Apheresis in patients with sepsis: A multicenter retrospective study

Background and objectivesTo consider the effectiveness of apheresis, which is a supportive treatment method, in sepsis.Materials and methodsA hundred and eleven adults with sepsis or septic shock were included in this retrospective study. The demographic characteristics of the patients, the focus and source of infection causing sepsis or septic shock, characteristics of the pathogen, Acute Physiological and Chronic Health Assessment (APACHE) II score, routine laboratory values, which apheresis method was used, the characteristics of the replacement fluids used during the apheresis procedure, the number of apheresis procedures, complications related to the apheresis procedure, the follow-up time after the procedure, and mortality were recorded. The primary outcome was 28-day mortality.ResultsSixty-nine (62.2 %) of the patients were male. The mean age of the patients was 47.7 ± 18.6 years. The most common source of sepsis was hospital-acquired (79.3 %), the most common pathogen causing sepsis was gram-negative bacteria (41.4 %), and the most common infection site was the respiratory tract (58.7 %). The median APACHE II score was 19 (13−24). 92 (82.9 %) of the patients had septic shock. Theropeutic plasma exchange (TPE) was performed in 11.7 % of the patients and immunoabsorbtion IA in 88.3 %. The median number of sessions was 3 (3−5). No procedure-related fatal complication was observed in the study. While 28-day mortality was 61.3 % in all patients, when the mortality according to the apheresis procedures was examined, it was 11.3 % and 88.2 % in the patients who underwent TPE and IA, respectively. The most common cause of mortality was multiorgan failure.ConclusionsApheresis in sepsis can be considered as a salvage treatment. The indication for apheresis in sepsis is still at the level of patient-based individualized decision in line with the studies done so far, including our study. However, there is a need for a multicenter randomized controlled study with a large number of patients in order to give positive or negative recommendations about its effectiveness.     

Platelet and soluble CD40L in meningococcal sepsis

Objective To determine the influence of meningococcal sepsis on levels of platelet derived CD40L and on endothelial CD40 expression.Design and setting Prospective observational study in two tertiary paediatric intensive care units.Patients and participants 63 children with meningococcal sepsis and 10 age-matched controls.Measurements and results (a) sCD40L ELISA of plasma from patients with meningococcal sepsis (n = 49) and age matched controls (n = 10). This demonstrated higher sCD40L levels in patients (median 0.29 ng/ml, IQR 0.2–0.41) than controls (0.09 ng/ml, 0.08–0.12). However, there was no relationship between plasma sCD40L level and platelet count or disease severity. (b) Flow cytometry of fresh blood from patients with meningococcal sepsis (n = 11) and age-matched controls (n = 10) for membrane bound CD40L and CD62P on circulating platelets. This demonstrated low levels of CD40L and CD62P in patients and controls. CD40L⁺ platelets were 3.5% (3.0–4.8) in patients and 4.9% (3.5–4.3) in controls. CD62P⁺ platelets were 10.7% (6.4–12.8) in patients and 7.9% (5.9–13.0) in controls. (c) Immunohistochemistry of skin biopsy specimens from six patients, staining for endothelial CD40 expression at sites of microthrombus formation, which demonstrated preserved CD40 expression in vascular endothelium at sites of microthrombus formation.Conclusions The elevated sCD40L level in meningococcal sepsis implies release of sCD40L from platelets. However, there was no relationship between plasma sCD40L level and the degree of thrombocytopenia or disease severity. Furthermore, platelet surface bound CD40L was similar in controls and patients. Thus, further investigation is needed to determine whether platelet CD40L contributes to inflammation and thrombosis in MCS.D.P.I. and S.N.F. were supported by the Medical Research Council, UK     

Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: A prospective study

Introduction

Thrombocytopenia is prevalent in patients with severe sepsis, and it is associated with mortalities. Effectively adjunctive treatment might be needed to reverse low platelet counts (PCs). With a growing understanding of thrombocytopenia, recombinant human thrombopoietin (rhTPO) is considered a promising beneficial drug. The present study was dedicated to evaluate the efficiency of rhTPO in improving PCs in patients with severe sepsis.

Materials and Methods

We performed a prospective study in patients with severe sepsis between March 2012 and February 2013. All enrolled patients were divided into rhTPO group and control group, depending on whether rhTPO was prescribed or not. Platelet counts and other parameters were measured initially and in the following 15 days.

Results

Totally, 72 patients (38 in the rhTPO group and 34 in the control group) were included. All enrolled parameters exhibited no significant differences between groups at the baseline. Platelet counts showed a significant increase over time in both groups. Faster improvement of PCs in the rhTPO group was observed with a significant difference. Less platelet transfusion occurred in patients who received rhTPO in our study, as well. No drug-related adverse event during the rhTPO therapy was recorded.

Conclusion

The use of rhTPO in combination with conventional medical therapies could significantly improve the PCs in patients with severe sepsis and thrombocytopenia and effectively reduce the platelet transfusion possibility.     

脓毒症患者血小板膜糖蛋白的表达及其临床意义

目的 研究脓毒症患者血小板膜糖蛋白表达的变化,探讨其与病情严重程度及预后的关系.方法 将80例脓毒症患者根据病情严重程度分为一般脓毒症组和严重脓毒症组,根据预后情况分为生存组和死亡组.在诊断脓毒症的24h内行急性生理与慢性健康评分Ⅱ(APACHE Ⅱ)、全身性感染性器官功能衰竭评分(SOFA),在诊断脓毒症后第1、3、7天采用流式细胞仪检测血小板膜糖蛋白CD62P、CD63的表达.结果 脓毒症组血小板膜糖蛋白CD62P、CD63表达显著高于正常对照组(P<0.01),严重脓毒症组在第1、3、7天CD62P、CD63表达均显著高于一般脓毒症组(P<0.01).一般脓毒症组CD62P、CD63表达在第3天达高峰,第7天逐渐下降.严重脓毒症组CD62P、CD63表达在第7天仍保持高水平,且在各个时点均显著高于一般脓毒症组.生存组CD62P、CD63表达在第3天达高峰,第7天逐渐下降.死亡组CD62P、CD63表达在伤后第7天持续保持高水平,且在各个时点均显著高于生存组(P<0.01).相关性分析显示,CD62P、CIM3与APACHE Ⅱ评分、SOFA评分呈显著正相关(P<0.01).结论 脓毒症患者血小板处于高激活状态,容易发生多器官功能障碍,血小板激活指标可判断其严重程度和预后.     

脓毒症患者血小板计数及体积变化趋势的临床意义

目的:观察脓毒症患者血小板计数(PC)、血小板体积(MPV)变化趋势,探讨两者相关性及其临床意义。方法:应用HEMACELLPlus全自动二十二项五类血细胞分析仪,通过阻抗法检测80例脓毒症患者发病后1、3、7、10d的PC、MPV,并回顾性将脓毒症患者分为死亡组和存活组,分析其PC、MPV变化趋势,并进行两者相关性分析。结果:(1)入院时存活组和死亡组患者PC均低于正常生理范围,死亡组PC在各时相点均低于存活组(1、3dP>0.05,7、10dP<0.01)。存活组PC在入ICU第3天明显下降(P<0.01),继之于第7、10天持续上升(均P<0.01)。死亡组PC则呈持续下降趋势(均P<0.01)。(2)入院时存活组和死亡组患者MPV均基本上处于正常生理范围,但是死亡组MPV值比存活组患者高(均P<0.05),病程中存活组患者MPV呈进行性下降趋势,而死亡组患者MPV呈进行性上升趋势(均P<0.01)。(3)PC与MPV呈显著负相关。结论:PC、MPV的变化可能成为脓毒症患者血小板生成和活性紊乱以及骨髓反应的间接标志,常规检测脓毒症患者的PC、MPV变化趋势,尤其早期检测MPV,可能成为评价脓毒症病情及骨髓反应情况的一种快速、可信的手段。     

Ionized calcium level predicts in-hospital mortality of severe sepsis patients: A retrospective cross-sectional study

Objective: To evaluate the effect of serum ionized calcium levels on the prognosis of severe sepsis patients. Methods: This retrospective cross-sectional study included sepsis patients who were hospitalized in an intensive care unit between January 2011 and December 2014. The demographic and baseline data of the patients who died and survived were compared. The cutoff value of ionized calcium for in-hospital mortality was determined by the receiver operating characteristics curve (ROC). In-hospital mortalities and the survival rates were compared between patients with different ionized calcium levels. Besides, the risk factor of in-hospital mortality was determined. Results: This study included 145 patients with 113 patients who died in the hospital. The patients who died had significantly lower ionized calcium levels (U=2.25, P=0.034). A cut-off value of 0.93 mmol/L of ionized calcium was determined by the ROC curve. The patients with ionized calcium>0.93 mmol/L showed a significantly lower morality (χ2=9.90, P=0.002) and higher survival rate than with ≤0.93 mmol/L (log rank=6.20, P=0.010). Multivariate Cox regression revealed that ionized calcium ≤0.93 mmol/L was a risk factor of in-hospital mortality. Conclusions: Ionized calcium level≤0.93 mmol/L was an independent predictor of in-hospital mortality of severe sepsis.     

他汀类药物对中国老年脓毒症患者住院期间病死率的影响

目的探讨他汀类药物对中国老年脓毒症患者住院病死率的影响。 方法对212例2009年3月至2012年3月在浙江大学医学院附属第一医院老年科住院的老年脓毒症患者进行研究。以出院为观察终点,将患者分为死亡组和存活组。采用多因素Logistic回归模型分析,以确定应用他汀类药物是否为住院期间病死率的的独立影响因素。 结果存活组使用他汀类药物的患者比例高于死亡组[13.9%（5/36）vs. 34.7%（61/176）,χ² = 6.014,P = 0.014],调整后的比值比（OR）有统计学意义（OR：0.17;95%CI：0.04 ~ 0.85;P = 0.03）。 结论他汀类药物的使用可能可以降低中国老年脓毒症患者住院期间的病死率。     

艾司洛尔联合米力农对严重脓毒症患者心功能炎性因子及预后的影响

目的观察艾司洛尔联合米力农对严重脓毒症患者的治疗效果及探讨其可能作用机制。方法将90例符合严重脓毒症诊断标准且经早期目标导向治疗（ EGDT ）后心率≥95次／min的患者,随机分为对照组（ C组）、米力农组（ M组）和艾司洛尔联合米力农组（ ME组）。 C组按照脓毒症指南常规治疗。 M组在C组常规治疗基础上给予米力农持续静脉泵入,负荷剂量为30μg／kg,然后以0.375～0.5μg／（kg? min）维持。 ME组应用艾司洛尔持续静脉泵入,将患者心率控制在75～94次／min,余治疗方案同M组。采用脉搏指示连续心排血量监测（ PiCCO）检测患者心脏指数（CI）及每搏指数（SVI）等心功能指标,同时连续观察治疗前及治疗后12、24、48、72、96 h平均动脉压（MAP）、中心静脉压（CVP）、心率（HR）、氧合指数（PaO2／FiO2）和血乳酸（Lac）,并检测TNF－α、IL－6、HMGB－1、CK－MB、cTnI及BNP水平。结果治疗前各组MAP、CVP、HR、PaO2／FiO2及Lac比较差异无统计学意义,治疗后各组MAP、CVP及PaO2／FiO2比较差异无统计学意义,治疗后12 h ME组HR显著低于C组和M组,治疗后48 h M组、ME组Lac显著低于C组。治疗前各组CI及SVI比较差异无统计学意义,治疗后12 h M组、ME组CI及SVI显著高于C组。治疗前各组血浆TNF－α、IL－6、HMGB－1、CK－MB、cTnI及BNP水平比较差异无统计学意义,治疗后24 h ME组血浆TNF－α、IL－6、HMGB－1、CK－MB、cTnI及BNP水平显著低于C组和M组。 ME组28天生存率和96小时心率达标率显著高于C组和M组。结论艾司洛尔联合米力农可显著改善严重脓毒症患者心功能及28天生存率,同时显著降低心率并抑制全身炎症反应。     

A retrospective study on oral anticoagulant prophylaxis in 103 Italian patients with hereditary thrombophilia and thrombosis

Summary The clinical records of 103 Italian patients with inherited thrombophilia and thrombosis were reviewed to estimate the incidence of thrombotic recurrences and major bleeding complications according to the different duration of oral anticoagulant prophylaxis (OAP). The incidence of the first thrombotic recurrence was 2.9, 7.4 and 10.8×100 patients/year, respectively, in subjects receiving lifelong OAP, stopping OAP after a mean of 9 months (range 1–30 months) or not receiving OAP. The probability to remain free from thrombotic recurrences in patients undergoing lifelong OAP, as estimated by the Kaplan-Meier method, was significantly higher in comparison with untreated patients (p<0.001), but did not reach the statistical significance in comparison with patients who stopped prophylaxis. The incidence of further thrombotic recurrences was 1.2, 21.1 and 22.3×100 patients/year, respectively, in the three groups defined above. The difference between patients who prolonged indefinitely OAPvs those who stopped or did not receive OAP was statistically significant (p=0.003). Two intracranial bleedings, one of which fatal, were observed in patients undergoing lifelong OAP, whereas no major bleeding complications occurred in the other two groups. Our study supports the recommendations to continue indefinitely OAP in patients with inherited thrombophilia and recurrent thrombosis, but suggests caution in starting lifelong prophylaxis soon after the first thrombotic event in all patients. Members of the Study Group: F. Baudo (Milano); M. Berrettini (Perugia); G. Castaman (Vicenza); N. Ciavarella (Bari); S. Coccheri (Bologna); V. De Stefano (Roma); A. G. Dettori (Parma); N. Erba (Merate); G. Leone (Roma); P. M. Mannucci (Milano); C. Manotti (Parma); M. G. Mazzucconi (Roma); G. Palareti (Bologna); F. Panicucci (Pisa); E. Pogliani (Monza); F. Rodeghiero (Vicenza); A. Tripodi (Milano).     

Renal outcome after vancomycin treatment and renal replacement therapy in patients with severe sepsis and septic shock: A retrospective study

Purpose

Acute kidney injury during systemic infections is common; however, renal outcome is poorly investigated. The increase of multiresistant pathogens leads to the use of potential nephrotoxic antibiotics as vancomycin. We investigated the impact of vancomycin and renal replacement therapy (RRT) for renal recovery during sepsis.

Materials and methods

This is a retrospective data analysis of 1159 patients with severe sepsis or septic shock. Logistic regression models were performed.

Results

In total, 390 (33.6%) patients required RRT during intensive care unit (ICU) stay; 233 (20.1%), at discharge. Admission estimated glomerular filtration rate (eGFR) predicted the need of RRT during stay (odds ratio [OR] 0.969 [0.959-0.979] per increase of 1 mL/min, P < .001) and the prolonged need of RRT at ICU discharge (OR 0.979 [0.967-0.990], P < .001). Survivors without any RRT showed an improvement of eGFR at discharge, whereas patients after RRT did not (7.1 vs 0.8 mL/[min 1.73 m²], P < .001). The use (OR 1.648 [1.067-2.546], P < .05) and duration of vancomycin treatment (OR 1.043 [1.004-1.084] per each additional treatment day, P < .05) were predictors for ongoing RRT at discharge.

Conclusions

Estimated GFR at ICU admission predicts renal outcome, whereas the use of vancomycin increases the probability of a prolonged need for RRT at discharge from ICU. The use of alternative antibiotics for certain patients, indicated by eGFR at admission, might be considered.     

Incidence and risk factors for sepsis in surgical patients: a cohort study

Purpose

The aim of the study was to evaluate risk factors for infection and sepsis in surgical patients admitted to the intensive care unit (ICU).

Materials and Methods

Data were prospectively collected from a cohort of surgical patients from January 2005 to December 2007. We analyzed the incidence of infection and sepsis and certain other variables from the pre-, intra-, and postoperative periods as risk factors for infection and sepsis.

Results

We studied 625 surgical patients. The mortality rate was 18.2%, and the mean age of the subjects was 53.1 ± 18.8 years. The incidences of severe sepsis and septic shock were 5% and 11.5%, respectively. A multivariate analysis showed that the following variables were associated with sepsis in the postoperative period: urgent surgery (odds ratio, 2.63; 95% confidence interval [CI], 1.50-4.63), fluid resuscitation (odds ratio, 1.90; 95% CI, 1.18-3.05), vasoactive drugs (odds ratio, 2.58; 95% CI, 1.61-4.14), and mechanical ventilation (odds ratio, 5.51; 95% CI, 3.07-9.89). A Sequential Organ Failure Assessment was associated with infection or sepsis upon ICU admission (area under the curve, 0.737 ± 0.019; 95% CI, 0.748-0.825).

Conclusions

This study showed that sepsis has high incidence and mortality in surgical patients admitted to the ICU. Urgent surgeries, mechanical ventilation, fluid resuscitation, and vasoactive drugs in the postoperative period and Sequential Organ Failure Assessment at ICU admission were risk factors for sepsis.     

重组人血小板生成素治疗脓毒症相关血小板减少症患者的临床研究

目的评估重组人血小板生成素（rhTPO）对严重脓毒症患者伴发血小板减少症患者的疗效。 方法将2013年10月至2015年9月期间收治的严重脓毒症合并血小板减少症的患者66例分成实验组（35例）和对照组（31例）。所有患者均予以治疗原发病及积极控制感染,实验组患者于血小板下降的第1天给予rhTPO治疗,300 U·kg^-1·d^-1,皮下注射,当血小板计数绝对值升高≥ 50 × 10⁹/L时即停用,疗程一般不超过14 d。检测所有患者治疗前即刻、治疗后1、2、3、5、7、9、14 d血小板计数、C反应蛋白及丙氨酸转氨酶（ALT）水平。比较两组患者血小板输注例数、急性病生理学和长期健康评价（APACHE）Ⅱ评分、体温下降至正常时间、临床症状消失时间、肺部影像学恢复时间、ICU治疗后28 d病死率及住院时间。记录不良反应发生情况,并比较实验组患者治疗前后活化部分凝血活酶时间、ALT水平、C反应蛋白水平及总胆红素水平。 结果实验组患者仅血小板计数治疗后3、5 d较对照组明显升高[（56 ± 19）× 10⁹/L vs.（42 ± 18）× 10⁹/L,t = 3.112,P < 0.05;（67 ± 22）× 10⁹/L vs.（54 ± 21）× 10⁹/L,t = 2.520,P< 0.05],且实验组患者血小板输注例数明显低于对照组患者（5/35 vs. 11/31,χ² = 4.022,P = 0.045）。两组患者治疗后的APACHEⅡ评分（t = 0.692,P< 0.05）、体温下降至正常的时间（t = 0.510,P< 0.05）、临床症状消失时间（t = 0.262,P< 0.05）、肺部影像系统恢复至正常时间（t = 0.685,P< 0.05）、28 d病死率（χ² = 0.001,P< 0.05）及ICU平均住院天数（t = 0.637,P< 0.05）比较,差异均无统计学意义。同时,研究中没有观察到rhTPO所致的药物不良反应,且经rhTPO治疗前后实验组患者活化部分凝血活酶时间（t = 0.697,P< 0.05）、ALT（t = 0.478,P< 0.05）、C反应蛋白（t = 0.110,P< 0.05）及总胆红素（t = 1.634,P< 0.05）比较,差异亦均无统计学意义。 结论针对脓毒症合并血小板减少症的患者,在传统治疗手段的基础上联合rhTPO治疗可以显著地提升血小板计数,减少输注血制品带来的风险以及医疗资源的消耗,改善患者预后。     

Effects of viral infection and microbial diversity on patients with sepsis: A retrospective study based on metagenomic next-generation sequencing

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for bloodcultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded.The correlations between pathogen types and sepsis severity and survival rate were evaluated.RESULTS: NGS produced higher positive results (105 of 118;88.98%) than blood cultures(18 of 118;15.25%) over the whole study period. Concomitant viral infection correlated closelywith sepsis severity and had the negative effect on the survival of patients with sepsis. However,correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and thesurvival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviraldrugs combined with antibiotics may be benefi cial to ICU sepsis patients.     

Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation

Summary.  Background:  Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se , but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. Objectives:  To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. Methods:  We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro . Results:  Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro , plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Conclusions:  Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.     

A model for the interplay of inflammatory mediators in sepsis —a study in 48 patients

Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these fnflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.     

脓毒症患者外周血miR-98-5p与全身炎症反应激活及预后的相关性研究

目的研究脓毒症患者外周血miR-98-5p与全身炎症反应激活及预后的相关性。方法选择2019年1月至2021年1月期间自贡市第四人民医院收治的102例脓毒症患者作为脓毒症组,同期体检的100例健康志愿者作为对照组,采用荧光定量PCR法检测外周血miR-98-5p的表达水平,采用Elisa法检测血清炎症细胞因子TNF-α、HMGB-1、IL-1β的含量,采用急性生理和慢性健康评分Ⅱ(APACHEII)、序贯性器官衰竭评分(SOFA)评分评估脓毒症病情,采用28d生存情况评估预后。结果脓毒症组患者外周血miR-98-5p的表达水平低于对照组,差异有统计学意义(P<0.05);脓毒症组中miR-98-5p表达≥中位数患者的APACHEII、SOFA评分低于miR-98-5p表达<中位数患者,差异有统计学意义(P<0.05);脓毒症组中miR-98-5p表达≥中位数患者的血清TNF-α、HMGB-1、IL-1β含量低于miR-98-5p表达<中位数患者,差异有统计学意义(P<0.05);经K-M曲线分析,脓毒症组中miR-98-5p表达≥中位数患者的28 d累积生...     

Systemic inflammatory response syndrome,sepsis, severe sepsis and septic shock: Incidence,morbidities and outcomes in surgical ICU patients

Objectives To determine the incidence of systemic inflammatory response syndrome (SIRS), sepsis and severe sepsis in surgical ICU patients and define patient characteristics associated with their acquisition and outcome.Design One-month prospective study of critically ill patients with a 28 day in-hospital follow up.Setting Surgical intensive care unit (SICU) at a tertiary care institution.Methods All patients (n=170) admitted to the SICU between April 1 and April 30, 1992 were prospectively followed for 28 days. Daily surveillance was performed by two dedicated, specifically-trained research nurses. Medical and nursing chart reviews were performed, and follow up information at six and twelve months was obtained.Results The in-hospital surveillance represented 2246 patient-days, including 658 ICU patient-days. Overall, 158 patients (93%) had SIRS for an incidence of 542 episodes/1000 patients-days. The incidence of SIRS in the ICU was even higher (840 episodes/1000 patients-days). A total of 83 patients (49%) had sepsis; among them 28 developed severe sepsis. Importantly, 13 patients had severe sepsis after discharge from the ICU. Patient groups were comparable with respect to age, sex ratio, and type of surgery performed. Apach II score on admission to the ICU and ASA score at time of surgery were significantly higher (p<0.05) only for patients who subsequently developed severe sepsis. The crude mortality at 28 days was 8.2% (14/170); it markedly differed among patient groups: 6% for those with SIRS vs. 35% for patients with severe sepsis. Patients with sepsis and severe sepsis had a longer mean length of ICU stay (2.1±0.2 and 7.5±1.5, respectively) than those with SIRS (1.45±0.1) or control patients (1.16±0.1). Total length of hospital stay also markedly differed among groups (35±9 (severe sepsis), 24±2 (sepsis), 11±0.8 (SIRS), and 9±0.1 (controls, respectively).Conclusions Almost everyone in the SICU had SIRS. Therefore, because of its poor specificity, SIRS was not helpful predicting severe sepsis and septic shock. Patients who developed sepsis or severe sepsis had higher crude mortality and length of stay than those who did not. Studies designed to identify those who develop complications of SIRS would be very useful.     

Microvesicles with mitochondrial content are increased in patients with sepsis and associated with inflammatory responses

BACKGROUNDEndothelial activation plays an important role in sepsis-mediated inflammation, but the triggering factors have not been fully elucidated. Microvesicles carrying mitochondrial content (mitoMVs) have been implicated in several diseases and shown to induce endothelial activation. AIMTo explore whether mitoMVs constitute a subset of MVs isolated from plasma of patients with sepsis and contribute to endothelial activation.METHODSMVs were isolated from human plasma and characterized by confocal microscopy and flow cytometry. Proinflammatory cytokines, including interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, and soluble vascular cell adhesion molecule (sVCAM)-1 were detected by ELISA. Human umbilical vein endothelial cells (HUVECs) were stimulated with the circulating MVs to evaluate their effect on endothelial activation.RESULTSMitoMVs were observed in plasma from patients with sepsis. Compared with those in healthy controls, expression of MVs, mitoMVs, proinflammatory cytokines and sVCAM-1 was increased. The number of mitoMVs was positively associated with TNF-α and sVCAM-1. In vitro, compared with MVs isolated from the plasma of healthy controls, MVs isolated from the plasma of patients with sepsis induced expression of OAS2, RSAD2, and CXCL10 in HUVECs. MitoMVs were taken up by HUVECs, and sonication of MVs significantly reduced the uptake of mitoMVs by HUVECs and expression of the above three type I IFN-dependent genes. CONCLUSIONMitoMVs are increased in the plasma of patients with sepsis, which induces elevated expression of type I IFN-dependent genes. This suggests that circulating mitoMVs activate the type I IFN signalling pathway in endothelial cells and lead to endothelial activation.     

骨髓增殖性肿瘤患者JAK2V617F基因突变与血栓栓塞相关性研究

目的 探讨骨髓增殖性肿瘤(MPN)患者JAK2V617F点突变发生情况及与血栓栓塞之间的相关性.方法 回顾性统计分析107例MPN患者的临床及实验室检查资料,应用等位基因特异性-聚合酶链反应(AS-PCR)及序列测定方法,检测MPN患者JAK2V617F点突变发生情况,结合JAK2V617F点突变阳性与阴性两组患者血栓栓塞发生情况,探讨其在疾病诊断及与血栓栓塞发生之间的意义.结果 ①107例MPN患者中共检出71例患者存在JAK2V617F突变,总突变率为66.4%.107例MPN患者共发现34例患者存在血栓栓塞(发生率为31.8%).②血栓发生率真性细胞增多症(PV)组为34.8%,原发性血小板增多症(ET)组32.6%,原发性骨髓纤维化(PMF)组22.2%,三组间χ2=0.96,P＞0.05.34例血栓患者中,JAK2V617F阳性患者28例,阴性患者6例,两组间χ2=5.71,P＜0.05.65例年龄≥60岁患者27例并发血栓栓塞(41.5%),42例年龄＜60岁者中7例并发血栓栓塞(16.7%),两组间比较χ2=7.28,P＜0.01.结论 MPN患者JAK2V617F发生率较高,JAK2V617F阳性及高龄(≥60岁)患者更易并发血栓栓塞,对不明原因血栓患者进行JAK2筛查可明确是否存在早期不典型MPN.