穴位埋线治疗进行性肌营养不良的疗效观察

目的观察穴位埋线联合糖皮质激素及神经营养药物治疗进行性肌营养不良的临床疗效。方法 50例进行性假肥大性肌营养不良患者,随机分为治疗组和对照组,每组25例。对照组采用糖皮质激素及神经营养药物治疗,治疗组在对照组基础上采用穴位埋线治疗。观察两组治疗前后10米步行时间和登梯时间及血清肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH)水平的变化,并比较两组临床疗效。结果两组治疗后及随访10米步行时间和登梯时间与同组治疗前比较,差异有统计学意义(P<0.05);两组治疗后及随访10米步行时间和登梯时间比较,差异有统计学意义(P<0.05)。两组治疗后及随访血清CPK、LDH水平较同组治疗前明显下降,差异有统计学意义(P<0.01);治疗组治疗后及随访血清CPK和LDH水平低于对照组(P<0.01)。治疗组总有效率为96.0%,对照组总有效率为72.0%,治疗组总有效率高于对照组(P<0.05)。结论穴位埋线联合糖皮质激素治疗进行性肌营养不良的临床疗效显著,可作为临床治疗进行性肌营养不良方案的优选方法。     

症状前期进行性肌营养不良患儿24例病例系列报告

背景：进行性肌营养不良（PMD）中Duchenne型肌营养不良(DMD)和Becker型肌营养不良(BMD)的临床表现、治疗和预后差异明显，目前国内外对症状前期PMD患儿的诊断尚无共识。 目的：探讨婴幼儿时期症状前期PMD患儿的临床特征和实验室检查特点，并探讨血清肌酶水平在DMD和BMD分型诊断中的价值。 设计：病例系列报告。 方法：收集2016年1月至2020年7月江西省儿童医院确诊的症状前期PMD患儿，分析临床特征和实验室检查特点，并以基因检测结果为诊断标准分为DMD组和BMD组，血清肌酶通过ROC曲线分析以约登指数最大值时的取值作为诊断界值，比较不同肌酶的诊断准确性。 主要结局指标：PMD患儿的临床表现、基因结果、血清酶水平（AST、ALT、LTH、CK、CK-MB）。 结果：24例PMD患儿纳入分析，其中DMD组18例，BMD组6例。22例（91.7%）因发现转氨酶升高就诊，2例（8.3%）因亲戚确诊前来就医。PMD患儿CK-MB、CK、LDH、AST和ALT水平均明显升高，DMD组均高于BMD组（除AST外，P均<0.05）。当ALT>224.5 U·L-1、CK>11 069 IU·L-1、CK-Mb>204 IU·L-1、LDH>1 349.5 IU·L-1时为DMD的可能性更高，尤其是LDH>1 349.5 IU·L-1具有高度特异性。 结论：血清肌酶水平增高为 PMD 患儿症状前期的主要表现。LDH＞1 349.5 IU·L-1对诊断DMD具有高度特异性。     

Full-length dystrophin restoration via targeted exon integration by AAV-CRISPR in a humanized mouse model of Duchenne muscular dystrophy

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Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

Lessons from an Experiential Approach to Patient Community Engagement in Rare Disease

Meaningful engagement between biopharmaceutical companies and patient communities has increasingly become an important part of the therapeutic-development process, as such engagement improves the understanding of the multifaceted challenges and unmet needs that communities experience and provides an opportunity to inform the approach to the development of new therapies and services. Presented here are learnings from a community-advisor program designed to engage families of patients with Duchenne muscular dystrophy (DMD) in a manner that enabled caregivers to make valuable contributions to the therapeutic-development process and to the DMD community. Parents of children with DMD, representing the broader DMD community, were identified in partnership with patient-advocacy organizations and invited to participate in a community-advisor meeting with members of Wave Life Sciences. The community-advisor meeting was designed to provide participants with an opportunity to share their personal experiences with DMD, to help to inform the therapeutic-development process, and to identify potential solutions for addressing unmet needs. Three community-advisor meetings were held with a total of 30 parents, representing 36 children with DMD. Key themes that emerged from the advisors' discussion included the importance of the community's emotional and mental support, the inconsistencies in DMD care, the increased challenges and disparities faced by underserved communities, and the need for more comprehensive, holistic approaches to the treatment and management of DMD. The advisors viewed the meetings as an opportunity to share their voices with a biopharmaceutical company, coupled with the advantage of meeting other families living with similar challenges. Most of the advisors stated that this was their first advisor meeting. This community-focused approach empowered participants to voice their needs and perspectives, to brainstorm potential solutions for addressing those needs, and to initiate and foster connections in ways that had a considerable impact on one another and on therapeutic-development programs at Wave Life Sciences.     

不同靶控浓度顺式阿曲库铵在肥胖患者胃袖状切除手术中的应用

目的探讨输注不同靶控浓度顺式阿曲库铵对肥胖患者胃袖状切除手术的影响。方法选取拟全身麻醉下行腹腔镜胃袖状切除术的肥胖患者105例,随机分为3组： 持续泵注顺式阿曲库铵低靶控浓度组（1.5μg/mL,A组）、中靶控浓度组（2.0μg/mL,B组）和高靶控浓度组（2.5μg/mL,C组）,每组35例。记录3组患者的年龄,体重指数,理想体重,美国麻醉医师协会分级（American Society of Anesthesiologist, ASA）分级,手术时间,睁眼时间,手术30、60min时的脑电双频指数（bispectral index, BIS）值,在四个成串刺激（train of four stimulation, TOF）达到0.25（T1）、0.75（T2）、和0.9（T3）的时间,同时记录拔除气管导管时的TOF;记录手术结束时及拔管后10min的心率（heart rate, HR）、平均动脉压（mean arterial blood pressure, MAP）;记录拔管后10min的呼吸频率、脉搏血氧饱和度（saturation of pulse oximetry, SpO2）。结果3组患者的年龄,BMI指数,理想体重,ASA分级,手术时间,手术30、60min时的BIS值,手术结束时及拔管后10min的HR、ABP,拔管后10min的呼吸频率、SpO2差异无统计学意义（P>0.05）。与A组比较,B、C两组患者睁眼时间、T1、T2、T3时间显著延长;与B组比较,C组患者睁眼时间、T1、T2、T3时间显著延长（P<0.05）。结论输注低靶控浓度肌松药用于行腹腔镜胃袖状切除术的肥胖患者,不仅缩短患者术后肌松恢复时间,且有利于肥胖患者术后快速复苏。     

肌内注射舒适体位的应用研究

目的探讨肌内注射的最舒适体位。方法对410例(共1045例次)肌内注射病人采取自身对照法,每例病人至少注射2次,交替取传统的侧卧位肌内注射体位即侧卧,上腿伸直,下腿弯曲(传统体位)和改进后的体位即侧卧,上腿弯曲,下腿伸直(改良体位),采用简化Mcgil疼痛评分表和自制的卧位舒适评定表进行评定,对比两种不同注射体位注射时病人的疼痛和舒适程度。结果两种体位的疼痛评分无显著性差异(P=0.314),但两种体位的舒适度评分有显著性差异(P<0.0001),病人感觉采取改良体位注射较为舒适。结论上腿弯曲、下腿伸直的侧卧注射体位较传统的上腿伸直、下腿弯曲的体位更加舒适,较易为病人接受。     

One Year Outcome of Boys With Duchenne Muscular Dystrophy Using the Bayley-III Scales of Infant and Toddler Development

BackgroundThe pathogenesis of Duchenne muscular dystrophy starts before birth. Despite this, clinical trials exclude young boys because traditional outcome measures rely on cooperation. We recently used the Bayley-III Scales of Infant and Toddler Development to study 24 infants and boys with Duchenne muscular dystrophy. Clinical evaluators at six centers were trained and certified to perform the Bayley-III. Here, we report 6- and 12-month follow-up of two subsets of these boys.PatientsNineteen boys (1.9 ± 0.8 years) were assessed at baseline and 6 months. Twelve boys (1.5 ± 0.8 years) were assessed at baseline, 6, and 12 months.ResultsGross motor scores were lower at baseline compared with published controls (6.2 ± 1.7; normal 10 ± 3; P < 0.0001) and revealed a further declining trend to 5.7 ± 1.7 (P = 0.20) at 6 months. Repeated measures analysis of the 12 boys monitored for 12 months revealed that gross motor scores, again low at baseline (6.6 ± 1.7; P < 0.0001), declined at 6 months (5.9 ± 1.8) and further at 12 months (5.3 ± 2.0) (P = 0.11). Cognitive and language scores were lower at baseline compared with normal children (range, P = 0.002-<0.0001) and did not change significantly at 6 or 12 months (range, P = 0.89-0.09). Fine motor skills, also low at baseline, improved >1 year (P = 0.05).ConclusionDevelopment can reliably be measured in infants and young boys with Duchenne muscular dystrophy across time using the Bayley-III. Power calculations using these data reveal that motor development may be used as an outcome measure.     

MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60–65% of mutations, duplications for 5–10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009–2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45–54 and 3–21, whereas most duplications involved exons 3–18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots – different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers.