MET抑制剂在晚期肝癌中的应用进展

目前晚期肝细胞癌的标准药物治疗是索拉菲尼,但其临床效果是有限的,而且副作用较大。但除索拉菲尼以外,在所有完成的Ⅲ期临床对照研究中,没有药物在作为一线或二线用药时能明显提高生存率。最近一项Ⅱ期随机对照研究结果的亚组分析显示,一种选择性MET抑制剂ARQ197,在全身治疗失败或不耐受全身治疗的伴有MET扩增的晚期肝细胞癌患者中应用,能明显提高总生存率。在本文中,我们对所有目前正在进行及已经完成临床试验的MET抑制剂做一综述。旨在进一步了解MET抑制剂在肝癌中的应用情况,为晚期肝癌的药物治疗提供新的策略。     

生物型人工肝的肝细胞源研究进展

各种原因所致的肝功能衰竭是一种病死率高的并发症。肝移植是治疗肝衰竭最有效的手段。为了替代肝脏移植,以肝细胞为基础的生物型人工肝(BAL)成为目前肝功能衰竭治疗的基础与临床研究的重点和热点。肝细胞是BAL的生物部分,起着核心作用;应用于BAL的肝细胞主要有:原代肝细胞(包括同源的人肝细胞及异种肝细胞)、各种不同来源的肝细胞株、干细胞等。此文就涉及肝细胞源研究的最新进展作简要综述。     

人工肝设备和技术的进展与临床评价

人工肝脏技术是人体重要的器官支持治疗，有望成为重型肝炎肝衰竭及其它一些肝病最常用和最有效的治疗方法之一。由于肝脏在人体代谢的中枢地位、复杂性及肝病的多发性，使得人工肝支持系统比其它任何人工器官更具发展潜力和挑战性。本文综述了几种主要人工肝技术的进展与临床应用情况，并对人工肝脏治疗存在的困难及发展方向进行了讨论和展望。     

生物人工肝技术的现状与展望

生物人工肝逐渐成为肝功能衰竭治疗研究的热门课题,很有可能像人工肾曾经为肾衰竭治疗带来革命性变化一样,为肝衰竭的现代治疗提供有效手段。文章就人工肝分类、生物人工肝组成、研究进展及存在的问题与展望等方面进行了深入、全面的阐述,目的是让广大医院管理者对人工肝,尤其是生物人工肝的研究现状及应用前景等有一个比较全面、系统的了解。     

Preventing pneumonia in ventilated patients

The application of oropharyngeal chlorhexidine is mainly active on Gram-positive microorganisms with only a minimal impact on colonisation by Gram-negative microorganisms. Seven randomized clinical trials have been published that showed a significant reduction in ventilator associated pneumonia (VAP) incidence, but not on survival. Some questions remain unanswered: it is presently unclear whether patients who benefit can be selected from the population at risk, and optimal formulation and dosage of chlorhexidine has not yet been established. International recommendations for using oro-pharyngeal topical chlorhexidine in ventilated patients have now been roborated by two Dutch studies.     

Role of beta-blockers in the treatment of chronic heart heart failure

Role of beta-blockers in the treatment of chronic heart failure has been changed over a 25-year period from contraindication to an established indication. To date, controlled clinical trials performed in more than 13,000 patients with chronic heart failure have consistently shown that the long term administration of beta-blockers is associated with significant improvement in left ventricular function, clinical symptoms, and survival. This favorable clinical trial experiences support a recommendation that beta-blockers should be used in all heart failure patients with stable symptoms due to left ventricular systolic dysfunction unless contraindicated. Ongoing beta-blocker studies address further new topics, such as treatment of elderly patients and direct comparison of different agents. Although, the use of beta-blockers for heart failure tends to increase, implementation of the experiences from the clinical trials to the everyday practice still remains a challenge.     

Liver transplantation in acute liver failure

Acetaminophen and idiosyncratic drug induced hepatotoxicity are the most commonly identified etiologies of acute liver failure in Western countries. Infectious complications and cerebral edema remain the leading causes of death. Moderate hypothermia and other medical interventions may improve cerebral edema in selected patients with acute liver failure. In addition, pilot studies suggest that recombinant factor VIIa infusions may allow for the safe placement of intracranial pressure monitoring devices in patients with cerebral edema and severe coagulopathy. Auxiliary liver transplantation and bioartificial liver devices offer the hope of temporary liver support for selected patients with a high likelihood of native liver regeneration. Prognostic survival models that include arterial lactate levels may improve our ability to identify acetaminophen overdose patients in urgent need of liver transplantation. The lower 1-year patient survival following liver transplantation for acute liver failure compared to chronic liver failure (60 vs 80%) is in part due to the emergent nature of surgery, concomitant vital organ failure, and the higher incidence of immunologically mediated graft dysfunction. Vaccination against hepatotrophic viruses and other public health measures designed to minimize the incidence of both intentional and non-intentional acetaminophen overdose may help reduce the future incidence of acute liver failure. In the meanwhile, it is recommended that acute liver failure patients be managed in experienced centers with ready access to liver transplantation to optimize outcomes in this rare but frequently fatal illness.     

Interferon for adjuvant therapy in melanoma; although approved, not indicated

The Dutch melanoma group reconsidered their 1997 consensus statement on treatment of melanoma because new studies on adjuvant treatment with interferon(IFN)-alpha have been published. These have resulted in its registration for stage IIa; for stage IIb/III IFN-alpha was already registered. Overall survival should be the main endpoint of adjuvant clinical studies, especially when treatment is associated with toxicity. Since a benefit has not been unequivocally demonstrated in melanoma with Breslow thickness > 1.5 mm and/or regional lymph node metastases, there is no need to change the Dutch consensus statement. Drug registration authorities and medical professionals should cooperate more closely.     

Economic evaluation of end stage renal disease treatment

This paper examines the cost-effectiveness of end stage renal disease (ESRD) treatments. Empirical data on costs of treatment modalities and quality of life of patients were gathered alongside a clinical trial and combined with data on patient and technique survival from the Dutch Renal Replacement Registry. A Markov-chain model, based on the actual Dutch ESRD program as of January 1st 1997, predicted the cost-effectiveness and cost-utility of dialysis and transplantation over the 5-year period 1997-2001. Total annual costs amounted to DFL 650 million (1.1% of the health care budget). Centre Haemodialysis was found to be the least cost-effective treatment, while transplantation and Continuous Ambulatory Peritoneal Dialysis (CAPD) were the most cost-effective treatments. The Markov-chain model was used to study the influence of substitutive policies on the overall cost-effectiveness of the ESRD treatment program. The influence of such policies was found to be modest in the Dutch context, where a high percentage of patients is already being treated with more cost-effective treatment modalities. In countries where Centre Haemodialysis is still the only or the major treatment option for ESRD patients, substitutive policies might have a more substantial impact on cost-effectiveness of ESRD treatment.     

慢性肝病患者肠外肠内营养支持与膳食干预专家共识

肝脏是人体最重要的代谢器官，肝脏发生疾病时可出现复杂的营养素代谢改变和不同程度的营养不良（不足），而营养状态又反过来影响肝病的发生、发展和预后，形成恶性循环。营养支持（肠外营养支持、肠内营养支持、膳食干预）在慢性肝病患者（代偿期/失代偿期肝硬化、慢加急/亚急性肝衰竭、慢性肝衰竭）的治疗中起重要作用。但此领域缺少大样本、高质量的临床研究报告，且国内尚无有关临床诊疗的“共识”。从合理应用营养支持疗法，改善慢性肝病患者临床结局出发，本“共识”专家组系统总结相关文献，并结合我国慢性肝病的临床实践，完成此共识，以期为慢性肝病诊疗有关的医师、护士（师）、营养师、药剂师们提供临床参考。     

The LIFESTYLE study: costs and effects of a structured lifestyle program in overweight and obese subfertile women to reduce the need for fertility treatment and improve reproductive outcome. A randomised controlled trial

Background

In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome.

Methods/Design

Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m². Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders. In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient's weight.

Outcome measures and analysis

The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs. Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group.

Discussion

The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients.

Trial registration

Dutch Trial Register NTR1530     

肝实质细胞和肝非实质细胞及非肝细胞的共培养

生物人工肝有望成为肝衰竭患者有效的体外肝支持治疗手段,而建立生物人工肝的前提是要获得足够数量高活性和良好功能的肝细胞.大量研究发现,肝细胞共培养能明显增强肝细胞功能,保持肝细胞的表型.此文就近年来肝细胞和非实质细胞、非肝细胞共培养的效果、方法和可能的机制作了综述.     

Registration of clinical trials: a statement from the International Committee of Medical Journal Editors

Altruistic motives and trust are central to scientific investigations involving people. These prompt volunteers to participate in clinical trials. However, publication bias and other causes of the failure to report trial results may lead to an overly positive view of medical interventions in the published evidence available. Registration of randomised controlled trials right from the start is therefore warranted. The International Committee of Medical Journal Editors has issued a statement to the effect that the 11 journals represented in the Committee will not consider publication of the results of trials that have not been registered in a publicly accessible register such as www.clinicaltrials.gov. Patients who voluntarily participate in clinical trials need to know that their contribution to better human healthcare is available for decision making in clinical practice.     

微囊化肝细胞在急性肝衰竭中的研究进展

急性肝衰竭(acute liver failure,ALF)是一种严重的临床综合征,常导致大量的肝细胞坏死,病死率非常高,治疗上及时的肝功能支持非常重要。大量研究表明肝细胞在替代肝功能方面具有很大优势,目前主要有肝细胞型生物人工肝(bioartificial liver,BAL)和肝细胞移植(hepatocyte transplantation),而微囊化(microencapsulation)技术可以为两者提供有效的免疫隔离屏障。文中就微囊化肝细胞(microencapsulatedhepatocyte)的制备、材料选择、ALF中的研究及存在问题进行综述。     

Early diagnosis of colorectal cancer: technical problems and acceptability

Summary There has been little change in the survival rate of colorectal cancer over the last 20 years. Earlier diagnosis probably offers the best hope for improving this survival. At the present time, the only practical method of population screening is by the detection of occult blood in the faeces. Almost all published screening trials are uncontrolled. Although cancer detected by occult blood screening tends to be at a relatively early stage, only controlled trials can answer the critical question of whether screening decreases mortality from bowel cancer. High risk patients (prior adenoma or colorectal cancer, extensive colitis of more than 10 years duration, family history of polyposis) should have colonoscopy at regular intervals.     

Application Status and Prospect of Bio-artificial Liver

Liver failure which can be caused by viral hepatitis,alcohol,drugs,metabolic diseases,autoimmune processes or other fac tors is the end stage of chronic liver disease.Although liver transplantation is currently considered to be the primary treatment measures of chronic liver disease.Due to donor shortages,surgical complications and immune rejection,cell therapy has been extensively studied.?Hepa tocyte transplantation and artificial liver have evolved into a simpler alternative to liver failure treatment.Artificial liver can be used as Liver replacement therapy in patients who were waiting for the liver transplantation with chronic liver disease.The ideal biological artificial liver must have the liver material metabolism,detoxification,synthesis and secretion and other functions.Nowadays bio-artificial liver has carried out a large number of clinical trials and get some progress.?This article is now discuss the status of bio-artificial liver and its re placement therapy prospects.     

A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population

Background  

The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals.     

Hepatic assist devices

Acute liver failure (ALF) is associated with significant morbidity and mortality. Better understanding of the pathophysiology of the disease and improvements in patient management have resulted in increased survival. Liver transplantation remains the only proven therapeutic modality. Primarily because of organ donor shortage, a number of strategies have been developed in an attempt to support patients with severe ALF until either an organ becomes available for transplantation or until they recover. Liver support strategies include use of either non-biological or biological systems. Non-biological systems include plasma exchange, hemodialysis, hemofiltration, charcoal and resin hemoperfusion. These systems are able to remove toxins, but their utility is limited by their inability to provide missing liver synthetic function. Biological liver support systems include ex vivo liver perfusion and use of hepatocyte-based extracorporeal devices. Like non-biological systems, biological ones provide a means of detoxification and in addition biotransformation and biosynthetic functions. The major limitation of these systems is the lack of availability of an effective highly differentiated human hepatocyte line for clinical use. Currently clinically tested liver support systems use either porcine hepatocytes or human hepatoma cell lines. As liver support therapy evolves, there will be a role for both biological and non-biological liver support systems to treat specific forms of liver failure.