Explore the vast range of titles available.

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Autoimmune myasthenia gravis (MG) is a neuromuscular junction disorder marked clinically by fatigable muscle weakness and serologically by the presence of autoantibodies against acetylcholine receptors (AChRs), muscle-specific kinase (MuSK), or lipoprotein-related protein 4 (LPR4). Over the past few decades, the mortality of patients with MG has seen a dramatic decline secondary to evolving interventions in critical care and medical management. In the past 2 to 3 years, there have been several changes in standard of care for the treatment of MG. These changes include confirmation of the benefit of thymectomy versus medical management alone in AChR patients and a new US Food and Drug Administration-approved medication for refractory MG. There are also several exciting new prospective drugs in the pipeline, which are in different stages of clinical trial testing.

Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. Design: Ongoing, multicenter, phase III open-label extension (OLE) study. Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11–4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (n = 52, 26%) and COVID-19 (n = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline −6.06 [−7.09, −5.03]) and were sustained through to Week 60 (−6.04 [−7.21, −4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (−6.46 [−8.19, −4.72]), and were sustained through to Week 60 (−6.51 [−8.37, −4.65]). Consistent results were observed in other efficacy endpoints. Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses. Trial registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871)

Background: Zilucoplan, a peptide complement component 5 (C5) inhibitor, is self-administered as a subcutaneous (SC) injection, which offers an alternative to intravenous infusion of antibody-based complement C5 inhibitors. Objective: To evaluate subcutaneous zilucoplan in adults with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG) who switched from intravenous complement C5 inhibitors to zilucoplan. Design: MG0017 (NCT05514873) was a phase IIIb, open-label, single-arm study. Methods: Eligible patients had clinically stable gMG on an intravenous complement C5 inhibitor and were willing to switch to zilucoplan. Patients received a 12-week treatment period of daily subcutaneous zilucoplan 0.3 mg/kg. Incidence of treatment-emergent adverse events (TEAEs) was the primary endpoint. Change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 12 was a secondary endpoint. Treatment preference (Week 12) and treatment satisfaction (9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)) were both exploratory endpoints. Assessments by prior intravenous complement C5 inhibitor were conducted post hoc. Results: Twenty-six patients enrolled and received zilucoplan; 16 switched from eculizumab and 10 from ravulizumab. TEAEs occurred in 19/26 (73.1%) patients and were mostly mild in severity. At Week 12, least squares (LS) mean (95% confidence interval) MG-ADL scores improved from baseline by −1.15 (−2.11, −0.19), p = 0.0217 and Quantitative MG (QMG) scores by −1.24 (−2.64, 0.16), p = 0.0802. Clinically meaningful improvement from baseline in mean MG-ADL and QMG scores was observed at Week 12 among patients who switched from ravulizumab (−2.41 (−4.52, −0.30; p = 0.0307) and −3.52 (−6.14, −0.90; p = 0.0149), respectively). At Week 12, 76.9% (n = 20) patients preferred subcutaneous injection compared with intravenous infusion. Mean (standard deviation) changes from baseline in the TSQM-9 Global Satisfaction, Effectiveness and Convenience subscores at Week 12 were +19.410 (27.429), +13.889 (21.534) and +21.739 (19.955), respectively. Complement inhibition increased from baseline and was complete (>95%) by Week 2 and maintained to Week 12. Conclusion: Zilucoplan demonstrated a favourable safety profile. gMG symptoms improved during zilucoplan treatment; this was clinically meaningful for those switching from ravulizumab. Trial registration: ClinicalTrials.gov (NCT05514873); 22 August 2022. https://clinicaltrials.gov/study/NCT05514873 Plain language summary Experiences of patients with myasthenia gravis who switched their treatments from intravenous infusions of ravulizumab or eculizumab to self-administered daily injections of zilucoplan: effects on symptoms, safety, and patient preference Myasthenia gravis (MG) is a chronic autoimmune disease. Complement, part of the immune system, is overactive in MG. This damages the connections between muscles and nerves, causing muscle weakness. Symptoms can be reduced by blocking complement activity. Ravulizumab and eculizumab are complement inhibitors that are given as intravenous (into a vein) infusions by a healthcare professional in a hospital or clinic. Zilucoplan is another type of complement inhibitor, which patients can inject subcutaneously (under the skin) themselves. This study followed patients with MG who wanted to switch from ravulizumab or eculizumab to zilucoplan. Side effects were recorded throughout the study. Patients’ symptoms were measured to see if there was any change since switching treatment. All 26 patients who enrolled in the study had stable symptoms with their current treatment (which was ravulizumab in 10 patients, and eculizumab in 16 patients). Once enrolled, patients switched to daily zilucoplan for 12 weeks. Their main reasons for wanting to switch treatment were challenges with intravenous infusions, including travelling to hospital and long infusion times. Some patients also felt their current treatment was wearing off. After 12 weeks of zilucoplan treatment, symptoms across the group as a whole had improved. Symptoms had either improved or stayed the same in approximately 75% of patients. Symptom improvements were greatest in patients who switched from ravulizumab to zilucoplan. At the end of the study, 76.9% (20 out of 26) patients said they preferred injections with zilucoplan to intravenous infusions of their previous treatment. Side effects occurred in 73.1% of patients, which were mostly mild. Although the study was short and limited to a small number of patients, the results suggest that switching to zilucoplan is an option for patients with MG who would prefer self-injections to intravenous infusions. Longer-term studies are needed to confirm these findings.

ObjectivesTo approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.DesignRetrospective cohort study.SettingClinics across North America.ParticipantsThe study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.MethodsPhenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.ResultsAmong 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.DiscussionThe familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

Background Systemic light chain (AL) amyloidosis is a clonal plasma‐cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co‐exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis. Aim: The study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high‐risk cardiac AL patients. Materials & Methods This retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log‐rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups. Results FISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy‐overall (38%). Hyperdiploidy‐overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) Conclusions Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high‐risk cardiac AL population. Hyperdiploidy in AL amyloidosis patients was associated with poor PFS and OS and cardiac AL patients had a strong association with del 13q.

BackgroundIn the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved myasthenia gravis (MG)-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the ongoing, open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. Here, we evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT.MethodsRAISE-XT enrolled adults who completed the Phase 2 or RAISE studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Change from baseline (CFB) in MG Activities of Daily Living (MG-ADL) score was described for each category.Results200 patients enrolled. At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced or discontinued corticosteroids (mean reductions: 14mg and 16mg). Among these patients, mean (standard deviation [SD]) CFB in MG-ADL score was −5.00 (3.96) and −5.67 (6.89). At Week 60, 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups) with mean (SD) CFB in MG-ADL score of −4.86 (2.55) and −9.75 (4.57). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022).ConclusionsWhile receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.

Valosin‐containing protein (VCP)‐associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP‐associated MSP have myopathy, but there is no consensus‐based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on VCP myopathy was reviewed to better understand the different aspects of management of VCP myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP myopathy has a heterogeneous clinical phenotype and should be considered in patients with limb‐girdle muscular dystrophy phenotype, or any myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP myopathy, and single‐variant testing in the case of a known familial VCP variant, or multi‐gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP myopathy will optimize patient care and help future research initiatives.

Amyloidosis is a rare, systemic disease that can result in significant functional impairment. Specific guidelines for the rehabilitation assessment of amyloidosis patients have yet to be established. The purpose of this study was to identify functional deficits and assess differences based on disease type, organ involvement, age, and gender of patients with amyloidosis. Materials and Methods: The multidisciplinary Comprehensive Amyloidosis Clinic (CAC) at Ohio State University (OSU) has developed structured assessment guidelines for amyloidosis patients. A retrospective, single-institution review of patients assessed in CAC between December 2017 and April 2020 was performed. Outcome measure data from the Timed Up and Go (TUG), 30 s sit-to-stand, and physical function portion of the SF 36 were gathered by chart review. Comparisons were made between CAC patient scores and normative data. Kruskal–Wallis tests were used to compare scores across the disease types (light chain, transthyretin wild-type, and hereditary variant transthyretin) and the Mann–Whitney U test was used for pairwise comparisons within disease types and cardiac involvement. Linear regression models were used to assess associations between patient characteristics (including age, gender, disease type, and cardiac involvement) and performance scores. Results: Data from sixty-four patients was evaluated. On the 30-s sit-to-stand test, patients with light chain amyloidosis performed 3.32 fewer repetitions than patients with transthyretin wild-type, p = 0.03. Patients with cardiac involvement had 2.55 fewer repetitions than patients without cardiac involvement, p = 0.03. Older patients were found to have slower TUG performance, and a 10-year increase in age was associated with an 11% increase in TUG scores. Conclusions: Findings indicate patients with light chain amyloidosis and patients with cardiac involvement, when compared to other amyloidosis patients, present with more physical impairments.

Hirayama disease is a nonprogressive cervical myelopathy associated with epidural venous engorgement and spinal canal narrowing. It has been unclear whether dural venous pressure influences spinal cord injury in this illness. An 18-year-old man presented with profound hand weakness and atrophy that had developed over a period of 1 year. Electromyographic, magnetic resonance imaging, and angiographic findings are presented. The epidural space was accessed using a microcatheter technique. Pressure measurements were recorded with and without Valsalva maneuver in the inferior vena cava, vertebral veins, and epidural space at C4 and C6 in both the flexion and neutral positions. Cervical epidural venous pressure measurements in flexion and neutral positions are presented. The patient underwent duraplasty with C4 to T1 laminectomies and fusion using lateral mass screws and facet arthrodeses. Lack of significant pressure change with neck flexion suggested that dural venous engorgement is passive and not the direct cause for spinal cord injury. Data presented herein and review of the literature suggest that surgical treatment targeting the underlying pathophysiological mechanism in Hirayama disease can benefit patients, especially early in the course of the disease.