scholarly journals Unveiling the Efficacy, Safety, and Tolerability of Anti-Interleukin-1 Treatment in Monogenic and Multifactorial Autoinflammatory Diseases

2019 ◽  
Vol 20 (8) ◽  
pp. 1898 ◽  
Author(s):  
Alessandra Bettiol ◽  
Giuseppe Lopalco ◽  
Giacomo Emmi ◽  
Luca Cantarini ◽  
Maria Letizia Urban ◽  
...  
Keyword(s):  
Observational Studies ◽  
Interleukin 1 ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Clinical Manifestations ◽  
Autoinflammatory Diseases ◽  
Negative Consequences ◽  
Adherence To Treatment ◽  
Appropriate Treatment ◽  
Sustained Reduction

Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of interleukin-1(IL-1)β that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients’ quality of life. IL-1β blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1β antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.

Biologic disease-modifying antirheumatic drugs in the treatment of major monogenic autoinflammatory diseases: literature review and clinical observation

2021 ◽  
Vol 15 (6) ◽  
pp. 95-100
Author(s):  
S. O. Salugina ◽  
E. S. Fedorov
Keyword(s):  
High Efficiency ◽  
Interleukin 1 ◽  
Autoinflammatory Diseases ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying ◽  
Factor Α ◽  
Genetically Determined ◽  
Late Stages

Autoinflammatory diseases (AIDs) are a heterogeneous group of rare genetically determined conditions, the main manifestations of which are episodes of fever in combination with other signs of systemic inflammation: skin rashes, musculoskeletal and neurological disorders, damage to the organs of vision, hearing, etc., as well as acute phase markers and the absence of autoantibodies. The use of biological therapy, especially inhibitors of interleukin 1 (iIL1), in most common monogenic AIDs (mAID) – FMF, TRAPS, HIDS/MKD, CAPS – has shown its high efficiency and led to significant progress in the treatment of these patients. Currently, iIL1 are the first-line drugs for mAIDs therapy, primarily CAPS. In the case of their ineffectiveness or intolerance in certain situations, other biologic disease-modifying antirheumatic drugs can also be used – inhibitors of tumor necrosis factor α and iIL6, but this issue needs further investigation. The article describes a patient with mAID, in whom the diagnosis was made more than 40 years after the onset; administration of targeted therapy even in the late stages of the disease led to a significant improvement in many symptoms and quality of life. 

scholarly journals Golimumab in the treatment of extra-skeletal manifestations of ankylosing spondylitis

2019 ◽  
Vol 13 (4) ◽  
pp. 110-115
Author(s):  
A. B. Demina
Keyword(s):  
Ankylosing Spondylitis ◽  
Observational Studies ◽  
Clinical Manifestations ◽  
Large Sample Size ◽  
Efficacy And Safety ◽  
High Efficacy ◽  
Treatment Regimens ◽  
Insufficient Response ◽  
Inflammatory Changes

Extra-skeletal manifestations (EMs) of ankylosing spondylitis (AS) can occur and proceed in parallel with inflammatory changes in the joints and spine and often dominate in the clinical picture of AS, determining its high activity and significantly worsening the quality of life in patients. In a number of cases, EMs are characterized by an insufficient response to standard anti-inflammatory therapy for back pain, arthritis, and enthesitis; and there is a need to prescribe another class of drugs.The review highlights the results of studies evaluating the efficacy of golimumab (GLM) in treating EMs in patients with AS: uveitis (GO-EASY Study) and ulcerative colitis (UC) (PURSUIT-SC, PURSUIT-M studies). Analysis of these studies have shown the high efficacy and safety of GLM in reducing the clinical manifestations of AS and in preventing the exacerbations of uveitis and UC. However, despite the successes achieved in treating AS and its EMs, there are many unresolved issues, including those related to the elaboration of optimal treatment regimens, which required longer observational studies with a large sample size.

scholarly journals Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

Blood ◽  
2011 ◽  
Vol 117 (14) ◽  
pp. 3720-3732 ◽  
Author(s):  
Charles A. Dinarello
Keyword(s):  
Disease Severity ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Immunosuppressive Drugs ◽  
Autoinflammatory Diseases ◽  
Inflammatory Conditions ◽  
Sustained Reduction ◽  
Anti Inflammatory ◽  
Smoldering Myeloma ◽  
Acute And Chronic Inflammation

Abstract More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.

scholarly journals The off-label use of anakinra in pediatric systemic autoinflammatory diseases

2020 ◽  
Vol 12 ◽  
pp. 1759720X2095957
Author(s):  
Valerio Maniscalco ◽  
Sarah Abu-Rumeileh ◽  
Maria Vincenza Mastrolia ◽  
Edoardo Marrani ◽  
Ilaria Maccora ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Case Series ◽  
Autoinflammatory Diseases ◽  
Off Label Use ◽  
Off Label ◽  
Rheumatologic Diseases ◽  
Valuable Treatment ◽  
Label Use

Interleukin 1 (IL-1), a central mediator of innate immunity, is considered a master cytokine of local and systemic inflammation. IL-1 has emerged as pivotal in the pathogenesis of autoinflammatory diseases (AIDs), and blockade of its pathway has become a crucial target for therapy. Anakinra (ANA), a recombinant IL-1β receptor antagonist, was the first anti-IL-1 agent employed in clinical practice. ANA is currently approved for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still’s disease, and cryopyrin-associated autoinflammatory syndrome. It has also been successfully used for off-label treatment of various monogenic, polygenic, or undefined etiology systemic AIDs. This review describes currently available evidence for the off-label use of ANA in pediatric rheumatologic diseases. Specifically, the use of ANA in Kawasaki disease, idiopathic recurrent pericarditis, Behçet disease, monogenic AIDs, undifferentiated AIDs, chronic non-bacterial osteomyelitis, macrophage activation syndrome, and febrile infection-related epilepsy, in terms of its safety and efficacy. In selected pediatric rheumatic disorders, the off-label administration of ANA appears to be effective and safe. In order to control severe and/or relapsing disease, ANA should be considered as a valuable treatment option in children suffering from rare inflammatory diseases. However, currently available data consist of retrospective studies and short case series; thus, randomized controlled trials and larger series with long-term follow up are mandatory to better assess the efficacy and cost effectiveness of ANA in these challenging patients.

scholarly journals The impact on parents of having a child with haemophilia

2016 ◽  
Vol 3 (2) ◽  
pp. 4-14 ◽  
Author(s):  
Kate Khair ◽  
Steve Chaplin
Keyword(s):  
Literature Review ◽  
Health Professionals ◽  
Observational Studies ◽  
Intervention Studies ◽  
Well Being ◽  
Family Quality Of Life ◽  
Appropriate Treatment ◽  
The Family ◽  
The Impact

Abstract Wider access to modern treatment of haemophilia has led to a growing interest in the family’s role in management. An increasing amount of research has sought to understand the psychosocial impact of living with a child with haemophilia. Understanding how such demands affect parents and families who live with the daily threat of bleeding can help health professionals to provide effective support. A literature review was undertaken with the aim of summarising the key findings from studies published since 2000. The literature review describes many common themes from observational studies that were generally consistent with those emerging from interviews of parents of children with haemophilia. Few intervention studies were identified. Overall, this evidence shows that raising a child with haemophilia can be challenging for parents and the family. Quality of life is impaired in the parents of a child with haemophilia and that many aspects of life are affected. However, providing care can also be rewarding and programmes of support, education and appropriate treatment evidently improve the well-being of parents and families.

scholarly journals Pathogenesis, Diagnosis, and Management of Primary Antibody Deficiencies and Infections

2009 ◽  
Vol 22 (3) ◽  
pp. 396-414 ◽  
Author(s):  
Ari J. Fried ◽  
Francisco A. Bonilla
Keyword(s):  
Clinical Manifestations ◽  
Primary Antibody ◽  
Total Serum ◽  
B Cell Differentiation ◽  
Increase Life Expectancy ◽  
Primary Antibody Deficiencies ◽  
Appropriate Treatment ◽  
Specific Antigens ◽  
Increased Susceptibility

SUMMARY Primary antibody deficiencies are the most common primary immunodeficiency diseases. They are a heterogeneous group of disorders with various degrees of dysfunctional antibody production resulting from a disruption of B-cell differentiation at different stages. While there has been tremendous recent progress in the understanding of some of these disorders, the etiology remains unknown for the majority of patients. As there is a large spectrum of underlying defects, the age at presentation varies widely, and the clinical manifestations range from an almost complete absence of B cells and serum immunoglobulins to selectively impaired antibody responses to specific antigens with normal total serum immunoglobulin concentrations. However, all of these disorders share an increased susceptibility to infections, affecting predominantly the respiratory tract. A delay of appropriate treatment for some diseases can result in serious complications related to infections, while timely diagnosis and adequate therapy can significantly decrease morbidity and increase life expectancy and quality of life.

Assessing the Quality of Management of Transformation Processes in Economic Systems

2020 ◽  
Vol 26 (9) ◽  
pp. 952-956
Author(s):  
M. V. Malyshkina ◽  
M. V. Miroslavskaya
Keyword(s):  
Systems Approach ◽  
Mutual Influence ◽  
Organizational Transformation ◽  
Quality Criterion ◽  
Economic Transformation ◽  
Economic Systems ◽  
Negative Consequences ◽  
Management Actions ◽  
Transformation Processes

Aim. The presented study aims to develop the methodology for assessing the quality of management of organizational transformation processes. Tasks. To achieve the set aim, the authors solve the following problems: determine the essence and content of socio-economic transformation, formulate quality assurance principles for the management of transformation processes, draw attention to the problem of selecting a unified quality criterion for the management of organizational transformation processes. Methods. This study uses general scientific methods of cognition, including analysis and synthesis. It also applies a systems approach to identify the major problems of assessing the quality of management of transformation processes, including the problem of selecting a unified quality criterion for the management of transformation processes and formulating the principles of ensuring the quality of management of transformation processes. Results. The global problem of managing transformation processes in the economic system consists in the complexity of the managed processes, which increases due to the multidimensionality, mutual influence, and the resulting uncertainty of interactions between the elements of the system. It is concluded that the methodology for assessing the quality of management of transformation processes is based on the principle of integrating separate measures to improve the quality of management of system elements into a single system of management actions and the principle of ensuring that management actions are primarily aimed at preventing possible negative consequences of the transformation of economic systems, i.e. reducing the potential impact of unfavorable events and their consequences. To assess the effectiveness of targeted management actions and productive actions aimed at organizing, controlling, and guiding the transformation process, the authors actualize the problem of selecting an adequate quality criterion for the management of transformation processes in economic systems and put forward a hypothesis about a possible unified criterion of management quality. Conclusions. The principle of integrating separate measures to improve the quality of management of system elements and the principle of ensuring that management actions are aimed at preventing possible negative consequences lie at the core of the methodology for assessing the quality of management of transformation processes in economic systems. The quality assessment methodology should be developed in the direction of finding a unified quality criterion for managing transformation processes in economic systems.

Effects and Risks of Distance Learning in Higher Education

2020 ◽  
pp. 61-73
Author(s):  
Yu. M. Tsygalov
Keyword(s):  
Higher Education ◽  
Distance Learning ◽  
Online Education ◽  
New Technology ◽  
Negative Consequences ◽  
Higher Education System ◽  
First Results ◽  
Spread Of Infection ◽  
The Cost

The forced work of Russian universities remotely in the context of the pandemic (COVID-19) has generated a lot of discussion about the benefits of the new form of education. The first results were summed up and reports were presented, the materials of which showed that the main goal of online education — the prevention of the spread of infection, - has been achieved. Against this background, proposals and publications have appeared substantiating the effectiveness of the massive introduction of distance learning in Russia, including in higher education. However, the assessment of such training by the population and students in publications and in social networks was predominantly negative and showed that the number of emerging problems exceeds the possible benefits of the new educational technology. Based on the analysis of the materials of publications and personal experience of teaching online, the potential benefits and problems of distance learning in higher education in Russia are considered. It is proposed to consider the effects separately for the suppliers of new technology (government, universities) and consumers (students, teachers, society). It is substantiated that the massive introduction of online education allows not only to reduce the negative consequences of epidemics, but also to reduce budgetary funding for universities, optimize the age composition of teachers, and reduce the cost of maintaining educational buildings. However, there will be a leveling / averaging of the quality of education, and responsibility for the quality of training will shift from the state/universities to students. The critical shortcomings of online education are the low degree of readiness of the digital infrastructure, the lack of a mechanism for identifying and monitoring the work of students, information security problems, and the lack of trust in such training of the population. The massive use of online education creates a number of risks for the country, the most critical of which is the destruction of the higher education system and a drop in the effectiveness of personnel training. The consequences of this risk realization are not compensated by any possible budget savings.

scholarly journals Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mouzarllem B. Reis ◽  
Fernanda L. Rodrigues ◽  
Natalia Lautherbach ◽  
Alexandre Kanashiro ◽  
Carlos A. Sorgi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Acetylcholine Release ◽  
Interleukin 1 ◽  
Clinical Manifestations ◽  
Prostaglandin E ◽  
High Dose ◽  
Scorpion Envenomation ◽  
Risk Of Death ◽  
Include Heart Failure

Abstract Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

scholarly journals The Prevalence of Sarcopenia and Its Impact on Clinical Outcomes in Lumbar Degenerative Spine Disease—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (4) ◽  
pp. 773
Author(s):  
Wei-Ting Wu ◽  
Tsung-Min Lee ◽  
Der-Sheng Han ◽  
Ke-Vin Chang
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Clinical Manifestations ◽  
Current Evidence ◽  
Degenerative Spine ◽  
Degenerative Spine Disease ◽  
Spine Disease

The association of sarcopenia with poor clinical outcomes has been identified in various medical conditions, although there is a lack of quantitative analysis to validate the influence of sarcopenia on patients with lumbar degenerative spine disease (LDSD) from the available literature. Therefore, this systematic review and meta-analysis aimed to summarize the prevalence of sarcopenia in patients with LDSD and examine its impact on clinical outcomes. The electronic databases (PubMed and Embase) were systematically searched from inception through December 2020 for clinical studies investigating the association of sarcopenia with clinical outcomes in patients with LDSD. A random-effects model meta-analysis was carried out for data synthesis. This meta-analysis included 14 studies, comprising 1953 participants. The overall prevalence of sarcopenia among patients with LDSD was 24.8% (95% confidence interval [CI], 17.3%–34.3%). The relative risk of sarcopenia was not significantly increased in patients with LDSD compared with controls (risk ratio, 1.605; 95% CI, 0.321–8.022). The patients with sarcopenia did not experience an increase in low back and leg pain. However, lower quality of life (SMD, −0.627; 95% CI, −0.844–−0.410) were identified postoperatively. Sarcopenia did not lead to an elevated rate of complications after lumbar surgeries. Sarcopenia accounts for approximately one-quarter of the population with LDSD. The clinical manifestations are less influenced by sarcopenia, whereas sarcopenia is associated with poorer quality of life after lumbar surgeries. The current evidence is still insufficient to support sarcopenia as a predictor of postoperative complications.

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