SHOCK最新文献

Abstract: Background: There is growing evidence suggesting that the dysregulation of circular RNAs (circRNAs) plays a significant role in various myocardial disorders, including myocardial ischemia. This study aimed to explore the function of hsa_circ_0068655 (circ_0068655) in hypoxia-induced cardiomyocyte injury. Methods: Human AC16 cardiomyocyte cells were cultured under anaerobic condition to induce an in vitro model of myocardial ischemia. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate staining and caspase-3 and caspase-9 activity assays. Cell proliferation was analyzed by 5-ethynyl-2'-deoxyuridine incorporation assay. Inflammation was evaluated by enzyme-linked immunosorbent assays. Circ_0068655, miR-370-3p, and BCL-2-like 11 (BCL2L11) expression were detected by real-time quantitative polymerase chain reaction or western blotting. The target interactions among circ_0068655, miR-370-3p, and BCL2L11 were predicted using bioinformatics tools and validated using dual-luciferase reporter assays and RNA immunoprecipitation assays. Results: Hypoxia treatment led to upregulated expression of circ_0068655 and BCL2L11, and downregulated expression of miR-370-3p in AC16 cells. This treatment also resulted in reduced cell viability, increased apoptosis rate, elevated caspase-9/3 activities and cleavage, and enhanced production of TNF-α, IL-6, and IL-1β. Notably, knockdown of circ_0068655 alleviated these detrimental effects. In addition, circ_0068655 silencing-mediated effects were restored by decreasing miR-370-3p expression in hypoxia-treated AC16 cells. Moreover, ectopic BCL2L11 expression remitted the effects of miR-370-3p overexpression on hypoxia-treated AC16 cells. Mechanistically, circ_0068655 was found to act as a sponge for miR-370-3p, thereby regulating BCL2L11 expression. Conclusion: Circ_0068655 silencing ameliorated hypoxia-induced human cardiomyocyte injury through the miR-370-3p/BCL2L11 axis.

Abstract: Background : Hypotension after induction of general anesthesia may lead to severe complications in elderly patients. This study investigated whether the respiratory variation of velocity time integral (ΔVTI) and peak velocity (ΔVpeak) of left ventricular outflow tract (LVOT) could predict hypotension after induction of general anesthesia in elderly patients. Methods : 120 elderly patients undergoing selective operation under general anesthesia were enrolled in this study. ΔVTI and ΔVpeak of LVOT were measured by transthoracic echocardiography before induction of general anesthesia. After induction, mean arterial pressure (MAP) was recorded every 1 min for 15 min. Hypotension was defined as a decrease of more than 30% in MAP at baseline or MAP below 65 mmHg from the start of induction. Receiver operating characteristic curves with gray zone and multivariate logistic regression analysis were used to assess the ability of ΔVTI and ΔVpeak of LVOT to predict hypotension after induction of general anesthesia. Results : Hypotension occurred in 64 (53.3%) patients after induction of general anesthesia. The area under receiver operating characteristic curves (AUC) for δVpeak of LVOT to predict hypotension after induction of general anesthesia was 0.811, and the optimal cutoff value was 13.1% with a gray zone of 9.9% to 13.8%, including 45.0% of patients. The AUC for ΔVTI of LVOT was 0.890, and the optimal cutoff value was 13.8% with a gray zone of 11.1% to 13.9%, including 25.8% of patients. After adjusting for confounders, ΔVTI (Odds ratio = 2.24) and ΔVpeak (Odds ratio = 2.09) of LVOT were two significant independent predictors of hypotension after induction of general anesthesia. Conclusions : ΔVTI of LVOT was a reliable predictor of hypotension after the induction of general anesthesia in elderly patients. ΔVpeak of LVOT should be used cautiously to predict hypotension after induction of general anesthesia due to nearly half of elderly patients in the gray zone. Trial registration : This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300077117).

Abstract: Background: Sepsis-induced cardiomyopathy ( SIC ), one of the most common complications of sepsis, seriously affects the prognosis of critically ill patients. Choline metabolism is an important biological process in the organism, and the mechanism of its interaction with SIC is unclear. The aim of this study was to reveal the choline metabolism genes (CMGs) associated with SIC and to provide effective targets for the treatment of SIC . Methods: Through a comprehensive analysis of the microarray dataset GSE79962 (comprising 20 SIC patients and 11 healthy controls) from the GEO database, suspected co-expression modules and differentially expressed genes (DEGs) in SIC were identified. Hub CMGs were obtained by intersecting choline metabolism database with DEGs and key model genes. Afterward, hub CMGs most significantly involved in prognosis were further analyzed for the verification of major pathways of enrichment analysis. Finally, the expression of hub CMGs in in vivo and in vitro SIC model was verified by immunohistochemistry staining and quantitative real-time polymerase chain reaction analysis (qPCR). Results: Weighted gene co-expression network analysis identified 1 hub gene panel and 3,867 hub genes, which were intersected with DEGs and CMGs to obtain the same 3 hub CMGs:HIF-1α, DGKD, and PIK3R1. Only HIF-1α shows significant association with mortality ( P = 0.009). Subsequent differential analysis based on the high and low HIF-1α expression yielded 63 DEGs and then they were uploaded into Cytoscape software to construct a protein-protein interaction network and 6 hub genes with the highest priority were obtained (CISH, THBS1, IMP1, MYC, SOCS3, and VCAN). Finally, a multifactorial COX analysis revealed a significant correlation between HIF-1α and survival in SIC patients, which was further validated by in vitro and in vivo experiments. Conclusion: Our findings will provide new insights into the pathogenesis of SIC , and HIF-1α may have important applications as a potential biomarker for early detection and therapeutic intervention in SIC .

Abstract: Background: Acute lung injury (ALI) is a common respiratory emergency with high incidence and mortality. Among its main pathologic mechanisms is the rapid and intense inflammatory response. Ozone is a naturally occurring compound and is known for its properties as an oxidizing agent. Ozone therapy is the clinical application of a mixture of ozone (O 3 ) and oxygen, used within nontoxic, safe concentrations. It could be used for the treatment of several diseases. Ozone rectal insufflation (O 3 -RI) is a treatment in which medical O 3 is introduced into the rectum to treat and prevent disease. Although O 3 therapy exerts anti-inflammatory effects, its function in ALI remains unclear. The aim of this study was to preliminarily investigate the role and function of O 3 -RI in ALI. Methods: A mouse model of ALI was established by intratracheal administration of LPS. O 3 -RI was administered 4 h following the modeling procedure. Lung histopathology, lung wet/dry ratio, protein content in bronchoalveolar lavage fluid (BALF), and myeloperoxidase activity in lung tissues, as well as the number of inflammatory cells and inflammatory cytokines in BALF, were assessed. The expression levels of NOD-like receptor thermal protein domain associated protein (NLRP3)/apoptosis-associated speck-like protein (ASC)/caspase-1 axis-related proteins in lung tissues were examined by real-time fluorescence quantitative polymerase chain reaction and Western blotting. Results: Ozone therapy reduced the wet/dry ratio of lung tissue and total protein content in BALF and attenuated lung edema and microvascular leakage in ALI mice. Ozone therapy reduced the myeloperoxidase content in the lung tissue, the number of inflammatory cells, and the content of inflammatory cytokines in BALF and attenuated lung tissue inflammation in mice with ALI. Ozone therapy ameliorated lung tissue morphological damage in ALI mice. Ozone therapy downregulated the expression of NLRP3/ASC/caspase-1 axis-related proteins. Conclusion: Ozone therapy attenuated LPS-induced ALI in mice, possibly by inhibiting NLRP3/ASC/caspase-1 axis. Ozone therapy is a valuable potential therapeutic modality for ALI.

Abstract: Purpose: Observational studies showed that frailty is common in the intensive care unit and associated with poor outcomes. However, relevant data from interventional trials are scarce, and it is unknown whether outcomes improved over time. We endeavored to estimate temporal trends of representation and outcomes of frail participants in randomized controlled trials of acute respiratory distress syndrome (ARDS). Methods: We performed a secondary analysis of five ARDS Network and PETAL Network trials published between 2006 and 2019. Based on requirement for everyday assistance prior to hospitalization, we categorized participants into frail versus nonfrail. Results : Out of 3,630 participants with ARDS, 701 (19.3%) were frail. Representation of frail participants increased over time ( P = 0.001), while mortality remained stable ( P = 0.403) and as high as 39.4%. A total of 60.6% of frail participants were younger than 65 years old. Frailty was independently associated with 90-day mortality (odds ratio 1.62, 95% confidence interval 1.34-1.96, P < 0.001). Frail had fewer ventilator-free days and were more likely to have subsequent disability than nonfrail participants. Conclusion: In trials of ARDS, representation of frail participants increased, while their mortality did not improve over time. The ever-increasing vulnerable group of frail participants should be taken into consideration in the design of trials.

Abstract: Objective: Patients with sepsis often experience reductions or increases in platelet counts, but the implications of these temporal patterns on prognosis remain unclear. The aim of this study was to investigate the impact of changes in platelet trajectories on the clinical prognosis of sepsis. Methods: This study was a retrospective analysis using data from the Medical Information Mart for Intensive Care IV database. Patients with sepsis were identified from the database, and their platelet trajectories were categorized into four distinct models based on the changes in platelet counts over a period of 14 days after diagnosis of sepsis. The effect of these trajectories on patient prognosis was subsequently evaluated. Results: A total of 15,250 patients with sepsis were included to construct a model, and the following four distinct platelet count trajectories were identified: normal platelet levels (phenotype 1); persistently low platelet levels (phenotype 2); gradually increasing platelet levels exceeding the normal range (phenotype 3); and consistently significantly elevated platelet levels (phenotype 4). Statistically significant differences were found in the 28-day mortality, in-hospital mortality, and 90-day mortality among the four phenotypes. Multivariate regression analysis showed that compared to the group with normal platelet levels (phenotype 1), the group with persistently low platelet levels (phenotype 2) had higher in-hospital mortality (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 1.16-1.54), 28-day mortality (OR = 1.69, 95% CI: 1.47-1.94), and 90-day mortality (OR = 1.50, 95% CI: 1.32-1.69). There was no difference in in-hospital mortality between phenotypes 3 and 4 compared to phenotype 1, although phenotype 4 showed an increase in 28-day mortality ( P < 0.05), and phenotype 3 showed a decreasing trend in 90-day mortality ( P < 0.05). The results of inverse probability weighting adjusted by regression were basically consistent with the above findings, except that there was no statistical difference in 28-day mortality between phenotype 4 and phenotype 1. In the subgroups based on age, weight, and antiplatelet drugs or therapies, there was an interaction between platelet levels and these factors. Conclusions: In patients with sepsis, a decrease in platelet count is associated with increased mortality, while a moderate increase in platelet count can reduce 90-day mortality. However, for patients with persistently elevated platelet counts, caution is advised when using antiplatelet drugs or therapies, as it may increase mortality.

Abstract: Background: Whole blood (WB) resuscitation has been shown to provide mortality benefit. However, the impact of whole blood transfusions on the risk of venous thromboembolism (VTE) remains unclear. We sought to compare the VTE risk in patients resuscitated with WB versus component therapy (COMP). Methods: Trauma patients aged 18 and older, admitted to two Level 1 trauma centers between 2016 and 2021, who received at least one unit of emergency-release blood products were identified. Clinical and transfusion data were collected. Patients that received any WB during resuscitation were compared to those who received only COMP therapy. The primary outcome was VTE incidence, defined as deep vein thrombosis and/or pulmonary embolism. Results: 3,468 patients met inclusion criteria (WB: 1,775, COMP: 1,693). WB patients were more likely to be male (82 vs. 68%), receive tranexamic acid (21 vs. 16%), and had higher Injury Severity Score (26 vs. 19; all P < 0.001). WB patients exhibited less hospital-free days (11 vs. 15), intensive care unit-free days (23 vs. 25), and 30-day survival (74 vs. 84; all P < 0.001). The WB group had lower VTE incidence (6 vs. 10%, P < 0.001). Logistic regression revealed WB was protective against VTE (OR 0.70, 95% CI 0.54-091, P = 0.009), while red blood cell transfusions and tranexamic acid (TXA) exposure increased VTE risk. Discussion: Using WB as part of resuscitation was associated with a 30% reduction in VTE, while TXA and red blood cell transfusion increased VTE risk. Further research is needed to evaluate VTE risk with empiric use of TXA in the setting of early WB transfusion capability.

Abstract: The reversal of microcirculation dysfunction is crucial for assessing the success of shock resuscitation and significantly influences patient prognosis. However, hemodynamic incoherence is observed when microcirculatory dysfunction persists despite the restoration of macrocirculatory function after resuscitation. Recent advancements in technology have enabled bedside assessment of microcirculation in shock patients, allowing for direct visualization of microcirculatory morphology and quantitative evaluation of its functional status. This article reviews the pathophysiological mechanisms that lead to hemodynamic incoherence. It also introduces the current understanding and classification framework for the different phenotypes of hemodynamic incoherence. Existing evidence indicates that the diverse mechanisms leading to microcirculatory disorders result in varied manifestations among patients experiencing hemodynamic incoherence, highlighting the heterogeneity of this population. Some classification frameworks have been proposed to enhance our understanding of these phenotypes. By integrating pathophysiological mechanisms, clinical symptoms, indicators of macrocirculation, microcirculation, tissue metabolism, and biomarkers, we can summarize certain clinical features of phenotypes in hemodynamic incoherence to form a conceptual framework. Additionally, strategies for creating targeted treatments based on different phenotypes require further validation.

Abstract: Background: Early, accurate determination of disease severity in an emergency setting is paramount for improving patient outcomes and healthcare costs. Monocyte anisocytosis, quantified as monocyte distribution width (MDW), has been shown to correspond with immune dysregulation. We hypothesize that MDW is broadly associated with illness severity related to sepsis and serious infection in children. Methods: We designed a retrospective study to analyze MDW, as measured by UniCel DxH 900 analyzer, on whole blood samples that were collected from children presenting for medical care between April 2020 and September 2022. SIRS criteria and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated, and source of infection was documented. Outcomes were compared by t test or ANOVA, and receiver operating characteristic (ROC) curves assessed accuracy of MDW in identifying sepsis in children. Results: We analyzed samples from 394 children presenting with illness to two pediatric medical centers. MDW was significantly higher in children with sepsis (28.2 ± 7.8) than children with suspected or confirmed infection who did not display signs of sepsis (21.5 ± 5.2). An ROC curve comparing MDW of children with sepsis against infected children without sepsis displayed an area under the curve of 0.78, suggesting MDW may serve as a useful tool in identifying children with sepsis. Discussion: When children present to the urgent care/emergency setting with signs of infection, MDW may serve as a prompt tool to aid clinicians in identifying those who are at high risk for severe illness and require closer monitoring/intervention compared to those who may be safely discharged home.