A clinical and immunological study on late onset Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder of neuromuscular transmission caused by antibodies to the acetylcholine receptor and related components on the post synaptic membrane of the neuromuscular junction. Recent evidence has shown that the incidence of late-onset myasthenia gravis, defined as onset at more than 50 years of age, has been increasing. We sought to prospectively recruit patients newly diagnosed with myasthenia gravis and look at their clinical and immunological profile to see if there are any differences between early onset and late-onset myasthenia gravis. Methods: This was a multicentre study across Nottingham, Birmingham and Oxford. We recruited 150 patients with myasthenia gravis across the three sites, newly diagnosed within the preceding 12 months. We did clinical examinations, completed MG composite scores (MGC), MG Quality of life scores (MG QOL), and blood tests including serum for antibodies, and whole blood for PBMC isolation and T-cell studies. These were repeated at annual follow up. The antibody studies were performed at Oxford by radioimmunoassay (RIA) and cell based assays (CBA) for acetylcholine receptor antibodies (AChR), muscle specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. Results: We recruited 150 patients with myasthenia gravis, 76% of whom had LOMG, with a female to male ratio of 1:1.6. EOMG patients more frequently had ocular myasthenia compared to LOMG patients, 94.7% of patients were seropositive for either AChR, MuSK or LRP4 antibodies. T-cell studies showed that the pro-inflammatory and anti-inflammatory cytokine balance is disrupted in all MG patients with decreased Treg percentages and increased production of IL10, IL17 and TNF alpha, which is more pronounced in patients with AChR antibodies. The clinical presentation did not show any difference between the different antibody subgroups, but there was a milder, more indolent course in seronegative patients, and AChR + MuSK double positive patients were more likely to need steroids on generalisation. The majority of the patients responded well to treatment with improvement in MGC, MG QOL and AChR RIA titres with time. Conclusions: To our knowledge, this is the largest prospective study on the clinical and immunological aspects of late-onset myasthenia gravis to date. Further studies on B cells in MG along with micro-RNAs as biomarkers in MG are being done

A clinical and immunological study on late onset Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder of neuromuscular transmission caused by antibodies to the acetylcholine receptor and related components on the post synaptic membrane of the neuromuscular junction. Recent evidence has shown that the incidence of late-onset myasthenia gravis, defined as onset at more than 50 years of age, has been increasing. We sought to prospectively recruit patients newly diagnosed with myasthenia gravis and look at their clinical and immunological profile to see if there are any differences between early onset and late-onset myasthenia gravis. Methods: This was a multicentre study across Nottingham, Birmingham and Oxford. We recruited 150 patients with myasthenia gravis across the three sites, newly diagnosed within the preceding 12 months. We did clinical examinations, completed MG composite scores (MGC), MG Quality of life scores (MG QOL), and blood tests including serum for antibodies, and whole blood for PBMC isolation and T-cell studies. These were repeated at annual follow up. The antibody studies were performed at Oxford by radioimmunoassay (RIA) and cell based assays (CBA) for acetylcholine receptor antibodies (AChR), muscle specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. Results: We recruited 150 patients with myasthenia gravis, 76% of whom had LOMG, with a female to male ratio of 1:1.6. EOMG patients more frequently had ocular myasthenia compared to LOMG patients, 94.7% of patients were seropositive for either AChR, MuSK or LRP4 antibodies. T-cell studies showed that the pro-inflammatory and anti-inflammatory cytokine balance is disrupted in all MG patients with decreased Treg percentages and increased production of IL10, IL17 and TNF alpha, which is more pronounced in patients with AChR antibodies. The clinical presentation did not show any difference between the different antibody subgroups, but there was a milder, more indolent course in seronegative patients, and AChR + MuSK double positive patients were more likely to need steroids on generalisation. The majority of the patients responded well to treatment with improvement in MGC, MG QOL and AChR RIA titres with time. Conclusions: To our knowledge, this is the largest prospective study on the clinical and immunological aspects of late-onset myasthenia gravis to date. Further studies on B cells in MG along with micro-RNAs as biomarkers in MG are being done

Is Distributed Database Evaluation Cloud-Ready?

The database landscape has significantly evolved over the last decade as cloud computing enables to run distributed databases on virtually unlimited cloud resources. Hence, the already non-trivial task of selecting and deploying a distributed database system becomes more challenging. Database evaluation frameworks aim at easing this task by guiding the database selection and deployment decision. The evaluation of databases has evolved as well by moving the evaluation focus from performance to distribution aspects such as scalability and elasticity. This paper presents a cloud-centric analysis of distributed database evaluation frameworks based on evaluation tiers and framework requirements. It analysis eight well adopted evaluation frameworks. The results point out that the evaluation tiers performance, scalability, elasticity and consistency are well supported, in contrast to resource selection and availability. Further, the analysed frameworks do not support cloud-centric requirements but support classic evaluation requirements

Data transformation as a means towards dynamic data storage and polyglot persistence

Legacy applications have been built around the concept of storing their data in one relational data store. However, with the current differentiation in data store technologies as a consequence of the NoSQL paradigm, new and possibly more performant storage solutions are available to all applications. The concept of dynamic storage makes sure that application data are always stored in the most optimal data store at a given time to increase application performance. Additionally, polyglot persistence aims to push this performance even further by storing each different data type of an application in the data store technology best suited for it. To get legacy applications into dynamic storage and polyglot persistence, schema and data transformations between data store technologies are needed. This usually infers application redesigns as well to support the new data stores. This paper proposes such a transformation approach through a canonical model. It is based on the Lambda architecture to ensure no application downtime is needed during the transformation process, and after the transformation, the application can continue to query in the original query language, thus requiring no application code changes

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension