SHOCK最新文献

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 minute 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 registrationThis study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300077117).

Abstract: Sepsis-associated acute kidney injury (SAKI), a common complication in intensive care units (ICUs), is linked to high morbidity and mortality. Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, has been shown to have distinct effects on autophagy regulation compared to other sirtuins, but its role in SAKI remains unclear. This study explored the potential of SIRT2 as a therapeutic target for SAKI. We found that inhibition of SIRT2 with the antagonist AGK2 improved the survival of septic mice. SIRT2 inhibition reduced kidney injury, as indicated by lower levels of KIM-1, NGAL, serum creatinine (Scr), blood urea nitrogen (BUN), and proinflammatory cytokines following cecal ligation and puncture (CLP). Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells (RTECs) and upregulated LC3 II expression in the renal cortex. Consistent with in vivo findings, SIRT2 gene silencing promoted autophagy in LPS-treated HK-2 cells, whereas SIRT2 overexpression inhibited it. Mechanistically, SIRT2 inhibition increased FOXO1 acetylation, inducing its nuclear-to-cytoplasmic translocation, which promoted kidney autophagy and alleviated SAKI. Our study suggests SIRT2 as a potential target for SAKI therapy.

Background: There is growing evidence suggesting that the dysregulation of circular RNAs (circRNAs) plays a significant role in various myocardial disorders, including myocardial ischemia (MI). 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 MI. 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 (EdU) 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 tumor necrosis factor (TNF)-α, interleukin (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: 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 post-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.

Objective: The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP.

Methods: Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163.

Results: The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression.

Conclusion: FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.

Abstract: Objective: This study aimed to explore the clinical application of three-dimensional arterial spin labeling (3D-ASL) and diffusion-weighted magnetic resonance imaging (DWI) in transient ischemic attacks. Methods: Forty patients with transient cerebral ischemia in our hospital were selected and included from July 2020 to March 2022. All subjects were detected by DWI and 3D-ASL technology. The positive rate, relative cerebral blood flow (rCBF), and the receiver operating characteristic curve of the two methods in the diagnosis of transient cerebral ischemia were compared; the objective was to compare the relationship between the frequency of transient ischemic attack and hypoperfusion, and vascular stenosis. Results: The 3D-ASL examination showed two cases of hypoperfusion in the healthy control group (5.00), and the magnetic resonance imaging examination showed four cases of vascular stenosis in the healthy control group (10.00). The rCBF ratio in the cerebral ischemia group was significantly lower than that in the cerebral ischemia group, which was significantly lower than that in the healthy control group ( P < 0.05). The area under the curve (AUC) of 3D-ASL in the diagnosis of transient cerebral ischemia was 0.800, and the AUC of DWI in the diagnosis of transient cerebral ischemia was 0.725. The AUC of the combination of the two methods in transient cerebral ischemia was 0.850. There was a significant difference in the attack frequency of patients with transient cerebral ischemia with different perfusion ( P < 0.05). There was a significant difference in attack frequency between patients with transient ischemic attack and patients without vascular stenosis ( P < 0.05). Conclusion: 3D-ASL and DWI technology have higher diagnostic efficiency for transient cerebral ischemia.

Abstract: Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. Methods: 326 children with severe sepsis underwent whole exome sequencing in an observational cohort. We compared children with and without central nervous system dysfunction (Glasgow Coma Scale <12) to assess for associations with clinical characteristics and pooled rare variants in ABCC8 and TRPM4. Sites of variation were mapped onto protein structure and assessed for phenotypic impact. Results: Pooled rare variants in either ABCC8 or TRPM4 associated with decreased odds of central nervous system dysfunction in severe pediatric sepsis (OR 0.14, 95% CI 0.003-0.87), P = 0.025). This association persisted following adjustment for race, organ failure, viral infection, and continuous renal replacement therapy (aOR 0.11, 95% CI 0.01-0.59, P = 0.038). Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4 . Conclusion : This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.

Abstract: Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. Globally, we found 2,404 unique features in the plasma of patients undergoing CPB. Metabolites related to arginine biosynthesis were the most altered by CPB. Correlation of metabolic profiles with endothelial-dependent (acetylcholine [ACh]) or endothelial-independent (sodium nitroprusside [SNP]) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.

Abstract: Introduction: The maximal norepinephrine (NE) dose >1 μg/kg/min during circulatory shock apparently is associated with higher mortality, but this threshold needs confirmation. This study aimed at investigating whether NE infusion at a dose >1 μg/kg/min could predict early intensive care unit (ICU) mortality (first 5 days). The secondary objective was to assess the day-by-day relationship between NE dose during the first 4 days of ICU stay and subsequent mortality. Methods: We conducted a retrospective analysis of data from ICU patients receiving NE for circulatory shock at the Nimes University Hospital (France) from January 2016 to December 2019. Results: A total of 5,735 patients were admitted, 3,693 were screened, and 3,423 were analyzed. NE infusion at a dose >1 μg/kg/min was associated with day-5 mortality (hazards ratio: 7.40, P < 0.0001). The area under the receiver operating characteristic was 0.79 to predict day-5 mortality in ICU for maximal NE >1 μg/kg/min. The calculated threshold of 1.13 μg/kg/min for maximal NE was the best prognostic value (sensitivity: 67%, specificity: 80%, positive predictive value: 45%). When the 1.2 μg/kg/min threshold was crossed either on the first, second, third, or fourth day of ICU stay, the probability of subsequent death was 47%, 49%, 60%, and 40%, respectively. Along the first 4 days of ICU stay, the risk of death increased with increasing NE infusion dose. Conclusions: An NE infusion rate >1.13 μg/kg/min predicts day-5 mortality in ICU patients with circulatory shock. The time to reach maximal NE infusion rate was shorter in survivors than in nonsurvivors.

Abstract: Hemorrhagic shock (HS) is a life-threatening condition with high mortality rates despite current treatments. This study investigated whether targeted temperature management (TTM) could improve outcomes by modulating inflammation and protecting organs following HS. Using a rat model of HS, TTM was applied at 33°C and 36°C after fluid resuscitation. Surprisingly, TTM at 33°C increased mortality, while TTM at 36°C significantly improved survival rates. It also reduced histological damage in lung and kidney tissues, lowered serum lactate levels, and protected against apoptosis and excessive reactive oxygen species production. TTM at 36°C inhibited the release of high mobility group box 1 protein (HMGB1), a key mediator of inflammation, and decreased proinflammatory cytokine levels in the kidneys and lungs. Moreover, it influenced macrophage behavior, suppressing the harmful M1 phenotype while promoting the beneficial M2 polarization. Cytokine array analysis confirmed reduced levels of proinflammatory cytokines with TTM at 36°C. These results collectively highlight the potential of TTM at 36°C as a therapeutic approach to improve outcomes in HS. By addressing multiple aspects of injury and inflammation, including modulation of macrophage responses and cytokine profiles, TTM at 36°C offers promising implications for critical care management after HS, potentially reducing mortality and improving patient recovery.