术前减黄治疗肝门部胆管癌的临床研究

目的 探讨术前减黄治疗肝门部胆管癌的临床价值.方法 选取2005年1月-2015年12月在武汉大学人民医院接受手术治疗的肝门部胆管癌患者52例,按照术前是否行减黄治疗分为两组:减黄组24例,术前行减黄治疗;未减黄组28例,直接行手术治疗.比较两组患者手术时间,术中出血量,住院时间,围手术期肝功能变化情况,术后并发症发病率,肿瘤复发率,1、3、5年生存率等指标.采用SPSS 19.0软件进行统计学分析.对两组患者术后采用电话、门诊检查或住院复查等随访方式,随访时间8 ～ 60个月.结果 减黄组住院时间较未减黄组延长,差异有统计学意义(P＜0.05).两组手术时间、术中出血量、术后复发率、术后并发症发病率(包括胆瘘、出血、发热、胸腔积液、腹腔感染、伤口感染、肺部感染、肝功能衰竭等),差异无统计学意义(P＞0.05).减黄组减黄前丙氨酸氨基转移酶为(98.0±51.7) U/L、天门冬氨酸氨基转移酶为(94.2 ±44.2) U/L、总胆红素为(177.5 ±64.1) μmol/L、直接胆红素为(160.2 ±61.9) μmol/L;减黄后丙氨酸氨基转移酶为(71.2±13.8) U/L、天门冬氨酸氨基转移酶为(60.0±12.1) U/L、总胆红素为(93.5±20.7) μmol/L、直接胆红素为(76.3±18.1) μmol/L,差异有统计学意义(P＜0.05).减黄前后白蛋白差异无统计学意义(P＞0.05).减黄组随访患者21例,未减黄组随访患者25例,其他失访.两组患者术后1、3、5年生存率差异无统计学意义(P＞0.05).结论 术前减黄可在一定程度上改善肝门部胆管癌患者肝功能情况.但对于一般情况较好的患者,术前减黄并不能改善患者的预后,故不推荐常规术前减黄.     

Deinococcus Mn2+-peptide complex: A novel approach to alphavirus vaccine development

Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses.In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections.Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000 Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma-inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost-effective manner.     

Current treatment options and investigational drugs for Waldenstrom’s Macroglobulinemia

Introduction: Waldenström’s Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data.

Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM. Recently, the Bruton’s tyrosine kinase inhibitor ibrutinib has been licensed for use in WM with exciting results. Several investigational single agent and combination regimens are being evaluated for response, efficacy and tolerability in phase II clinical trials, including new generation monoclonal antibodies (ofatumumab), immunomodulatory agents (thalidomide and lenalidomide), proteasome inhibitors (bortezomib and carfilzomib), Bruton’s tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin pathway inhibitors (everolimus and perifosene), and histone deacetylase inhibitors (panobinostat) both in the setting of newly diagnosed and relapsed/refractory disease.

Expert opinion: WM therapeutic approach should be individualized for each patient in accordance to the intensity of the disease characteristics, age, comorbidities, efficacy, tolerability and safety profile of each drug.     

Emerging translational science discoveries,clonal approaches,and treatment trends in chronic myeloproliferative neoplasms

The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post‐ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.     

The 21st Century Cures Act and Early Feasibility Studies for Cardiovascular Devices: What Have We Learned,Where Do We Need to Go?

Performance of early feasibility studies in the United States can advance the goal of evaluating the safety and effectiveness of new devices aimed at unmet clinical needs and facilitating earlier access for U.S. patients to new technology. Early feasibility studies are an important component of the 21st Century Cures Act, enacted by Congress in 2016. Although regulatory processes have improved since the introduction of the Early Feasibility Studies Program, impediments at the hospital and clinical site level remain. In this paper, the authors review these issues and outline the structure and function of a clinical site consortium designed to address the problems and improve the U.S. clinical trial ecosystem.     

特应性皮炎治疗药物研究进展

【摘要】 特应性皮炎的发病机制尚未完全清楚,可能与免疫紊乱、皮肤屏障功能障碍及环境因素有关。特应性皮炎最重要的症状是严重瘙痒,并可极大地影响患者的生活质量。目前其治疗仍然是一个挑战。多数患者可通过避免激发因素、基础皮肤护理和外用抗炎药得到较好疗效;少部分患者皮损广泛且对常规治疗抵抗,需要系统治疗。生物制剂在中重度特应性皮炎患者中已得到较广泛地应用。本文综述特应性皮炎的药物治疗研究进展。     

超脉冲CO2点阵激光治疗甲真菌病疗效观察

目的 评估超脉冲CO2点阵激光治疗甲真菌病的疗效及安全性。 方法 收集临床具有甲真菌病典型临床表现且真菌真接镜检阳性病例,给予超脉冲CO2点阵激光治疗8次,根据患者年龄、病甲感染类型、甲板厚度、感染面积、甲板感染长度等进行临床甲真菌病临床评分指数（SCIO）和甲真菌病严重度指数（OSI）评估,比较治疗前、治疗结束、疗后1个月和疗后3个月的临床评分变化,计算真菌学清除率,记录观察激光治疗的不良反应。 结果 共入组20例甲真菌病患者共75个病甲,完成治疗及随访18例71个病甲。治疗前、治疗结束、疗后1个月及3个月SCIO分别为13.07 ± 6.47、9.03 ± 6.14、8.51 ± 6.99、7.89 ± 7.26,OSI分别为21.11 ± 11.94、13.63 ± 12.10、14.18 ± 13.65、13.70 ± 13.93,疗后3个时间点真菌学清除率分别为57.75%（41/71）、59.15%（42/71）、61.97%（44/71）,SCIO、OSI与治疗前相比差异均有统计学意义（均P < 0.05）。其中远端侧位甲下型SCIO和OSI治疗前分别为12.48 ± 5.41和16.44 ± 9.89,疗后3个月降至5.01 ± 5.56和6.44 ± 8.26;而全甲营养不良型SCIO和OSI治疗前分别为17.86 ± 3.98和34.05 ± 2.56,疗后3个月分别为15.88 ± 4.10和31.00 ± 7.28。治疗过程中偶有一过性轻微疼痛,未发生甲下出血等其他不良反应。 结论 超脉冲CO2点阵激光治疗远端侧位甲下型等轻中度甲真菌病,尤其甲板侵入较浅且甲板生长速度较快时疗效可靠。超脉冲CO2激光对真菌仅表现为直接的抑制和杀伤作用,治疗时应根据病情适当延长疗程。     

手法复位加单臂外固定架治疗高龄股骨转子间骨折的临床研究

目的：探讨手法复位加单臂外固定架治疗高龄股骨转子间骨折的临床疗效。方法：将符合要求的90例患者随机分为2组,治疗组60例,对照组30例。治疗组采用手法复位加单臂外固定支架固定治疗;对照组采用动力髋螺钉固定治疗。分别观察记录2组患者的手术时间、术中出血量、骨折愈合时间及术后骨折并发症发生情况,并于患者骨折愈合后采用创伤性髋关节功能评分标准对患者进行髋关节功能评分。结果：①治疗组手术时间、术中出血量及骨折愈合时间均小于对照组（t=15.338,P=0.000;t=33.610,P=0.000;t=21.855,P=0.000）,2组髋关节功能评分比较,差异无统计学意义（t=-1.720,P=0.090）。②术后对照组发生深部感染2例,髋内翻1例,螺钉松动部分退出1例,深静脉血栓形成3例;治疗组无骨折并发症发生。结论：手法复位加单臂外固定架在恢复高龄股骨转子间骨折患者髋关节功能方面与动力髋螺钉固定相当,但手术时间短、术中出血量少、骨折愈合时间短、术后并发症也较少,是治疗高龄股骨转子间骨折的有效方法,值得推广应用。     

股骨远端微创固定系统与髁部支持钢板治疗股骨远端C型骨折的疗效分析

目的:分析比较股骨远端微创内固定系统与髁部支持钢板固定治疗股骨远端C型骨折的临床疗效。方法:回顾性分析2003年1月至2010年4月在福建医科大学附属第二医院采用股骨远端微创内固定系统固定治疗的63例(Ⅰ组)及采用髁部支持钢板固定治疗的76例(Ⅱ组)股骨远端C型骨折患者的病历资料,比较2组患者的手术时间、术中出血量、骨折愈合时间及术后3个月、6个月及12个月时的HSS膝关节评分。结果:①Ⅰ组患者的手术时间、术中出血量及骨折临床愈合时间均少于Ⅱ组,差异有统计学意义(U=3.863,P=0.000;U=3.759,P=0.000;U=5.007,P=0.000)。②两组HSS膝关节评分比较,存在时间效应(F=105.801,P=0.000),不存在组别效应(F=0.344,P=0.558),测量时间与处理方案间不存在交互作用(F=0.069,P=0.856)。结论:对于股骨远端C型骨折患者而言,股骨远端微创固定系统和髁部支持钢板固定相比有术中出血量少、手术时间短、骨折愈合快的优势,但二者对患者膝关节功能的疗效无差别。