Direct hemoperfusion with a polymyxin B-immobilized fiber column eliminates neutrophils and improves pulmonary oxygenation--a comparison of two cases with acute exacerbation of idiopathic pulmonary fibrosis]

Idiopathic pulmonary fibrosis (IPF) is characterized by radiographically evident interstitial infiltrates predominantly affecting the lung bases and by progressive dyspnea and worsening pulmonary function. Acute exacerbation of IPF is recognized widely as an accelerated phase occurring suddenly in the course of IPF, which leads to a catastrophic outcome. No treatment has proven to be effective so far. We describe two cases of acute exacerbation of IPF which were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX) after steroid pulse therapy. One patient died on the 21st day after direct hemoperfusion and the other is alive at present. The survivor showed significant improvement of pulmonary oxygenation correlating with a decrease in the neutrophil count, SP-D and KL-6 after direct hemoperfusion with PMX. On the other hand, the non-survivor showed no improvement of pulmonary oxygenation, SP-D and KL-6 despite a decrease in neutrophil count comparable with that of the survivor. Neutrophil count which decreased temporarily after direct hemoperfusion with PMX soon convert to increase in the non-survivor, which is a characteristic difference between two. We reached the conclusions that (1) direct hemoperfusion with PMX absorbs neutrophils and this mechanism is effective to improve pulmonary oxygenation, (2) sometimes neutrophil absorption is not enough to control pulmonary inflammation in patients with acute exacerbation of IPF.     

Two cases of acute exacerbation of interstitial pneumonia treated with polymyxin B-immobilized fiber column hemoperfusion treatment

The effect of polymixin B-immobilized fiber column (PMX) hemoperfusion treatment for acute exacerbation of interstitial pneumonia (IP) has been reported. Here, we report 2 cases of acute exacerbation of IP successfully treated with PMX hemoperfusion. One is a 55-year-old woman who was diagnosed as microscopic polyangiitis (MPA) with IP. The other is a 58-year-old man, diagnosed as having idiopathic pulmonary fibrosis. Both cases were treated with PMX hemoperfusion and other therapies. One died on day 44 and the other is still alive. The PMX hemoperfusion treatment decreased the serum levels of several cytokines and activated neutrophil percentage in bronchoalveolar lavage fluid.     

血清高速泳动族蛋白B1水平与糖尿病患者急性冠状动脉综合征关系的研究

目的:探讨血清高速泳动族蛋白B1(HMGB1)水平与2型糖尿病(DM)患者急性冠状动脉综合征(ACS)发生的关系。方法:选取218例ACS患者,其中不稳定型心绞痛(UAP)95例,急性心肌梗死(AMI)123例。健康体检者234名作为对照;采用酶联免疫吸附法(ELISA)检测血清HMGB1、高敏C反应蛋白(hsCRP)和肿瘤坏死因子α(TNF-α)的水平。并对血清HMGB1水平与TNF-α、hsCRP和血糖水平进行相关性分析。结果:与对照组相比,AMI组、UAP组血清HMGB1[(12.70±6.72)μg/L、(7.68±3.63)μg/L比(3.83±1.72)μg/L,P<0.01]水平均明显升高。在对照组、UAP组和AMI组的亚组中,DM患者血清HMGB1水平均高于非DM者(均P<0.05)。血清HMGB1水平与hsCRP,TNF-α、血糖水平均呈正相关(均P<0.05)。结论:ACS患者HMGB1水平显著升高,且合并DM的ACS患者HMGB1水平高于非DM患者,表明HMGB1有可能参与ACS的发生、发展过程,且在糖尿病时对ACS的病理生理过程影响更大。     

急性胰腺炎患者血清高迁移率族蛋白B1水平的变化及意义

目的 检测急性胰腺炎(AP)患者血清高迁移率族蛋白B1(high mobility group box-1protein,HMGB1)的水平变化,探讨HMGB1在AP发生发展中的作用.方法 以33例重症急性胰腺炎(SAP)、38例轻症急性胰腺炎(MAP)以及28例健康体检者为研究对象,在发病72 h内收集血标本,采用ELISA法检测血清HMGB1水平,分析其与患者性别,年龄,病因,发病时间,Ranson评分,Balthazar CT评分,血清C-反应蛋白(CRP)、乳酸脱氢酶(LDH)、肌酐、总胆红素等指标,局部和(或)全身并发症的关系.结果 健康对照组、MAP组、SAP组血清HMGB1水平分别为(1.82±0.64)μg/L、(6.13±5.80)μg/L、(11.48±6.94)μg/L,SAP组显著高于MAP组,MAP组又显著高于健康对照组(P值均<0.05).在发病24 h内患者血清HMGB1水平开始增高,48 h内达峰值,后开始下降,至72 h仍维持在高于正常值水平.血清HMGB1水平与患者性别、年龄、病因无关;与Ranson评分、Balthazar CT评分、CRP、LDH、血肌酐值呈正相关关系.有局部和(或)全身并发症患者血清HMGB1水平高于无并发症者,但差异不显著.结论 HMGB1是一种晚期炎症介质,与AP病情的严重程度相关,并可能参与了SAP时肾功能不全的发生.     

Clinical analysis of the acute exacerbation in patients with idiopathic pulmonary fibrosis]

The clinical course of idiopathic pulmonary fibrosis (IPF) is chronic, but some patients with IPF have phases of accelerated deterioration superimposed on the chronic course of their illness, which is referred to as acute exacerbation (Aex) of IPF. To evaluate the clinical feature of Aex of IPF, we analyzed clinical findings of the 112 patients with IPF admitted to our hospital from 1994 to 2004. Of the 112 patients 56 with IPF died during the observation period due to Aex (42.9%), lung cancer (21.4%), chronic respiratory failure (14.3%), and lower respiratory infections (8.9%). Aex of IPF was seen 28 of 112 patients with IPF (25.0%) and 24 patients (85.7%) died with Aex. The median survival time (MST) after the onset of Aex was 0.9 months. The 5-yr survival rate of all patients with IPF was 38.3% and the MST was 3.1 yrs after diagnosis. On the other hand, the 5-yr survival rate and MST was 10.7% and 0.6 yrs in patients with Aex of IPF. We treated the patients with Aex with methylprednisolone pulse therapy in combination with cyclophosphamide or cyclosporine A, which did not significantly improve the outcome of Aex. In conclusion, there is little evidence that currently accepted treatments are effective in Aex of IPF, and further studies are needed to clarify the pathogenesis and contribute to the prevention of Aex.     

Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction

BackgroundHigh mobility group box-1 (HMGB1) protein, a critical mediator of inflammatory processes, is a novel predictor of adverse post-infarction clinical outcomes, being involved in the healing process after MI. Heart rate recovery (HRR), a marker of autonomic function defined as the fall in heart rate during the first minute after exercise, is a powerful predictor of mortality in post-infarction patients. The present study was designed to test the hypothesis that HMGB1 is associated with autonomic dysfunction in post-infarction patients.MethodsSixty-seven consecutive patients (mean age 59.3 years, 84% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise and HMGB1 assay.ResultsHMGB1 levels were inversely correlated with peak oxygen consumption (VO_2peak) (r = ?0.449, P < 0.001), with left ventricular ejection fraction (LVEF) (r = ?0.360, P = 0.003), and with HRR (r = ?0.387, P < 0.001). In a linear regression analysis adjusted for multiple confounders, we found a significant inverse association between HMGB1 levels and HRR independent of age, gender, body mass index, VO_2peak, slope of increase in ventilation over carbon dioxide output (VE/VCO_2slope), and presence of diabetes (β = ?0.377, P = 0.034).ConclusionsThis study provided the first evidence for a significant association between increased HMGB1 levels and autonomic dysfunction expressed by post-exercise slower HRR in post-infarction patients. The prognostic implication of such association needs to be explored as well as whether HMGB1 could represent a valid marker for risk stratification either during the acute phase or long-term after MI.     

血清高迁移率族蛋白B1在急性化脓性胆管炎发生中的作用及意义研究

目的 检测急性化脓性胆管炎(ASC)患者血清高迁移率族蛋白B1(HMGB1)的水平变化,探讨HMGB1在疾病发生中的作用及意义.方法 以30例重症急性胆管炎、42例轻症急性胆管炎以及50例健康体检者为研究对象,在起病72 h内收集血标本,采用酶联免疫吸附方法(ELISA)检测血清HMGB1水平,用实时荧光定量PCR检测血清HMGB1 mRNA的表达,分析其与病情轻重的关系以及HMGB1与其他生化指标的相关性.结果 健康对照组、轻症组、重症组血清HMGB1水平分别为(1.82 ±0.64) μg/L,(10.46±3.75) μg/L、(18.89 ±6.86) μg/L,轻症组显著高于健康对照组,重症组显著高于轻症组(P＜0.05);胆管炎患者HMGB1 mRNA表达明显增高,重症组高于轻症组(P＜0.05).胆汁和(或)血培养阳性的患者血清HMGB1水平高于培养阴性者;重症急性胆管炎行急诊鼻胆管引流术后血清HMGB1水平较术前明显降低(P＜0.05).血清HMGB1水平与白细胞、C反应蛋白、总胆红素、直接胆红素、碱性磷酸酶呈正相关关系;通过Logistic回归分析血清HMGB1水平与疾病严重程度相关.结论 血清HMGB1水平在急性胆管炎时显著升高,重症急性化脓性胆管炎患者明显高于轻症患者,并与脓毒血症相关.鼻胆管引流可明显降低其血清水平,血清HMGB1水平对疾病严重程度有一定预测价值.     

Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure

BackgroundPolymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy.MethodsPatients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy.ResultsFourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P < 0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P < 0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P < 0.01 and P < 0.05), these levels did not change after treatment.ConclusionsPMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.     

Effectiveness of polymyxin B-direct hemoperfusion (PMX-DHP) therapy using a polymyxin B-immobilized fiber column in patients with post-esophagectomy sepsis

Background

Post-esophagectomy complications have an extremely poor prognosis. Recently, polymyxin B-direct hemoperfusion (PMX-DHP) therapy using a polymyxin B-immobilized fiber column was reported to be beneficial in gram-negative and/or gram-positive bacterial sepsis. The present retrospective study investigated the effectiveness and safety of PMX-DHP therapy in severe sepsis or septic shock after esophagectomy.

Methods

Fifteen severe sepsis or septic shock patients were included. Seven (four, pneumonia; two, anastomotic leakage; and one, reconstructed colon necrosis) patients received 2–5 h of PMX-DHP therapy (PMX-DHP therapy group), whereas 8 (three, pneumonia; three, anastomotic leakage; and two, gastric tube necrosis) received conventional therapy (control group).

Results

Length of stay in the intensive care unit (ICU) was significantly shorter in the PMX-DHP therapy group than in the conventional therapy group (P = 0.040). In the comparison of pre- and post-PMX-DHP therapy groups, the total Sequential Organ Failure Assessment (SOFA) score, respiratory system score, and P/F ratio improved (P = 0.0027, P = 0.025, and P = 0.0087, respectively) in the post-PMX-DHP therapy group. In the comparison of conventional and PMX-DHP therapy groups, the variations in the total SOFA score, respiratory system score, and P/F ratio improved (P = 0.019, P = 0.0063, and P = 0.0015, respectively) in the PMX-DHP therapy group. Moreover, the respiratory system score was lower (P = 0.0062) in the PMX-DHP therapy group at the time of discharge from the ICU. No adverse effects were observed during the course of PMX-DHP therapy.

Conclusions

PMX-DHP therapy was safe and effective in improving respiratory and general conditions of patients with severe sepsis and septic shock after esophagectomy and decreased the length of stay in the ICU.     

高迁移率族蛋白-1在实验性急性肝衰竭中的作用

高迁移率族蛋白-1（HMGB1）是广泛存在于真核细胞内高度保守的非组蛋白染色体蛋白。研究表明HMGB1可由巨噬细胞等主动分泌或由坏死细胞被动释放到细胞外基质内。作为晚期炎症因子参与脓毒症、关节炎等病理生理反应过程，并认为它有可能是肿瘤坏死因子α（TNFα）、白细胞介素-1（IL-1）的下游因子。急性肝衰竭（AHF）往往导致严重的肠源性内毒素血症，并介导TNFα等细胞因子释放。但HMGB1在急性肝衰竭中是否参与其病理生理过程，目前尚不清楚。本实验通过D-氨基半乳糖和内毒素诱导的大鼠急性肝损伤模型，探讨了HMGB1在AHF中的变化和意义。     

特发性肺纤维化急性加重的最新研究进展

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种病因不明的慢性进展性纤维化型间质性肺炎,组织学表现为普通型间质性肺炎.IPF通常是缓慢进展,但部分IPF患者可以出现急剧、原因不明的临床明显恶化,称之为IPF急性加重.IPF急性加重难以预测、病死率高、缺乏有效的治疗措施.本文就近年来IPF急性加重的发病率、危险因素、病理生理、发病机制、诊断和治疗等方面的研究进展进行综述.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

INTRODUCTIONIn severe acute pancreatitis (SAP), multiple organ dysfunction syndrome (MODS) in the early phase[1,2] and complications of infection (infected pancreatic necrosis and sepsis) in the late phase are contributors to high mortality in SAP[3,4]. M…     

降钙素原在鉴别特发性肺纤维化急性加重和合并肺部细菌感染中的临床价值

目的：评价降钙素原(PCT)在特发性肺纤维化急性加重及特发性肺纤维化合并肺部细菌感染中的鉴别诊断作用。方法共入选15例特发性肺纤维化急性加重和15例特发性肺纤维化无急性加重伴肺部细菌感染患者。入选第1天、第7天测定各项炎症指标,采用免疫比浊法检测 C 反应蛋白(CRP),同时采用双抗体夹心免疫荧光法测定血 PCT 浓度并进行比较,记录患者白细胞和中性粒细胞计数。结果特发性肺纤维化伴肺部感染组 PCT 浓度明显高于特发性肺纤维化急性加重组[(1.89±0.31)μg/L vs (0.72±0.40)μg/L,P =0.001]。特发性肺纤维化伴肺部感染组 CRP 浓度为(75.13±33.40)mg/L,特发性肺纤维化急性加重组浓度为(53.61±23.52)mg/L,两组比较差异无统计学意义(P >0.05)。结论①PCT 鉴别特发性肺纤维化急性加重和特发性肺纤维化合并肺部感染的敏感性较传统炎症指标高。②PCT 在特发性肺纤维化急性加重患者中并无明显升高。③PCT 诊断特发性肺纤维化合并肺部感染的敏感性、特异性、诊断正确率均较 CRP 等传统炎症指标高。