Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis

Introduction: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti–muscle-specific kinase (MuSK)-MG. Methods: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG. Results: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12–1.53, P = 0.19). Discussion: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404–410, 2019     

羟乙基淀粉溶液对猪小肠移植缺血再灌注损伤的保护作用

目的 探讨羟乙基淀粉溶液做为器官灌洗液对猪小肠移植缺血再灌注损伤的保护机制。方法 建立同种异体猪原位节段性小肠移植模型。对照组和实验组分别采用0．9％生理盐水（n=6）和3％羟乙基淀粉氯化钠溶液（n=6）灌洗,移植小肠（截取供体约500cm小肠）保存于4℃0．9％生理盐水2h。分别于移植前30mim和再灌注后30min采取肠液和血清,检测ALT、CK、LDH的变化;测定再灌注后肠液分泌量;检测血清肿瘤坏死因子-α（TNF—α）、白细胞介素-1（IL-1）、IL-6的含量。同时取移植小肠行病理学检查。结果 再灌注30min后,实验组肠液分泌量明显少于对照组（P〈0．05）,两组肠液中CK水平较术前明显增加（P〈0．05）,实验组肠液中CK水平明显低于对照组（P〈0．01）;对照组再灌注30min后血清TNF—d、IL-6、IL-1的含量较术前明显增加（P〈0．05）,实验组与术前无明显变化（P〉0．05）;两组再灌注30min后肠液和血清ALT、LDH的水平与术前无明显变化（P〉0．05）;对照组血清中CK明显低于实验组（P〈0．05）;实验组肠黏膜的组织损伤程度较对照组减轻。结论 3％羟乙基淀粉氯化钠溶液可能通过抑制TNF—d、IL-6、IL-1水平,阻止毛细血管渗漏,减轻细胞水肿,防止肠缺血再灌注损伤,再灌注后肠液分泌量及肠液CK水平可用来判定肠组织损伤程度。     

Update on Inclusion Body Myositis

Purpose of Review

While sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease after age 50, the pathogenesis of this disease is still poorly understood. In this review, we discuss our current state of knowledge in sIBM and provide an update on our current understanding of its pathophysiology and management.

Recent Findings

Lines of evidence in support of an inflammatory pathogenesis include inflammatory infiltrates in the target organ, NFκB activation, cytokine response, MHC I upregulation, and cN1A antibody. Refractoriness to immunotherapies has led to suggestion of a degenerative pathophysiology. Evidence for impaired protein homeostasis with misfolding burden is coupled with findings of endoplasmic reticulum stress, proteasome dysfunction, and mitochondrial lesion. Recent treatment trials have focused more on correcting the degenerative process or muscle growth rather than controlling the inflammation.

Summary

There has been growing evidence toward degeneration as the primary process in sIBM. This is consistent with the refractory nature of this disease. Improving our understanding of this disease pathogenesis will propel efforts to find an effective therapy.

     

Retrospective chart review of duloxetine and pregabalin in the treatment of painful neuropathy

The primary aims of our study were to compare pregabalin and duloxetine in a neuromuscular clinic for diabetic neuropathic pain (DPN) and to study the effect of these medications in cryptogenic sensory polyneuropathy. We performed a retrospective chart review of 143 patients who were started on pregabalin or duloxetine during a 10-month period in a tertiary neuromuscular outpatient center for neuropathic pain. Duloxetine and pregabalin were started in 103 and 91 patients, respectively. Ninety-two patients tried only one of the two medications while both medications were used at different time periods in 51 patients. Follow-up was available for 87 patients on pregabalin and 89 patients on duloxetine. More patients with neuropathic pain reported an improvement with pregabalin (33%) than duloxetine (21%). Duloxetine (38%) had a higher frequency of side effects compared to pregabalin (30%). However, these differences between pregabalin and duloxetine were not statistically significant. Despite the study's limitations of retrospective design, these findings suggest that both pregabalin and duloxetine are probably effective for neuropathic pain, secondary to diabetes or cryptogenic sensory peripheral neuropathy in a tertiary care academic neuromuscular center. Prospective randomized controlled comparative effectiveness studies are required for both drugs in the treatment of neuropathic pain.