Field Of Rheumatic Diseases Research Articles

Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2022

To detail the unmet clinical and scientific needs in the field of rheumatology. After a 2-year hiatus due to the SARS-CoV-2 pandemic, the 22nd annual international Advances in Targeted Therapies...

Insights Gained and Future Outlook From scRNAseq Studies in Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases have a major impact on public health as one of the most common morbidities, and many of these disorders involve both local and systemic manifestations with severe consequences for patient health and quality of life. However, treatment options for many of these diseases remain inadequate for a substantial portion of patients, and progress in developing novel therapeutics has been slow. This lack of progress can be largely attributed to an insufficient understanding of the complex mechanisms driving pathogenesis. Recently, the emergence of single-cell RNA sequencing (scRNAseq) has offered a powerful new tool for interrogating rheumatic diseases, with the potential to assess biological heterogeneity and individual cell function in rheumatic diseases. In this review, we discuss the major insights gained from current scRNAseq interrogations of human rheumatic diseases. We highlight novel cell populations and key molecular signatures uncovered, and also raise a number of hypotheses for follow-up study that may be of interest to the field. We also provide an outlook into two emerging single-cell technologies (repertoire sequencing and spatial transcriptomics) that have yet to be utilized in the field of rheumatic diseases, but which offer immense potential in expanding our understanding of immune and stromal cell behavior. We hope that scRNAseq may serve as a wellspring for the generation and interrogation of novel hypotheses regarding autoreactive lymphocytes and tissue infiltration patterns, and help uncover novel avenues for therapeutic development.

Resolution of the Expert Council «The role of type I interferon inhibitor in the treatment of patients with systemic lupus erythematosus»

On April 28, 2021, a meeting of the Council of Experts was held with the participation of the leading experts in the field of rheumatic diseases, approaches to the treatment of patients with systemic lupus erythematosus (SLE) were discussed. The issues of medical care for patients with SLE and their routing, key points of Russian and international clinical guidelines for the management of patients with SLE, as well as the role of interferon (IFN) type I in the pathogenesis of the disease were discussed. It is noted that the management of patients with SLE requires a multidisciplinary approach. The basis of therapy is the use of glucocorticoids (GC), immunosuppressive drugs and their combinations. But long-term use of GC in patients with SLE leads to severe complications. Early prescription of biological disease-modifying antirheumatic drugs (bDMARDs) allows to achieve the greatest effect and prevent the development of irreversible organ damage associated with SLE. Currently data from three clinical trials on the efficacy and safety of the type I IFN inhibitor anifrolumab are available. During the discussion, experts defined the clinical profile of a patient with SLE, for whom administration of bDMARD therapy is indicated. According to experts, the use of a type I IFN inhibitor in routine clinical practice can improve disease outcomes in both short and long term.

Predicting Biologic Therapy Outcome of Patients With Spondyloarthritis: Joint Models for Longitudinal and Survival Analysis.

BackgroundRheumatic diseases are one of the most common chronic diseases worldwide. Among them, spondyloarthritis (SpA) is a group of highly debilitating diseases, with an early onset age, which significantly impacts patients’ quality of life, health care systems, and society in general. Recent treatment options consist of using biologic therapies, and establishing the most beneficial option according to the patients’ characteristics is a challenge that needs to be overcome. Meanwhile, the emerging availability of electronic medical records has made necessary the development of methods that can extract insightful information while handling all the challenges of dealing with complex, real-world data.ObjectiveThe aim of this study was to achieve a better understanding of SpA patients’ therapy responses and identify the predictors that affect them, thereby enabling the prognosis of therapy success or failure.MethodsA data mining approach based on joint models for the survival analysis of the biologic therapy failure is proposed, which considers the information of both baseline and time-varying variables extracted from the electronic medical records of SpA patients from the database, Reuma.pt.ResultsOur results show that being a male, starting biologic therapy at an older age, having a larger time interval between disease start and initiation of the first biologic drug, and being human leukocyte antigen (HLA)–B27 positive are indicators of a good prognosis for the biological drug survival; meanwhile, having disease onset or biologic therapy initiation occur in more recent years, a larger number of education years, and higher values of C-reactive protein or Bath Ankylosing Spondylitis Functional Index (BASFI) at baseline are all predictors of a greater risk of failure of the first biologic therapy.ConclusionsAmong this Portuguese subpopulation of SpA patients, those who were male, HLA-B27 positive, and with a later biologic therapy starting date or a larger time interval between disease start and initiation of the first biologic therapy showed longer therapy adherence. Joint models proved to be a valuable tool for the analysis of electronic medical records in the field of rheumatic diseases and may allow for the identification of potential predictors of biologic therapy failure.

Reactivation of hepatitis B virus infection in rheumatic diseases: risk and management considerations.

In patients with rheumatic diseases undergoing immunosuppressive treatment, hepatitis B virus reactivation (HBVr) has been long recognized as a major treatment-related adverse event with substantial morbidity and mortality. Because HBVr is easily preventable with appropriate screening and monitoring strategies, and, when indicated, prophylactic antiviral treatment, awareness of this complication is of the utmost importance, especially in the era of biologic treatments. As a condition, it continues to be topical, in view of the emergence of novel classes of immunosuppressive drugs (i.e. Janus kinase inhibitors) acquiring licenses for a variety of rheumatic diseases. The class-specific risk of these agents for HBVr has not yet been determined. Moreover, ambiguity still exists for the management of patients planned to be treated with traditional agents, such as cyclophosphamide and glucocorticoids, particularly in the setting of resolved HBV infection. Clinicians in the field of rheumatic diseases should be tailoring their practice according to the host’s profile and treatment-specific risk for HBVr. In this review, the authors attempt to critically review the existing literature and provide practical advice on these issues.

Generation of a human control iPS cell line (ESi080‐A) from a donor with no rheumatic diseases

Here, we report the establishment of the human iPS cell line N1-FiPS4F#7 generated from skin cells of a patient with no rheumatic diseases, thus obtaining an appropriate control iPS cell line for researchers working in the field of rheumatic diseases. The reprogramming factors Oct4, Sox2, Klf4 and c-Myc were introduced using a non-integrating reprogramming strategy involving Sendai Virus.

The Role of Monocyte Percentage in Osteoporosis in Male Rheumatic Diseases.

Osteoporosis is easily overlooked in male patients, especially in the field of rheumatic diseases mostly prevalent with female patients, and its link to pathogenesis is still lacking. Attenuated monocyte apoptosis from a transcriptome-wide expression study illustrates the role of monocytes in osteoporosis. This study tested the hypothesis that the monocyte percentage among leukocytes could be a biomarker of osteoporosis in rheumatic diseases. Eighty-seven males with rheumatic diseases were evaluated in rheumatology outpatient clinics for bone mineral density (BMD) and surrogate markers, such as routine peripheral blood parameters and autoantibodies. From the total number of 87 patients included in this study, only 15 met the criteria for diagnosis of osteoporosis. Both age and monocyte percentage remained independently associated with the presence of osteoporosis. Steroid dose (equivalent prednisolone dose) was negatively associated with BMD of the hip area and platelet counts were negatively associated with BMD and T score of the spine area. Besides age, monocyte percentage meets the major requirements for osteoporosis in male rheumatic diseases. A higher monocyte percentage in male rheumatic disease patients, aged over 50 years in this study, and BMD study should be considered in order to reduce the risk of osteoporosis-related fractures.

Yrjö Tapio Konttinen 1952–2014

Yrjö Tapio Konttinen 1952–2014

SP0001 The Value of Health Professionnals in Europe: A Personal View and Vision for the Future

A lot of studies have demonstrated or suggested the interest of health professionnals led management/therapeutical programs in the field of rheumatic diseases. However, there is a huge room of improvement...

AB0006 Microrna expression profiles in peripheral blood mononuclear cells of early rheumatoid arthritis

BackgroundRheumatoid arthritis(RA) is a chronic inflammatory joint disorder characterized by immune-driven inflammation of synovial membrane which results in erosion, joint destruction and disability. The etiology of RA is still unknown...

A new initiative in the field of Rheumatology and Clinical Immunology

It is a pleasure to write a forward for the launch of Internet Journal of rheumatology and clinical immunology, a new initiative to fill in the gap of open access journals in India. It will be dedicated to clinicians and researchers to publish and share their data in the field of rheumatic diseases. As the number of rheumatologists and clinical immunologists with varied experiences are growing, an open access journal with a multidisciplinary focus will be an ideal platform to further our knowledge.

Intracellular signaling transduction pathways

Even though biologics, frequently combined with conventional DMARD therapy, represent a significant advance in the treatment of rheumatic diseases, they have disadvantages such as high costs of production and parenteral administration. Therefore, oral small-molecule drugs are a potential alternative. Major targets for such small-molecule therapeutics are intracellular signaling molecules. This article will briefly discuss potential intracellular targets for therapeutics in the field of rheumatic diseases. How therapeutic signaling inhibitors will be used in clinical practice will depend on a number of factors: their overall effectiveness, their effectiveness in patients who did not or insufficiently respond to conventional DMARD therapy and/or treatment with biologics, their effectiveness when combined with other therapeutics, their side effects, and their cost-benefit ratio.The English full-text version of this article is available at SpringerLink (under "Supplemental").

Statistical Methods for Individual-Level Data in Cohort Mortality Studies of Rheumatic Diseases

In the field of rheumatic diseases, prospective individual-level data on (prevalent) cohorts of patients over a long period of time are collected. One of the many uses of such data is to investigate mortality. Excess mortality, time trends (temporal variation) in mortality rates, life expectancy and life years lost of patients, and risk factors for mortality may all be of interest. In this article, we show how careful application of Poisson and Cox relative risk regression models can be used to tackle these questions, illustrating the methods with cohort data from patients with systemic lupus erythematosus and psoriatic arthritis. For external comparisons of a cohort with a standard (or reference) population, Poisson regression can be used to generalize the usual standardized mortality ratio (SMR) analyses. For assessing the pattern of (excess) mortality over time, unadjusted and adjusted “rolling average” SMRs are developed and shown to provide further insight concerning an observed decline in SMR over time for psoriatic arthritis patients. An extension of the traditional life expectancy and years of life lost calculations is also derived. For comparisons within a cohort, we demonstrate how Cox regression models can incorporate time measured on a variety of scales to allow the identification of a calendar time decline in mortality risk for lupus patients which is demonstrably independent of possible declines with disease duration and/or time in clinic and of other disease related explanatory variables.

Capillaroscopy

Raynaud's phenomenon (RP) is the most common and significant clinical condition with an indication for a microvascular analysis to be carried out as soon as possible. Microvascular involvement is a key feature of RP and several rheumatic diseases are characterised by the presence of RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, non-invasive and inexpensive. Well recognised nailfold videocapillaroscopic patterns (NVC) have been described mainly in systemic sclerosis (SSc) patients with secondary RP. The peripheral microvascular damage in SSc is characterised by increasing structural alterations of the capillaries (giant capillaries and microhaemorrhagies) with a progressive decrease in their density. The detection of the scleroderma NVC pattern allows an early distinction between the primary RP (functional, not disease associated) and the secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NVC and the clinical symptoms, severity of the disease and the laboratory findings.

Nailfold video-capillaroscopy in systemic sclerosis

The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.

Role of gene therapy in tissue engineering procedures in rheumatology: the use of animal models

Tissue engineering is not only the application of cells and scaffolds to generate a new tissue but should also bring into play biological principles to guide cellular behavior. A way to modify cellular behavior is genetic modification of the cells used for tissue engineering (gene therapy). In the field of rheumatic diseases, cellular modification by overexpressing anabolic factors, such as insulin-like growth factor-I or transforming growth factor β, or inhibitors of catabolic cytokines or proteolytic enzymes can protect tissues form further destruction and stimulate tissue repair. To test the effect of transgenes on tissue engineering adequate test systems have to be available. Initial testing can be done in simple in vitro systems. However, animal models are unavoidable to study the interaction between the environment and tissue engineering. Optimal models to study gene therapy in combination with tissue engineering in the field of rheumatology are not available at this moment. Arthritis models are mainly developed in small animals while high-quality tissue engineering experiments ask for a large animal model. Development of animal models that can be used for tissue engineering experiments and mimic end stage arthritic diseases is needed.

Rheumatology education in an undergraduate program of physical therapy. A new outlook.

Few physical therapy education programs offer formal rheumatology courses taught by specialists in the field of rheumatic diseases. We modified, evaluated, and formalized a rheumatology course for undergraduate physical therapy students taught by a rheumatologist and a specially trained physical therapist. Although the course is applicable to our undergraduate program, the process we used to modify and evaluate the course content could be useful to others in their development of similar courses elsewhere. Our intent in discussing this process, the course content, and the rationale for our study is to stimulate a national review of rheumatology course content in physical therapy education programs.

Stoffwechsel und degenerativer Rheumatismus, Symposium, Bad Nauheim, 1964.

The 18 dissertations and the discussion of them at a symposium on rheumatology held in Bad Nauheim, Germany, April 24-26, 1964, provide both orientation and stimulation for physicians interested in the rheumatic diseases. They summarize considerable existing knowledge and add add some new personal observations of the investigators. Research with histochemical models, of keratosufate transformation, in molecular pathology, of mesenchymal and cartilaginous metabolism, and in the biochemical alterations of synovial fluid demonstrate important precursors of the rheumatic state. In the fibrositis syndrome, intramuscular pressure was elevated as shown by manometric readings and the circulation was impaired as shown by delayed disappearance of radioactive iodine from a depot. Primary metabolic abnormalities produce secondary skeletal manifestations; special attention is given to phenylalanine and tyrosine, ochronosis, thyroid activity, and diabetes. This is the 36th volume of a series of detailed presentations in the field of rheumatic diseases published since the founding of the

Treatment of primary gout: the present status.

AbstractThe following article was delivered by Dr. Gutman as the W. Paul Holbrook Memorial Lecture at the annual meeting of the Arthritis and Rheumatism Association, in June, 1965, a variation in lay terms having been presented at the annual meeting of The Arthritis Foundation in October, 1964. It is one of two memorial lectureships established by The Arthritis Foundation to honor physicians who have made outstanding contributions to the field of rheumatology with the objective, as well, of encouraging interest among all physicians and scientists in the field of rheumatic diseases. The other lecture, in honor of Walter Bauer, was delivered by Halstead R. Holman at the interim meeting of the ARA in December, 1964. The lectureship awards are part of the National Scientific Awards Program of The Arthritis Foundation.

Steroid therapy in rheumatoid diseases.

Ten years have elapsed since cortisone (Cortisone, Cortogen, Cortone) acetate was first given to a patient with rheumatoid arthritis. This occurred on Sept. 21, 1948, at the Mayo Clinic under the direction of the team composed of Drs. Hench, Kendall, Slocumb, and Polley. 1 Spearheaded by the immediate spectacular changes in the symptomatology of rheumatoid arthritis, there resulted a great increase in interest in the field of rheumatic diseases, with expanded research and improved care for the arthritic patients. Also, as a result, there has been a search for better understanding of the underlying immunological and pathological states in these diseases. This discussion concerns rheumatoid diseases which include gout, acute rheumatic fever, rheumatoid spondylitis, collagen or connective tissue diseases, and rheumatoid arthritis. Gout and Gouty Arthritis Adrenal cortical steroids have been used orally in the treatment of acute attacks of gouty arthritis since 1949, with varying grades of effectiveness. In