Analysis of Key Factors Associated with Response to Salvage High-Dose Methotrexate Rechallenge in Primary Central Nervous System Lymphoma with First Relapse

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin’s lymphoma that occurs in the central nervous system. Although sensitive to chemotherapy, 35–60% of PCNSL patients still relapse within 2 years after the initial treatment. High-dose methotrexate (HD-MTX) rechallenge is generally used in recurrent PCNSL, especially for patients who have achieved a response after initial methotrexate (MTX) treatment. However, the overall remission rate (ORR) of HD-MTX rechallenge is about 70–80%. Additionally, the side effects of HD-MTX treatment endanger the health of patients and affect their quality of life. Methods: This is a retrospective study of patients with first relapse PCNSL at Huashan Hospital, Fudan University between January 2000 and November 2020. By comparing the clinical characteristics and radiological manifestations of first relapsed PCNSL patients with remission and non-remission after receiving HD-MTX rechallenge, we screened out the key factors associated with HD-MTX rechallenge treatment response, to provide some help for the selection of salvage treatment strategies for patients with recurrent PCNSL. Additionally, patients with remission after HD-MTX rechallenge were followed up to identify the factors related to progression-free survival of the second time (PFS2) (time from the first relapse to second relapse/last follow-up). The Kruskal–Wallis and Pearson chi-square tests were performed to examine the univariate association. Further, multivariable logistic regression analysis was used to study the simultaneous effect of different variables. Results: A total of 207 patients were enrolled in the study based on the inclusion criteria, including 114 patients in the remission group (RG) and 81 patients in the non-remission group (nRG), and 12 patients were judged as having a stable disease. In Kruskal–Wallis and Pearson chi-square tests, progression-free survival rates for first time (PFS1) and whether the initial treatment was combined with consolidated whole brain radiotherapy (WBRT) were related to the response to HD-MTX rechallenge treatment, which was further validated in regression analysis. Further, after univariate analysis and regression analysis, KPS was related to PFS2. Conclusions: For PCNSL patients in their first relapse, HD-MTX rechallenge may be an effective salvage treatment. PFS1 and whether initial treatment was combined with consolidation WBRT were associated with HD-MTX rechallenge treatment response. In addition, patients with higher KPS at the time of the first relapse had a longer PFS2 after HD-MTX rechallenge treatment.     

Low-quality employment trajectories and the risk of common mental health disorders among individuals with Swedish and foreign background – a register-based cohort study

ObjectiveThis study aimed to examine the effects of low-quality employment trajectories on severe common mental disorders (CMD) according to Swedish and foreign background.MethodsIn this longitudinal study based on Swedish population registries (N=2 703 687), low- and high-quality employment trajectories were the main exposures observed across five years (2005–2009), with severe CMD as outcome variable (2010–2017). Adjusted hazard ratios (HR) were calculated by means of Cox regression models and stratified according to Swedish and foreign background [first-generation (i) EU migrants, (ii) non-EU migrants, (iii) second-generation migrants, (iv) Swedish-born of Swedish background] and sex. The reference group was Swedish-born of Swedish background in a constant high-quality employment trajectory.ResultsSecond-generation migrants had an increased risk of CMD compared to Swedish-born of Swedish background when following low-quality employment trajectories [eg, male in constant low-quality HR 1.54, 95% confidence interval (CI) 1.41–1.68]. Female migrant workers, especially first-generation from non-EU countries in low-quality employment trajectories (eg, constant low-quality HR 1.66, 95% CI 1.46–1.88), had a higher risk of CMD compared to female Swedish-born of Swedish background. The risk for CMD according to employment trajectories showed little differences between first- and second-generation migrants.ConclusionLow-quality employment trajectories appear to be determinants of risk for CMD in association with Swedish or foreign background of origin and sex. Our study shows a higher risk for severe CMD in second-generation and non-EU migrant compared to Swedish-born of Swedish background in constant low-quality employment. Further qualitative research is recommended to understand the mechanism behind the differential mental health impact of low-quality employment trajectories according to foreign background.     

Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review

ObjectiveAntipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients.MethodsWe reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsMost studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%–82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders.ConclusionsCurrently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.     

First Trimester Screening – Current Status and Future Prospects After Introduction of Non-invasive Prenatal Testing (NIPT) at a Tertiary Referral Center

Objective To investigate the uptake of different components of first trimester screening (FTS) and the impact on invasive diagnostic testing (IPT) since the introduction of non-invasive prenatal testing (NIPT) at a level III center. Methods Retrospective data analysis was conducted for singleton pregnancies that presented for FTS between 01/2019–12/2019 (group 1, n = 990). Patients were categorized into three risk groups: low risk for trisomy 21 (< 1 : 1000), intermediate risk (1 : 101–1 : 1000) and high risk (≥ 1 : 100). Uptake of NIPT and IPT was analyzed for each of the risk groups. Results were compared to a previous cohort from 2012/2013 (immediately after the introduction of NIPT, group 2, n = 1178). Results Group 1 showed a significant increase in the use of NIPT as part of FTS (29.5% vs. 3.7% for group 2, p = 0.001) in all three risk groups. Overall IPT rates were lower in group 1 (8.6%) vs. group 2 (11.3%, p = 0.038), mainly due to a significant reduction of IPT in the intermediate risk group. IPT rates in the high-risk group remained stable over time. Conclusion Appropriate clinical implementation of NIPT is still currently a challenge for prenatal medicine experts. Our data suggest that widespread uptake of NIPT is becoming more common these days; however, a contingent approach might prevent redundant uptake.     

藏族和汉族上颌第一恒磨牙近中颊根的CBCT对比研究

目的:比较藏族和汉族上颌第一恒磨牙近中颊根数据,为临床提供参考.方法:随机收集藏族和汉族患者上颌第一恒磨牙近中颊根CBCT图像440例,测量根长、弯曲度、弯曲位置、是否有第二近颊根(MB2)、MB-MB2距离.结果:藏族第一恒磨牙近中颊根长度较汉族长,差异有统计学意义(P<0.05).近中颊根根管弯曲度比较,藏汉族有统...     

显微CT与体视显微镜测量根管锥度的体外研究

目的:通过显微CT和体视显微镜测量根管直径,计算下颌第一前磨牙根管的初始锥度,为根管器械和材料的锥度设计、临床选择器械锥度提供参考.方法:首先对23颗13～23岁下颌第一前磨牙(单根管)进行树脂包埋,应用显微CT对包埋体进行断层扫描,并对管径进行测量;再通过制样机对同组样本1 mm等距离磨除,体视显微镜对根管断面管径进行摄片及测量,最后应用数学公式计算各组根管锥度.结果:通过显微CT得到根管近远中向冠、中及尖1/3段锥度分别为:0.05、0.08、0.06;颊舌向分别为:0.11、0.27、0.20.体视镜得到近远中向锥度为:0.07、0.06、0.07;颊舌向为:0.15、0.24、0.17.两种方法所得对应结果经t检验均无显著性差别(P>0.05).结论:13～23岁下颌第一前磨牙根管自根尖起为自下而上的扁圆形,其近远中向锥度远远小于颊舌向锥度.根管并非为一连续的锥形,根管锥度在颊舌向的不同部位有明显差异.     

OSCE考核模本在护生急救技能评价体系中的应用

目的评估在护理学生急救护理技能考核评价中引入OSCE模本的应用效果。方法选取2020年10月—2021年10月期间在本院急诊科轮转的98名实习护生为研究对象,在急救考核中应用OSCE模本,通过四个考站的考核,考核和评价护生在各考站的急救技能和综合能力、急诊常见疾病的预检分诊、护生急诊急救临床能力、转运过程及突发事件的应对,并让护生在参加考核后完成问卷调查。结果 OSCE考核成绩(73.36±6.57)分,考试成绩总体上基本服从正态分布,校标关联效度系数(r=0.66,P <0.05),难度系数为0.70,区分度为0.56,护生对OSCE考核模本在护生急救技能评价体系中的应用认可度和满意度分别为84.21%和78.95%。结论可在原有的基础上进一步完善OSCE考核模式,使其更基础更广泛地应用于护生教学和考核中应用中。     

486例2型糖尿病患者非糖尿病一级亲属中医体质类型调查分析

目的:初步了解浙江平湖地区2型糖尿病患者非糖尿病一级亲属中医体质类型分布情况。方法:采用王琦《中医体质分类研究》问卷对就诊我院糖尿病专科门诊及入住糖尿病专科病房的2型糖尿病患者子女进行方便抽样横断面现场调查486例。结果:平和质52例(26.3%),单纯偏颇体质220例,兼夹偏颇体质214例;偏颇体质类型中累计频率由高到底依次为气虚质(61.4%)、阴虚质(56.4%)、痰湿质(50.8%)、阳虚质(21.6%)、气郁质(20.2%)、湿热质(17.9%)、血瘀质(10.5%)、特禀质(7.2%);兼夹偏颇体质中2种体质兼夹125例,其中气虚兼阴虚质42例,气虚兼痰湿质48例3,种体质兼夹40例,4种体质兼夹26例,5种体质兼夹14例,6种体质兼夹9例。结论:2型糖尿病患者非糖尿病一级亲属人群9种中医体质分布存在差异,偏颇及兼夹偏颇体质多见为主要特征。     

益智仁盐炙对水负荷多尿模型大鼠缩尿作用的研究

目的:通过比较盐炙益智仁对水负荷多尿模型大鼠的缩尿作用,进一步验证益智仁盐炙人肾传统炮制理论的正确性.方法:SD大鼠按尿量、体重均匀分成正常组、模型组、缩泉丸组、益智仁石油醚部位生品(低、中、高剂量)组、盐炙品(低、中、高剂量)9组,缩泉丸组剂量为1.5 g·kg-1,益智仁石油醚部位生品和盐炙品低、中、高剂量分别为含生药4.5,9,18g·kg-1.各组按10 mL·kg-1体积灌胃给药1周后,用1％盐水造成大鼠水负荷多尿模型.采用代谢笼法测定大鼠尿量、首次排尿时间,并计算6h排泄率;放免法测定大鼠血清精氨酸加压素(AVP)含量.结果:与模型组相比,益智仁生、炙品(除生品低剂量组外)能显著降低0～1h段大鼠尿量(P＜0.01),延长大鼠首次排尿时间(生品高剂量组P＜0.05,盐炙品低、中、高剂量组P ＜0.01),显著降低大鼠6h排泄率(生品高剂量组P＜0.05,盐炙品高剂量组P＜0.01).与模型组相比,各组AVP含量均升高,其中生品高剂量、盐炙品中、高剂量组有极显著性差异(P＜0.01).结论:益智仁石油醚部位具有缩尿作用,盐炙能增强其作用.     

2837例妊娠中期孕妇羊水间期细胞荧光原位杂交检测胎儿染色体异常的残余风险

目的 评估妊娠中期羊水间期细胞荧光原位杂交(fluorescence in situ hybridization,FISH)检测后漏诊非13、18、21、X或Y染色体非整倍体异常核型的残余风险. 方法 对中国医学科学院北京协和医学院北京协和医院2010年1月1日至2013年7月31日2 837例妊娠中期行羊膜腔穿刺术同时行间期细胞FISH检测和传统核型分析的病例及其结果进行回顾性分析.采用GLP 13/GLP21/CSP 18/CSPX/CSPY探针针对13、18、21、X或Y染色体进行间期细胞FISH检测.计算具有三大产前诊断指征(孕妇高龄、母体血清学筛查18或21-三体高风险、妊娠23周前超声发现胎儿有结构异常)的孕妇间期细胞FISH检测的检出率以及残余风险. 结果 2 837例标本中,共85例(3.0％)羊水细胞染色体核型分析异常.85例中的73例为13、18、21、X或Y染色体非整倍体的异常核型,间期细胞FISH结果均为阳性,其中21-三体共43例(包括2例嵌合体)、18-三体1 5例、13-三体l例、性染色体非整倍体14例(包括4例嵌合体).12例(14.1％)异常结果为非13、1 8、21、X或Y染色体的非整倍体,包括平衡性结构重排6例、非平衡性结构重排5例、其他染色体非整倍体1例.这12例中,间期细胞FISH结果阳性3例,均涉及21号染色体的不平衡性结构异常;阴性9例,其中4例遗传性平衡性重排和2例新生平衡性重排.2 837例病例间期细胞FISH分析对染色体异常的检出率为89.4％(76/85),异常核型漏诊率为14.1％(12/85),残余风险为0.43％(12/2 761). 结论 间期细胞FISH检测是核型分析的有效补充,但不能取代核型分析,单纯间期细胞FISH检测进行产前诊断可能漏诊部分染色体结构异常.在产前遗传咨询时,应向患者解释间期细胞FISH的检出率和残余风险,合理选择产前诊断方法.