SHOCK最新文献

Abstract: Objective : To evaluate if mechanical left ventricular unloading could reduce mortality in patients with cardiogenic shock undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods : We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials and propensity score-matched studies published until December 20, 2023. The primary outcome was mortality at the longest follow-up. We used a Mantel-Haenszel random effects meta-analysis and reported the pooled results with a risk ratio (RR) and 95% confidence interval (CI). The review protocol was registered on PROSPERO International prospective register of systematic review (CRD42024498665). Results : We identified two randomized controlled trials and 11 propensity score-matched studies, totaling 9,858 patients. Mechanical left ventricular unloading was significantly associated with reduced mortality at the longest follow-up (RR, 0.89; 95% CI, 0.84-0.94; P = 0.0001; moderate certainty of evidence), which was confirmed in studies using intra-aortic balloon pump. Benefits of mechanical unloading were also observed in terms of successful VA-ECMO weaning (RR, 1.15; 95% CI, 1.02-1.29; P = 0.02; low certainty of evidence) and favorable neurological outcome (two studies; RR, 2.45; 95% CI, 1.62-3.69; P < 0.0001; low certainty of evidence), although we observed an increased incidence of major bleeding (RR, 1.27; 95% CI, 1.02-1.59; P = 0.03; low certainty of evidence) and hemolysis (RR, 1.49; 95% CI, 1.10-2.02; P = 0.01; moderate certainty of evidence). Conclusions : Among adult patients with cardiogenic shock treated with VA-ECMO, mechanical left ventricular unloading was associated with reduced mortality, which was confirmed in studies using intra-aortic balloon pump as an unloading device.

Abstract: Sepsis remains a significant cause of morbidity and mortality worldwide. Although many more patients are surviving the acute event, a substantial number enters a state of persistent inflammation and immunosuppression, rendering them more vulnerable to infections. Modulating the host immune response has been a focus of sepsis research for the past 50 years, yet novel therapies have been few and far between. Although many septic patients have similar clinical phenotypes, pathways affected by the septic event differ not only between individuals but also within an individual over the course of illness. These differences ultimately impact overall immune function and response to treatment. Defining the immune state, or endotype, of an individual is critical to understanding which patients will respond to a particular therapy. In this review, we highlight current approaches to define the immune endotype and propose that these technologies may be used to "prescreen" individuals to determine which therapies are most likely to be beneficial.

Abstract: Septic cardiomyopathy is linked to a dysregulation in mitochondrial integrity and elevated mortality rates, for which an efficacious treatment remains elusive. PDS is a panaxadiol saponin extracted from ginseng stem and leaf. This study identified the protective effects of PDS and DEX in LPS-induced cardiomyopathy and explored the mechanism of them treating LPS-induced cardiomyopathy from the perspectives of mitochondrial quality control. DEX and PDS enhance antioxidant defense by degrading Keap1 to activate Nrf2; activate mitochondrial occurrence protein PGC-1α and fusion protein OPA1, Mfn1, and Mfn2 expression; and inhibit phosphorylation of mitochondrial fission protein Drp1, aiming to maintain normal structure and function of mitochondrial, thereby preserving oxidative phosphorylation capacity. In summary, our findings highlighted the protective efficacy of PDS and DEX in maintaining mitochondrial in LPS-induced cardiomyopathy, and mechanism improving mitochondrial quality control at least in part by promoting Nrf2 activation.

Abstract: Introduction: Veno-venous extracorporeal membrane oxygenation (VV ECMO) improves hypoxemia and carbon dioxide clearance in patients with severe respiratory derangements. A greater understanding of the potential benefits of VV ECMO in trauma patients could lead to broader adoption. We hypothesize that trauma patients who receive VV ECMO have improved mortality outcomes when compared to those receiving conventional ventilator management given the rapid stabilization VV ECMO promotes. Methods: We performed a single-center, propensity score-matched cohort study. All trauma patients from January 1, 2014, to October 30, 2023, who were placed on VV ECMO or who would have met institutional guidelines for VV ECMO but were managed with conventional ventilator strategies were matched 1:1. The primary outcome analysis was survival at hospital discharge. Significance was defined as P < 0.05. Results: Eighty-one trauma VV ECMO patients and 128 patients who received conventional management met criteria for inclusion. After matching, VV ECMO and conventional treatment cohort characteristics were similar in age and mechanism of injury. Matched ISS, SI, lactate levels, and frequency of traumatically brain injured were also similar. Finally, respiratory parameters including preintervention, pH, partial pressure of carbon dioxide, lactate levels, and oxygen saturation were similar between matched groups. VV ECMO patients had higher survival rates at discharge when compared to the matched conventional treatment group (70% vs. 41%, P < 0.001). Corresponding hazard ratio for VV ECMO use was 0.31 (95% CI 0.18-0.52; P < 0.001). The odds ratio of mortality in matched trauma patients who receive VV ECMO versus conventional treatment was 0.29 (95% CI 0.14-0.58; P < 0.001). Conclusion: VV ECMO may represent a safe, alternative treatment approach for appropriately screened trauma patients with acute respiratory failure; however, further studies are warranted.

Abstract: Background : Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20 to 25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). Methods : Using the MIMIC-IV database, adult patients who received CKRT for more than 24 h were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 mL/kg/h. Results : Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and <13 mL/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 mL/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 mL/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 mL/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 mL/kg/h. Conclusion : This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.

Abstract: Introduction: Unplanned intensive care unit (ICU) admissions are associated with increased morbidity and mortality. This study uses interpretable machine learning to predict unplanned ICU admissions for initial nonoperative trauma patients admitted to non-ICU locations. Methods: TQIP (2020-2021) was queried for initial nonoperative adult patients admitted to non-ICU locations. Univariable analysis compared patients who required an unplanned ICU admission to those who did not. Using variables that could be known at hospital admission, gradient boosting machines (CatBoost, LightGBM, XGBoost) were trained on 2021 data and tested on 2020 data. SHapley Additive exPlanations (SHAP) were used for interpretation. Results: The cohort had 1,107,822 patients; 1.6% had an unplanned ICU admission. Unplanned ICU admissions were older (71 [58-80] vs. 61 [39-76] years, P < 0.01), had a higher Injury Severity Score (ISS) (9 [8-13] vs. 9 [4-10], P < 0.01), longer length of stay (11 [7-17] vs. 4 [3-6] days, P < 0.01), higher rates of all complications, and most comorbidities and injuries ( P < 0.05). All models had an AUC of 0.78 and an F1 score of 0.12, indicating poor performance in predicting the minority class. Mean absolute SHAP values revealed ISS (0.46), age (0.29), and absence of comorbidities (0.16) as most influential in predictions. Dependency plots showed greater SHAP values for greater ISS, age, and presence of comorbidities. Conclusions: Machine learning may outperform prior attempts at predicting the risk of unplanned ICU admissions in trauma patients while identifying unique predictors. Despite this progress, further research is needed to improve predictive performance by addressing class imbalance limitations.

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, blood urea nitrogen, and proinflammatory cytokines following cecal ligation and puncture. Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells 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.

Abstract: Background: Acute kidney injury (AKI) is a common, fatal complication of acute cholangitis (AC). The link between AC and AKI is poorly understood. Aims: To delineate the incidence trends, clinical outcomes and healthcare utilization of inpatients with AKI following AC and to explore the risk factors for AKI following AC. Methods: This population-based retrospective study used the National Inpatient Sample database from 2010 to 2018 to compare the demographics, complications, in-hospital mortality and healthcare utilization between AC patients with and without AKI. Predictors of AKI and the prognostic impact of AKI on in-hospital outcomes were defined using multivariate logistic regression. Results: The overall incidence of AKI was 24.06% among AC patients. Its trend generally increased annually. AKI was associated with more complications, greater invasive therapy requirements, longer hospital stays, costlier total hospital charges, and higher in-hospital mortality. The risk factors for AKI following AC were advanced age, Black race, multiple comorbidities, large hospitals, teaching hospitals, urban hospitals, hospitals in the southern and western United States, choledocholithiasis/cholelithiasis, surgery, percutaneous transhepatic biliary drainage, deficiency anemia, congestive heart failure, coagulopathy, diabetes, hypertension, chronic liver disease, obesity, chronic kidney disease excluding end-stage renal disease, weight loss, acute pancreatitis, and severe sepsis. Female sex, private insurance, elective admission, and endoscopic retrograde cholangiopancreatography were protective factors against AKI in AC patients. Conclusion: AKI often follows AC and is strongly associated with poor prognosis and increased healthcare utilization. Healthcare professionals should make more efforts to identify patients with AC at risk of AKI and start management promptly to limit adverse outcomes.

Abstract: Chronic kidney disease (CKD)-related vascular calcification (VC) is a common degenerative phenomenon of the vessel wall and its pathological basis is the phenotypic transformation of vascular smooth muscle cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have been reported to be expressed in the aortic tissues in a rat model of VC. This work is conducted to reveal the functions of ZBTB16 on VC in CKD and to probe its involved reaction mechanisms. In vivo CKD rat models were established by adenine and VSMC calcification were stimulated with high phosphate (Pi) in vitro . Renal function indexes were estimated with relevant assay kits. Renal tissues were histologically examined with hematoxylin and eosin staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR and western blot were used to detect ZBTB16 expression. Western blot, immunohistochemistry, and immunofluorescence staining were used to detect osteogenic markers and smooth muscle cell markers. Western blot was used to measure the expressions of proteins implicated in Wnt/β-catenin pathway. In the blood samples of CKD patients with VC, aortic tissues of CKD rats, and Pi-treated VSMCs, ZBTB16 expression was significantly increased. ZBTB16 knockdown reduced renal dysfunction, calcium deposition and inhibited VSMCs osteoblast differentiation both in vitro and in vivo . Moreover, silencing with ZBTB16 inactivated Wingless-related integration site (Wnt)/β-catenin pathway. LiCl (Wnt/β-catenin agonist) reversed the protective effects of ZBTB16 knockdown on the calcification and osteoblastic transformation in vitro . Together, ZBTB16 silencing may downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.

Abstract: 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. TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay. 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.