Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia

Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells.

Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML.

Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease.     

Efficacy and Feasibility of Allogeneic Hematopoietic Stem-Cell Transplantation in the Treatment of Refractory Acute Myeloid Leukemia

Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.

女性难治性膀胱过度活动症患者心理弹性及保护性因素研究

目的探讨女性难治性膀胱过度活动症患者心理弹性状况及保护性因素，为改善其身心健康提供依据。方法采用心理弹性量表、症状自评量表、艾森克人格问卷、社会支持量表、焦虑及抑郁量表对80例女性难治性膀胱过度活动症患者进行问卷调查。结果女性难治性膀胱过度活动症患者心理弹性得分为（54.10±8.27）分，显著低于国内常模（P＜0.05）。患者的一般情况（病程、年龄、文化程度）对心理弹性的预测作用不明显（R2=0.14，F=18.10），当社会支持、SCL-90、人格特质、SAS、SDS进入方程后，对患者的心理弹性具有较明显的预测作用（R2=0.67，△R2=0.46，F=115.22）。结论女性难治性膀胱过度活动症患者心理弹性较差，社会支持、SCL-90、人格特质、焦虑抑郁情绪是其重要的影响因素，应重视患者存在的心理问题，发掘心理弹性的保护性因素并积极干预，促进其身心健康。     

难治性胃食管反流病临证研究

难治性胃食管反流病是临床疑难病,症状反复,缠绵难愈,治疗棘手。中医药治疗“反酸”“吞酸”证历久源远,充分挖掘古籍,深研病机,提炼治法,发挥中医药特色,对治疗本病意义深远。     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

老年难治性胃食管反流病患者食管动力学特征和反流特点分析

目的 分析老年难治性胃食管反流病（rGERD）患者食管动力学特征和反流特点。方法 以我院2017 年2 月～2019 年12 月收治的100 例rGERD 患者为观察对象。按照年龄分为老年组（年龄≥60 岁）42 例和非老年组（年龄＜60 岁）58 例。比较两组基线资料、临床表现特征、食管动力学特征、反流特点。结果 老年组与非老年组在性别、BMI 指数、吸烟及饮酒方面比较，差异均无统计学意义（P＞0.05）。老年组胸痛、上腹部不适及慢性咳嗽发生率均高于非老年组，差异均有统计学意义（P＜0.05）。老年组LESP 及LEPP 水平均低于非老年组，差异均有统计学意义（P＜0.05）。老年组酸反流、弱酸反流、非酸反流、气体反流、气液混合反流次数均高于非老年组，差异均有统计学意义（P＜0.05）。结论 老年rGERD 患者存在明显的食管动力学异常，且该类患者的反流主要是弱酸反流、非酸反流、气体反流、气液混合反流。     

EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

硫喷妥钠治疗小儿难治性惊厥持续状态疗效观察

目的 探讨对小儿难治性惊厥持续状态的有效治疗方法。方法 对14例小儿难治性惊厥持续状态采用硫喷妥钠治疗并观察疗效。结果 硫喷妥钠治疗有效率为100％，1例出现呼吸抑制，3例于停药后复发。结论 硫喷妥钠对小儿难治性惊厥持续状态有明显疗效，但易发生呼吸抑制。惊止后应维持一段时间，以免复发。     

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

 In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics. Received: 10 March 1997 / Accepted: 18 May 1997