MIS-C is a newly defined post-viral myocarditis and inflammatory vasculopathy of children following COVID-19 infection. This review summarizes the literature on diagnosis, parameters of disease ...severity, and current treatment regimens. The clinical perspective was analyzed in light of potential immunopathogenesis and compared to other post-infectious and inflammatory illnesses of children affecting the heart. In this paradigm, the evidence supports the importance of endothelial injury and activation of the IL-1 pathway as a common determinant among MIS-C, Kawasaki disease, and Acute Rheumatic fever.
We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This ...combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This review updates recent trends in the classification of the juvenile idiopathic inflammatory myopathies (JIIM) and the emerging standard of treatment of the most common form of JIIM, juvenile ...dermatomyositis. The JIIM are rare, heterogeneous autoimmune diseases that share chronic muscle inflammation and weakness. A growing spectrum of clinicopathologic groups and serologic phenotypes defined by the presence of myositis autoantibodies are now recognized, each with differing demographics, clinical manifestations, laboratory findings, and prognoses. Although daily oral corticosteroids remain the backbone of treatment, disease-modifying anti-rheumatic drugs are almost always used adjunctively and biologic therapies may benefit patients with recalcitrant disease.
Objective
This open‐label, 24‐week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).
Methods
Ten patients ≥7 years of age ...with moderate disease activity were enrolled in a 24‐week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)–regulated gene score was performed on whole‐blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.
Results
Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down‐trending IFN‐regulated gene scores and galectin‐9 expression at week 24. Decreases in IFN‐regulated gene scores and in levels of interferon‐γ‐inducible protein 10kDa, galectin‐9, and interleukin‐2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment‐emergent adverse events were observed.
Conclusion
This open‐label study demonstrated that abatacept may be beneficial for patients with treatment‐refractory juvenile DM.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The most challenging aspect of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID remains for the discordance between the viral damage from acute infection in the recent past and ...susceptibility of Long COVID without clear evidence of post infectious inflammation or autoimmune reactions. In this communication we propose that disarray of pericytes plays a central role in emerge of Long COVID. We assume pericytes are agents with "Triple-A" qualities, i.e., analyze-adapt and advance, necessary for sustainability of host homeostasis. Based on this view, we further suggest Long COVID may provide a model system to integrate system theory and complex adaptive systems to explore a new class of maladies those are currently not well defined and with no remedies.
Mesenchymal stem cells have recently been recoined as medicinal signaling cells (MSC) for their ability to promote tissue homeostasis through immune modulation, angiogenesis and tropism. During the ...last 20 years, there has been a plethora of publications using MSC in adults and to lesser extent neonates on a variety of illnesses. In parts of the world, autologous and allogeneic MSCs have been purified and used to treat a range of autoimmune conditions, including graft versus host disease, Crohn's disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Generally, these reports are not part of stringent clinical trials but are of note for good outcomes with minimal side effects. This review is to summarize the current state of the art in MSC therapy, with a brief discussion of cell preparation and safety, insights into mechanisms of action, and a review of published reports of MSC treatment of autoimmune diseases, toward the potential application of MSC in treatment of children with severe autoimmune diseases using multicenter clinical trials and treatment algorithms.
Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful ...applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (
n
= 46) or late aGvHD (
n
= 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 10
6
/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 10
6
/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3–4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3–4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (
p
= 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25–62%) versus 71% (95% CI, 59–86%), respectively (
p
= 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37–74%) versus 28% (95% CI, 13–40%), respectively (
p
= 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive ...immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models.
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a ...natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered
via
jet nebulizer. Patients received 1-5x10
10
nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) 20.8% (P < 0.05), oxygen saturation (SpO
2
) 6,7% (P < 0.05) and partial pressure of oxygen to the fraction of inspired oxygen (PaO
2
/FiO
2
) 127.9% (P < 0.05) that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
PDF
