{"title":"Glucocorticoid triggers endothelial cell ferroptosis via NOX4-mediated reactive oxygen species and lipid peroxidation","authors":"Lijun Fang, Jiazheng Chen, Wenqiang Li, Linmao Lyu","doi":"10.1097/ec9.0000000000000148","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000148","url":null,"abstract":"Abstract Background Glucocorticoids (GCs) are widely used in acute and critical illnesses, but long-term and high-dose use of GCs can cause several vascular side effects. However, the underlying mechanisms are not well-understood. Ferroptosis, a novel form of reactive oxygen species (ROS)-dependent cell death, is characterized by intracellular iron accumulation and lipid peroxidation. NADPH oxidase 4 (NOX4) is a major source of ROS. The roles of ferroptosis and NOX4 in GC-induced endothelial injury remain unknown. Methods Human umbilical vein endothelial cells (HUVECs) were exposed to varying concentrations of dexamethasone (DEX) to evaluate ferroptosis and NOX4 expression. Further mechanistic studies were conducted using NOX4-overexpressing adenovirus (Ad-NOX4), NOX4 small interfering RNA (siRNA), ferrostatin-1 (FER-1), and erastin. Results Our findings demonstrate that DEX induces ferroptosis in HUVECs. Inhibition of ferroptosis with FER-1 prevents DEX-induced reduction in HUVEC viability. Furthermore, DEX treatment increases NOX4 expression in HUVECs, and NOX4 overexpression with Ad-NOX4 promotes ferroptosis. NOX4 knockdown with siRNA suppresses DEX-induced ROS production, lipid peroxidation, and ferroptosis, thereby improving the viability, angiogenesis, and migration capacity of DEX-treated HUVECs. However, the protective effect of NOX4 knockdown is negated by the reactivation of ferroptosis with erastin. Conclusion GC-induced endothelial cell ferroptosis occurs through NOX4-mediated ROS production and lipid peroxidation, leading to cell death, impaired angiogenesis, and migration dysfunction. Inhibition of ferroptosis and NOX4 knockdown ameliorate GC-induced endothelial damage and dysfunction.","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"5 4","pages":"194-200"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147901011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Song, Zhentian Cui, Hongyan Ju, Yue Sun, Dandan Liu, Guang-Yu Li
{"title":"Clinical analysis of patients with deep sternal wound infection-induced sepsis: a retrospective cohort study","authors":"Bin Song, Zhentian Cui, Hongyan Ju, Yue Sun, Dandan Liu, Guang-Yu Li","doi":"10.1097/ec9.0000000000000115","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000115","url":null,"abstract":"\u0000 \u0000 \u0000 This study aimed to summarize the clinical characteristics of patients with deep sternal wound infection-induced sepsis after median sternotomy and improve the treatment outcomes of infection-related sepsis.\u0000 \u0000 \u0000 \u0000 A retrospective cohort study was conducted on 21 patients with deep sternal wound infection-induced sepsis after median sternotomy who were admitted to the Department of Critical Care. The clinical manifestations, laboratory test results, infection control, and organ and nutritional support of the patients were summarized, and the follow-up data were obtained.\u0000 \u0000 \u0000 \u0000 The primary symptoms of deep sternal wound infection-induced sepsis included dyspnea, high fever, chills, and altered state of consciousness. Laboratory test results revealed increased inflammatory markers and decreased oxygenation index. Renal and liver function injury were observed in 8 and 4 patients, respectively; 18 and 12 patients demonstrated elevated D-dimer and N-terminal Pro B type natriuretic peptide levels, respectively. Of the 8 patients whose wound secretions tested positive for bacteria, Acinetobacter baumannii and Staphylococcus aureus infections were present in 6 and 2 patients, respectively. One of the 6 patients whose blood cultures tested positive for bacteria demonstrated Candida albicans infection. Fifteen patients received ventilator-assisted ventilation and 2 patients received renal replacement therapy. Of all the 21 patients, 17 were cured, 2 died, and 2 were discharged.\u0000 \u0000 \u0000 \u0000 Postmedian sternotomy sepsis attributed to a deep sternal wound infection usually results from a preexisting condition. The most prominent clinical manifestation is dyspnea, which is sometimes accompanied by the impairment of organ function. Infection prevention, proper nutrition support, and maintenance of healthy organ function are the cornerstones for successful treatment outcomes.\u0000","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"2012 31","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140718701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anmol Multani, Greg Stahl, Kerry Johnson, Scott Goade, R. Arnce
{"title":"Exploring the effects of coronary artery disease as a preexisting comorbidity on mortality in hospitalized septic patients: a retrospective observation study","authors":"Anmol Multani, Greg Stahl, Kerry Johnson, Scott Goade, R. Arnce","doi":"10.1097/ec9.0000000000000109","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000109","url":null,"abstract":"\u0000 \u0000 \u0000 Sepsis has high prevalence and mortality rate, and it is imperative to identify populations at risk of poor sepsis outcomes. Septic patients with preexisting chronic comorbidities are shown to have worse sepsis outcomes. By identifying comorbidities with greater influence on sepsis progression, we can direct limited resources to septic patients with comorbidities and reduce health care costs. Chronic comorbidities can impact the risk of developing sepsis and having worse outcomes. Coronary artery disease (CAD) is a common comorbidity, especially in the elderly, and a leading cause of death globally. We wished to investigate the influence of CAD as a comorbidity on sepsis and hypothesized that preexisting CAD would increase mortality in hospitalized septic patients.\u0000 \u0000 \u0000 \u0000 We conducted retrospective observational study using patient data from Freeman Health System in Joplin, MO. We analyzed patient records from Freeman Health System database from January 1, 2019, to June 30, 2020. Septic patients were identified using the International Classification of Diseases, Tenth Revision sepsis codes. To identify septic patients with preexisting CAD, we used International Classification of Diseases, Tenth Revision codes for CAD. We compared mortality rates for septic patients with and without CAD.\u0000 \u0000 \u0000 \u0000 Two-sample proportion test was conducted to test the difference in mortality between septic patients with and without preexisting CAD. The difference in mortality for the total population was −0.016 (P = 0.553). In the male and female subgroups, the differences in mortality were 0.0122 (P = 0.739) and −0.0511 (P = 0.208), respectively. The differences in mortality in patients aged 40 to 64 years and 65 years and older were −0.0077 (P = 0.870) and 0.0007 (P = 0.983), respectively. The statistical tests failed to find significant differences when comparing septic patients with and without preexisting CAD. There was no significant difference in the age and sex subgroups.\u0000 \u0000 \u0000 \u0000 Our study showed that CAD alone was not associated with higher mortality due to sepsis in our population.\u0000","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"293 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140233288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An unusual anterior mitral leaflet perforation in a patient with no infective endocarditis: a case report","authors":"Kaiming Wei, Yu Yao, Chuanzhen Liu, Yuan Cao","doi":"10.1097/ec9.0000000000000111","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000111","url":null,"abstract":"\u0000 \u0000 \u0000 Mitral valve perforation refers to the occurrence of cracks or openings in the structure of the mitral valve, allowing blood to escape through these gaps. Typically, this is caused by infective endocarditis and the most common site is the anterior leaflet. However, it is crucial to explore other potential causes of valve damage, particularly when conventional risk factors are not apparent.\u0000 \u0000 \u0000 \u0000 We present a case of a middle-aged male patient who developed mitral valve perforation because of aortic valve regurgitation in the absence of infective endocarditis.\u0000 \u0000 \u0000 \u0000 Exploring such rare cases contributes to a deeper understanding of valvular diseases and enhances clinical decision making for effective management.\u0000","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"42 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140411552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirko Barone, Regina Frontera, Rita Vaia Liouras, Massimo Ippoliti, Luca Serano, Carmine Giovanni Iovino, I. Dell’Atti, Luigi Vetrugno, F. Mucilli, S. M. Maggiore
{"title":"Non-occlusive mesenteric ischemia in critically ill patients: does bedside laparoscopy offer any real benefit?","authors":"Mirko Barone, Regina Frontera, Rita Vaia Liouras, Massimo Ippoliti, Luca Serano, Carmine Giovanni Iovino, I. Dell’Atti, Luigi Vetrugno, F. Mucilli, S. M. Maggiore","doi":"10.1097/ec9.0000000000000107","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000107","url":null,"abstract":"\u0000 Non-occlusive mesenteric ischemia in critically ill patients still has a poor prognosis. Despite several established risk factors, the interaction between clinical conditions and perfusion mismatch often leads to progressive organ failure. Workup is challenging because of the absence of typical abdominal signs and symptoms due to sedation, poor reactivity, need for ventilation, and confounding comorbidities. Moreover, imaging has poor specificity with findings often inconclusive. A bedside exploratory laparoscopy, as a complementary strategy, would allow for early and prompt diagnosis. Limits of a minimally invasive surgical rationale lie upon the effects of pneumoperitoneum induction, surgical stress, logistical resources, expertise, and costs.","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"142 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139604497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management and outcome of pancreatic trauma: a 6-year experience at a level I trauma center: Erratum","authors":"","doi":"10.1097/ec9.0000000000000113","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000113","url":null,"abstract":"","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"503 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139023347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Congestive heart failure and sepsis a retrospective study of hospitalization outcomes from a rural hospital in Southwest Missouri: Erratum","authors":"","doi":"10.1097/ec9.0000000000000112","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000112","url":null,"abstract":"","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"273 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138989758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of cathepsin B protects pancreatic acinar cells against apoptosis in early pancreatic trauma in rats: Erratum","authors":"","doi":"10.1097/ec9.0000000000000116","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000116","url":null,"abstract":"","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"1154 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139019235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic value of elevated cardiac and inflammatory biomarkers in patients with severe COVID-19: a single-center, retrospective study: Erratum","authors":"","doi":"10.1097/ec9.0000000000000114","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000114","url":null,"abstract":"","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"25 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139018682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of clarithromycin for patients with sepsis or septic shock: a systematic review and meta-analysis","authors":"Pengyue Zhao, Renqi Yao, Jiaqi Yang, Wei Wen, Yongming Yao, Xiaohui Du","doi":"10.1097/ec9.0000000000000106","DOIUrl":"https://doi.org/10.1097/ec9.0000000000000106","url":null,"abstract":"Clarithromycin exerts an immunomodulatory role in several human diseases. However, whether this effect improves the prognosis in patients with sepsis remains controversial, and higher levels of clinical evidence are urgently needed. To the best of our knowledge, no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis. A comprehensive literature search of PubMed, EMBASE, and the Cochrane Library was conducted up to December 31, 2022. Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included. Data were pooled by applying a fixed-effects model and a relative risk (RR) estimate with 95% confidence intervals (CIs) using Review Manager (version 5.3; Cochrane Collaboration, Copenhagen, Denmark). Three randomized controlled trials involving a total of 910 patients were included. The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome (RR: 1.51; 95% CI: 1.02–2.25; P = 0.04; I 2 = 0%), 28-day mortality (RR: 1.09; 95% CI: 0.87–1.36; P = 0.46; I 2 = 0%), and 90-day mortality (RR: 0.86; 95% CI: 0.71–1.03; P = 0.10; I 2 = 81%) in patients with sepsis or septic shock. Moreover, there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group (RR: 1.02; 95% CI: 0.87–1.19; P = 0.83; I 2 = 18%). Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin. However, administration of clarithromycin did not increase the risk of adverse events.","PeriodicalId":72895,"journal":{"name":"Emergency and critical care medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139235234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}