Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study

ObjectivePatients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.MethodsPatients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients.ResultsWe enrolled 25 MuSK-MG patients (20 females), aged 16–79 years at the study time, with disease duration ranging 0.6–48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005).ConclusionsCholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease.SignificanceR-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is.     

新疆生产建设兵团第十师羊小反刍兽疫抗体监测与评价

为了评估新疆生产建设兵团第十师北屯市(以下简称师市)羊群小反刍兽疫强制免疫效果,应用酶联免疫吸附试验(ELISA)对2017-2020年全师8个农牧团场采集的4 010份血清进行小反刍兽疫抗体检测,并按单位、年份、类别对检测结果进行了统计分析。结果表明,2018-2020年全师8个农牧团场小反刍兽疫血清抗体平均合格率为84.69%(3 396/4 010),均符合国家农业农村部相关规定,高于平均值的三家单位是E 87.22%(157/180)、G 86.45%(268/310)、H 88.67%(798/900),合格率最低的是D 76.11%(137/180);养殖合作社的抗体合格率为84.81%(1 340/1 580),养殖大户为84.65%(2 057/2 430)均接近于平均合格率,两者差异不显著(P>0.05)。总体来看,师市羊群小反刍兽疫免疫效果较好,为确保师市辖区内重大动物疫病免疫无疫提供技术保障。     

多发性骨髓瘤免疫治疗进展

嵌合抗原受体T细胞(CAR-T)和新型靶向治疗等生物免疫疗法的临床应用开辟了多发性骨髓瘤(MM)治疗的新领域。靶向B细胞成熟抗原(BCMA)、同种异体CAR-T、抗体偶联药物(ADC)及靶向BCMA的双特异性抗体在多项临床研究中获得了令人瞩目的疗效及较好的安全性。文章结合第62届美国血液学会(ASH)年会的相关报道对MM免疫治疗进展进行介绍。     

3种中和剂对常用消毒剂在Vero细胞上的中和效果

 目的  研究0.5%硫代硫酸钠、10%胰蛋白胨大豆肉汤（tryptic soy broth， TSB）培养基、10%Letheen肉汤培养基对实验室常用的4种消毒剂的中和效果，为疫苗生产和检定中科学选择中和剂提供依据。 方法  取生长良好的Vero细胞接种于96孔培养板，每组8个复孔，置于37 ℃、5% CO2培养过夜。将3种中和剂分别与杀孢子剂、0.5%“84”消毒液、酸性苯酸盐、碱性苯酚盐4种消毒剂中和后，接种于单层生长的Vero细胞，显微镜下观察细胞生长情况。结果  0.5%硫代硫酸钠分别与杀孢子剂、0.5%“84”消毒液中和后接种细胞，8孔细胞全部存活；而0.5%硫代硫酸钠分别与酸性苯酚盐和碱性苯酚盐的中和产物接种细胞后，细胞全部死亡。10% TSB培养基分别与酸性苯酚盐、碱性苯酚盐中和后接种细胞，8孔细胞全部存活；而10% TSB培养基分别与杀孢子剂和0.5%“84”消毒液的中和产物接种细胞后，细胞全部死亡。10%Letheen肉汤培养基接种细胞后，8个孔细胞全部死亡。结论  0.5%硫代硫酸钠可中和杀孢子剂和0.5%“84”消毒液的消毒作用，10%TSB培养基可中和酸性苯酚盐和碱性苯酚盐的消毒作用。10%Letheen肉汤培养对Vero细胞有毒性作用。     

超敏C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体联合血清淀粉样蛋白A检测在类风湿性关节炎诊断中的应用价值

目的探讨超敏C反应蛋白(hs-CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP抗体)联合血清淀粉样蛋白A(SAA)检测诊断类风湿性关节炎的价值。方法以该院2018年1月至2018年12月收治的102例类风湿性关节炎患者作为实验组,同期82例健康体检者作为对照组,使用特种蛋白分析仪OTTMAN-1及配套试剂盒检测全血hs-CRP和SAA,使用日立7600生化分析仪及配套试剂检测抗CCP抗体及RF,比较四项指标水平。结果实验组患者的hs-CRP、RF、抗CCP抗体和SAA平均水平均明显高于对照组(P<0.05);实验组患者hs-CRP、RF、抗CCP抗体和SAA阳性检出率分别为88.24%、91.18%、81.37%和91.18%,高于对照组的1.22%、0.00%、57.32%和0.00%(P<0.05);实验组患者hs-CRP、RF、抗CCP抗体联合SAA检测阳性检出率为98.04%,高于单一指标检出率(P<0.05)。结论hs-CRP、RF、抗CCP抗体联合SAA检测有利于提高类风湿性关节炎诊断准确性。     

Diagnostic value of bright spotty lesions on MRI after a first episode of acute myelopathy

Background and purposeTo determine the diagnostic value of bright spotty lesions (BSLs) for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD^AQP4+), the predictive value of axial-BSLs for AQP4-IgG seropositivity, and the radio-clinical differences in NMOSD^AQP4+ patients with and without axial-BSLs.Materials and methodsRetrospective study that included patients aged ≥ 16 years, with a first acute spinal cord syndrome between 2005 and 2018 and abnormal spinal cord MRI with axial and sagittal T2 sequences. Patients with MRI findings consistent with compressive myelopathy were excluded. All spinal cord MRI were retrospectively evaluated for the presence of BSLs by 2 radiologists blinded to the diagnosis of acute myelopathy.ResultsA total of 82 patients were included; 15 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients (NMOSD^AQP4+), and 67 other patients, considered as the other causes of myelopathy (OM) group. The specificity of axial-BSLs for NMOSD^AQP4+ patients was 94.0% (95% CI [85.6 to 97.7]). The sensitivity was 40.0% (95% CI [19.8 to 64.3]). In the multivariable analysis, the only MRI characteristic associated with AQP4-IgG positivity was the presence of axial-BSLs (OR: 9.2, 95% CI [1.2 to 72.9]; P = 0.022). In NMOSD^AQP4+ patients, the median of cord expansion ratio was higher with axial-BSL (1.2, IQR [1.1–1.3]) than without axial-BSL (1.1, IQR [1.0–1.2]; P = 0.046).ConclusionAfter a first acute spinal cord syndrome, the presence of axial-BSLs on spinal cord MRI seems very specific for NMOSD^AQP4+ and seems to be a predictor radiological marker of AQP4-IgG positivity.     

Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km² followed by three years (2014–2016) of evaluation at 300 baits/km². We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km² to 300/km² corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.     

Is weight-based IV dosing of trastuzumab preferable to SC fixed-dose in some patients? A systematic scoping review

Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity.This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included.Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy.The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.     

血小板抗体检测在新生儿血小板减少症诊治中的应用

目的: 探讨检测血小板相关抗体( PAIg) 的表达水平在新生儿血小板减少症诊断及治疗过程中的应 用价值。方法: 选择 2015－01～ 2017－12 我院收治的 60 例血小板减少症新生儿作为患儿组，同期选择 60 例健康 新生儿作为对照组，采用流式细胞术检测所有新生儿的外周血 PAIg 的表达水平，分析 PAIg 对新生儿血小板减 少症的诊断价值; 新生儿血小板减少症患儿采用血小板输注治疗并在治疗后检测 PAIg 的表达水平，分析 PAIg 对治疗效果的影响。结果: 新生儿血小板减少症患儿的 PAIgA、PAIgM 及 PAIgG 表达水平均明显高于对照组( P ＜0．05) ; 重症组患儿的 PAIgA、PAIgM 及 PAIgG 表达水平均明显高于轻度组患儿( P＜ 0．05) ; 经治疗后 42 例 ( 70．00%) 患儿有效，18 例( 30．00%) 患儿无效; 治疗前，有效组患儿的 PAIgM、PAIgG 表达水平均明显高于有效 组患儿( P＜0．05) ; 有效组患儿的 PAIgA 与对照组无明显差异( P＞0．05) ; 治疗后，有效组患儿的 PAIgA、PAIgM 及 PAIgG 表达水平均明显低于治疗前( P＜0．05) ; 而无效组治疗前后 PAIgA、PAIgM 及 PAIgG 表达水平无明显差异 ( P＞0．05) 。结论: PAIg 的表达水平与新生儿血小板减少症病情严重程度密切相关，是重要的诊断依据，同时 PAIg M 和 PAIg G 的表达水平与血小板输注的疗效密切相关，是判定治疗效果的重要指标。