Nutrition et sclérose en plaques : le point de la littérature

Introduction and objectives

Nutritional data on multiple sclerosis are discordant and have a low accuracy. The objective of this article was to focus on the nutritional factors involved in multiple sclerosis, from the prevention of disease to the specific management of patients.

Bayesian design for two-arm randomized Phase II clinical trials with endpoints from the exponential family using multiple constraints

Frequentist design for two-arm randomized Phase II clinical trials with outcomes from the exponential dispersion family was proposed previously, where the total sample sizes are minimized under multiple constraints on the standard errors of the estimated group means and their difference. This design was generalized from an approach specific for dichotomous outcomes. The two previous approaches measure the central tendency of each group and treatment effect based on mean and difference in means. Other measures such as median or hazard ratio are more appropriate under certain situations. In addition, the frequentist approaches assume that unknown parameters are fixed values. This does not reflect the reality that uncertainty always exists for unknowns. Compared to the frequentist methods, the Bayesian approach offers a flexible way to measure central tendency and treatment effect, and incorporate uncertainty in parameters of interest into considerations. In this article, we generalize a Bayesian design for Phase II clinical trials with endpoints in the exponential family from the two previously developed frequentist approaches. The proposed design minimizes the total sample sizes under pre-specified constraints on the expected length of posterior credible intervals for measures of treatment effect and central tendency in each group. The design is applicable for trials with fixed or optimal randomization allocation ratio and can be applied under adaptive procedure. Examples of method implementations are provided for different types of endpoints from the exponential family in both fixed and adaptive settings.     

Oracle and adaptive false discovery rate controlling methods for one‐sided testing: theory and application in treatment effect evaluation

Economists are often interested in identifying effective policies or treatments together with subpopulations of individuals who respond positively (or with a sign that is expected) to these treatment interventions. In this paper, we propose an optimal false discovery rate controlling method that is especially useful for such one‐sided testing problems. The proposed procedure is optimal in the sense of minimizing the false non‐discovery rate while controlling the false discovery rate at a pre‐specified level; it uses a deconvolution method based on non‐parametric maximum likelihood estimation, which allows for a broader class of treatment effect distributions than existing methods do. The proposed test demonstrates good small‐sample performance in Monte Carlo simulations and it is applied to study the effect of attending a more selective high school in Romania. The application reveals strong evidence of treatment effect heterogeneity, in that students who marginally gain access to higher‐ranked schools are more likely to benefit if the higher‐ranked school has a relatively high admission score cut‐off – or, in other words, is more selective.     

冠状动脉旁路移植手术与经皮冠状动脉介入治疗多支血管病变合并糖尿病患者的预后比较

目的比较冠状动脉旁路移植手术(CABG)与经皮冠状动脉介入(PCI)治疗多支血管病变(MVD)合并糖尿病(DM)患者的预后结果。方法连续收集2010年1月至2012年12月于咸阳市中心医院住院接受CABG和PCI的MVD合并DM患者入组。收集并获取患者基线资料,包括性别、年龄、既往病史、左心室射血分数、血生化指标、住院天数、住院费用、出院诊断等信息,并进行术后定期随访。结果本研究共收集MVD合并DM患者625例,其中接受CABG的共205例,接受PCI的共420例。与PCI组相比,CABG患者冠状动脉狭窄程度及左主干狭窄程度更严重(P<0.001),患者遭受的并发症更多(P<0.001);CABG组的主动脉内球囊反搏使用率高,住院总花费也显著偏高(P<0.001);CABG组患者的住院死亡率(1.5%)略高于PCI组患者(0.5%),但差异不显著(P>0.05);CABG组的五年生存率(98.0%)显著高于PCI组(74.5%);CABG组患者的预后显著优于PCI组,五年内发生心梗和心脑血管不良事件的概率也更低(P<0.05)。结论对于MVD合并DM患者,CABG手术的长期预后结局优于PCI手术。     

The hypothetical roles of arsenic in multiple sclerosis by induction of inflammation and aggregation of tau protein: A commentary

Multiple sclerosis (MS) is a disease which manifests demyelination of neuronal cells in the brain. Despite extensive research on the mechanisms of disease development and progression, the exact mechanism is not elucidated yet, which has hampered drug development and subsequent treatment of the disease. We have recently shown that the serum levels of arsenic and malondialdehyde, a lipid peroxidation marker, are high in MS patients. In this article, we would like to formulate the hypothesis that arsenic may cause MS by induction of inflammation, degeneration, and apoptosis in neuronal cells. The induction of ROS generation in cells upon exposure to arsenic as a heavy metal may be involved in the pathogenesis of MS. Tau protein, a member of the family of microtubule-associated proteins, is mainly expressed in neurons and contribute to the assembly of neuronal microtubules network. Arsenic may affect the hyperphosphorylation and aggregation of tau proteins and may be involved in the cascade leading to deregulation of tau function associated with neurodegeneration. For validation of this hypothesis, studies might be conducted to evaluate the association of arsenic levels and tau protein levels in MS patients. Further studies might also focus on the trafficking along microtubules in neurons of MS patient with regard to hyperphosphorylation of tau protein. This hypothesis may add a new dimension to the understanding of MS etiology and help to design novel therapeutic agents against potential targets that might be discovered. If this hypothesis proves to be true, tau phosphorylation inhibitors can be potential candidates for MS drug development.     

包头地区某医院就诊女性患者HPV感染现状及基因分型分析*

目的:探索包头地区HPV感染人群的分布情况及主要基因分型,为防治提出对策措施。方法:采用描述性研究方法,选取2020年7月—12月检测HPV的就诊女性作为研究对象,调查研究对象的一般情况、疾病状况,同时采集其宫颈上皮脱落细胞,采用PCR-反向点杂交法进行HPV分型检测。结果:调查的1 138例患者中检测出HPV感染者254例,感染率22.32 %;其中低危型感染率为13.59 %,高危型感染率为86.41 %;多重感染76例,占29.92 %。感染前5位分别为HPV16:19.69 %;HPV52:17.32 %;HPV53、HPV58、HPV42:11.02 %。年龄分组中,60～70岁组检测感染率最高,为32.69 %。就诊分布中,妇科门诊为226人(88.98 %)。就诊原因中,仅12人(4.72 %)主动进行HPV感染检测。结论:HPV感染主要以单一型感染为主,高危型感染占比高;应加强健康教育,提高主动检测意识,利于HPV感染的早发现、早诊断、早治疗。     

I-Bil、Cys C、APTT对胡蜂蛰伤发生多器官功能障碍综合征的联合预测价值

分析间接胆红素（I-Bil）、胱抑素C（Cys C）、活化部分凝血活酶时间（APTT）对胡蜂蛰伤患者发生多器官功能障碍综合征（MODS)的预测价值。方法 回顾性分析2014～2020年川北医学院附属医院急诊科、肾内科、重症医学科收治的129例胡蜂蜇伤患者临床资料,将患者分为MODS组、非多器官功能障碍综合征（NMODS）组。比较两组患者的实验室检查指标,将两组差异指标采用单因素分析,以多因素Logistic回归分析MODS在胡蜂蜇伤患者中发生的独立危险因素,并用受试者工作特征性（ROC）曲线分析该独立危险因素的预测价值。结果 129例胡蜂蛰伤患者,其中MODS组44例,NMODS组85例。与NMODS组比较,MODS组WBC、GR、hsCRP、ALB、ALT、AST、I-Bil、Cys C、MPV、APTT、CK-MB水平明显升高（P＜0.05）。其中I-Bil（OR=1.196, P＜0.001）、Cys C（OR=7.214,P=0.016）、APTT（OR=1.032,P=0.047）是胡蜂蛰伤患者发生MODS 的独立危险因素;I-Bil、Cystatin C、APTT水平联合对预测胡蜂蜇伤患者发生 MODS的ROC曲线下与坐标轴围成的面积（AUC）为0.987（P＜0.001),最佳截断值为63.31时敏感度为0.93,特异度为0.986。结论 I-Bil、Cys C、APTT水平是胡蜂蛰伤患者发生MODS的独立危险因素,三者联合对胡蜂蛰伤患者发生MODS具有更高的预测价值。     

BCMA靶向的嵌合抗原受体T细胞治疗复发/难治多发性骨髓瘤患者发生肿瘤溶解综合征的危险因素

目的：探究应用B细胞成熟抗原（BCMA）靶向的嵌合抗原受体（CAR）T细胞治疗的复发/难治多发性骨髓瘤（MM）患者发生肿瘤溶解综合征（TLS）的危险因素。方法：收集浙江大学医学院附属第一医院2018年7月至2021年12月共99例接受BCMA靶向的CAR-T细胞治疗MM患者的临床资料,通过单因素分析及多因素logistic回归分析患者接受BCMA靶向的CAR-T细胞治疗后发生TLS的危险因素。结果：99例患者中,17例发生TLS（TLS组）,发生率为17.2%,发生时间为BCMA靶向的CAR-T细胞输注后（8.9±3.0）d。TLS组均出现TLS相关临床表现,其中出现肾功能不全17例,心律失常8例。TLS组均发生细胞因子释放综合征（CRS）,发生时间为BCMA靶向CAR-T细胞输注后1.0（1.0,6.5）d,其中3~4级CRS 13例。TLS组治疗前血肌酐、血尿酸较非TLS组高,3~4级CRS患者的比例也高于非TLS组（P<0.01或P<0.05）。Logistic回归分析结果显示,高血肌酐水平（OR=1.015,P<0.01）和严重CRS（OR=9.371,P<0.01）是TLS发生的独立危险因素。结论：接受BCMA靶向的CAR-T细胞治疗的复发/难治MM患者具有较高的TLS发生率,高血肌酐水平和严重CRS是TLS的主要危险因素,临床可通过降低血肌酐、控制CRS严重程度预防TLS的发生。     

多次法根管治疗与一次性根管治疗在治疗牙体牙髓病患者中的应用效果及对咀嚼功能的影响

目的分析多次法根管治疗与一次性根管治疗在治疗牙体牙髓病患者中的应用效果及对咀嚼功能的影响。方法选取2019年8月至2020年9月本院接收的牙体牙髓病患者78例作为研究对象,按照治疗方案的不同分为对照组(采取多次法根管治疗)与观察组(采取一次性根管治疗),每组39例,比较两组咀嚼功能、治疗效果及不良反应发生率。结果观察组咀嚼效率高于对照组(P<0.05);观察组治疗总有效率高于对照组(P<0.05);观察组不良反应发生率低于对照组(P<0.05)。结论与多次法根管治疗相比,一次性根管治疗在治疗牙体牙髓病患者中的效果更优,更利于促进患者症状的改善及咀嚼功能的恢复,且可降低不良反应发生率。