF15 and FGF21 levels: Implications for glycemic status and weight loss outcomes.","authors":"Laura Salmón-Gómez, Victoria Catalán, Beatriz Ramírez, Maite Aguas-Ayesa, Amaia Rodríguez, Sara Becerril, Víctor Valentí, Rafael Moncada, Carolina M Perdomo, Camilo Silva, Javier Escalada, Gema Frühbeck, Javier Gómez-Ambrosi","doi":"10.1111/eci.70069","DOIUrl":"https://doi.org/10.1111/eci.70069","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is a comorbidity commonly associated with obesity. Elevated concentrations of growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) are associated with these conditions, making both cytokines interesting candidates to combat them. This study aimed to analyse the relationship between changes in plasma GDF15 and FGF21 levels and the resolution of T2D or obesity improvements after bariatric surgery.</p><p><strong>Methods: </strong>Plasma samples from 104 patients (52 with obesity and normoglycemia and 52 with obesity and impaired glucose tolerance or T2D) were analysed before and after Roux-en-Y-gastric bypass surgery.</p><p><strong>Results: </strong>Plasma GDF15 levels increased significantly after bariatric surgery in patients with obesity and normoglycemia (p < 0.01), as well as in those with obesity and impaired glucose tolerance or T2D (p < 0.05). This increase was significant in patients analysed up to 8 months after surgery in both groups (p < 0.01) but not in those analysed between 8 to 15 months after surgery, suggesting that GDF15 concentrations exhibit an early increase after surgery but may return to baseline levels over time. In contrast, plasma FGF21 levels after bariatric surgery decreased significantly in patients with impaired glucose tolerance or T2D (p < 0.05). Pre-surgery FGF21 concentrations were negatively correlated with the percentage of excess weight loss and the percentage of fat loss.</p><p><strong>Conclusions: </strong>GDF15 and FGF21 exhibit a different behaviour after Roux-en-Y-gastric bypass surgery, with FGF21 being more closely associated with glycemic status and weight loss. Elevated pre-surgery FGF21 concentrations could predict a higher difficulty in losing the excess weight after surgery.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70069"},"PeriodicalIF":4.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076263","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 role of mean platelet volume in metabolic dysfunction associated steatotic liver disease.","authors":"Papagiouvanni Ioanna, Nervas Vasileios, Gouta Chrysoula, Savvidou Savvoula","doi":"10.1111/eci.70074","DOIUrl":"https://doi.org/10.1111/eci.70074","url":null,"abstract":"<p><strong>Background: </strong>Mean platelet volume (MPV) has been reported significantly higher in patients with metabolic dysfunction associated steatotic liver disease (MASLD), suggesting a thrombogenic effect with an inconclusive link to excess risk for cardiovascular disease (CVD). The aim of this cross-sectional study was to elucidate the role of MPV in MASLD and review the literature.</p><p><strong>Methods: </strong>A cohort of consecutive biopsy-proven MASLD patients was retrospectively investigated for possible associations of MPV with histological features of the disease and, separately, with patients' estimated risk for CVD. CVD Risk was assessed with three different scores: QRISK2, HellenicSCORE II and NAFLD CV Risk. Laboratory investigation included calculation of insulin resistance with the Homeostasis Model Assessment (HOMA) and measurement of serum adiponectin in a subgroup of patients.</p><p><strong>Results: </strong>In a total of 139 MASLD patients, 56 (40.3%) with advanced fibrosis (F3/F4) steatohepatitis were included. MPV exceeded the upper limit of normal (=10 fl) in a significant proportion of study participants (n = 28.1%), with an overall mean of 9.4 ± .9 fl. Statistically significant associations of MPV with platelet count (Pearson correlation, p < .001), with fibrosis stage (one-way ANOVA, p = .040), with adiponectin (Spearman's correlation, p = .033), and all three different CVD Risk scores were found. Finally, a strong negative correlation was detected between serum adiponectin and CVD Risk scores.</p><p><strong>Conclusions: </strong>In this study's cohort of MASLD patients, high MPV was associated with higher fibrosis stages and with increased estimated risk for CVD. Correlations of serum adiponectin to MPV and CVD risk scores support its implication as a cytokine-mediator that has to be further studied.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70074"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076633","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}
Janaina B Medina, Fábio França Vieira E Silva, Rafael Antônio Velôso Caixeta, Bruna de Oliveira Rech, Alba Perez-Jardón, María Elena Padín-Iruegas, Mario Pérez-Sayáns, Paulo Henrique Braz-Silva, Karem L Ortega
{"title":"Torque teno virus as a marker of immune status in immunocompromised patients: A systematic review.","authors":"Janaina B Medina, Fábio França Vieira E Silva, Rafael Antônio Velôso Caixeta, Bruna de Oliveira Rech, Alba Perez-Jardón, María Elena Padín-Iruegas, Mario Pérez-Sayáns, Paulo Henrique Braz-Silva, Karem L Ortega","doi":"10.1111/eci.70068","DOIUrl":"https://doi.org/10.1111/eci.70068","url":null,"abstract":"<p><strong>Background: </strong>Torque teno virus (TTV) is not known to cause disease in humans; however, chronic inflammatory conditions and immunosuppression states can favour TTV replication. This study aimed to verify the effectiveness of TTV as an immune biomarker.</p><p><strong>Methods: </strong>The protocol of this review was registered in PROSPERO (CRD42022331049) and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.</p><p><strong>Results: </strong>Thirty-three articles were selected and different groups of patients were assessed. In the solid organ and hematopoietic stem cell transplant groups, most studies reported that TTV viral load (VL) was highly detectable after transplantation and compared to controls, but the association with immune parameters showed conflicting results. In melanoma patients, no statistical difference in TTV VL was identified between susceptible and treatment-resistant patients. In lung cancer patients, viral load increases significantly with disease progression but decreases after chemotherapy. HIV-positive patients showed a higher VL than controls, but an inverse correlation with CD4+ was observed in half of the studies. Although 57.14% of all studies presented a low risk of bias, significant differences were observed between studies, particularly in the choice of the analyzed outcome, the parameter used to evaluate the patient's immune status, the presence of a control group, and the sample collection time points.</p><p><strong>Conclusions: </strong>Although TTV seems to have the potential to be a promising biomarker of immunosuppression, further high-quality prospective clinical studies are still needed.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70068"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076636","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}
Veronika Somova, Natalie Jaborova, Bianka Porubska, Daniel Vasek, Natalie Fikarova, Martin Prevorovsky, Zuzana Nahacka, Jiri Neuzil, Magdalena Krulova
{"title":"Mesenchymal stem cell-mediated mitochondrial transfer regulates the fate of B lymphocytes.","authors":"Veronika Somova, Natalie Jaborova, Bianka Porubska, Daniel Vasek, Natalie Fikarova, Martin Prevorovsky, Zuzana Nahacka, Jiri Neuzil, Magdalena Krulova","doi":"10.1111/eci.70073","DOIUrl":"https://doi.org/10.1111/eci.70073","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial transfer is becoming recognized as an important immunomodulatory mechanism used by mesenchymal stem cells (MSCs) to influence immune cells. While effects on T cells and macrophages have been documented, the influence on B cells remains unexplored. This study investigates the modulation of B lymphocyte fate by MSC-mediated mitochondrial transfer.</p><p><strong>Methods: </strong>MSCs labelled with MitoTracker dyes or derived from mito::mKate2 transgenic mice were co-cultured with splenocytes. Flow cytometry assessed mitochondrial transfer, reactive oxygen species (ROS) levels, apoptosis and mitophagy. Glucose uptake was measured using the 2-NBDG assay. RNA sequencing analysed gene expression changes in CD19+ mitochondria recipients and nonrecipients. Pathway analysis identified affected processes. In an LPS-induced inflammation model, mito::mKate2 MSCs were administered, and B cells from different organs were analysed for mitochondrial uptake and phenotypic changes. MSC-derived mitochondria were also isolated to confirm uptake by FACS-sorted CD19+ cells.</p><p><strong>Results: </strong>MSCs transferred mitochondria to CD19+ cells, though less than to other immune cells. Transfer correlated with ROS levels and mitophagy induction. Mitochondria were preferentially acquired by activated B cells, as indicated by increased CD69 expression and glycolytic activity. Bidirectional transfer occurred, with immune cells exchanging dysfunctional mitochondria for functional ones. CD19+ recipients exhibited increased viability, proliferation and altered gene expression, with upregulated cell division genes and downregulated antigen presentation genes. In vivo, mitochondrial acquisition reduced B cell activation and inflammatory cytokine production. Pre-sorted B cells also acquired isolated mitochondria, exhibiting a similar anti-inflammatory phenotype.</p><p><strong>Conclusions: </strong>These findings highlight mitochondrial trafficking as a key MSC-immune cell interaction mechanism with immunomodulatory therapeutic potential.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70073"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076696","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}
Federico Carbone, Jean-Pierre Després, John P A Ioannidis, Ian J Neeland, Gabriella Garruti, Luca Busetto, Luca Liberale, Stefano Ministrini, Gemma Vilahur, Thomas H Schindler, Maria Paula Macedo, Agostino Di Ciaula, Marcin Krawczyk, Andreas Geier, Gyorgy Baffy, Maria Felicia Faienza, Ilaria Farella, Nicola Santoro, Gema Frühbeck, Patricia Yárnoz-Esquiroz, Javier Gómez-Ambrosi, Emma Chávez-Manzanera, Verónica Vázquez-Velázquez, Jean-Michel Oppert, Dimitrios N Kiortsis, Paolo Sbraccia, Carmine Zoccali, Piero Portincasa, Fabrizio Montecucco
{"title":"Bridging the gap in obesity research: A consensus statement from the European Society for Clinical Investigation.","authors":"Federico Carbone, Jean-Pierre Després, John P A Ioannidis, Ian J Neeland, Gabriella Garruti, Luca Busetto, Luca Liberale, Stefano Ministrini, Gemma Vilahur, Thomas H Schindler, Maria Paula Macedo, Agostino Di Ciaula, Marcin Krawczyk, Andreas Geier, Gyorgy Baffy, Maria Felicia Faienza, Ilaria Farella, Nicola Santoro, Gema Frühbeck, Patricia Yárnoz-Esquiroz, Javier Gómez-Ambrosi, Emma Chávez-Manzanera, Verónica Vázquez-Velázquez, Jean-Michel Oppert, Dimitrios N Kiortsis, Paolo Sbraccia, Carmine Zoccali, Piero Portincasa, Fabrizio Montecucco","doi":"10.1111/eci.70059","DOIUrl":"https://doi.org/10.1111/eci.70059","url":null,"abstract":"<p><strong>Background: </strong>Most forms of obesity are associated with chronic diseases that remain a global public health challenge.</p><p><strong>Aims: </strong>Despite significant advancements in understanding its pathophysiology, effective management of obesity is hindered by the persistence of knowledge gaps in epidemiology, phenotypic heterogeneity and policy implementation.</p><p><strong>Materials and methods: </strong>This consensus statement by the European Society for Clinical Investigation identifies eight critical areas requiring urgent attention. Key gaps include insufficient long-term data on obesity trends, the inadequacy of body mass index (BMI) as a sole diagnostic measure, and insufficient recognition of phenotypic diversity in obesity-related cardiometabolic risks. Moreover, the socio-economic drivers of obesity and its transition across phenotypes remain poorly understood.</p><p><strong>Results: </strong>The syndemic nature of obesity, exacerbated by globalization and environmental changes, necessitates a holistic approach integrating global frameworks and community-level interventions. This statement advocates for leveraging emerging technologies, such as artificial intelligence, to refine predictive models and address phenotypic variability. It underscores the importance of collaborative efforts among scientists, policymakers, and stakeholders to create tailored interventions and enduring policies.</p><p><strong>Discussion: </strong>The consensus highlights the need for harmonizing anthropometric and biochemical markers, fostering inclusive public health narratives and combating stigma associated with obesity. By addressing these gaps, this initiative aims to advance research, improve prevention strategies and optimize care delivery for people living with obesity.</p><p><strong>Conclusion: </strong>This collaborative effort marks a decisive step towards mitigating the obesity epidemic and its profound impact on global health systems. Ultimately, obesity should be considered as being largely the consequence of a socio-economic model not compatible with optimal human health.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70059"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076912","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}
Carmen Barbero Linares, José Luis Martín-Conty, Begoña Polonio-López, Cristina Rivera Picón, Juan J Bernal-Jiménez, Francisca Torres Falguera, Joseba Rabanales Sotos, Miguel Antonio Sampedro-Nuñez, Fernando Sebastián-Valles, Miguel Ángel Castro Villamor, Carlos Del Pozo Vegas, Marta Pérez González, Raúl López-Izquierdo, Francisco Martín-Rodríguez, Ancor Sanz-García
{"title":"Emergency department glucose cut-off for 2-year mortality: A multicentre, prospective, cohort study.","authors":"Carmen Barbero Linares, José Luis Martín-Conty, Begoña Polonio-López, Cristina Rivera Picón, Juan J Bernal-Jiménez, Francisca Torres Falguera, Joseba Rabanales Sotos, Miguel Antonio Sampedro-Nuñez, Fernando Sebastián-Valles, Miguel Ángel Castro Villamor, Carlos Del Pozo Vegas, Marta Pérez González, Raúl López-Izquierdo, Francisco Martín-Rodríguez, Ancor Sanz-García","doi":"10.1111/eci.70066","DOIUrl":"https://doi.org/10.1111/eci.70066","url":null,"abstract":"<p><strong>Introduction: </strong>Admission glucose levels in acute illnesses are critical prognostic biomarkers; yet their impact on long-term outcomes has not been sufficiently studied, particularly in emergency medical services (EMS). This study aims to establish specific glucose cut-off points to predict 2-year mortality in patients treated in emergency departments (ED), stratified by diabetes status (Nondiabetic, Uncomplicated diabetes and Complicated diabetes).</p><p><strong>Methods: </strong>A multicentre, prospective cohort study was conducted, including 5632 adult patients with acute illnesses managed by EMS and admitted to EDs in three Spanish provinces. Patients were classified as nondiabetic, with uncomplicated diabetes, or with diabetes with complications. Multivariable analyses were used to identify predictors of 2-year mortality and determine specific glucose cut-off points.</p><p><strong>Results: </strong>In nondiabetic patients, admission glucose levels showed a U-shaped relationship with 2-year mortality, with key cut-off points at 76.1 and 143 mg/dL. Conversely, no significant association between glucose levels and mortality was observed in diabetic patients. Predictors of mortality included advanced age, high aCCI scores and organ dysfunction in nondiabetics, while diabetic patients exhibited additional alterations related to chronic inflammation and coagulation.</p><p><strong>Conclusion: </strong>Admission glucose levels are a key biomarker for predicting 2-year mortality in nondiabetic patients treated in EDs, emphasizing the importance of maintaining glucose within optimal ranges. These findings support the development of personalised management strategies based on the metabolic and clinical status of patients, optimising resources and outcomes in EMS and EDs.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70066"},"PeriodicalIF":4.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076481","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}
Rita Silva Ramos Madureira Simões, João Paulo Soeiro Terra Teodoro, Pedro Miguel Bule Gomes, Carlos Mendes Godinho de Andrade Fontes
{"title":"Bringing the heat: Thermostable analogs of Bst polymerase allow high-temperature LAMP.","authors":"Rita Silva Ramos Madureira Simões, João Paulo Soeiro Terra Teodoro, Pedro Miguel Bule Gomes, Carlos Mendes Godinho de Andrade Fontes","doi":"10.1111/eci.70071","DOIUrl":"https://doi.org/10.1111/eci.70071","url":null,"abstract":"<p><strong>Background: </strong>Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method that gained prominence during the early months of the COVID-19 pandemic due to its simplicity, sensitivity and robustness. However, this technique is susceptible to non-specific amplifications, raising concerns about false-positive results and reduced diagnostic accuracy. A primary contributor to false-positive testing is primer dimerization, which can theoretically be mitigated by performing reactions at higher temperatures. Unfortunately, the strand-displacing DNA polymerases typically used in LAMP, such as Bst, exhibit reduced efficiency at elevated temperatures. To address this limitation, we hypothesised that naturally occurring thermophilic analogs of Bst may be capable of supporting LAMP at higher temperatures, thereby improving reaction specificity.</p><p><strong>Methods: </strong>Bioinformatics and recombinant enzyme production allowed the identification and synthesis of several Bst analogs. These were tested in real-time LAMP assays to detect diverse targets, in a wide range of reaction temperatures (63°C-75°C) and in the presence of typical qPCR inhibitors.</p><p><strong>Results: </strong>Three polymerases-Bst_7, Bst_8 and Bst_15-demonstrated exceptional activity and robust stability at higher temperature conditions (up to 72.5°C), while displaying considerable resistance to common qPCR inhibitors.</p><p><strong>Conclusions: </strong>The identified thermophilic Bst analogs represent a potential solution for the mitigation of non-specific amplification in LAMP, further boosting the application of this technique in molecular diagnostic settings.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70071"},"PeriodicalIF":4.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959215","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":"In-house editorials and journalistic pieces comprise a massive corpus in the scientific literature that can be improved.","authors":"John P A Ioannidis, Michaéla C Schippers","doi":"10.1111/eci.70061","DOIUrl":"https://doi.org/10.1111/eci.70061","url":null,"abstract":"<p><p>In-house editorials and journalistic pieces are massively published in peer-reviewed scientific journals. This corpus has remained outside the efforts of evidence-based medicine and research reform, and it can be imbued with unchecked biases. High-impact journals publish such pieces massively and may generate strong support for specific narratives and perspectives. Pieces with a political slant are also a major issue. Besides high-impact journals, across the entire scientific corpus, such pieces may be (mis)used to boost impact factors, create implausibly prolific CVs (occasionally even fraudulent) and can be powerful instruments of opinion making favouring some sponsors. Here we propose how this influential literature corpus may be strengthened to maximize its benefits and diminish its potential harms. Helpful measures to consider may include bolstering transparency (on authorship, financial compensation, disclosures of publication-specific and generic conflicts of interest, handling of political issues, peer-review, commissioning and timing); self-regulation with limits per author, improvement of subject matter expertise (with experts, meta-researchers and methodologists); balance of perspectives (with debates and for choice of topics); and post-publication review, audit, correction and potential retraction, as needed. A systematic research agenda is needed to study better this phenomenon and also the effectiveness of proposed interventions.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70061"},"PeriodicalIF":4.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990789","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}