Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.     

多元化联合教学模式在超声引导下疼痛介入治疗中的应用

目的探讨多元化联合教学模式在超声引导下疼痛介入治疗教学中的应用效果。方法选择2018年1月至2020年12月在北京大学第三医院疼痛科进修的30名医师作为研究对象,将其分为对照组与观察组;对照组采用常规教学模式;观察组采用多元化联合教学模式,比较两组医师技能考核成绩、教学质量评分和满意度评分。结果观察组医师技能考核成绩优良率为93.3%,高于对照组的73.3%(P<0.05);观察组医师对基础理论知识掌握、临床思维能力的提高、学习兴趣的激发、疾病诊治能力的提高4个方面的评分均高于对照组(P<0.01)。结论多元化联合教学模式可促进超声引导下疼痛介入治疗技能的提高,有利于提高学员的综合临床能力。     

Silver Diamine Fluoride Protocol for Reducing Preventable Dental Hospitalisations in Victorian Children

IntroductionThis study was designed to assess whether a dental caries management protocol combining a single application of 38% silver diamine fluoride (SDF) with comprehensive oral health education will successfully divert high-risk children from dental treatment under dental general anaesthesia (DGA), arrest active caries in primary teeth, and improve parent-reported child oral health–related quality of life (OHRQoL).MethodsChildren aged 2 to 10 years, who attended two public dental agencies in Victoria, Australia, and were unable to tolerate restorative treatments in the clinic setting, elected to participate in either a 38% SDF intervention protocol or, alternatively, referral for DGA. Follow-up examinations were completed at 6 months to assess caries progression, decayed missing filled tooth index, PUFA index (pulpal involvement, ulceration, fistula, abscess), DGA referral rates, and OHRQoL (Early Childhood Oral Health Impact Scale [ECOHIS]).ResultsOf the total sample, 89.5% of children (n = 102) [mean (SD) age, 4.1 (1.0) years] with 401 active carious lesions elected to participate in the 38% SDF protocol; 10.5% (n = 12) of parents opted for referral for treatment under DGA. The proportion of active caries subsequently arrested at follow-up (number of arrested lesions/number of lesions treated) was 0.78 (95% CI, 0.69 to 0.87). There was an 88% reduction in referrals for DGA in eligible children over the 6-month period. The 38% SDF intervention group showed a significant improvement in ECOHIS scores at follow-up (P < .001).DiscussionAdoption of the 38% SDF intervention protocol resulted in a significant reduction in the rate of preventable dental hospitalisations. Most parents opted against referral for DGA. Parent-reported OHRQoL for children improved significantly.     

Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

活血化瘀方联合针灸治疗对脑梗后遗症患者脑血管血液流变动力学及神经功能的影响

目的:探讨血化瘀方联合针灸治疗对脑梗后遗症患者脑血管血液流变动力学及神经功能的影响。方法:选取2016年1月至2017年1月沈阳市第二中医医院收治脑梗后遗症患者120例作为研究对象,对照组61例患者接受针灸治疗;观察组59例患者接受活血化瘀方联合针灸治疗。2组连续治疗30 d。比较2组患者脑血流流变学指标、神经功能评分、中医证候积分、临床疗效。结果:治疗前2组患者脑部平均血流速度、左侧椎动脉血流量、右侧椎动脉血流量、基底动脉血流量比较,差异无统计学意义(P 0. 05)。治疗后观察组患者脑部平均血流速度、左侧椎动脉血流量、右侧椎动脉血流量、基底动脉血流量大于对照组(P 0. 05)。治疗前2组患者NIHSS评分、MMSE评分比较,差异无统计学意义(P 0. 05)。治疗后观察组患者NIHSS评分显著低于对照组,MMSE评分高于对照组(P 0. 05)。治疗前2组患者头晕目眩、语言謇涩、半身不遂、患侧麻木、舌苔白腻证候评分比较,差异无统计学意义(P 0. 05)。治疗后研究患者头晕目眩、语言謇涩、半身不遂、患侧麻木、舌苔白腻证候评分显著低于对照组(P 0. 05)。2组患者临床疗效比较,差异有统计学意义(Z=-5. 626,P=0. 000)。结论:活血化瘀方联合针灸能改善脑梗后遗症患者脑血管血液流变动力学指标,保护神经功能。     

Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.