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FINDING THE SWEET SPOT: THE ASSOCIATION BETWEEN WHOLE BLOOD TO RED BLOOD CELLS RATIO AND OUTCOMES OF HEMORRHAGING CIVILIAN TRAUMA PATIENTS. 寻找最佳点:全血与红细胞比率与平民创伤出血患者的预后之间的关系。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-05-30 DOI: 10.1097/SHK.0000000000002405
Hamidreza Hosseinpour, Collin Stewart, Omar Hejazi, Stanley E Okosun, Muhammad Haris Khurshid, Adam Nelson, Sai Krishna Bhogadi, Michael Ditillo, Louis J Magnotti, Bellal Joseph

Abstract: Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients.

目的:评估全血(WB)对失血性休克平民创伤患者预后的剂量依赖性影响:我们对 ACS-TQIP 数据集进行了为期两年(2020-2021 年)的回顾性分析。纳入了休克指数 (SI) >1 的成年(≥18 岁)创伤患者,这些患者在入院后 4 小时内至少接受了 5 个单位的 PRBC 和 1 个单位的 WB。主要结果为 6 小时、24 小时和院内死亡率。次要结果为主要并发症、住院时间和重症监护室住院时间(LOS):结果:共发现 830 名外伤患者,平均(标清)年龄为 38(16)岁。4小时WB和PRBC需求量的中位数[IQR]分别为2[2-4] U和10[7-15] U,WB:RBC比率的中位数为0.2[0.1-0.3]。WB:RBC 比值每增加 0.1,24 小时死亡率(aOR:0.916,p = 0.035)和院内死亡率(aOR:0.878,p < 0.001)就会降低。尤登指数确定 0.25(1 U WB 对 4 U PRBC)是降低 24 小时死亡率的最佳 WB:PRBC 比率。与低比例组相比,高比例组(≥0.25)24 小时死亡率(aOR:0.678,p = 0.021)和院内死亡率(aOR:0.618,p < 0.001)的调整后几率较低:结论:WB:PRBC 比率越高,失血性休克创伤患者的早期和晚期死亡率越高。鉴于美国各地的创伤中心都有 WB 可供使用,因此每四个 PRBC 单位可至少使用一个 WB 单位,以提高大出血平民创伤患者的存活率。
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引用次数: 0
IMPLICATIONS OF YWHAH GENE EXPRESSION IN THE EARLY DETECTION OF SEPSIS. YWHAH 基因表达在败血症早期检测中的意义。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-06-21 DOI: 10.1097/SHK.0000000000002409
Hua Yao, Yue Zhou, Zhengguang Geng, Fei Gao, De Su, Yan Kang, Bao Fu

Abstract: Sepsis, a complex and multifaceted condition, is a common occurrence with serious implications for critically ill patients in the intensive care unit (ICU). The YWHAH gene encodes the 14-3-3n protein, a member of the 14-3-3 protein family. While existing research primarily focuses on the role of 14-3-3n in conditions such as schizophrenia and various cancers, our study revealed that the expression of the YWHAH gene remained relatively stable in both infected individuals and healthy controls. Through Venn plot analysis following weighted gene correlation network analysis, we observed a potential association between elevated YWHAH expression and the transition from infection to sepsis. In a comprehensive analysis of public single-cell transcriptome databases, the expression of YWHAH was found to be distinctive in cases of sepsis and infection. These findings were corroborated through an in vitro analysis utilizing real-time polymerase chain reaction. This study represents the initial identification of variations in YWHAH gene expression between patients with infection and sepsis, potentially offering insights for the development of early detection and treatment strategies for sepsis.

摘要:败血症是一种复杂的、多方面的疾病,是重症监护室(ICU)中严重影响危重病人的常见病。YWHAH 基因编码 14-3-3 蛋白家族成员之一的 14-3-3n 蛋白。现有研究主要关注 14-3-3n 在精神分裂症和各种癌症等疾病中的作用,而我们的研究发现,YWHAH 基因的表达在感染者和健康对照组中都保持相对稳定。通过加权基因相关网络分析(WGCNA)后的维恩图分析,我们观察到 YWHAH 表达的升高与从感染到败血症的转变之间存在潜在的联系。在对公共单细胞转录组数据库进行的综合分析中,我们发现 YWHAH 的表达在败血症和感染病例中各不相同。利用实时聚合酶链反应进行的体外分析证实了这些发现。这项研究首次发现了感染和败血症患者之间 YWHAH 基因表达的变异,有可能为开发败血症的早期检测和治疗策略提供启示。
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引用次数: 0
CHANGES OF HISTIDINE-RICH GLYCOPROTEIN LEVELS IN CRITICALLY ILL SEPTIC PATIENTS. 重症脓毒症患者富含组氨酸糖蛋白水平的变化。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI: 10.1097/SHK.0000000000002406
Ayu Nabila Kusuma Pradana, Tomohiko Akahoshi, Jie Guo, Yukie Mizuta, Shuntaro Matsunaga, Sayoko Narahara, Masaharu Murata, Ken Yamaura

Abstract: Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 μg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management.

背景:富含组氨酸糖蛋白(HRG)是脓毒症的潜在预后因素,但其与脓毒症诱发休克、弥散性血管内凝血(DIC)和急性呼吸窘迫综合征(ARDS)发病机制的相关性尚不明确。本研究调查了 HRG 浓度与这些危重症之间的关系:方法:在九州大学医院的重症监护病房,采集了 53 名重症患者入院后第 1、3、5 和 7 天的血液样本。结果:血清中的 HRG 浓度明显降低:结果:脓毒性休克和 DIC 患者的血清 HRG 浓度在第 3、5 和 7 天明显降低,而 ARDS 患者的血清 HRG 浓度则没有明显降低。虽然第一天的初始 HRG 水平与存活率无关,但非存活者的 HRG 水平下降,尤其是在入住重症监护室后的第 3、5 和 7 天。幸存者的 HRG 水平保持稳定。逐步下降与较高的死亡率有关,尤其是在第 5 天和第 7 天。第 5 天,HRG 水平的临界值为 25.5 μg/mL,灵敏度为 0.77,特异度为 0.75,表明存活率显著降低(对数秩检验,P < 0.05):HRG为重症脓毒症患者提供了一种潜在的干预措施,为改善预后提供了一种新策略。需要进一步研究探讨 HRG 在脓毒症治疗中的治疗潜力。
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引用次数: 0
SERUM TRANSACTIVE RESPONSE DNA BINDING PROTEIN 43 ASSOCIATES WITH POOR SHORT-TERM NEUROLOGIC OUTCOME AFTER RETURN OF SPONTANEOUS CIRCULATION FOLLOWING CARDIAC ARREST. 血清转录反应 DNA 结合蛋白 43 与心脏骤停后恢复自主循环后的短期神经功能不良有关。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-05-23 DOI: 10.1097/SHK.0000000000002378
Zhangping Sun, Dongping Yu, Peijuan Li, Ling Wang, Yushu Chen, Xiaojun Wei, Ping Gong

Abstract: Objective : To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest. Methods : We performed a study between January and December 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected, and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and 10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurologic function was assessed by the cerebral performance category scores on day 28 after ROSC. Results : A total of 92 patients were included, with 51 and 41 patients in the good and poor neurologic outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group ( P < 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (all P < 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area under curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated. Conclusion : Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.

目的探讨心脏骤停后自发循环恢复(ROSC)患者血清转录反应DNA结合蛋白43(TDP-43)与28天不良神经功能预后的关系:我们在 2023 年 1 月至 12 月期间进行了一项研究。我们在 2023 年 1 月至 12 月期间进行了这项研究。收集了他们的基线特征,并测量了 ROSC 后 24 小时血清中 TDP-43、肿瘤坏死因子-α、白细胞介素-6 和-10、C 反应蛋白和神经元特异性烯醇化酶(NSE)的水平。ROSC后第28天,通过脑功能分类评分评估神经功能:结果:共纳入 92 例患者,其中神经功能预后良好组和不良组分别为 51 例和 41 例。神经功能预后不良组血清 TDP-43 明显高于神经功能预后良好组(P < 0.05)。单变量和多变量逻辑回归分析表明,TDP-43、Witnessed CA、IL-6 和 NSE 与 28 天神经功能预后差相关(均 P < 0.05)。限制性三次样条分析显示,血清中 TDP-43 水平为 11.64 pg/mL 可能是区分神经功能预后好坏的理想临界值。血清 TDP-43 的曲线下面积(AUC = 0.78)与血清 NSE 的曲线下面积(AUC = 0.82)接近。结合 TDP-43、Witnessed CA、IL-6 和 NSE,构建并验证了一个动态提名图预测模型:结论:血清 TDP-43 水平升高与 Witnessed CA、IL-6 和 NSE 相关,可用于预测心脏骤停后 ROSC 患者 28 天的不良神经功能预后。
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引用次数: 0
EXAMINING THE IMPACT OF PERMISSIBILITY HYPERCAPNIA ON POSTOPERATIVE DELIRIUM AMONG ELDERLY PATIENTS UNDERGOING THORACOSCOPIC-LAPAROSCOPIC ESOPHAGECTOMY: A SINGLE-CENTER INVESTIGATIVE STUDY. 探讨允许性高碳酸血症对接受胸腔镜-腹腔镜食管切除术的老年患者术后谵妄的影响:单中心调查研究。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-05-30 DOI: 10.1097/SHK.0000000000002400
Jie Song, Yan-Mei Shao, Guang-Hui Zhang, Bing-Qian Fan, Wen-Hui Tao, Xiao-Fen Liu, Xiao-Ci Huang, Xian-Wen Hu

Abstract: Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO 2 35-45 mm Hg (group N) or 46-55 mm Hg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO 2 , cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for 3 postoperative days. Results: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO 2 and rSO 2 during surgery ( P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 ( P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV ( P < 0.05). Group H had lower pH and higher OI at T2-4 ( P < 0.05). CRP and CAR levels rose less in group H on the first day and 1 week later ( P < 0.05). Conclusions: Maintaining PaCO 2 at 46-55 mm Hg reduces POD incidence, possibly by enhancing rSO 2 levels and stabilizing intraoperative respiration/circulation.

目的本研究探讨了肺保护性通气的关键环节--允许性高碳酸血症如何影响胸腔镜手术后老年患者的术后谵妄:安徽医科大学第二医院的一项单中心试验涉及 136 名接受胸腔镜食管癌切除术的老年患者。随机分配维持 PaCO2 35-45 mmHg(N 组)或 46-55 mmHg(H 组)。主要结果:术后 1-3 天的术后谵妄 (POD) 发生率。次要终点包括在特定时间点监测 rSO2、心血管参数(MAP、HR)、pH 值、OI 和呼吸参数(VT、RR、Cdyn、PIP)。围手术期测试评估了 CRP/ALB 比值(CAR)和全身炎症指数(SII)。术后三天记录 VAS 评分:术后,H 组的 POD 发生率明显低于 N 组(7.4% 对 19.1%,P = 0.043)。H 组患者术中的 PaCO2 和 rSO2 均较高(P < 0.05)。H 组患者的心血管稳定性更好,T2-4 期血压更高,心率更低(P < 0.05)。H 组呼吸参数更稳定,TV、RR 和 PIP 更低,OLV 期间 Cdyn 更高(P < 0.05)。H 组在 T2-4 期的 pH 和 OI 更低(P < 0.05)。H 组的 CRP 和 CAR 水平在第一天和一周后上升较少(P < 0.05):将 PaCO2 保持在 46-55 mmHg 可降低 POD 发生率,这可能是通过提高 rSO2 水平和稳定术中呼吸/循环实现的。
{"title":"EXAMINING THE IMPACT OF PERMISSIBILITY HYPERCAPNIA ON POSTOPERATIVE DELIRIUM AMONG ELDERLY PATIENTS UNDERGOING THORACOSCOPIC-LAPAROSCOPIC ESOPHAGECTOMY: A SINGLE-CENTER INVESTIGATIVE STUDY.","authors":"Jie Song, Yan-Mei Shao, Guang-Hui Zhang, Bing-Qian Fan, Wen-Hui Tao, Xiao-Fen Liu, Xiao-Ci Huang, Xian-Wen Hu","doi":"10.1097/SHK.0000000000002400","DOIUrl":"10.1097/SHK.0000000000002400","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO 2 35-45 mm Hg (group N) or 46-55 mm Hg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO 2 , cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for 3 postoperative days. Results: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO 2 and rSO 2 during surgery ( P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 ( P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV ( P < 0.05). Group H had lower pH and higher OI at T2-4 ( P < 0.05). CRP and CAR levels rose less in group H on the first day and 1 week later ( P < 0.05). Conclusions: Maintaining PaCO 2 at 46-55 mm Hg reduces POD incidence, possibly by enhancing rSO 2 levels and stabilizing intraoperative respiration/circulation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"319-326"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420640","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}
引用次数: 0
EVALUATION OF VASOPRESSOR INFLECTION POINT FOR SHORT-TERM PROGNOSIS OF PATIENTS WITH SEPTIC SHOCK. 评估脓毒性休克患者短期预后的血管加压拐点
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1097/SHK.0000000000002415
Mei Yang, Shao-Gui Chen

Abstract: Objective: The goal of this study is to investigate the clinical value of vasopressor inflection points in the evaluation of short-term prognosis among individuals afflicted with septic shock. Methods: A retrospective analysis was conducted on a cohort comprising 56 patients diagnosed with septic shock and receiving treatment at the department of critical care medicine of the hospital between January 2021 and March 2023. These patients were divided into two groups based on the prognostic outcome: a survival group consisting of 34 patients and a death group consisting of 22 patients. The determination of vasopressor inflection time and procalcitonin (PCT) inflection time of each patient was undertaken with the initiation of vasopressor therapy serving as the reference point. The vasopressor inflection point was defined as the time when the dosage of vasopressors commenced decreasing, while the PCT inflection point denoted the time when PCT levels began to decline. The incidence of patients reaching the vasopressor and PCT inflection points on the 2nd, 3rd, and 4th days following the initiation of vasopressor therapy was tabulated for both groups. The comparison of inflection points between the two groups at each time point was conducted using Fisher's exact test. Furthermore, logistic regression analysis was employed for univariate prognostic assessment. The diagnostic performance of vasopressor and PCT inflection point was assessed using the four-table method. The discrepancy and consistency between the two methods were evaluated through paired chi-squared test and Kappa consistency test. Results: The vasopressor inflection point demonstrates promising utility in the assessment of short-term prognosis among patients with septic shock, exhibiting sensitivities of 76.4%, 88.2%, and 100%, specificities of 90.9%, 90.9%, and 86.4%, positive predictive values of 92.9%, 93.8%, and 91.9%, and negative predictive values of 71.4% on the 2nd, 3rd, and 4th day, respectively. Correspondingly, the Youden indices were calculated as 0.673, 0.791, and 0.864 on these respective days. Notably, all metrics at comparable intervals surpassed those of the PCT inflection point. Conclusion : The vasopressor inflection point presents as a robust prognostic tool for the short-term outcomes in patients with septic shock and exhibits superiority over PCT in prognostic assessment.

研究目的本研究旨在探讨血管加压拐点在脓毒性休克患者短期预后评估中的临床价值:本研究对 2021 年 1 月至 2023 年 3 月期间在医院重症医学科接受治疗的 56 例脓毒性休克患者进行了回顾性分析。根据预后结果将这些患者分为两组:生存组(34 人)和死亡组(22 人)。以开始使用血管加压疗法为参照点,确定每位患者的血管加压器拐点时间和降钙素原(PCT)拐点时间。血管加压剂拐点的定义是血管加压剂用量开始减少的时间,而 PCT 拐点则表示 PCT 水平开始下降的时间。两组患者在开始使用血管加压素治疗后第 2、3 和 4 天达到血管加压素和 PCT 拐点的发生率均以表格形式列出。两组患者在每个时间点的拐点比较采用费雪精确检验。此外,单变量预后评估还采用了逻辑回归分析。使用四表法评估了血管加压和 PCT 拐点的诊断性能。通过配对卡方检验和 Kappa 一致性检验评估了两种方法之间的差异和一致性:结果:血管加压拐点在评估脓毒性休克患者的短期预后方面表现出良好的实用性,在第2天、第3天和第4天的敏感性分别为76.4%、88.2%和100%,特异性分别为90.9%、90.9%和86.4%,阳性预测值分别为92.9%、93.8%和91.9%,阴性预测值为71.4%。相应地,这些天的尤登指数分别为 0.673、0.791 和 0.864。值得注意的是,所有指标在可比时间间隔内都超过了 PCT 拐点的指标:结论:血管加压器拐点是脓毒性休克患者短期预后的可靠工具,在预后评估方面优于 PCT。
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引用次数: 0
HYDROGEN-RICH SALINE UPREGULATES THE SIRT1/NF-ΚB SIGNALING PATHWAY AND REDUCES VASCULAR ENDOTHELIAL GLYCOCALYX SHEDDING IN SEPSIS-INDUCED ACUTE KIDNEY INJURY. 富氢盐水可上调 Sirt1/NF-κB 信号通路,并减少脓毒症诱导的急性肾损伤中血管内皮糖萼的脱落。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI: 10.1097/SHK.0000000000002404
Liheng Lin, Deliang Qiu, Fei Yang, Yu Xia, Siyuan Cai, Xiaojun Liao, Wanxin Deng, Changxue Wu

Abstract: Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex hemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. Rats model of sepsis was established by cecal ligation and puncture, and septic rats were intraperitoneal injected with HRS (10 mL/kg). We found that in sepsis, the degree of glycocalyx shedding was directly proportional to the severity of sepsis. The seven-day survival rate of rats in the HRS+CLP group (70%) was higher than that of the CLP group (30%). HRS improved acidosis and renal function and reduced the release of inflammatory factors (TNF, IL-1β, and IL-6). The endothelial glycocalyx of capillaries in the HRS+CLP group (115 nm) was observed to be significantly thicker than that in the CLP group (44 nm) and EX527 (67.2 nm) groups by electron microscopy, and fewer glycocalyx metabolites (SDC-1, HS, HA, and MMP9) were found in the blood. Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signaling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate.

摘要:脓毒症会导致不同器官的功能障碍,但其背后的病理生理机制是相似的,主要涉及复杂的血流动力学和细胞功能障碍。微循环功能障碍在败血症中的重要性日益明显,其中内皮功能障碍和糖萼降解起着重要作用。本研究旨在探讨富氢盐水(HRS)对脓毒症肾衰竭肾微循环的影响,以及 Sirt1 是否参与了 HRS 的肾保护作用。通过盲肠结扎建立脓毒症大鼠模型,给脓毒症大鼠腹腔注射富氢盐水(10 毫升/千克)。我们发现,在败血症中,糖萼脱落的程度与败血症的严重程度成正比。HRS+CLP组大鼠的七天存活率(70%)高于CLP组(30%)。HRS改善了酸中毒和肾功能,减少了炎症因子(TNF、IL-1β和IL-6)的释放。电镜观察发现,HRS + CLP 组毛细血管内皮糖萼(115 nm)明显比 CLP 组(44 nm)和 EX527 组(67.2 nm)厚,血液中发现的糖萼代谢物(SDC-1、HS、HA 和 MMP9)也较少。与CLP组相比,HRS减少了肾脏凋亡,上调了Sirt1的表达,并抑制了NF-κB/MMP9信号通路。此外,HRS 也不会损害败血症大鼠的免疫功能。总之,我们的研究结果表明,HRS 可以减轻炎症反应,抑制糖萼脱落,改善脓毒症肾损伤,提高存活率。
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引用次数: 0
EXPLORING THE PROGNOSTIC NECROPTOSIS-RELATED GENES AND UNDERLYING MECHANISM IN SEPSIS USING BIOINFORMATICS. 利用生物信息学探索脓毒症预后坏死相关基因及其内在机制。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-06-24 DOI: 10.1097/SHK.0000000000002414
Jie Liu, Lin Li, Shuyang He, Xin Zheng, Dan Zhu, Guangyao Kong, Ping Li

Abstract: Sepsis is a life-threatening disease due to a dysregulated host response to infection, with an unknown regulatory mechanism for prognostic necroptosis-related genes (NRGs). Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers ( ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 ) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses. Afterward, the ingenuity pathway analysis (IPA) highlighted enrichment in hepatic fibrosis pathways and BEX2 protein. Moreover, we examined their regulatory targets and functional links with necroptotic signaling molecules via miRDB, TargetScan, Network analyst, and GeneMANIA. The molecular regulatory network displayed that hsa-miR-5195-3p and hsa-miR-145-5p regulated ATRX, BACH2, and CD40, while YY1 showed strong connectivity, concurrently controlling LEF1, ATRX, BCL2, BACH2, and CD40. CD40 exhibited similar expression patterns to RIPK3 and MLKL, and LEF1 was functionally associated with MLKL. Additionally, DrugBank analysis identified paclitaxel, docetaxel, and rasagiline as potential BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulation in sepsis samples, contrasting CD40's increased expression in CTL samples. In conclusion, ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 may be critical regulatory targets of necroptosis in sepsis, providing a basis for further necroptosis-related studies in sepsis.

摘要:脓毒症是一种危及生命的疾病,其原因是宿主对感染的反应失调,而预后坏死相关基因(NRGs)的调控机制尚不清楚。利用GEO数据集GSE65682和GSE134347,我们通过Kaplan-Meier(KM)和Receiver Operating Characteristic(ROC)分析确定了6个具有生存和诊断意义的NRG生物标志物(ATRX、TSC1、CD40、BACH2、BCL2和LEF1)。随后,巧妙通路分析(IPA)显示了肝纤维化通路和 BEX2 蛋白的富集。此外,我们还通过 miRDB、TargetScan、Network analyst 和 GeneMANIA 研究了它们的调控靶点以及与坏死信号分子的功能联系。分子调控网络显示,hsa-miR-5195-3p和hsa-miR-145-5p调控ATRX、BACH2和CD40,而YY1显示出很强的连接性,同时调控LEF1、ATRX、BCL2、BACH2和CD40。CD40 表现出与 RIPK3 和 MLKL 相似的表达模式,而 LEF1 与 MLKL 有功能关联。此外,DrugBank 分析发现紫杉醇、多西他赛和拉沙吉林是潜在的 BCL2 靶向败血症治疗药物。最后,实时定量 PCR 证实 ATRX、TSC1 和 LEF1 在败血症样本中下调,而 CD40 在 CTL 样本中表达增加。总之,ATRX、TSC1、CD40、BACH2、BCL2 和 LEF1 可能是脓毒症中坏死的关键调控靶点,为进一步研究脓毒症中的坏死相关问题提供了依据。
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引用次数: 0
SHOCK SYNOPSIS SEPTEMBER 2024. 冲击概要 2024 年 9 月。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 DOI: 10.1097/SHK.0000000000002469
Maria Fernanda Hutter, Stephanie Wojtowicz-Piotrowski, Marc G Jeschke
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引用次数: 0
HISTOLOGICAL COMPARISON OF REPEATED MILD WEIGHT DROP AND LATERAL FLUID PERCUSSION INJURY MODELS OF TRAUMATIC BRAIN INJURY IN FEMALE AND MALE RATS. 雌性和雄性大鼠创伤性脑损伤(TBI)模型中反复轻度体重下降和侧液叩击伤的组织学比较。
IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2024-09-01 Epub Date: 2024-05-23 DOI: 10.1097/SHK.0000000000002395
Sydney M Vita, Shealan C Cruise, Nicholas W Gilpin, Patricia E Molina

Abstract: In preclinical traumatic brain injury (TBI) research, the animal model should be selected based on the research question and outcome measures of interest. Direct side-by-side comparisons of different injury models are essential for informing such decisions. Here, we used immunohistochemistry to compare the outcomes from two common models of TBI, lateral fluid percussion (LFP) and repeated mild weight drop (rmWD) in adult female and male Wistar rats. Specifically, we measured the effects of LFP and rmWD on markers of cerebrovascular and tight junction disruption, neuroinflammation, mature neurons, and perineuronal nets in the cortical site of injury, cortex adjacent to injury, dentate gyrus, and the CA 2/3 area of the hippocampus. Animals were randomized into the LFP or rmWD group. On day 1, the LFP group received a craniotomy, and on day 4, injury (or sham procedure; randomly assigned). The rmWD animals underwent either injury or isoflurane only (randomly assigned) on each of those 4 days. Seven days after injury, brains were harvested for analysis. Overall, our observations revealed that the most significant disruptions were evident in response to LFP, followed by craniotomy only, whereas rmWD animals showed the least residual changes compared with isoflurane-only controls, supporting consideration of rmWD as a mild injury. LFP led to longer-lasting disruptions, perhaps more representative of moderate TBI. We also report that craniotomy and LFP produced greater disruptions in females relative to males. These findings will assist the field in the selection of animal models based on target severity of postinjury outcomes and support the inclusion of both sexes and appropriate control groups.

摘要:在临床前创伤性脑损伤(TBI)研究中,应根据研究问题和感兴趣的结果指标选择动物模型。不同损伤模型的直接并排比较对于做出此类决定至关重要。在这里,我们使用免疫组化技术比较了两种常见的 TBI 模型的结果,即成年雌性和雄性 Wistar 大鼠的侧向脑液叩击(LFP)和反复轻度体重下降(rmWD)。具体而言,我们测量了 LFP 和 rmWD 对脑血管和紧密连接破坏、神经炎症、成熟神经元以及损伤部位皮质、损伤邻近皮质、齿状回和海马 CA2/3 区神经元周围网的标记物的影响。动物被随机分为 LFP 组和 rmWD 组。第 1 天,LFP 组接受开颅手术,第 4 天接受损伤(或假手术;随机分配)。rmWD动物在这4天中的每一天都接受了损伤或仅异氟醚治疗(随机分配)。损伤七天后,收获大脑进行分析。总体而言,我们的观察结果表明,LFP造成的破坏最为明显,其次是单纯开颅手术,而与单纯异氟醚对照组相比,rmWD动物表现出的残余变化最小,这支持了将rmWD视为轻度损伤的观点。LFP 会导致更持久的破坏,也许更能代表中度创伤性脑损伤。我们还报告了开颅手术和 LFP 对女性造成的损伤大于男性。这些发现将有助于该领域根据伤后结果的目标严重程度选择动物模型,并支持将两性和适当的对照组纳入其中。
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SHOCK
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