Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders

Autoimmune neurological disorders, including neuromyelitis optica spectrum disorder, anti-N-methyl-D-aspartate receptor encephalitis, anti-MOG antibody-associated disorders, and myasthenia gravis, are clearly defined by the presence of autoantibodies against neurological antigens. Although these autoantibodies have been heavily studied for their biological activities, given the heterogeneity of polyclonal patient samples, the characteristics of a single antibody cannot be definitively assigned. This review details the findings of polyclonal serum and CSF studies and then explores the advances made by single-cell technologies to the field of antibody-mediated neurological disorders. High-resolution single-cell methods have revealed abnormalities in the tolerance mechanisms of several disorders and provided further insight into the B cells responsible for autoantibody production. Ultimately, several factors, including epitope specificity and binding affinity, finely regulate the pathogenic potential of an autoantibody, and a deeper appreciation of these factors may progress the development of targeted immunotherapies for patients.     

Hcy、NSE及IL-8水平变化与脑卒中患者神经功能恢复的关系研究

目的分析半胱氨酸(Hcy)、神经元特异性烯醇化酶(NSE)及白介素-8(IL-8)水平变化与脑卒中患者神经功能恢复的关系。方法选取2017年4月至2019年4月本科室收治的116例缺血性脑卒中急性期后康复患者作为研究组,根据急性期神经功能缺损程度,以及稳定期Brunnstrom分期和ADL指数另分为三个亚组:轻度依赖组46例,中度依赖组40例,重度依赖组30例。同时纳入同期本院健康体检正常者108例作为对照组。比较研究组与对照组Hcy、NSE及IL-8水平差异及Hcy、NSE及IL-8水平在神经功能缺损评分中的表达情况。绘制散点图,采用Pearson相关分析分别观察脑卒中患者Hcy、NSE及IL-8水平与神经功能评分的关系。结果研究组患者Hcy、NSE、IL-8水平显著高于对照组,差异具有统计学意义(P<0.05);不同神经缺损患者血清Hcy、NSE、IL-8水平:重度依赖组>中度依赖组>轻度依赖组,差异有统计学意义(P<0.05);脑卒中患者Hcy、NSE及IL-8与NIHSS评分呈正相关,与Brunnstrom分期和ADL指数呈负相关(P<0.05)。结论 Hcy、NSE及IL-8水平对脑卒中患者神经功能及康复指标具有重要意义,临床工作者可通过加强监测这三项指标,评估疾病进展与预后情况。     

The development and psychometric evaluation of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients scale

BackgroundValidated measures of ward nurses' safety cultures in relation to escalations of care in deteriorating patients are lacking.ObjectivesThis study aimed to develop and evaluate the psychometric properties of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients (CARED) scale for use among ward nurses.MethodsThe study was conducted in two phases: scale development and psychometric evaluation. The scale items were developed based on a systematic literature review, informant interviews, and expert reviews (n = 15). The reliability and validity of the scale were examined by administering the scale to 617 registered nurses with retest evaluations (n = 60). The factor structure of the CARED scale was examined in a split-half analysis with exploratory and confirmatory factor analyses. The internal consistency, test–retest reliability, convergent validity, and known-group validity of the scale were also analysed.ResultsA high overall content validity index of 0.95 was obtained from the validations of 15 international experts from seven countries. A three-factor solution was identified from the final 22 items: ‘beliefs about rapid response system’, ‘fears about escalating care’, and ‘perceived confidence in responding to deteriorating patients’. The internal consistency reliability of the scale was supported with a good Cronbach's alpha value of 0.86 and a Spearman-Brown split-half coefficient of 0.87. An excellent test–retest reliability was demonstrated, with an intraclass correlation coefficient of 0.92. The convergent validity of the scale was supported with an existing validated scale. The CARED scale also demonstrated abilities to discriminate differences among the sample characteristics.ConclusionsThe final 22-item CARED scale was tested to be a reliable and valid scale in the Singaporean setting. The scale may be used in other settings to review hospitals' rapid response systems and to identify strategies to support ward nurses in the process of escalating care in deteriorating ward patients.     

托吡酯与卡马西平治疗对脑梗死后继发癫痫患者神经功能缺损、日常活动能力及认知功能的影响

目的分析托吡酯与卡马西平治疗对脑梗死后继发癫痫患者神经功能缺损、日常活动能力和认知功能的影响,为临床治疗提供思路。方法选取2017年3月至2019年8月我院收入的脑梗死后继发癫痫138例患者。按随机数字表法分为A组(治疗上加以卡马西平)和B组(治疗上加以托吡酯)各69例。治疗6个月后比较两组临床效果,治疗前后神经功能缺损、日常活动能力和认知功能的评分及不良反应发生情况。结果治疗后B组疗效高于A组(P<0.05);B组神经功能缺损较治疗前明显下降,且低于A组,不同时间评估分神经功能缺损情况差异有统计学意义(P<0.001);两组日常活动能力和认知功能评分均较治疗前升高,且B组评分高于A组(P<0.05);两组不良反应发生率比较差异无统计学意义(P>0.05)。结论托吡酯的临床疗效优于卡马西平,对脑梗死后继发癫痫患者的预后恢复疗效更好,且不良反应程度轻微,值得临床推广。     

Low-Molecular-Weight Heparin or Dual Antiplatelet Therapy Is More Effective Than Aspirin Alone in Preventing Early Neurological Deterioration and Improving the 6-Month Outcome in Ischemic Stroke Patients

Background and Purpose

Dual antiplatelet therapy (DAT) with clopidogrel and aspirin has been shown to confer greater protection against early neurological deterioration (END) and early recurrent ischemic stroke (ERIS) than aspirin alone in patients who have experienced an acute ischemic stroke. However, few studies have compared the effects of anticoagulation therapy with low-molecular-weight heparin (LMWH), DAT, and aspirin.

Methods

Patients with acute ischemic stroke (n=1,467) were randomized to therapy groups receiving aspirin (200 mg daily for 14 days, followed by 100 mg daily for 6 months), DAT (200 mg of aspirin and 75 mg of clopidogrel daily for 14 days, then 100 mg of aspirin daily for 6 months), or LMWH (4,000 antifactor Xa IU of enoxaparin in 0.4 mL subcutaneously twice daily for 14 days, followed by 100 mg of aspirin daily for 6 months). The effects of these treatment strategies on the incidence of END, ERIS, and deep-vein thrombosis (DVT) were observed for 10-14 days after treatment, and their impacts on a good outcome were evaluated at 6 months.

Results

The DAT and LMWH were associated with a more significant reduction of END and ERIS within 14 days compared with aspirin-alone therapy. In addition, LMWH was associated with a significantly lower incidence of DVT within 14 days. At 6 months, DAT or LMWH improved the outcome among patients aged >70 years and those with symptomatic stenosis in the posterior circulation or basilar artery compared with aspirin.

Conclusions

LMWH or DAT may be more effective than aspirin alone for reducing the incidence of END and ERIS within 14 days, and is associated with improved outcomes in elderly patients and those with stenosis in the posterior circulation or basilar artery at 6 months poststroke.     

Recreational drug overdose-related cardiac arrests: Break on through to the other side

IntroductionThe annual rate of recreational overdose (OD)-related death is increasing exponentially, making unintentional overdose the leading cause of injury-related death in America. Unfortunately, little attention in the resuscitation community has focused on the post-arrest care of this rapidly growing population.MethodsWe included patients presenting between January 2009 and February 2014 after out-of-hospital cardiac arrest (OHCA) and abstracted baseline clinical characteristics and neurological outcomes. We considered an arrest to be an OD OHCA if toxicology screens were positive and not explained by therapeutic medication administration or home medications; or if there was a history strongly suggestive of OD. We compared the baseline clinical characteristics and outcomes between the OD and non-OD cohorts.ResultsIn total, 591 OHCA patients were admitted, of which 85 (14%) arrests were OD-related. OD OHCA patients were significantly younger, had fewer medical comorbidities, were more likely to present with non-shockable rhythms and had worse baseline neurological function. However, overall survival, neurological outcomes and length of stay did not vary between groups. OD OHCA patients who survived to discharge had a significantly higher rate of favorable discharge dispositions (83% of OD OHCA survivors discharged to home or acute rehabilitation vs 62% of non-OD OHCA (P = 0.03)).ConclusionPatients who have suffered an OD OHCA make up a significant proportion of the overall OHCA population. Despite poor baseline prognostic factors, survival after OD OHCA was no worse than after non-OD OHCA, and among survivors a majority had a good neurological outcome.     

简易认知量表和8条目痴呆筛查问卷在高龄老年人群早期认知功能下降筛查中的应用

目的探讨简易认知量表（Mini-Cog）和8条目痴呆筛查问卷（8-item ascertain dementia, AD8）对80岁以上老年人群早期轻度认知功能障碍（mild cognitive impairment, MCI）的筛查价值。 方法选取杭州市某福利中心的2014年10月前已入住的908名高龄老年人进行Mini-Cog和AD8筛查,随访5年后对仍然健在且能配合完成检查者进行二次认知功能评估。计算Mini-Cog和AD8初筛的敏感度和特异度,并分析随访5年后AD8的ROC曲线结果以及两种量表的一致性检验结果。 结果908例高龄老年人中523例确诊为痴呆（不计入后续筛查及随访调查）,余385例筛查结果显示：Mini-Cog、AD8诊断MCI的敏感度分别为54.88%、57.32%,特异度分别为85.52%、86.43%。随访5年后仍健在且接受二次评估的老年人共167名,其中认知功能正常106例（54例出现认知功能下降）,MCI 61例（36例出现认知功能进一步下降）。对于随访5年的认知功能正常者及MCI者,AD8诊断的AUC分别为0.572（95%CI=0.486-0.658）、0.723（95%CI=0.611-0.835）,Mini-Cog和AD8（以得分>3为分界线）诊断的一致性Kappa值分别为0.105、0.018和0.225、0.524。 结论AD8和Mini-Cog均具有一定的MCI评估效能,尤其适用于养老机构及社区高龄老年群体的认知功能筛查。     

Acute kidney injury in the pediatric intensive care unit at a tertiary care hospital of the Armed Forces: a cross-sectional observational study

BackgroundAcute kidney injury (AKI) is shown to be the commonest complication in critically ill children admitted to the pediatric intensive care unit (PICU). Kidney Disease: Improving Global Outcomes (KDIGO) classification and definition are now used universally. We undertook prospective observational study to study the etiology and maximum stage of AKI as defined by KDIGO and its complications and outcomes.MethodsAll children admitted to the PICU were included in the study. The diagnosis of sepsis and multiorgan dysfunction syndrome (MODS) was made according to the standard international guidelines. The patients were followed up till discharge/death. All children were screened for AKI at admission and subsequently using serum creatinine measured by modified Jaffe's method and urine output measurement.ResultsA total of 197 children were admitted to the PICU. 38 (19.28%) developed AKI, and 6 (15.78%) developed stage III AKI. Malignancies, serious neurological and renal disorders, and postsurgery complications accounted for most of the cases with AKI. Six were admitted with primary renal condition. Sepsis with or without MODS was seen in 12 patients with AKI and in 8 without AKI. Twenty-one children with AKI and 3 children without AKI were exposed to nephrotoxic drugs. Twenty-three children with AKI required inotropic support. The average length of stay (ALOS) of children with AKI in the PICU was 9.86 days, whereas ALOS of children without AKI was 6.23 days. Eighteen children with AKI (47.36%) and 36 (21.38%) with no AKI died.ConclusionsAKI in children in the PICUs of referral hospitals in the armed forces have varied etiologies and presentations. These children require early identification and management with close monitoring to prevent long-term renal morbidity and mortality.