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

Synthesis of calcium carbonate microspheres via inert gas bubbling for orthopedic applications

Calcium carbonate (CaCO3) microspheres consisting of vaterite polymorph have been widely used in biomedical applications. Specifically, vaterite microspheres having hollow cores showed significant potential in drug delivery, however the spontaneous transformation of vaterite to other polymorphs in aqueous environments reduced its controlled in vivo release capability. In this work, calcite and aragonite microspheres having hollow/porous inner cores were synthesized -for the first time-using sodium dodecyl sulfate (SDS) stabilized nitrogen (N-2) bubbles as CaCO3 template in ethylene glycol (EG) solution and water as the precipitation medium. Results demonstrated that porous aragonite microspheres could be synthesized via N-2 gas incorporation, yet for the synthesis of hollow calcite microspheres, N-2 bubbles had be stabilized with SDS to be utilized as CaCO3 templates. The synthesized aragonite and calcite microspheres were found to be stable up to 5 days in Dulbecco's Modified Eagle's Medium (DMEM), and thus would not allow polymorphic transformation in aqueous environments, while promoting proliferation of human bone cells (hFOB) up to 5 days of culture. These findings -for the first time-identified a viable synthesis route for hollow/porous calcite and aragonite microspheres and indicated their promising use in orthopedic applications

A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation

Osteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentalization as hydrophilic GEM being in core and lipophilic CLF sequestering in lipid-bilayer. Liposomes had high encapsulation efficiency (above 90%, GEM and above 80%, CLF). CLF release was enhanced while GEM release was slowed down in coloaded liposomes compared to single cases. GEM/CLF co-loaded liposomes significantly enhanced cytotoxicity than GEM or CLF loaded liposomes on osteosarcoma cell line. CLF and GEM had synergistic effect (CI < 1). Results of flow cytometry showed higher apoptotic cell ratio, caspase-3 activity, mitochondrial membrane depolarized cells' ratio for GEM/CLF co-loaded liposome treatments than other liposomes. Cytotoxicity of CLF on bone cancer cells and also its synergistic effect with GEM on osteosarcoma is reported for the first time with this study. CLF's loading with GEM into liposome was also a new approach for enhancement of anticancer effect on Saos-2 cells. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed as a novel approach for treatment of osteosarcoma

Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival

In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients

The Effect of Reduction Mammaplasty on the Vertebral Column: A Radiologic Study

Some studies emphasized that anatomic mechanisms of vertebral aberrations could be associated with large breasts. The effect of mammaplasty operation on the vertebral column and body posture seems to be beneficial; in this trial, it was planned to investigate the objective radiologic effect of reduction mammaplasty on the posture of the vertebral column in a group of patients operated due to the large breasts. Thirty-four white women with large breasts were enrolled in this study. The patients were divided into three groups according to their breast cup sizes. Anteroposterior and lateral radiographs of the lumbosacral and thoracic spine were taken at baseline preoperatively, and the same radiographic images were taken in an average of 12 months later than the reduction mammaplasty operation. All were evaluated and compared for thoracic kyphosis angle and lumbar lordosis angle both preoperatively and postoperatively. The mean thoracic kyphosis angle was 40,53 preoperatively and 39,38 postoperatively. However, there was no statistically significant difference between the preoperative and postoperative measurements in all groups (P>0,05). The mean lumbar lordosis angle was 54,71 preoperatively and 53,18 postoperatively. Regarding the preoperative and postoperative measurements of lumbar lordosis angles, no statistically significant difference was found between the groups (P>0,05). Although breast size may be an important factor that affects body posture, reduction mammaplasty operations have little or no radiologic effect on the vertebral column

Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival

In this retrospective study with case-control design, we aimed to determine the clinical and pathological characteristics of post-transplant glomerulonephritis (GN), and their effects on transplant recipients