A Comparison of the Clinical Outcomes of Haploidentical Transplantation and Other Graft Sources in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

BackgroundMost likely due to the availability of potential stem cell sources, there appears to be a growing usage of haploidentical (haplo) donors for cases of acute lymphoblastic leukemia involving high-risk features or relapse.Patients and MethodsThis study compared the outcomes of stem cell transplantations (SCTs) using haplo and other stem cell sources, namely, matched sibling donors (MSDs), matched unrelated donors (MUDs), and cord blood transplantations (CBTs). Literature searches were conducted of the MEDLINE and Embase databases from inception to December 2020.ResultsTwenty-eight studies were examined (17 retrospective and 11 prospective). There were no significant differences in the overall survival of haplo and those of the other stem-cell sources. For haplo versus matched donor (MSD or MUD), the pooled odds ratio (OR) was 0.94 (95% CI, 0.79-1.12; I², 22%); while for haplo versus CBT, the OR was 1.24 (95% CI, 0.78-1.96; I², 28%). The cumulative relapse incidence was significantly higher for MSD than haplo (OR, 0.69; 95% CI, 0.48-0.99; I², 48%). Both grade II-IV acute and long-term graft-versus-host disease (GVHD) were significantly higher for haplo than MSD (OR, 1.78; 95% CI, 1.15-2.74; I², 28%; and OR, 1.33; 95% CI, 1.00-1.77; I², 14%, respectively). The other clinical outcomes did not demonstrate any statistical differences.ConclusionThe outcomes of patients treated with haplo-SCT appear comparable with those of the SCTs using other sources. The higher probability of developing GVHD supports the need for a novel method to harness T-cell alloreactivity     

Method’s corner: Allergist’s guide to network meta-analysis

Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.     

帕金森病与炎症相关的研究进展

帕金森病是一种进展性的中枢神经系统变性疾病，主要病理特征是黑质多巴胺能神经元变性死亡和脑干神经元内α突触核蛋白积聚形成路易体。其病因主要为遗传因素和环境因素。该病主要会引起静止性震颤、运动迟缓、肌肉僵直等一系列的运动症状。然而其发病机制并不明确，主要可能与线粒体功能障碍、氧化应激、蛋白质改变及炎症反应相关。小胶质细胞与炎症反应密切相关，而小胶质细胞过度激活是帕金森病发病的病理生理基础。血清炎症因子升高与帕金森病有关，可用于早期诊断并预测疾病预后。目前抗炎治疗成为帕金森病新的研究热点。该文主要综述帕金森病的炎症机制、相关的炎症因子及抗炎药物的研究进展。     

A comparison of two Fendrix hepatitis B vaccination schedules in patients with inflammatory bowel disease

Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations. In this retrospective cohort study, we examined the serological response after a modified vaccination schedule which includes an initial double dose of Fendrix in patients with IBD and compared the results with the serological responses of patients with IBD who received the standard schedule. Seroprotection rates were 86.2 % and 88.9 % in the modified and standard schedule groups respectively. One-third of patients obtained seroprotection after only one double dose vaccine. A double dose may be considered in patients with IBD at high short-term risk of HBV infection when a rapid protective response is warranted.     

An 8-week aerobic cycling intervention elicits improved gait velocity and biomechanics in persons with Parkinson’s disease

BackgroundIt is unknown if improvements in gait velocity following an aerobic cycling intervention are accompanied by improved gait biomechanics in individuals with Parkinson’s disease (PD) or if gait abnormalities are exaggerated in response to increased velocity.Research questionCan an 8-week aerobic cycling intervention elicit improvements in locomotor function in individuals with mild to moderate PD?MethodsA secondary analysis of data from a randomized clinical trial was conducted in individuals with mild to moderate idiopathic PD (N = 28). Participants were randomized to an aerobic cycling intervention (PD_ex, N = 14) consisting of 24 sessions at a targeted aerobic intensity of 60–80% of heart rate reserve or to a no intervention control group (PD_control, N = 14). Change in comfortable walking speed in addition to gait kinematics, kinetics, and spatiotemporal variables using motion capture were obtained at baseline and end of treatment (EOT).ResultsThe PD_ex group made significantly greater improvements in the primary outcome, change in comfortable gait velocity, from 0.86 ± 0.24 m/s at baseline to 1.00 ± 0.23 m/s at EOT compared to the PD_control group who declined from 0.91 ± 0.23 m/s at baseline to 0.80 ± 0.29 at EOT (P = 0.002). Improvements in gait velocity for the PD_ex group were accompanied by improvements in gait kinematics, kinetics, and spatiotemporal parameters, while the PD_control group demonstrated slight worsening in all gait parameters over the 8-week period.SignificanceThe 8-week moderate- to high-intensity cycling intervention elicited significantly greater improvements in gait velocity compared to the PD_control group. Increased gait velocity was accompanied by normalization of gait biomechanics, rather than an exaggeration of existing gait deviations. Aerobic cycling may be a viable treatment approach to improve gait velocity and gait biomechanics in individuals with mild to moderate PD and may mitigate declines in mobility.     

社区动脉粥样硬化风险研究的进展和展望

社区动脉粥样硬化风险（ARIC）研究是1987年由美国心、肺和血液研究所资助的关注非洲裔美国人心血管健康的最大研究。旨在调查心脏病的危险因素以及心血管疾病与认知之间的联系。ARIC研究的许多发现加深了对动脉粥样硬化性心血管病病因的了解,在心血管病预防领域做出了重大贡献,证明了以人群为基础的研究对改善健康和预防疾病的重要性。主要概述ARIC研究的起源、目的、研究设计、对心血管医学的贡献以及未来的发展方向。     

稳定性冠心病血瘀证的血浆定量蛋白质组学探析＊

目的 基于数据非依赖性采集的定量蛋白质组学技术（data independent acquisition，DIA）对稳定性冠心病血瘀证患者的血浆蛋白质进行研究分析，初步探索冠心病血瘀证的关键生物学过程与核心靶点。方法 选择中国中医科学院广安门医院心血管科收治的5例稳定性冠心病患者作为疾病观察组，同时选取健康成人5人作为对照组，采用DIA蛋白质组学技术对受试者的血浆进行检测，确定蛋白质表达量后进行差异蛋白质表达分析、GO富集分析、KEGG信号通路图查询和蛋白质互作网络分析。结果 在差异倍数为1.5倍时，疾病观察组相比于健康对照组，共鉴定到22个蛋白质下调，9个蛋白质上调。进一步的生物信息学分析表明，冠心病血瘀证的生物学过程与补体参与的慢性炎症反应有关，关键信号通路是补体与凝血级联反应的信号通路，核心蛋白质为C反应蛋白、转甲状腺素蛋白、补体因子H、维生素D结合蛋白等。结论 冠心病血瘀证的生物学过程与补体参与的慢性炎症反应有关。     

Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.