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Combined Age with Mean Decrease Rates of Total Bilirubin and MELD Score as a Novel and Simple Clinical Predictor on 90-Day Transplant-Free Mortality in Adult Patients with Acute Liver Failure Undergoing Plasma Exchange: A Single-Center Retrospective Study 结合年龄、总胆红素平均下降率和MELD评分作为急性肝衰竭患者血浆置换术后90天无移植死亡率的一种新颖简单的临床预测指标:一项单中心回顾性研究
4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-11-07 DOI: 10.1155/2023/6115499
Di Jin, Kai Kang, Bing-zhu Yan, Jian-nan Zhang, Jun-bo Zheng, Zhi-hui Wang, Di Wu, Yu-jia Tang, Xin-tong Wang, Qi-qi Lai, Yang Cao, Hong-liang Wang, Yang Gao
Background. Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods. This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results. A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first
背景。急性肝衰竭(ALF),以前被称为暴发性肝衰竭,由于药物滥用、病毒感染、代谢损伤和自身免疫原因的不断增加,已成为重症监护病房(ICU)常见的、快速进展的、危及生命的灾难性肝病。目前,血浆置换(PE)是ICU临床治疗ALF的主要有效替代治疗方法,大容量血浆置换(HVP)已被美国血液分离学会(ASFA)指南列为ALF治疗的一级推荐。然而,对于成年ALF患者行肺移植后90天无移植死亡率的临床预测,现有模型均不能提供满意的表现。我们的研究旨在确定一种新的、简单的临床预测因子,预测成年ALF患者接受肺移植后90天无移植死亡率。方法。本回顾性研究纳入了2017年1月至2020年12月在哈尔滨医科大学第二附属医院内科ICU (MICU)接受肺栓塞治疗的成年ALF患者。收集基线和临床资料,并在PE前在ICU入院时计算,包括性别、年龄、身高、体重、体重指数(BMI)、病因、总胆红素、直接胆红素、间接胆红素、凝血酶原活性、终末期肝病模型(MELD)评分、顺序器官衰竭评估(SOFA)评分。根据医疗记录和电话随访,将纳入的成年ALF患者在出院时和90天内分为生存组和死亡组。每次PE后,根据临床参数计算总胆红素下降率、MELD评分和凝血酶原活性升高率。在临床实践中,不同患者的PE时间不同,因此得出总胆红素和MELD评分的平均下降率和凝血酶原活性的平均升高率,以便进一步统计分析。结果。我们的回顾性研究共纳入73例接受204次肺叶移植的成年ALF患者,其出院和90天无移植死亡率分别为6.85%(5/73)和31.51%(23/73)。所有死亡均可归因于alf引起的严重和危及生命的并发症,甚至多器官功能障碍综合征(MODS)。纳入的成年ALF患者以男性为主(76.71%,56/73),中位年龄48.77岁。各种肝炎病毒感染、病因不明、自身免疫性肝病、药物性肝损伤和急性胰腺炎(AP)分别占成年ALF患者病因的75.34%、12.33%、6.85%、4.11%和1.37%。单因素分析显示,死亡组和生存组在年龄、总胆红素和MELD评分平均下降率、凝血酶原活性平均升高率、总胆红素和MELD评分下降率、第一次PE后凝血酶原活性升高率等方面存在显著差异。多因素分析显示,年龄、总胆红素平均下降率和MELD评分与成年ALF患者行肺移植术后90天无移植死亡率密切相关。总胆红素和MELD评分每增加1个单位,90天无移植死亡率分别为原值的1.081倍、0.908倍和0.893倍。受试者年龄、总胆红素平均下降率、MELD评分及三者之和的ROC曲线下面积分别为0.689、0.225、0.123、0.912。年龄、总胆红素平均下降率、MELD评分及三者联合的临界值分别为61.50、3.12、1.21、0.33。结合年龄、总胆红素平均下降率和MELD评分预测成年ALF行PE患者90天无移植死亡率的特异性和敏感性分别为87%和14%。结论。结合年龄与总胆红素平均下降率及MELD评分作为一种新颖、简便的临床预测指标,能够准确预测成年ALF行PE患者90天无移植死亡率,值得在临床实践中推广应用,特别是在鉴别潜在移植候选者方面。
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引用次数: 0
Pumilio RNA-Binding Family Member 1 Plays a Promoting Role on Pancreatic Cancer Angiogenesis. Pumilio rna结合家族成员1在胰腺癌血管生成中的促进作用
IF 2.6 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2022-12-14 eCollection Date: 2022-01-01 DOI: 10.1155/2022/9202531
Haisu Dai, Yan Jiang, Zhipeng Liu, Xingxing Su, Yishi Yang, Zhiyu Chen

Our previous studies showed that Pumilio RNA-binding family member 1 (PUM1) gene is abnormally expressed in pancreatic cancer (PC) tissues, and its knockdown suppresses the growth and metastasis of PC cells. Here, we aimed to further investigate its role in angiogenesis. Immunohistochemical assays were carried out to analyze CD31 and PUM1 expression levels in PC tissues and in subcutaneous xenograft tumors. CD31 levels in PC tissues are expressed as microvessel density (MVD). MVD value was positively correlated with PUM1 protein expression. PUM1 was successfully overexpressed or silenced in the PC cell lines. The proliferation, migration, invasion, and tube formation ability of HUVECs were enhanced when cocultured with PC cells overexpressing PUM1. PUM1 overexpression increased extracellular and intracellular VEGFA protein levels in PC cells. Moreover, angiogenesis-related signaling in HUVECs was activated when HUVECs were cocultured with PC cells overexpressing PUM1. Nevertheless, PC cells silenced with PUM1 had the opposite effect. Moreover, subcutaneous xenograft tumors overexpressing PUM1 have the higher expression level of CD31, while subcutaneous xenograft tumors silencing PUM1 have the lower expression level of CD31. In conclusion, PUM1 in PC cells may play a promoting role in PC angiogenesis. PUM1 may be a new regulator of angiogenesis in PC cells.

我们前期研究发现Pumilio rna结合家族成员1 (PUM1)基因在胰腺癌(PC)组织中异常表达,其敲低可抑制PC细胞的生长和转移。在此,我们旨在进一步研究其在血管生成中的作用。免疫组化分析CD31和PUM1在PC组织和皮下异种移植肿瘤中的表达水平。PC组织中的CD31水平以微血管密度(MVD)表达。MVD值与PUM1蛋白表达呈正相关。PUM1在PC细胞系中成功过表达或沉默。与过表达PUM1的PC细胞共培养后,HUVECs的增殖、迁移、侵袭和成管能力增强。在PC细胞中,PUM1过表达增加细胞外和细胞内VEGFA蛋白水平。此外,当HUVECs与过表达PUM1的PC细胞共培养时,HUVECs中血管生成相关的信号被激活。然而,用PUM1沉默的PC细胞却有相反的效果。此外,过表达PUM1的皮下异种移植物肿瘤CD31的表达水平较高,而沉默PUM1的皮下异种移植物肿瘤CD31的表达水平较低。由此可见,PC细胞中的PUM1可能在PC血管生成中起促进作用。PUM1可能是PC细胞血管生成的新调控因子。
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引用次数: 0
Lactate and Bilirubin Index: A New Indicator to Predict Critically Ill Cirrhotic Patients’ Prognosis 乳酸和胆红素指数:预测危重肝硬化患者预后的新指标
IF 2.7 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2021-02-11 DOI: 10.1155/2021/6624177
Xiao-Fu Chen, Yuan Zhao, Wei-Zhen Chen, Xin Shao, Zhiming Huang
Objectives. We aimed to perform external validation of the prognostic value of the lactate and bilirubin (LB) index, a new indicator, and compare the ability of the LB index and other scoring systems to predict both short- and long-term mortality in critically ill cirrhotic patients. Materials and Methods. A number of 479 cirrhotic patients admitted into ICU were included in our research. We measured prognostic scores in the first 24 hours including LB index, Child–Pugh, SOFA, CLIF-SOFA, and MELD scores. The LB index was calculated as follows: ln [1000 × lactate (mmol/L) × bilirubin (µmol/L)]/2. The primary outcomes were 28-day and 3-year all-cause mortality. Multivariate logistic regression analyses were used to investigate the independent association between the LB index and the mortality in critically ill cirrhotic patients. The area under the receiver operating characteristic curve was used to assess the prediction accuracy of short- and long-term mortality of the clinical score. Calibration of the score was evaluated by Hosmer–Lemeshow goodness-of-fit test for significance. Results. Multivariate logistic regression analysis identified that the LB index (odds ratio: 5.487, 95% confidence interval: 3.542–8.501, P < 0.001 ) was the strongest predictor for 28-day mortality. The LB index gave the highest area under the curve (0.791, 95% confidence interval: 0.747–0.836) in predicting 28-day mortality. For predicting 3-year mortality, the model for end-stage liver disease (MELD) score showed better discrimination ability with an area under the curve of 0.726 (95% confidence interval: 0.680–0.771). The risk of mortality significantly increased when the clinical scores were ≥ the optimal cutoff values. Conclusions. The LB index, a simple prognostic indicator, performs well in predicting critically ill cirrhotic patients’ short-term prognosis, while, for long-term prognosis, the MELD score is more appropriate.
目标。我们旨在对新指标乳酸和胆红素(LB)指数的预后价值进行外部验证,并比较LB指数和其他评分系统预测危重肝硬化患者短期和长期死亡率的能力。材料和方法。我们的研究包括479名入住ICU的肝硬化患者。我们测量了前24小时的预后评分,包括LB指数、Child-Pugh、SOFA、CLIF-SOFA和MELD评分。LB指数计算如下:ln[1000 × 乳酸(mmol/L) × 胆红素(µmol/L)]/2。主要转归为28天和3年全因死亡率。多变量逻辑回归分析用于研究LB指数与危重肝硬化患者死亡率之间的独立相关性。受试者操作特征曲线下面积用于评估临床评分对短期和长期死亡率的预测准确性。评分的校准通过Hosmer–Lemeshow拟合优度检验进行显著性评估。后果多元逻辑回归分析表明,LB指数(比值比:5.487,95%置信区间:3.542-8.501,P<0.001)是28天死亡率的最强预测因子。LB指数在预测28天死亡率方面给出了最高的曲线下面积(0.791,95%置信区间:0.747-0.836)。对于预测3年死亡率,终末期肝病(MELD)评分模型显示出更好的辨别能力,曲线下面积为0.726(95%置信区间:0.680–0.771)。当临床评分≥最佳临界值时,死亡率风险显著增加。结论。LB指数是一个简单的预后指标,在预测危重肝硬化患者的短期预后方面表现良好,而对于长期预后,MELD评分更合适。
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引用次数: 2
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Canadian Journal of Gastroenterology and Hepatology
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