Innovation in Orthopaedics: Part 2—How to Translate Ideas and Research into Clinical Practice

Purpose of ReviewThis paper presents some approaches and techniques for translating an idea or research into clinical practice, considering the innovation development process.Recent FindingsInnovative tools have been a key solution for healthcare problems, such as musculoskeletal disorders, which represent a great economic burden and are among the leading causes of disability. There has been an increase in publications on this topic, but there has been no analysis of the process of innovation development. This review describes the innovation phases for translating an idea or research into clinical practice, considering the stages of discovering the opportunity, innovation creation, project specification, technology development, and innovation launch.SummaryAn analysis of the innovation development process to translate an idea or research into clinical practice, including concepts, approaches, and techniques that shows the “why”, “how”, and “what” of innovation.     

MAGE—A1，A2，A3，A4在膀胱移行细胞癌组织及细胞株中基因表达的研究

目的：研究膀胱移行细胞癌（TCC）中黑色素瘤抗原（MAGE）基因表达。方法：逆转录聚合酶链反应（RT—PCa）技术检测20例膀胱TCC患者癌组织和3株膀胱TCC细胞株124、EJ、BIU87中MAGE—A1、A2、A3、A4基因mRNA表达。结果：20例膀胱，TCC癌组织中19例（95％）至少表达一种MAGE—A基因，12例MAGE—A1阳性（60％），16例MAGE—A2阳性（80％），11例MAGE—A3阳性（55％），18例MAGE—A4阳性（90％），MAGE—A1—4均阳性8例（40％）。膀胱，TCC细胞株T24中MAGE—A1—4基因均表达，口中MAGE—A3、A4基因表达，BIU87中MAGE—A2、A3、A4基因表达。结论：MAGE基因在膀胱TCC中有较高表达，可望成为膀胱，TCC免疫治疗的靶基因。     

经食管二维超声心动图在二尖瓣成形术中的临床应用

目的评价经食管二维超声心动图（2D-TEE）在二尖瓣成形术中的临床应用价值。方法共收集二尖瓣脱垂并中度以上返流行心脏外科二尖瓣成形手术的患者35例。术中行2D-TEE检测二尖瓣病变类型与扇叶分区定位,与手术发现进行对照,并于术后即刻评价二尖瓣成形手术效果。结果35例患者中发现病变部位共40处,36处病变部位与术中所见相符（符合率90％）,其中5例（14％）术后监测发现2级以上瓣膜返流,立即改行人工瓣置换术。结论2D-TEE在二尖瓣成形术中具有对病变部位分区定位、指导术式选择,具有缩短手术时间、提高手术成功率的重要临床应用价值。     

川芎嗪微乳的脑靶向性研究

目的制备川芎嗪微乳,初步考察其在小鼠体内的脑靶向性。方法分别给小鼠口服川芎嗪微乳和川芎嗪片剂混悬液,在给药后不同时点分别观察并比较小鼠脑部川芎嗪的血药浓度。结果川芎嗪微乳总靶向效率(overall targeting efficiency,TE)=18.75%,川芎嗪片剂混悬液TE=12.25%;靶向指数(targetingindex,TI)=606.00%,相对靶向效率(relative overall targeting efficiency,RTE)=53.06%。结论小鼠口服川芎嗪微乳后,川芎嗪在脑部的含量明显高于小鼠口服川芎嗪片剂混悬液后脑部川芎嗪含量,且川芎嗪在脑部平均滞留时间(mean residence time,MRT)也明显延长,说明川芎嗪微乳具有脑靶向性和缓释性。     

肝脏移植术后移植物抗宿主病的诊断和治疗

【目的】 探讨肝脏移植术后移植物抗宿主病（GVHD）的诊断和治疗。【方法】 分析我院2003年10月至2009年6月完成的772例肝脏移植的临床资料,总结肝脏移植术后GVHD的诊断和治疗经验。【结果】 772例肝脏移植术后5例病人发生GVHD,发病率为0.65%（5/772）,5例患者均在肝脏移植后2～5周出现发热、皮疹、腹泻和全血细胞减少,肝功能均接近正常,经皮肤活检和骨髓穿刺检查证实,并排除巨细胞病毒（CMV）和EB病毒感染。经过调整免疫抑制剂,加用IL-2受体单克隆抗体,积极抗感染和支持对症治疗,2例患者痊愈,3例患者死于严重感染、消化道出血和多器官功能衰竭。【结论】 肝脏移植术后GVHD死亡率高,早期诊断,及时调整免疫抑制剂方案,积极抗感染和营养支持是治疗的关键。     

雄激素剥夺条件下阻断自噬增加LNCaP细胞凋亡

目的 探讨雄激素剥夺条件下阻断自噬后LNCaP细胞凋亡变化与半胱天冬酶(caspase)激活的关系.方法 应用激光共聚焦显微镜、RT-PCR方法观察雄激素剥夺致细胞自噬增加后,利用DAPI染色观察细胞凋亡变化及药物抑制caspase后对凋亡的影响.结果 ①雄激素去除后LNCaP细胞自噬体增加,标准培养基(CM)培养下LNCaP细胞自噬体数量为1.90分;无血清培养基(SF)中细胞自噬体数量增高为2.64分;加入双氧睾酮(SFA组)后细胞自噬体下降至1.85分(P<0.01).CM中LNCaP细胞LC3 mRNA表达率为23%,血清饥饿12 h后,LC3表达量上调至100%,而SFA组LC3 mRNA表达量为86%;血清饥饿24 h后,SF组LC3 mRNA表达量为62%,SFA组为35%.②SF组和SFA组LNCaP细胞基础凋亡率分别为(3.19±1.09)0A和(3.01±0.33)%,加入3-甲基腺嘌呤(3-MA)阻断自噬24 h后,SF组凋亡率为(10.90±2.91)%,SFA组为(4.63±1.69)%.SF+3-MA组中加入Z-VAD-FMK后,细胞凋亡减至(1.16±0.52)%.组间差异有统计学意义(P<0.01).结论 剥夺雄激素后LNCaP细胞中自噬明显增加,阻断自噬后凋亡发生率增加.     

颅外段椎动脉先天发育异常的超声诊断价值

目的探讨彩色多普勒超声对颅外段椎动脉发育异常的诊断价值及其临床意义。方法对2012年1月至2013年3月来我院疑诊为椎动脉型颈椎病患者进行颅外段椎动脉超声检查,观测椎动脉管腔结构、血管走行、血流信号等变化。其中152例颅外段椎动脉发育异常患者同时进行磁共振血管成像（MRA）或血管造影检查。结果发现236例患者椎动脉发育异常,其中椎动脉发育不良者为114例,椎动脉走行变异者为75例,椎动脉发育不良合并椎动脉走行变异者为47例。其中152例患者同时进行磁共振血管成像（MRA）或血管造影检查,其多普勒超声与MRA或血管造影的诊断结果完全符合。结论彩色多普勒超声能准确、快捷的诊断颅外段椎动脉发育异常,且无创、检查费用较低,具有很高的临床应用价值。     

Endomiocardite de Löffler – a propósito de um caso clínico

Loeffler's endocarditis is an acute form of primary restrictive cardiomyopathy. We report the case of a young woman with pleuritic chest pain associated with fever and hypereosinophilia. She was hospitalized with suspected acute myopericarditis and was treated with aspirin, leading to clinical improvement. Ten days after discharge, she was rehospitalized due to recurrence of chest pain. The echocardiogram showed what appeared to be a mass filling the apex of the right ventricle (RV). She was referred for magnetic resonance imaging, which revealed marked myocardial thickening in the apex of the RV. The patient underwent an endomyocardial biopsy, resulting in a diagnosis of eosinophilic endocarditis. After treatment with prednisolone, all symptoms and the eosinophilia disappeared, and there was complete remission of the RV abnormalities. After three years of follow-up, the patient remains asymptomatic. This case shows that, even without an etiologic diagnosis of eosinophilia, the prognosis for Loeffler's endocarditis can be favorable if treatment is initiated early.     

Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

The aims of the present study were (i) to assess the in vitro genetic stability of S19 and RB51 Brucella abortus vaccines strains and (ii) to evaluate the ability of multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) as a tool to be used in the quality control of live vaccines against brucellosis. Sixty-three batches of commercial S19 (n = 53) and RB51 (n = 10) vaccines, produced between 2006 and 2009, were used in this study. S19 and RB51 vaccines were obtained from, respectively, seven and two different manufacturers. Ten in vitro serial passages were performed on reference strains and on selected batches of commercial vaccines. All batches, reference strains and strains of serial passages were typed by the MLVA16. The results demonstrated that B. abortus S19 and RB51 vaccine strains are genetically stable and very homogeneous in their respective groups. Anyway, batches of S19 from one manufacturer and batches of RB51 from another presented genotypes distincts from the reference vaccine strains. In both cases, differences were found on locus Bruce07, which had addition of one repeat unit in the case of S19 batches and the deletion of one repeat unit in the case of RB51 batches. In summary, MLVA16 proved to be a molecular tool capable of discriminating small genomic variations and should be included in in vitro official tests.     

Health related quality of life among patients with chronic hepatitis C: a cross-sectional study of sociodemographic,psychopathological and psychiatric determinants

IntroductionChronic hepatitis C virus infection patients have higher rates of psychiatric disorders than the general population. Chronic hepatitis C virus infection is known to be associated with impaired health related quality of life. To our knowledge, there is no previous research of health related quality of life in chronic hepatitis C patients that combined structured psychiatric interview and careful psychopathological evaluation, including depression, anxiety and fatigue instruments. The aim of this study was to evaluate health related quality of life of chronic hepatitis C patients and to investigate the association with sociodemographic, psychopathological and psychiatric factors.Materials and methodsEighty-one individuals with chronic hepatitis C virus infection receiving care at a Brazilian public university-based outpatient service for infectious diseases were enrolled in the study. The World Health Organization Quality of Life Scale Brief Version was used to assess health related quality of life. Standard psychiatric interview (Mini International Neuropsychiatric Interview-Plus) was conducted to establish Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I psychiatric diagnosis. Further instruments completed psychopathological investigation: Beck Depression Inventory, Hospital Anxiety and Depression Scale, Brief Fatigue Inventory, Hamilton Depression Scale and Hamilton Anxiety Scale. Pearson Chi-Square and Kruskal–Wallis were performed for categorical and continuous univariate analysis, respectively. Correlation between psychopathological and health related quality of life scores was performed according to Spearman's correlation. Multivariate analysis was performed according to stepwise forward ordinal logistic regression. The significance threshold was fixed at α = 0.05.ResultsDepressive disorders were associated with worse scores in overall health related quality of life and in all domains. Fatigue was associated with lower scores in physical and psychological domains, and married status with higher scores in psychological health related quality of life. We found strong correlation among scores of depression, fatigue and health related quality of life.ConclusionDepression and fatigue must be properly investigated and managed in HCV patients in order to improve HRQL. WHOQOL-BREF proved to be a useful instrument to assess HRQL in HCV patients.