Diagnosis and management of meningococcal disease: the need for centralized care

Meningococcal infection remains a significant health problem in children, with a significant mortality and morbidity. Prompt recognition and aggressive early treatment are the only effective measures against invasive disease. This requires immediate administration of antibiotic therapy, and the recognition and treatment of patients who may have complications of meningococcal infection such as shock, raised intracranial pressure (ICP) or both. Encouragingly, its mortality has fallen in recent years. This is the result of several factors such as the centralization of care of seriously ill children in paediatric intensive care units (PICUs), the establishment of specialized mobile intensive care teams, the development of protocols for the treatment of meningococcal infection, and the dissemination by national bodies and charities of guidance about early recognition and management. We will review the pathophysiology and management of the different presentations of meningococcal disease and examine the possible role of adjunctive therapies.     

Extracorporeal life support in cardiogenic shock: indications and management in current practice

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.     

How to achieve better outcome in treatment of asthma in general practice.

The symptoms of many asthmatic patients are poorly controlled, and there are several reasons why this may be so. Doctors fail to find out about symptoms that asthmatic patients are experiencing. Doctors wrongly assume that regular use of bronchodilators in small doses is satisfactory treatment for asthma and that taking high doses of bronchodilator in an asthma attack may be dangerous. Doctors think that inhaled steroids may be dangerous and are reluctant to use them in effective doses. Doctors do not check that patients can use their inhalers properly and do not make enough use of large volume spacers, the best available method for giving inhaled asthma treatment. Doctors undermine patients'' confidence in advice on treatment by failing to ensure that consistent advice is given and often make the management of asthma more troublesome for the patient than the symptoms of asthma.     

The clinical use of antishock trousers.

In 34 (71%) of 48 consecutive patients who were in shock (systolic blood pressure less than 80 mm Hg) the application of antishock trousers by ambulance personnel or emergency room staff produced rapid increases of 20 mm Hg or more in the systolic blood pressure. The trousers were applied to a 49th patient only to stabilize a fractured femur. The most common indication for the device was shock resulting from hemorrhage in the upper gastrointestinal tract. Of 20 such patients, 17 (85%) responded rapidly, as did all 5 patients who were treated for a ruptured abdominal aortic aneurysm. The proper application and management of antishock trousers are simple enough for use in the field, although deflation of the device before adequate replacement of fluids would precipitate a return to a state of shock.     

Bacteremic Shock—A Medical Emergency

Bacteremic shock is second in frequency only to myocardial infarction as a cause of hypotension and death in hospitalized medical patients. The clinical course is marked by fever, usually with chills, and hypotension with a full pulse and warm extremities, followed by shock, often resistant to treatment. Anticipation of this complication in patients with certain predisposing diseases or factors facilitates early recognition of the symptoms and signs of bacteremic shock and prompt treatment. Early and effective treatment of the offending infection often prevents progression of hypotension to the stage of frank vascular collapse.     

耐亚胺培南肺炎克雷伯菌腹腔感染患者的临床特征及预后

目的 研究耐亚胺培南肺炎克雷伯菌所致腹腔感染患者的临床特征、感染危险因素、治疗方案及临床预后。方法 回顾性调查2011年1月至2014年10月浙江大学医学院附属第一医院住院患者中由耐亚胺培南肺炎克雷伯菌所致腹腔感染患者的基础疾病、临床表现、实验室指标、微生物学检测结果等临床特征;了解腹腔感染发生前的侵入性操作、手术、抗菌药物使用、免疫抑制剂使用等高危因素;分析腹腔感染的治疗措施及抗菌药物的使用情况,患者对治疗的临床反应及30 d病死率。目标变量使用单因素、多因素分析,χ2检验及风险评估进行分析。结果 本研究入选43例腹腔感染患者,其病原菌均为亚胺培南耐药的肺炎克雷伯菌。病例年龄17~92岁,平均（54.8±15.9）岁;男性31例（72.1%）;APACHEⅡ评分22~33分,平均（27.7±2.2）分。全部患者在其样本培养阳性前2周内有侵入性操作,其中100.0%的患者留置腹腔引流管、95.3%的患者留置导尿管、93.0%的患者留置中心静脉管、76.7%的患者气管插管或切开;有36例患者（83.7%）感染前90 d内有手术史（均为经腹腔手术）;32例（74.4%）患者曾有30 d内ICU入住病史;38例（88.4%）患者在其标本培养阳性前2周内曾接受抗生素治疗。发热（74.4%）为腹腔感染耐亚胺培南肺炎克雷伯菌的主要临床表现,其次为腹痛（44.2%）。分别有13例（30.2%）和6例（14.0%）患者合并血流感染和/或痰液中检出耐亚胺培南肺炎克雷伯菌,17例（37.2%）患者出现感染性休克。在多因素分析中,感染性休克是30 d病死唯一的危险因素（OR：0.693,95%CI：1.591~30.245,P=0.010）。累计30 d病死率37.2%,存活时间2~28 d,平均（12.3±9.4）d;合并血培养阳性者的病死率为46.2%。使用替加环素治疗后30 d病死率较未用替加环素治疗低（19.0% vs 54.5%,P=0.027）。结论 腹腔感染耐亚胺培南肺炎克雷伯菌患者的病死率较高,感染性休克是30 d内病死的危险因素。使用替加环素进行抗菌治疗能降低30 d病死率、改善临床预后。     

Heat shock proteins protect platyfish (Xiphophorus maculatus) from Yersinia ruckeri induced mortality

The significant disadvantages accompanied with the use of antibiotics in aquaculture, emphasize the need for developing alternative disease control strategies, like novel vaccine approaches and immunostimulating measures. Several studies have already pointed out the ability of heat shock proteins (HSPs) to modulate innate and adaptive immune responses, what makes them potent candidates for the development of a new disease prevention method. In this study, the use of self and non-self heat shock proteins as a new prophylactic treatment against bacterial diseases in freshwater aquaculture was investigated. Therefore, an infection model was developed with platyfish as a host for Yersinia ruckeri infections. In this infection model, the effect of different treatments with HSPs on the survival of the fish after bacterial infection was tested: non-lethal heat shock, intracoelomal injection with two recombinant bacterial HSPs, GroEL and DnaK, and a combination of a non-lethal heat shock and an injection with bacterial HSPs. The results show that a non-lethal heat shock could not protect fish against a subsequent infection with Y. ruckeri. However, when the fish received an injection with bacterial HSPs, Y. ruckeri induced mortality was reduced. This effect became significant when the administration of bacterial HSPs was combined with a non-lethal heat shock. These data suggest a possible role for heat shock proteins as an immunostimulating treatment in fish against bacterial infections.     

Role of endothelins in septic,cardiogenic, and hemorrhagic shock

Shock is a condition where blood flow is inadequate for tissue needs. In all forms of shock, the concentrations of endothelins (ETs) are elevated, and they are especially high in septic shock. The rise in ETs plasma levels may initially have some positive homeostatic effects, for ETs can help restore normal vascular tone. However, high levels of ETs compromise the appropriate matching of flow to tissue needs and contribute to the pathophysiology of shock. Attempts at regulating the effects of ETs by the use of pharmacological blockers is made complicated by important interactions between the ETA and ETB receptors and potentially different effects on different tissues. We conclude that antagonism of ET receptors is unlikely to be helpful for cardiogenic or hemorrhagic shock. Furthermore, selective blockade is unlikely to be helpful. However, moderate doses of a mixed ET receptor antagonist may be of use for the management of septic patients.     

Serum triglycerides, the liver and the pancreas

Massive hypertriglyceridaemia associated with fatty liver and abdominal pain or frank pancreatitis (the chylomicronaemia syndrome) is uncommon, but clinically important and under-recognized. It may arise as a result of severe genetic defects in lipolysis or, more commonly, from a moderate primary hypertriglyceridaemia that is exacerbated by a secondary cause. The latter include several drugs, among which the protease inhibitors, used for the treatment of human immunodeficiency virus infection, are increasingly apparent. In the acute situation plasma exchange, fat-free parenteral nutrition and acute insulin treatment, even in nondiabetic persons, may be valuable. A potentially major advance in prophylaxis is the use of high-dose antioxidant therapy, which has been shown to reduce attacks of pancreatitis even in the absence of a reduction in serum triglycerides. Asymptomatic patients with abnormal liver function tests are common in the lipid clinic, and can be a difficult group in which to make management decisions. Among those who are not taking excessive amounts of alcohol, many will have nonalcoholic steatohepatitis. The care of these patients is discussed, but there remains considerable uncertainty regarding their optimum management and prognosis.     

Invasive aspergillosis: clinical manifestations and treatment

During the last decade the incidence of invasive aspergillosis has substantially grown due to the increasing use of powerful immunosupressive drugs in more patients. Unfortunately, the associated mortality with this infection is still very high and has not decreased in recent years. Pulmonary aspergillosis is by far the most frequent clinical picture of this infection, followed by sinus, tracheo-bronchial and central nervous system disease. The degree of immunosupression is the main factor influencing the evolution and dissemination of aspergillosis. Conventional amphotericin B has been the first-line therapy of invasive aspergillosis for the last 30 years, and most authors have long considered amphotericin B related toxicity as one of the main causes for the poor results obtained in the outcome of patients who developed this infection. Fortunately, in the last few years new safer and more effective drugs have been developed for the treatment of this entity. However, if we are really trying to substantially decrease invasive aspergillosis associated-mortality we should use these drugs earlier in the development of the infection, using new more sensitive diagnostic tests and/or a riskbase strategy which could identify patients at the highest risk to develop this infection.     

Acute respiratory distress in diabetic ketoacidosis: possible contribution of low colloid osmotic pressure.

The "shock lung" syndrome may occur in diabetic ketoacidosis in association with disseminated intravascular coagulation; occasionally it occurs alone after treatment of the ketoacidosis. Two patients developed pulmonary opacities with clinical features of acute respiratory distress such as are seen in the shock lung syndrome; in both, however, the findings suggested a different mechanism from that occurring in the syndrome. Hypoalbuminaemia was prominent, and it is postulated that a low plasma osmotic pressure caused by high volume crystalloid infusions may have precipitated the acute respiratory complications. Plasma osmotic pressure may be an important variable in patients given large volumes of crystalloid infusions; further studies are required to elucidate mechanisms of pulmonary oedema in such patients.     

脓毒性心肌功能障碍

脓毒症是由感染引起的全身炎症反应综合征,证实有感染灶存在或有高度可疑的感染灶。脓毒症是ICU内重症患者的主要死亡原因,且发病率随着年龄的增长而逐渐增加。近十年来,虽然政府在救治脓毒症患者中投入了巨大的资金和技术支持,但源于脓毒症或脓毒性休克患者的病死率仍高达30%~60%。心血管系统在脓毒症与脓毒性休克的病理生理学中扮演着重要着色。过去的四五十年,开展了很多脓毒性心肌功能障碍方面的研究,也积累了不少循证医学证据。然而,心脏只是心血管系统的一部分。诸如脓毒症患者机体血流动力学的变化系脓毒症对心脏的直接效应,还是脓毒症引起心脏前、后负荷及神经体液因素的变化,继而引起心脏继发改变的研究,至今仍在继续。本文概述了近年来脓毒性心肌功能障碍的研究进展,使读者更全面地了解脓毒性心肌功能障碍的病理生理学改变,合理有效地指导脓毒症和脓毒性休克患者的临床救治。     

Does mitochondrial dysfunction during antiretroviral therapy in human immunodeficiency virus infection suggest antioxidant supplementation as a beneficial option?

Over the last few years, a relative decline of the morbidity and mortality of human immunodeficiency virus (HIV) infection in industrialised countries has been observed due to the use of a potent combined therapy known as high active antiretroviral therapies (HAARTs). It has led to a decrease of viral load and a quantitative and qualitative improvement of immune function in patients, especially CD4+ T-lymphocyte count, having as a consequence a decrease of infectious complications and a global clinical improvement. Besides the positive effects of HAARTs on immune and metabolic alterations during HIV infection, it has been reported that the commonly used drugs AZT, ddI, and ddC are toxic to hepatocytes. Recent reports continue to point to the mitochondria as targets for toxicity. The prevalence of these symptoms is continued during acquired immunodeficiency syndrome (AIDS). The effects of oxidative stress occurring as a consequence of mitochondrial toxicity may amplify some of the pathophysiological and phenotypic events during infection. Mitochondrial stabilisation and antioxidative strategies are possible new therapeutic aims since the antiretroviral treatment is prolonged with increased longevity from AIDS, which has become a more manageable chronic illness. The aim of the present review article is to summarize the current knowledge about mitochondrial dysfunction during HAART and its consequence for patients with chronic treatment. Oxidative stress may serve as one pathway for cellular damage in AIDS and its treatment. One important future goal is to prevent or attenuate the side effects of HAART so that improved disease management can be achieved.     

Disorders of urine volume in the critically ill child.

This article will provide a pathophysiologic basis for the assessment of critically ill children who have developed disorders of urine volume. The anatomical and pathophysiologic causes of oliguria and polyuria are considered. The physiologic basis for the use of urinary sodium and osmolarity as a guide to the assessment of patients with disorders of urine volume are discussed in detail. In addition, guidelines for the management of children with acute renal failure, with particular emphasis on the consideration for nutritional support of these patients, is discussed as a part of the comprehensive approach to this problem. This article emphasizes an understanding of the pathophysiology of salt and water excretion by the kidney as a foundation to the diagnosis and management of patients with oliguria and polyuria.     

Effect of exercise on plasma paraoxonase1 activity in rugby players: Dependance on training experience

Abstract

Over the last few years, a relative decline of the morbidity and mortality of human immunodeficiency virus (HIV) infection in industrialised countries has been observed due to the use of a potent combined therapy known as high active antiretroviral therapies (HAARTs). It has led to a decrease of viral load and a quantitative and qualitative improvement of immune function in patients, especially CD4⁺ T-lymphocyte count, having as a consequence a decrease of infectious complications and a global clinical improvement. Besides the positive effects of HAARTs on immune and metabolic alterations during HIV infection, it has been reported that the commonly used drugs AZT, ddI, and ddC are toxic to hepatocytes. Recent reports continue to point to the mitochondria as targets for toxicity. The prevalence of these symptoms is continued during acquired immunodeficiency syndrome (AIDS). The effects of oxidative stress occurring as a consequence of mitochondrial toxicity may amplify some of the pathophysiological and phenotypic events during infection. Mitochondrial stabilisation and antioxidative strategies are possible new therapeutic aims since the antiretroviral treatment is prolonged with increased longevity from AIDS, which has become a more manageable chronic illness. The aim of the present review article is to summarize the current knowledge about mitochondrial dysfunction during HAART and its consequence for patients with chronic treatment. Oxidative stress may serve as one pathway for cellular damage in AIDS and its treatment. One important future goal is to prevent or attenuate the side effects of HAART so that improved disease management can be achieved.     

Rehabilitation of patellar tendinopathy

Patellar tendinopathy is a common musculoskeletal disorder characterized by progressive activity-related anterior knee pain and patellar tendon dysfunction. It is highly prevalent in sports which involve running and jumping. Various treatment methods are used in the management of PT including rest, activity modification, anti-inflammatory medication, injection therapies, taping, eccentric exercises, extra corporeal shock wave therapy, percutaneous electrolysis, and surgery. Even though various treatment options are available for patellar tendinopathy, no single method has proven to result in a consistent and near complete recovery in patients. Conservative management is considered to be the first line of treatment. This study presents an overview of the current practice about the management of patellar tendinopathy with an emphasis on rehabilitation. This review can act as a guide to sports medicine and rehabilitation professionals’ decision making in the management of this disorder.     

限制性输液与充分液体复苏在感染性休克患者围手术期麻醉中的应用研究

目的:探究限制性输液与充分液体复苏在感染性休克患者围手术期麻醉中的应用,从而为患者治疗提供相关科学依据。方法:回顾性分析2007年2月至2015年6月期间因感染性休克入院接受治疗的82例患者的临床资料,按输液方式的不同分为研究组(限制性输液)与对照组(充分液体复苏)各41例,观察两组患者转归情况,记录患者心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)、动脉血氧分压(PaO_2)、出血量、总输液量、尿量、术后机械通气时间及ICU住院时间。结果:术后研究组患者出现弥散性血管内凝血(DIC)5例、成人呼吸窘迫综合征(ARDS)3例,2例病情控制不佳者转为多器官功能障碍综合征(MODS),1例死亡,总发生率为26.83%;对照组患者出现DIC 8例,ARDS 7例,MODS 5例,最终出现3例死亡,总发生率为56.10%,两组患者术后转归状况比较,差异有统计学意义(P0.05);研究组患者MAP、CVP、HR、出血量、总输液量及尿量等指标低于对照组,差异有统计学意义(P0.05),研究组患者PaO_2显著高于对照组,差异有统计学意义(P0.05);研究组患者术后机械通气时间及ICU住院时间比对照组短,差异有统计学意义(P0.05)。结论:限制性输液较充分液体复苏能够显著改善感染性休克患者组织血流灌流状况,术中出血量少、术后并发症少,效果更显著,更适合在围手术期麻醉中使用。     

Changes in Circulating Procalcitonin Versus C-Reactive Protein in Predicting Evolution of Infectious Disease in Febrile,Critically Ill Patients

Objective

Although absolute values for C-reactive protein (CRP) and procalcitonin (PCT) are well known to predict sepsis in the critically ill, it remains unclear how changes in CRP and PCT compare in predicting evolution of: infectious disease, invasiveness and severity (e.g. development of septic shock, organ failure and non-survival) in response to treatment. The current study attempts to clarify these aspects.

Methods

In 72 critically ill patients with new onset fever, CRP and PCT were measured on Day 0, 1, 2 and 7 after inclusion, and clinical courses were documented over a week with follow up to Day 28. Infection was microbiologically defined, while septic shock was defined as infection plus shock. The sequential organ failure assessment (SOFA) score was assessed.

Results

From peak at Day 0–2 to Day 7, CRP decreased when (bloodstream) infection and septic shock (Day 0–2) resolved and increased when complications such as a new (bloodstream) infection or septic shock (Day 3–7) supervened. PCT decreased when septic shock resolved and increased when a new bloodstream infection or septic shock supervened. Increased or unchanged SOFA scores were best predicted by PCT increases and Day 7 PCT, in turn, was predictive for 28-day outcome.

Conclusion

The data, obtained during ICU-acquired fever and infections, suggest that CRP may be favoured over PCT courses in judging response to antibiotic treatment. PCT, however, may better indicate the risk of complications, such as bloodstream infection, septic shock, organ failure and mortality, and therefore might help deciding on safe discontinuation of antibiotics. The analysis may thus help interpreting current literature and design future studies on guiding antibiotic therapy in the ICU.