Treating acute myeloid leukemia in the modern era: A primer

Recent years have seen tremendous advances in treating acute myeloid leukemia (AML), largely because of progress in understanding the genetic basis of the disease. The US Food and Drug Administration approved 7 agents for AML in the last 2 years: the first new drugs in decades. In this review, the authors discuss these new approvals in the backdrop of an overall strategy for treating AML today. Treating AML in the modern era requires: 1) access to and use of upfront genetic and cytogenetic testing, not only to describe prognosis but also to help identify the best available therapy; 2) effectively working new therapies into a conventional backbone of treatment, including transplantation; and 3) continued commitment to clinical trials designed to capitalize on advances in genetics and immunology to foster the next wave of drug approvals.     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

激素受体阳性乳腺癌患者在不同内分泌治疗用药时间的类更年期症状及生命质量

目的探讨激素受体阳性(HR+)乳腺癌患者在不同内分泌治疗时间的类更年期症状和生命质量状况。方法采用横断面研究设计,收集2011—2017年就诊于四川省肿瘤医院经病理确诊的167例HR+乳腺癌患者,按内分泌治疗时间分为<12个月组、12~36个月组、>36个月组。应用改良Kupperman量表和乳腺癌生命质量测定量表(FACT-B)测量类更年期症状和生命质量。采用方差分析及χ2检验比较不同用药时间及用药类型患者的类更年期症状差异,采用协方差分析和多重线性回归分析不同用药时间患者的生命质量得分差异和类更年期症状对生命质量的影响。结果167例乳腺癌患者的类更年期症状得分为(14.5±7.6)分,现患率为87.4%(146/167),以失眠率最高(73.7%,123/167)。除失眠易激动外,选择性雌激素受体调节剂(SERM)使用者以潮热症状最多(64.8%,79/122),芳香化酶抑制剂使用者以骨关节痛症状最多(62.2%,28/45)。患者的FACT-B总得分为(104.5±15.5)分,达标率高达89.8%(150/167),但各维度状况参差不齐,以社会家庭及功能维度达标率最低,分别为73.0%(122/167)和50.9%(85/167)。<12个月组、12~36个月组和>36个月组患者的Kupperman总分分别为(15.0±1.3)分、(14.0±6.9)分和(14.5±7.4)分;FACT-B总得分分别为(102.7±17.8)分、(105.0±12.9)分和(105.6±16.7)分,差异均无统计学意义(均P>0.05)。多重线性回归分析结果显示,患者服用SERM类药物期间类更年期症状对生命质量存在负向影响,<12个月组、12~36个月组和>36个月组患者的标准偏回归系数分别为-0.67、-0.30和-0.50,影响程度在12~36个月组中最小。结论HR+乳腺癌患者回归社会、家庭和功能恢复情况较差,应重点关注。类更年期症状在内分泌治疗期间普遍存在,应积极处理以改善生命质量。     

Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.     

luminal型乳腺癌患者戈舍瑞林用药依从性现状及影响因素分析

目的了解luminal型乳腺癌患者戈舍瑞林用药依从性情况，分析影响其依从性的相关因素。 方法根据纳入及排除标准，收集2015年1月至2017年12月重庆医科大学附属第一医院内分泌乳腺外科使用戈舍瑞林治疗的luminal型乳腺癌女性患者174例进行回顾性分析。中位随访时间16个月(范围：1～54个月)，完成随访154例，失访20例，失访率为11.5%(20/174)。采用问卷调查评价其用药依从性，使用χ²检验和Mann-Whitney U检验比较不同特征患者依从性的差异；用Logistic回归分析影响患者依从性的相关因素。将患者分为≤40岁(103例)和>40岁(51例)2个亚组，进行亚组分析。 结果在完成随访的154例患者中，依从性好82例(53.2%，82/154)，依从性差72例(46.8%，72/154)。≤40岁组患者中，55.3%(57/103)依从性好，而>40岁组患者中仅49.0%(25/51)依从性好。全部患者中，文化程度、医保类型、不良反应和是否了解疗程时间均与乳腺癌患者戈舍瑞林用药依从性有关(χ²＝13.586、13.042、7.880、14.251，P均<0.050)；Logistic回归分析结果显示：高中及以下学历、居民医保和不了解戈舍瑞林的疗程时间为影响依从性的危险因素(OR＝2.772，95%CI：1.243～6.183，P＝0.013；OR＝5.188，95%CI：1.383～19.465，P＝0.015; OR＝3.363，95%CI：1.645～6.878，P＝0.001)。亚组分析显示：文化程度、职业、医保类型和是否了解疗程时间是≤40岁患者戈舍瑞林用药依从性的影响因素(χ²＝15.992、5.978、7.701、10.376，P均<0.050)；不良反应及医保类型是>40岁患者用药依从性的影响因素(χ²＝4.763、7.471，P均<0.050)。Logistic回归分析表明：高中及以下文化程度和不了解疗程时间是≤40岁患者用药依从性的危险因素(OR＝5.126，95%CI：2.086～12.598，P<0.001; OR＝3.631, 95%CI：1.500～8.792，P＝0.004)；居民医保是>40岁患者用药依从性的危险因素(OR＝64.315，95%CI：2.513～1 646.042，P＝0.012)，不良反应是>40岁患者用药依从性的保护因素OR＝0.189，95%CI＝0.047～0.759，P＝0.019)。 结论luminal型乳腺癌患者戈舍瑞林用药依从性较差，文化程度、医保类型及是否了解疗程时间都可能影响患者的依从性。≤40岁组和>40岁组患者依从性有差异，且影响因素不同，建议对不同年龄患者用药采用不同的干预措施。     

EGFR敏感突变晚期非小细胞肺癌一线治疗研究进展

分子靶向治疗是在驱动基因指导下的治疗，开启了非小细胞肺癌“个体化”与“精准”治疗时代。非小细胞肺癌驱动基因包括表皮生长因子受体（EGFR）、间变淋巴瘤激酶（ALK）和原癌基因-1（Ros-1）等。EGFR 突变是非小细胞肺癌最常见的靶点，表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）是治疗EGFR 突变晚期非小细胞肺癌的最有效药物，已广泛用于临床治疗，但后期耐药问题不可避免。近年来，为优化TKI 治疗，EGFR-TKI 联合治疗应运而生，不断探索有效的EGFR-TKI 联合治疗的方案。如EGFR-TKI 联合抗血管生成药物、化疗和免疫治疗等。本文就一线EGFR-TKI 药物及EGFR-TKI 联合治疗在一线探索的有关临床研究进展进行综述。     

基于肾络理论浅析慢性肾脏病的辨证施治

慢性肾脏病是指肾脏结构、功能障碍超过3 个月，可有蛋白尿、血尿、水肿、肾功能减退等诸多表现，属于临床难治性疾病范畴，最终往往进展至终末期肾病。而从中医肾络理论出发，肾络网络分布于肾脏，是肾之气血津液运行输布的重要通道，由于六淫外邪、瘀血、痰饮、浊毒等致病因素侵袭肾络，久病入络，致使络道气机郁滞、血行不畅，脏腑功能紊乱，从而引起尿浊、尿血、水肿、癃闭等诸多病变。“肾络瘀阻”是肾络病发生的核心病机，久之肾络渐损，即可进一步进展为“溺毒”“关格”等肾功能衰竭的病理阶段。基于肾络理论，运用中医药疗法对慢性肾脏病辨证施治，可有效减轻肾络病症，改善肾功能，从而控制疾病进展。     

连续性肾脏替代治疗联合中药灌肠对急性肾损伤患者尿KIM-1、NGAL水平的影响

目的:探讨连续性肾脏替代治疗(CRRT)联合中药灌肠对重症急性肾损伤患者尿肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平和预后的影响。方法:回顾性分析89例重症急性肾损伤患者临床资料,依据不同治疗方式分为对照组43例和研究组46例,对照组采用CRRT治疗,研究组采用CRRT联合中药灌肠治疗。比较两组尿量恢复时间、重症医学科(ICU)住院时间、治疗前后肾功能、尿KIM-1、NGAL水平,序贯器官衰竭估计评分(SOFA)、急性生理与慢性健康评分表(APACHEⅡ)评分和预后情况。结果:研究组尿量恢复时间、ICU住院时间均少于对照组(P<0.05)。治疗前,两组肾功能、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分比较,差异无统计学意义(P>0.05); 治疗后,两组肾功能指标、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分均较治疗前下降,研究组低于对照组,差异有统计学意义(P<0.05)。研究组死亡率较对照组低(P<0.05)。结论:CRRT联合中药灌肠能够促进重症急性肾损伤患者肾功能的恢复,降低尿KIM-1、NGAL水平,改善预后。     

蒲地蓝消炎口服液联合氢定乳膏治疗PICC局部湿疹临床观察

目的观察蒲地蓝消炎口服液联合应用氢定乳膏治疗PICC局部湿疹的疗效。方法采用病例对照研究的方法,选择PICC门诊2014年1月-2018年12月PICC局部湿疹患者80例,随机分为实验组39例和对照组41例,观察组用蒲地蓝消炎口服液联合氢定乳膏加局部敷料开窗法进行护理。对照组用氢定乳膏加局部敷料开窗法,比较2组的临床疗效。结果观察组39例,总有效34例(87.18%);对照组41例,总有效23例(56.10%)。2组比较差异具有统计学意义(P<0.01)。结论蒲地蓝消炎口服液联合氢定乳膏治疗PICC局部湿疹的效果优于对照组。