Treatment of septic thrombocytopenia with immune globulin

Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet-associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise;P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures.     

Leptin RIA在大鼠脓毒败血症模型中的应用

目的:研究脓毒败血症对外周血瘦素(Leptin)表达水平的影响,探讨Leptin在急性创伤炎症反应中的作用.方法:建立大鼠盲肠结扎穿孔模型,设立假手术组、单纯损伤组和脂肪乳、雌二醇、胰岛素组等干预能量代谢和神经-内分泌功能的实验组,每组10只,并采用自建的高灵敏大鼠Leptin RIA测量损伤后12h血清Leptin浓度的变化.结果:所用Leptin RIA标准曲线形态良好,可获得各实验组血清Leptin浓度.与伤后假手术组血清Leptin水平相比,其他四组与之无显著差异,脂肪乳组有升高的趋势,而其他三组均为降低的趋势.另外,脂肪乳组显著高于单纯损伤组和雌二醇组.结论:脓毒败血症引起内源性Leptin表达不足,早期给予能量补充有望升高Leptin表达水平,而干扰下丘脑-垂体轴功能或降低能量储备则会抑制Leptin所发挥的保护效应.     

Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis.

In a prospective double-blind study, standard intravenous immunoglobulin (IVIG) was compared with an IgM-enriched IVIG in the treatment of neonatal sepsis. The two treatment groups were also compared with matched controls. One hundred and thirty babies (65 in each group) ranging from 0 to 24 days old, 480 to 4200 g in weight and born between 24 and 42 weeks of gestation who had, or were suspected of having, sepsis were given either standard IVIG or IgM-enriched IVIG (250 mg/kg per day) for 4 days in addition to supportive and antibiotic therapy. A further 65 babies who received similar supportive, antibiotic and fluids but not IVIG were used as matched controls. Mortality from infection in 'culture proven sepsis' was 3/44 (6.8%) in the IgM-enriched IVIG group, 6/42 (14.2%) in the standard IVIG group, and 11/43 (25.5%) in the control group (P = 0.017, IgM versus control, P = 0.19 standard IVIG versus control). There was no statistical difference in the outcome between the two immunoglobulin therapy groups (P = 0.25). The study indicates that IVIG improves outcome in neonatal sepsis when used as an adjunct to supportive and antibiotic therapy, but larger studies are required to confirm this.     

Risk factors,clinical course and outcomes of pregnancy-related group A streptococcal infections: retrospective 13-year cohort study

Objectives

To investigate the incidence, risk factors, clinical course and outcomes of pregnancy-related group A streptococcus (GAS) infection.

A series of Infections due to Capnocytophaga spp. in immunosuppressed and immunocompetent patients

Objective  To investigate the epidemiology, microbiology and outcome of infections caused by Capnocytophaga spp. at a single center.
Methods  We report on ten documented infectious episodes caused by Capnocytophaga observed between 1994 and 1999 at the Innsbruck University Hospital.
Results  In seven of ten patients, Capnocytophaga septicemia was diagnosed during periods of neutropenia. In contrast, the remaining three patients had normal white blood cell counts when acquiring Capnocytophaga septicemia (one) and pleural empyema (two). Blood cultures containing long, slender, Gram-negative rods, which grew slowly under anaerobic conditions and lacked susceptibility to metronidazole, were subcultivated in a CO₂-enriched atmosphere (5%). Subcultivation yielded Capnocytophaga in all ten cases within 2–12 days. The patients were then placed on appropriate antibiotic therapy, with or without additional surgical intervention, and the organism was eradicated.
Conclusion  Identification of Capnocytophaga facilitates appropriate, and in most cases effective, antimicrobial therapy.     

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia

This study examined the hypothesis that nicotinamide could attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and nitric oxide. Ten healthy male volunteers participated in a randomised, double-blind, cross-over design with regard to the effects of nicotinamide. The volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h preceding the experiment (total dose of 8 g). Endotoxin (E. coli, 2 ng/kg), was administered intravenously. Blood samples and haemodynamic data were collected prior to and up to 6 h after the endotoxin infusion. Orally exhaled NO was measured hourly. Following endotoxin, body temperature increased from baseline 36.3 +/- 0.09 degrees C to a maximum of 38.0 +/- 0.1 degrees C for all (mean +/- SEM, P < 0.001) and heart rate increased from 59 +/- 1.9 to 87.0 +/- 2.6 beats/min after 3 h (mean +/- SEM, P < 0.001). Endotoxin challenge also markedly elevated the TNF-alpha, IL-6, IL-8 and IL-10 concentrations (P < 0.001 versus baseline for all) during the study period. Orally exhaled NO also increased (P < 0.01) compared to baseline. Nicotinamide treatment did not influence the patterns of cytokine and NO response to endotoxin. In conclusion, there was no effect on the inflammatory parameters by oral nicotinamide at a dose of 8 g, limiting the potential use of this agent for anti-inflammatory purpose in man.     

Vital signs of the systemic inflammatory response syndrome in adult patients with acute infections presenting in out-of-hours primary care: A cross-sectional study

BackgroundSigns of the systemic inflammatory response syndrome (SIRS) – fever (or hypothermia), tachycardia and tachypnoea – are used in the hospital setting to identify patients with possible sepsis.ObjectivesTo determine how frequently abnormalities in the vital signs of SIRS are present in adult out-of-hours (OOH) primary care patients with suspected infections and assess the association with acute hospital referral.MethodsWe conducted a cross-sectional study at the OOH GP cooperative in Nijmegen, the Netherlands, between August and October 2015. GPs were instructed to record the body temperature, heart rate and respiratory rate of all patients with suspected acute infections. Vital signs of SIRS, other relevant signs and symptoms, and referral state were extracted from the electronic registration system of the OOH GP cooperative retrospectively. Logistic regression analysis was used to evaluate the association between clinical signs and hospital referral.ResultsA total of 558 patients with suspected infections were included. At least two SIRS vital signs were abnormal in 35/409 (8.6%) of the clinic consultations and 60/149 (40.3%) of the home visits. Referral rate increased from 13% when no SIRS vital sign was abnormal to 68% when all three SIRS vital signs were abnormal. Independent associations for referral were found for decreased oxygen saturation, hypotension and rapid illness progression, but not for individual SIRS vital signs.ConclusionAlthough patients with abnormal vital signs of SIRS were referred more often, decreased oxygen saturation, hypotension and rapid illness progression seem to be most important for GPs to guide further management.     

PD-1/PD-L1与脓毒症的免疫紊乱

 脓毒症（sepsis）在1991年初次被定义为感染所致的机体全身炎症反应综合征（SIRS）。2016年脓毒症国际共识更新至Sepsis 3.0,即由感染所致宿主免疫反应失调引起的威胁生命的器官功能障碍。在脓毒症免疫抑制阶段,程序性死亡受体1（programmed cell death protein-1,PD-1）与程序性死亡受体-配体1（programmed cell death 1 ligand 1,PD-L1）相结合能够抑制部分免疫细胞活化增殖从而达到负性调节免疫系统的作用。本综述主要围绕脓毒症中PD-1/PD-L1在T细胞、树突状细胞（DCs）、单核细胞、巨噬细胞等免疫细胞发挥免疫功能中的作用,以及对抗PD-1/PD-L1抗体疗法的应用前景进行阐述。     

基于多途径联合效应的甘草防治脓毒血症活性成分筛选及作用机制研究

目的 研究甘草中有效组分对脓毒血症的防治作用及机制。方法 采用小鼠骨髓来源巨噬细胞(bone marrow-derived macrophages,BMDM)构建体外NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体激活模型及H2O2诱导的氧化应激模型筛选出甘草抗炎、抗氧化应激的有效组分,采用ip脂多糖(lipopolysaccharide,LPS,20 mg/kg)诱导C57BL/6小鼠脓毒血症致死模型以及脓毒血症模型,评价致死模型中小鼠的生存率及脓毒血症模型小鼠腹腔灌洗液中巨噬细胞和中性粒细胞在渗出细胞中的占比以及外周血和腹腔灌洗液中白细胞介素-1β(interleukin-1β,IL-1β)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果 基于BMDM细胞NLRP3炎症小体激活模型筛选出甘草中有效组分刺甘草查耳酮,可显著抑制半胱氨酸天冬氨酸蛋白酶-1(cystein-asparate protease-1,Ca...