512例胆管细胞癌的临床及预后特点

目的： 胆管细胞癌(cholangiocarcinoma，CCA)恶性程度较高，总体预后较差，初诊时分期较晚，治疗手 段有效率欠佳。本研究探索影响CCA发生、发展的临床特点及预后相关因素，以期为CCA的早期诊断及临床治疗提 供潜在的手段。方法： 回顾性分析中南大学湘雅二医院2002 年以来经病理确诊且临床资料完善的512 例CCA患者的 病历资料。利用Kaplan-Meier 法绘制生存曲线、log-rank 进行单因素分析，多元Cox回归法对有意义的变量进行多因 素分析。结果： CCA发病率≤60 岁者高于>60 岁者(61.13% vs 38.87%)，男性略高于女性(52.54% vs 47.46%)，糖类抗 原19-9(carbohydrate antigen 19-9，CA19-9)≥35 μg/L 者占66.21%，病理分期III 和IV 期患者居多(分别占49.22%和 17.58%)。单因素分析发现ALB，ALP，CA19-9 等因素与预后相关，多因素Cox 生存分析发现ALP，CA19-9，肿瘤 最大直径等是CCA预后独立影响因素。结论：CCA发病率≤60 岁人群较高，初诊时分期较晚，CA19-9 是较为敏感的 实验室指标。ALP，CA19-9，肿瘤最大直径，合并子瘤，肝硬化及TNM分期是影响CCA预后的独立因素。     

Accessibility and Perceived Clinical Utility of the GMFM-66

The 66-item Gross Motor Function Measure (GMFM-66) requires a computer program for scoring. The primary purpose of this study was to pilot test the scoring software and examine the perceived clinical utility of the GMFM-66 as judged by 48 pediatric physical therapists. Sixty-one percent of therapists were confident in their ability to interpret the information from the computer program following one hour spent reading the tutorial and interpretation guidelines. Ninety-three percent of respondents perceived the overall clinical utility of the GMFM-66 in terms of administration, scoring and interpretation to be the same or more clinically useful than the GMFM-88.     

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows

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The wobbly evidence base of reproductive medicine

In assisted reproduction, there is strong evidence for some things done, but no or only very weak evidence for others. There are several reasons for this. Most assisted reproduction procedures have small signal-to-noise ratios. This means that their treatment effect is sometimes only little better than the spontaneous conception rate, or the conception rate with traditional treatment. Hence, large trials are required. These demand complex multicentre logistics. The latter require substantial funding and funding for reproductive medicine in most countries is notoriously difficult to obtain (as opposed, for example, to oncology research or cardiovascular research). Apart from these funding issues, the creation of embryos specifically for research is only allowed in a limited number of European countries, thus tempting clinicians to skip preclinical studies altogether and go directly for clinical application in their patients, raising an ethical issue. Introducing new treatments into the clinic without proper evidence, however, is perhaps even more of an ethical issue. Subfertile couples are very vulnerable and should not be exploited.In assisted reproduction, we have strong evidence for some things we do, but no or only very weak evidence for others. There are several reasons for this. Most assisted reproduction procedures have small signal-to-noise ratios. Which means that their treatment effect is sometimes only little better than the spontaneous conception rate, or the conception rate with traditional treatment. Hence large trials are required. These demand complex multicentre logistics. The latter require substantial funding and funding for reproductive medicine in most countries is notoriously difficult to obtain (as opposed to, for example, oncology research or cardiovascular research). Apart from these funding issues, the creation of embryos specifically for research is only allowed in a limited number of European countries, thus tempting clinicians to skip preclinical studies altogether and go directly for clinical application in their patients, an ethical issue. Introducing new treatments into the clinic without proper evidence, however, is perhaps even more of an ethical issue. Subfertility couples are very vulnerable, they should not be exploited.VIDEO LINK: http://sms.cam.ac.uk/media/1401622     

Natural killer cells: from bench to cancer therapy

Natural killer (NK) cells are effectors of the innate immune system that play an important role in host response against viruses and tumour cells through the production of cytokines and direct cytolytic activity. There has been limited success reported from clinical trials in cancer patients treated with activated NK cells. Over the last decade, a better understanding of the biology of NK cells, NK cell receptors and the role of interleukin-15 has led to the development of new strategies using NK cells as immunotherapy for cancer treatment in the transplant and non-transplant settings.     

The Relationship of CCR5 Antagonists to CD4+ T-Cell Gain: A Meta-Regression of Recent Clinical Trials in Treatment-Experienced HIV-Infected Patients

Abstract

Purpose: Lower CD4+ T-cell counts are related to increased morbidity and mortality despite virologic suppression. CCR5 antagonists are associated with robust CD4+ T-cell responses. We examined the relationship of CCR5 antagonists to CD4+ T-cell gains. Design: Meta-regression of recent phase 2–3 trials evaluating new antiretroviral agents in treatment-experienced subjects. Methods: We analyzed the relationship of CCR5 antagonists to CD4+ T-cell count increase 24 weeks after initiating the new regimen using a linear model with generalized estimating equations controlling for differing rates of virologic suppression. Each treatment group was treated as a data point weighted by sample size. Results: We included 46 treatment groups from 17 trials (11 groups from 5 trials used CCR5 antagonists). Controlling for average baseline HIV-1 RNA and proportion of subjects achieving HIV-1 RNA <50 copies/mL, use of a CCR5 antagonist was associated with an additional significant CD4+ T-cell gain of +30/μL (95% CI, 19–42) at 24 weeks compared to treatment groups not using a CCR5 antagonist. Conclusions: Use of a CCR5 antagonist was associated with an enhanced CD4+ T-cell count response independent of virologic suppression. This observation supports further evaluation of CCR5 antagonists in patients with discordant immunologic and virologic responses to ART.     

Regulatory T cells: the future of autoimmune disease treatment

ABSTRACT

Introduction: CD4 + T regulatory cells (Tregs) have been described as the most potent immunosuppressive cells in the human body. They have been found to control autoimmunity, and clinical attempts have been made to apply them to treat autoimmune diseases. Some specific pathways utilized by Tregs in the regulation of immune response or Tregs directly as cellular products are tested in the clinic.

Areas covered: Here, we present recent advances in the research on the biology and clinical applications of Tregs in the treatment of autoimmune diseases.

Expert opinion: Regulatory T cells seem to be a promising tool for the treatment of autoimmune diseases. The development of both cell-based therapies and modern pharmacotherapies which affect Tregs may strongly improve the treatment of autoimmune disorders. Growing knowledge about Treg biology together with the latest biotechnology tools may give an opportunity for personalized therapies in these conditions.