Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

Digital care technologies in people with dementia living in long-term care facilities to prevent falls and manage behavioural and psychological symptoms of dementia: a systematic review

European Journal of Ageing - Fall prevention and management of behavioural and psychological symptoms of dementia (BPSD) in long-term care (LTC) facility is a major challenge. The objective of this...     

经胫骨隧道前交叉韧带双束八股解剖重建的临床研究

目的观察关节镜下采用自体腘绳肌腱经胫骨隧道前交叉韧带（anterior cruciate ligament, ACL）双束八股解剖重建的临床效果。方法随访上海交通大学附属第六人民医院运动医学科2018年12月—2020年1月收治的103例ACL断裂患者资料，其中男78例，女25例，年龄18~45岁，平均（26.8±5.86）岁；左侧47例，右侧56例，均采用关节镜下自体腘绳肌腱经胫骨隧道打股骨骨隧道，ACL双束八股解剖重建。按照Lysholm评分、国际膝关节评分委员会（IKDC）膝关节评分、Tegner膝关节评分标准和膝关节自我效能量表K-SES评价疗效。结果所有患者术后获随访12～42个月，平均（24±8.18）个月；手术前、末次随访评分比较，Lysholm评分分别为（48.41±4.44）分和（95.34±1.91）分，2组比较差异有统计学意义（P<0.001)；IKDC评分分别为（44.05±4.36）分和（95.66±1.89）分，2组比较差异有统计学意义（P<0.001)；Tegner评分分别为（2.84±0.95）分和（6.15±0.89）分，2组比较差异有统计学意义（P<0.001)；膝关节自我效能量表K-SES量表（3.10±0.83）分和（7.12±1.10）分，2组比较差异有统计学意义（P<0.001)。末次随访103例患者前抽屉试验阴性，轴移试验阴性。98例（95.1%）Lachman试验阴性，5例（4.9%）Lachman试验1°阳性。结论关节镜下采用自体腘绳肌腱经胫骨隧道双束八股解剖重建前交叉韧带是一种恢复膝关节稳定性，恢复伤前活动水平的有效方法。     

住院癌症患者衰弱风险预测模型的构建与验证

目的 调查住院癌症患者发生衰弱的危险因素，构建风险预测模型并检验预测效果。方法 选取广州市2所三级甲等医院住院癌症患者570例，分为建模集422例和验证集148例。采用一般资料调查表、Fried衰弱表型、安德森症状评估量表、医院焦虑抑郁量表、中文版失志量表、营养风险筛查2002、Barthel指数量表进行调查，同期收集患者的白细胞介素-6、C-反应蛋白等实验室指标，应用logistic回归分析筛选衰弱的独立危险因素，构建风险预测模型。结果 住院癌症患者衰弱发生率为33.7%,衰弱的影响因素分别为：造口、营养状况、抑郁、神经心理症状群、消化道症状群、D-二聚体、白细胞介素-6。建模集和验证集ROC曲线下面积为0.788、0.735;Brier得分为0.205,校准斜率为0.625,决策曲线分析表明模型具有一定的临床可用性。结论 住院癌症患者衰弱发生率较高，构建的列线图预测模型具有较好的风险预测价值，可有效识别和筛选住院癌症衰弱高危人群。     

肝内胆汁淤积对联合弹性成像评估肝纤维化的影响

目的评估肝内胆汁淤积对联合弹性成像诊断肝纤维化分期的影响。方法收集入组患者的弹性成像、生化学和组织学数据。比较不同总胆红素(TB)组的剪切波速度(Vs)及肝纤维化指数(LF index)。使用ROC曲线下面积计算联合成像的准确度。结果以肝活检为金标准,TB异常组的Vs高于正常组(P<0.001),LF index在TB正常组及异常组中无区别(P>0.05)。不同TB分组中联合成像的准确度并无明显差异。结论肝内胆汁淤积对LF index无任何影响,使Vs轻微升高,但不会降低联合弹性成像评估肝纤维化分期的整体诊断效能。     

相变型纳米粒在动脉血栓的溶栓效果与靶向深度相关性的实验研究

目的 探讨相变型（PT）纳米粒（NPs）靶向动脉血栓深度及其与体外溶栓效果的相关性。方法 通过双乳化法制备一种靶向纤维蛋白的PLGA-PFH-CREKA NPs，验证其理化特性。采集新西兰大白兔的动脉血制作动脉血栓，分别置于荧光标记的靶向PT、非靶向PT、靶向载双蒸水（NPT）的NPs中，并用1 W/cm2声功率密度的低强度聚焦超声（LIFU）辐照，记录前后的质量，计算溶栓率，同时将处理后的血凝块制成切片，通过共聚焦显微镜观察、测量穿透深度，线性回归分析穿透深度与溶栓率的相关性。建立SD大鼠腹主动脉血栓模型，采用靶向PT、非靶向PT NPs评价体内靶向能力。结果 制备的靶向纤维蛋白的PT NPs平均粒径（297.8±11.82）nm，表面电位（1.44±0.22）mV，结构呈均匀球形，分散性好；体外溶栓实验发现靶向PT组与非靶向PT组、NPT组的溶栓率差异有统计学意义（F=108.508，P<0.001）；靶向PT组对血栓的穿透性相较于非靶向PT组、NPT组差异有统计学意义（F=96.187，P<0.001），线性回归发现靶向PT组对血栓穿透深度与溶栓率呈正相关（R2=0.818，P<0.05）。在SD大鼠腹主动脉血栓模型观察到靶向相变组较非靶向相变组对血栓的靶向性更好。 结论 靶向纤维蛋白的相变型NPs，对血栓纤维蛋白有良好的靶向性，有较好的溶栓效果，对血栓有很好的穿透性，并且相变所致溶栓率与血栓穿透深度呈正相关。     

Explore the Application Law of Disperse Stagnation and Purge Heat with Bitter-Acrid Medicinals in Treating Endogenous Cough

内伤咳嗽以肺失宣肃、肺气上逆为基本病机。“苦辛通降助肺法”即借助药物气味的升降作用以使肺气宣降复常的治法，用于治疗内伤咳嗽可通过苦辛配伍来助肺宣降、调节气机。张之文教授为全国温病学泰斗，提出以“苦辛通降助肺法”治疗内伤咳嗽，临床效果显著。本研究以张老医案为基础，通过数据挖掘来管窥“苦辛通降助肺法”治疗内伤咳嗽的应用规律，为内伤咳嗽的治疗提供新的思路和方法。     

Characteristics of older adults living with HIV accessing home and community care services in British Columbia,Canada

ABSTRACT

Over half of people living with HIV (PLHIV) engaged in care in British Columbia (BC) are age ≥50. The public home and community care (HCC) system offers formal support that PLHIV may turn to as they age, but little is known about access specific to PLHIV. Using data from the STOP HIV/AIDS cohort, which includes linked treatment and demographic records for PLHIV accessing care in BC, we compared older PLHIV (defined as those age ≥50) who did and did not access HCC services. We estimated adjusted odds ratios (aORs) for factors associated with HCC service utilization using logistic regression. This study included 5,603 PLHIV age ≥50, 837 (14.94%) of whom accessed any HCC service between 2005 and 2015. Services most commonly used were community nursing (8.98%, n?=?503) and rehabilitation (7.73%, n?=?433). Those who received HCC were more likely to be female (aOR?=?1.56, 95% CI?=?1.24, 1.98), have a history of injection drug use (aOR?=?1.88, 95% CI?=?1.57, 2.25), have a higher Charlson comorbidity score (aOR?=?1.11, 95% CI:1.07, 1.15) and to have visited a general practitioner in the past year (aOR?=?2.17, 95% CI?=?1.77, 2.67). Approximately 15% of older PLHIV have accessed HCC, but the extent of potential unmet need for these services requires further research.     

Clinical and Contrast-enhanced Ultrasound Characteristics of Epithelioid and Classic Hepatic Angiomyolipoma: Comparison With Alpha-fetoprotein–negative Hepatocellular Carcinoma

Hepatic angiomyolipoma (HAML) comprises epithelioid angiomyolipoma (EAML) and classic hepatic angiomyolipoma (CAML). The imaging appearance of HAML varies widely, and EAML is more easily misdiagnosed as hepatocellular carcinoma (HCC) than as CAML. The clinical and contrast-enhanced ultrasound (CEUS) features of CAML, EAML and HCC with negative alpha-fetoprotein protein expression (HCC[AFP–]) were retrospectively reviewed. The hyper-vascular type was more commonly found in CAML and EAML lesions than in HCC lesions. Most lesions were hyper-enhanced in the arterial phase. CAMLs showed prolonged hyper-enhancement or iso-enhancement during the portal and late phases on CEUS, making them easily distinguishable from HCC(AFP–). Some EAML lesions (41.7%) were hypo-echoic, similar to HCC(AFP–). However, the hypo-enhancement of EAML lesions occurred later than that of HCC(AFP–) lesions. Thus, our findings may be useful in distinguishing among these lesions to improve diagnostic accuracy.