Drotrecogin alfa: a new approach in the treatment of severe sepsis

Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of sepsis. This recombinant form of the natural protein, activated protein C (Xigris^TM, Eli Lilly & Co.), has been shown to significantly reduce mortality in a large randomised, controlled Phase III study involving 1690 patients. The exact mode of action of drotrecogin alfa (activated) remains uncertain, although it clearly combines anticoagulant and anti-inflammatory properties. Although associated with an increased risk of bleeding, this is usually procedure-related rather than spontaneous. Although costly, this is a drug that effectively reduces mortality rates in patients with severe sepsis.     

Disabling inflammatory pathways with biologics and resulting clinical outcomes in severe asthma

Introduction: Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent hospital admissions and requirement for intensive and expensive medications. There is a compelling need for more effective and safer therapies to help severe asthma sufferers to achieve adequate control of their disease.

Areas covered: Expanding knowledge of innate and adaptive immune responses has led to development of new biologic approaches for severe asthma. Here, the authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma. Their specific role in distinctively targeted subpopulations of severe asthmatics will be also discussed.

Expert opinion: Defining and phenotyping severe asthma patients will become increasingly important as some patients who were previously classified as having severe asthma may become well-controlled with a targeted phenotype-specific treatment. However, pharmacoeconomic concerns should also be taken into account given the elevated acquisition costs of recombinant human monoclonals and of the diagnostic screening procedures for the identification of potential responders.     

What is next in sepsis: current trials in sepsis

17th International Symposium on Infections in the Critically Ill Patient

Barcelona, Spain, 3–4 February 2012

International experts reviewed and updated the most recent and relevant scientific advances on severe sepsis during the 17th International Symposium on Infections in the Critically Ill Patients in Barcelona (Spain) in February 2012. All new pharmacological therapeutic strategies have failed to demonstrate a survival benefit. Despite the large variability among countries and hospitals, the improvement of standard care according to the Surviving Sepsis campaign recommendations reduced the 28-day mortality to 24%. These results may have implications for future clinical trials in which much larger samples sizes of patients at high risk of death will be necessary. The identification of novel proinflammatory endogeneous signals and pathways may lead to the discovery of new drugs to reduce inflammatory reactions and end-organ dysfunction in critically ill patients with sepsis. Extracorporeal blood purification stem or progenitor cells have received increasing interest for the treatment of inflammation and organ injury. A better understanding of how these therapies work is essential and its benefit should be confirmed in future prospective randomized studies.     

Management of severe bacterial infections

Defining the severity of an infection can play a central role for a correct therapeutic choice, avoiding inadequate antimicrobial treatments. Severe bacterial infections are, in fact, characterized by high morbidity and mortality rates so that the appropriateness of therapy can have a profound clinical impact. Indeed, initial inappropriate empirical therapies, and the further need to modify them, substantially increase the mortality risk. Several strategies have been suggested to improve the clinical outcome of patients affected by severe bacterial infections, such as the use of guidelines, use of antibiotics in combination, de-escalation therapy, cycling therapy and the use of infectious disease specialist consultation. A closer collaboration between the medical staff in the wards and infectious disease specialists can possibly bridge the gap between different strategies and individual needs of the patient, thereby improving the decision-making process.     

重症溃疡性结肠炎临床和病理分析

目的:对重症溃疡性结肠炎进行临床和病理分析并讨论其临床意义。方法:重症溃疡性结肠炎(UC)患者119例。采取肠外静脉补充足够的营养,完全胃肠道休息,治疗4周后进行结肠镜检查。结果:重症UC经过4周治疗后临床痊愈36例(39.3%),好转65例(54.6%),无效18例(15.1%),总有效率84.9%。初发型,复发型和持续型UC内镜下和组织学存在一定差异,但治疗总有效率明显差异。结论:初发型,复发型和持续型UC内镜下和组织学存在一定差异,肠外静脉高营养疗法是一种有效可行的方法。     

早期乳酸清除率及APACHEⅡ评分对老年重症肺炎患者预后判断的研究

目的:探讨早期乳酸清除率和急性生理学和慢性健康状况Ⅱ(APACHEⅡ)评分对老年重症肺炎患者预后的临床意义。方法:对重症医学科收治的47例老年重症肺炎患者,平均年龄(83.1±8.4)岁,分别于入院时和明确诊断后6 h测定动脉血乳酸,计算乳酸清除率。在患者入院第1个24 h内进行APACHEⅡ评分。以患者入院后28 d预后为研究终点,将患者分为存活组和死亡组,比较两组患者早期乳酸清除率及APACHEⅡ评分。根据明确诊断后6 h乳酸清除率将患者分为高乳酸清除率组(乳酸清除率≥10%)和低乳酸清除率组(乳酸清除率<10%),比较两组患者APACHEⅡ评分、机械通气率、病死率。采用受试者工作特征(ROC)曲线分析乳酸清除率预测老年重症肺炎患者预后的价值。结果:存活组和死亡组的乳酸清除率分别为(19.7±6.4)%和(7.7±10.1)%,差异有统计学意义(P<0.01);高乳酸清除率组和低乳酸清除率组28 d病死率分别为26.7%(8/30)和58.8%(10/17),高乳酸清除率组低于低乳酸清除率组(P<0.05);乳酸清除率预测老年重症肺炎患者28 d病死率最佳临界点为20%,敏感性68.9%,特异性67.9%。结论:早期乳酸清除率与APACHEⅡ评分正相关,两者可作为判断老年重症肺炎患者预后的指标。     

重症手足口病患儿合并肺炎支原体感染实验室检测指标对于临床诊断及治疗的提示性作用

目的 探讨肠道病毒71型合并肺炎支原体感染的重症手足口患儿的检测指标对于临床诊断及治疗是否起到提示作用。方法 收集2014年3月至8月于首都医科大学附属北京地坛医院住院的手足口病患儿100例,非手足口病患儿50例,对其粪便标本采用荧光定量RT-PCR方法检测,得出核酸定性结果。对其血清标本采用被动凝集法检测以得出肺炎支原体抗体效价。分析肺炎支原体感染在手足口病组和非手足口病组中的差异,探讨肠道病毒71型合并肺炎支原体感染与手足口病严重程度的相关性。结果 重症手足口病组患儿的肺炎支原体阳性率(76%)高于轻症手足口病组患儿的肺炎支原体阳性率(48%),差异有统计学意义(χ²=8.319,P=0.004)。结论 肠道病毒71型阳性合并肺炎支原体感染的重症手足口病患儿,应在临床诊治中引起关注。对于降低重症手足口病患儿向危重症的转化具有提示意义。     

武汉市106例输入性恶性疟病例血液检验指标分析

目的 探讨输入性恶性疟血液临床检验指标特征,为诊断及预防重症提供科学依据。方法 收集2010—2017年武汉市输入性恶性疟确诊病例入院第1次的血常规和生化检验结果,将病例资料分为重症组和普通组,采用Wilcoxon秩和检验和t检验分析两组差异性。结果 共收集106份较完整的病例血液检测结果,其中重症组20例、普通组86例,血常规结果显示重症组红细胞（2.77±0.87）×10¹²/L、血红蛋白（84.52±25.57）g/L、红细胞压积（24.70±7.12）%,与普通组差异有统计学意义（P均<0.01）;同时重症组血小板均明显下降,差异有统计学意义（P<0.05）。生化结果显示重症组和普通组总胆红素（M=63.40,32.60）、直接胆红素（M=27.65,12.85）、间接胆红素（M=29.35,18.40）均明显上升,差异有统计学意义（P<0.05）;重症组天门冬氨酸氨基转移酶中位数82.00 U/L,与普通组差异有统计学意义（P<0.05）;重症组总蛋白（51.79±6.00） g/L、白蛋白（27.52±3.61） g/L,与普通组差异有统计学意义（P均<0.01）。重症组肾小球滤过率（56.06±42.05） mL/min、尿素（14.91±9.71） mmol/L、肌酐（161.93±36.21） μmol/L、胱抑素C 中位数2.22 mg/L,与普通组差异有统计学意义（P<0.01）。两组乳酸脱氢酶均明显上升,重症组（978.65±653.65）U/L,与普通组差异有统计学意义（P<0.01）;重症组钙下降,与普通组差异有统计学意义（P<0.01）。结论 恶性疟重症以严重贫血、低蛋白血症、严重肝肾功能损伤、乳酸脱氢酶升高及钙代谢紊乱为特征,对恶性疟重症诊断与预防具有一定的参考价值。     

儿童肺炎支原体肺炎临床特点及重症危险因素分析

目的:了解住院儿童肺炎支原体肺炎(MPP)的流行病学及临床特点,并分析儿童重症MPP的相关因素。方法: 收集2017年1月-2017年12月于天津医科大学第二医院儿科住院治疗的MPP患儿180例,进行回顾性分析。按病情严重程度分为重症组（SMPP组）73例、普通组（MPP组）107例进行比较,分析流行病学、临床特点以及SMPP相关因素。结果:（1）儿童MPP多以秋（84例,46.7%）、冬（56例,31.1%）季节为主。（2）SMPP组与MPP组比较,前者患病年龄大,发热时间长,影像学多表现为大片状实变影,住院时间偏长。（3）SMPP组与MPP组比较降钙素原（PCT）无差异,而外周血白细胞计数（WBC）、C-反应蛋白（CRP）、血清IgA、血清IgG、血清IgM、乳酸脱氢酶（LDH）和铁蛋白（SF）指标明显高于MPP组,差异有显著性。（4）二分类Logistic回归分析发现热程（OR=1.30,P=0.031）、CRP（OR=1.06,P=0.005）、LDH（OR=1.012,P= 0.001）及胸片大片状实变影（OR=11.57,P=0.000）共4个自变量为SMPP的独立相关因素。结论:儿童MPP多发生在秋冬季。SMPP多发生在学龄期,胸部影像学检查多表现为大片状实变影,WBC、CRP、LDH及SF等炎症指标升高明显,其中热程、CRP、LDH及影像学显示大片状实变影与病情严重程度有关。