Efek Obat Imunosupresan Pada Pasien Autoimun dengan COVID-19 (A Scoping Review of The Clinical Evidence)

The main modality in autoimmune disease is a long-term immunosuppressant treatment aiming to control disease progression and increase patient life expectancy. This scoping review aims to evaluate the effect of immunosuppressant treatment in autoimmune patients with COVID-19 on clinical outcomes and disease progression. This scoping review was conducted following the PRISMA extension for scoping review (PRISMA-ScR) guidelines. The Pubmed and Science Direct databases are used to find articles that match the study objectives. Thirteen articles met the inclusion criteria, and all of them were classified as observational studies. Most immunosuppressant treatments are the disease-modifying anti-rheumatic drugs (DMARD) and glucocorticoids. The highest number of autoimmune patients with rheumatoid arthritis (RA) was 43.4%, systemic lupus erythematosus (SLE) 13.6%, and others was 43%. Autoimmune patients with COVID-19 taking immunosuppressant medications, particularly glucocorticoids, significantly increased the risk of hospitalization and the use of ventilators. However, there was no mention of the dosage and duration of immunosuppressant therapy in most of the studies. In general, the use of immunosuppressant drugs was not associated with an increased risk of COVID-19 infection and mortality compared with the general population. Increasing age and comorbidities were associated with poor clinical outcomes. In conclusion, autoimmune patients with COVID-19 who are taking immunosuppressant therapy particularly glucocorticoid exacerbate clinical outcomes. Periodic clinical monitoring and appropriate pharmacological interventions are required in autoimmune patients with COVID-19 to improve clinical outcomes and prevent death.Keywords: Autoimmune, COVID-19, Immunosuppressant, Clinical outcome.

The Need for a Broad Differential: Intramedullary Neurosarcoidosis Case Report

BackgroundSarcoidosis, an idiopathic multisystem inflammatory disorder, involves the nervous system in as few as 5-15% of cases. We aim to detail how a rare case of intramedullary neurosarcoidosis spinal-cord lesion, present in less than 1% of sarcoidosis cases, presented with features mimicking a neoplasm. MethodsRetrospective chart review was performed to obtain pertinent details regarding history and examination, pathological findings, and treatment course.Case PresentationWe report a case of intramedullary sarcoidosis involving the cervical and thoracic spinal cord with syringomyelia, which presented as subacute neck pain, intermittent leg paresthesias, and difficult micturition. Historically, a spinal syrinx with concern for neoplasm has led surgeons to decompress the spinal cord for certain enhancing intramedullary lesions, which is unnecessary for neurosarcoidosis. Immunosuppressant treatment resulted in symptomatic resolution without the need for spinal cord biopsy or syrinx decompression in this case.Conclusions Expansile contrast-enhancing intramedullary lesions, most commonly neoplastic, may instead be non-neoplastic etiologies mimicking neoplastic features; therefore, it is the responsibility of any surgeon to maintain a broad differential diagnosis in the absence of a confirmed pathology.

P604 Evaluation of management heterogeneity and complications of Crohn’s disease in Catalonia. A population quality care study

Background Heterogeneity in the treatment of a disease is a marker of suboptimal quality of care. Recent studies suggest that there is a marked heterogeneity in the management of inflammatory bowel disease. The aim of this study is to evaluate the heterogeneity in the treatment used and the outcomes (rate of hospitalization and surgery) for Crohn’s disease (CD) in the different health areas of Catalonia. Methods All patients with CD included in the Catalan Health Surveillance System (CHSS) including data on more than 7 million individuals from 2011 to 2017 were identified using with the ICD-9-CM codes. The different Catalonian health areas were grouped into 19 groups according to the reference hospital (figure 1). Exposures to different treatments were retrieved from the electronic dispensation records. Data on hospitalizations and surgeries were also extracted from the CHSS according to ICD-9-CM codes. Treatment used rates (systemic corticosteroids, non-biological and biological immunosuppressant) and outcome rates (hospitalization and surgery) were calculated. Results The use of systemic corticosteroids presented a decreasing trend over the study period, with an average rate of use of the total number of patients in the different territories between 10% and 16% (figure 2). The use of non-biological immunosuppressant treatment has remained stable, with an average rate of use ranging from 20% to 40% (figure 3). On the other hand, the use of biological immunosuppressant treatment increased, with an average rate of use in the different territories ranging from 10 to 22% (figure 4). Hospitalizations for any reason showed an increasing trend between 2011–2017 with an average rate between 19% and 30% per year depending on the area. Contrarily, hospitalizations for CD presented a decreasing trend, with an average rate between 5% and 10% per year. Surgical treatment (both resections and ostomies) remained stable over time. Rates per year were between 1% and 2%. Conclusion In this population study we appreciated an important heterogeneity in the use of non-biological and biological immunosuppressant treatments, identifying use rates of almost the double in some of the areas. There is also a remarkable variability in the rate of hospitalizations for CD between certain areas of Catalan territory.

Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases

Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant. They express receptors for sphingosine-1-phosphate (S1P), which is actively produced by damaged cells, allowing circulating cells to selectively home to damaged tissue. Muse cells spontaneously differentiate on-site into multiple tissue-constituent cells with few errors and replace damaged/apoptotic cells with functional cells, thereby contributing to tissue repair. Intravenous injection of exogenous Muse cells to increase the number of circulating Muse cells enhances their reparative activity. Muse cells also have a specific immunomodulatory system, represented by HLA-G expression, allowing them to be directly administered without HLA-matching or immunosuppressant treatment. Owing to these unique characteristics, clinical trials using intravenously administered donor-Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, and amyotrophic lateral sclerosis. Muse cells have the potential to break through the limitations of current cell therapies for neurologic diseases, including amyotrophic lateral sclerosis. Muse cells provide a new therapeutic strategy that requires no HLA-matching or immunosuppressant treatment for administering donor-derived cells, no gene introduction or differentiation induction for cell preparation, and no surgery for delivering the cells to patients.

Effect of immunosuppressants on the parasite load developed in, and immune response to, visceral leishmaniasis: A comparative study in a mouse model

The increasing use of immunosuppressants in areas where visceral leishmaniasis (VL) is endemic has increased the number of people susceptible to developing more severe forms of the disease. Few studies have examined the quality of the immune response in immunosuppressed patients or experimental animals with VL. The present work characterises the parasite load developed in, and immune response to, Leishmania infantum-induced VL in C57BL/6 mice that, prior to and during infection, received immunosuppressant treatment with methylprednisolone (MPDN), anti-tumour necrosis factor (anti-TNF) antibodies, or methotrexate (MTX). The latter two treatments induced a significant reduction in the number of CD4+ T lymphocytes over the infection period. The anti-TNF treatment was also associated with a higher parasite load in the liver and a lower parasite load in the spleen. This, plus a possibly treatment-induced reduction in the number of cytokine-producing Th1 cells in the spleen, indicates the development of more severe VL. Interestingly, the MPDN and (especially) MTX treatments provoked a greater presence of soluble Leishmania antigen-specific multi-cytokine-producing T cells in the spleen and a lower liver parasite load than in control animals. These results highlight the need to better understand how immunosuppressant treatments might influence the severity of VL in human patients.

AChRAb and MuSKAb double-seropositive myasthenia gravis: a distinct subtype?

Introduction This study investigated the characteristics of double-seropositive myasthenia gravis (DSP-MG) in southern China for disease subtype classification. Methods A case-control study was carried out in which the characteristics of DSP-MG patients (n = 17) were compared to those of muscle-specific tyrosine kinase antibody-positive (MuSK)-MG and acetylcholine receptor antibody-positive (AChR)-MG patients (n = 8 and 27, respectively). We also performed a literature review of DSP-MG patients. Results Compared to AChR-MG, DSP-MG had greater bulbar dysfunction (47.1% vs 18.6%, P = 0.04), higher incidence of myasthenia crisis (41.2% vs 14.8%, P = 0.04), more severe Myasthenia Gravis Foundation of America classification at maximum worsening, greater autoantibody abnormalities (70.6% vs 33.3%, P = 0.015), greater need for immunosuppressant treatment (58.8% vs 3.7%, P < 0.001), and worse prognosis with less remission (11.8% vs 55.6%, P = 0.001). There were no differences between DSP-MG and MuSK-MG patients. DSP-MG described in published reports was comparable to MuSK-MG. Discussion DSP-MG in southern China may be a subtype of MuSK-MG.

Abstract 16368: Establishment of Administration Protocol of Immunosuppressive Drug for Ips Cell Derived Cardiomyocytes Patch Transplantation in Rat Myocardial Infarction Model

Background: Although Cardiomyogenesis therapy using iPS cells for heart failure should overcome immune rejection because of allogenic cell source, appropriate protocol of immunosuppressant to promise efficacy and safety has not been fully elucidated. In this study, we investigated the duration of immunosuppressant administration that could promise the efficacy of human iPS cell derived cardiomyocytes (hiPSCs-CM) patch transplantation as well as safety. Methods: The hiPSCs-CM patch were transplanted to myocardial infarction model rats with normal immune function in immunosuppressant treatment groups. Control were underwent sham operation and treated with no immunosuppressant (Group1). Immunosuppressant treatment groups were divided into three groups as follows: treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PSL) for 1month and 1 month tapering period (Group2); treated with TAC, MMF, and PSL for 2month and 1 month tapering period (Group3); and treated with TAC, MMF, and PSL for 3month and 1 month tapering period (Group4). After 6 months, cardiac function and histology were analyzed. Results: hiPSC-CM patch transplantation showed significant improvement cardiac fraction compared to the Group1 (ΔLVEF; Group2 22 ± 3 %, Group3 28 ± 5 %, Group4 23 ± 4 % versus Group1 -15 ± 8 %, P < 0.05) and did not show any differences in immunosuppressant treated groups. The hiPSCs-CM patch were detected for 2 months post-transplant and Improved Cardiac functions were maintained for at least 6 months despite disappearance of the transplanted patch. Fibrosis and cardiomyocyte size were significantly ameliorated in Group2-4 compared with Group1, however, there were significant differences in immunosuppressant treated groups. Furthermore, the Group 2, 3 and 4 showed a greater amount of structurally mature blood vessels compared with Group1, however, there were no significant in immunosuppressant treated groups. Tumor formation was not observed 6 months after transplantation in the Group 2, 3 and 4. Conclusion: 2 months administration of immunosuppressive agent may promise the safety and efficacy of hiPSCs-CM patch transplantation for rat ischemic heart failure model, proposing appropriate recipe of immunosuppressant in clinical trial.

Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients

Background East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies have described the clinical features and treatment of this disease, especially in France. Methods This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers. Results Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women. Conclusion We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients’ ethnicity.