Treatment Of Rheumatic Diseases Research Articles

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and toestablish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

Assessment of specificity of immunologic tests for detection of tuberculosis infection in children with juvenile idiopathic arthritis

Introduction. The use of genetic engineering biological agents (GEBA) in the treatment of rheumatic diseases over the past decades has led to a significant improvement in the prognosis in this group of patients. However, against the background of anti-tumor necrosis factor α therapy (anti TNF-α), the risk of developing tuberculosis increases tenfold.Aim. To evaluate the specificity and safety of Mantoux test, recombinant tuberculosis allergen (RTA) test, IGRA tests: TB-Feron IGRA, T-SPOT.TB, QuantiFERON-TB GIT in patients from 5 to 18 years of age, who are at risk for the development of tuberculosis, due to the use of immunosuppressive therapy, including GEBP.Materials and methods. This clinical trial is a prospective single-center open-label study with 120 patients under observation. Girls predominated among the patients – 71 (59.2%), the average age was 12 years (95% CI [5.2–17.4]). As part of the treatment of the underlying disease, patients in the vast majority of cases (78.3%) received iFNO-α drugs: etanercept (67 people), adalimumab (25 people), golimumab (2 people).Results and discussion. According to the results of a comprehensive medical examination, including CT scan of the chest organs, the presence of active tuberculosis was not established in any of the patients. A positive result of the RTA sample was registered in 0.8% of the subjects, Mantoux test in 46.6%, T-SPOT.TB – 1.7%, TB-Feron IGRA and QuantiFERON-TB GIT – 0.8% each. During the safety assessment, it was noted that within 28 days after the study, none of the 120 patients had any adverse events. Patients need appropriate screening before starting treatment and regular follow-up examinations.Conclusions. The Mantoux test with 2 TE has low specificity (0.49), and the sample with RTA (0.99), TB-Feron IGRA (0.99), T-SPOT.TB (0.98) and QuantiFERON-TB GIT (0.99) are highly specific and safe as tests for detecting tuberculosis infection in children with juvenile idiopathic arthritis.

Patient self-reported experience and satisfaction with golimumab and etanercept treatments for rheumatic diseases: A cohort study.

Golimumab and etanercept both exhibit good efficacy in treating rheumatic diseases, while the patient self-reported measurement of treatment improvement and injection experience lacks sufficient evidence. Hence, this study aimed to compare the satisfaction with disease improvement and injection experience and the level of injection site reactions (ISRs) between golimumab-treated and etanercept-treated patients with rheumatic diseases. A total of 312 patients with rheumatic diseases were serially enrolled. Among them, 158 patients received golimumab (golimumab group); the other 154 patients were treated with etanercept (etanercept group) according to the actual disease status, physician advice, and patient willingness. Satisfaction with disease improvement was assessed using the 7-point Likert scale; satisfaction with injection experience and level of ISRs were both determined by the 5-point Likert scale. Satisfaction degrees with global injection experience (P = .025), injection device (P = .008), injection frequency (P = .010), and injection convenience (P = .003) were superior in the golimumab group to the etanercept group, while satisfaction degrees with global disease improvement, symptom relief, and speed of action did not vary (all P > .050) between the 2 groups. Discomfort (P = .005), swelling (P < .001), pain (P = .028), and burning (P = .035) levels were lower in the golimumab group than in the etanercept group. In addition, among 56 patients with a history of tumor necrosis factor inhibitor treatment before golimumab, 40 (71.4%) patients preferred golimumab to other tumor necrosis factor inhibitor. After switching to golimumab treatment, the level of ISRs in most patients was reduced or comparable. Golimumab achieves a satisfying injection experience and relieves the level of ISRs over etanercept in patients with rheumatic diseases.

Exploring the potential molecular mechanism of Gualou Guizhi decoction in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking.

Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Gualou Guizhi Decoction (GGD) has long been used as a folk medicine for the treatment of rheumatic diseases, but its bioactive components and therapeutic mechanisms are still unclear. An integrated approach using network pharmacology and molecular docking and using methotrexate as a positive control drug. We obtained 157 active ingredients of GGD, 7542 RA disease targets and 49 intersecting targets. GO and KEGG enrichment analysis revealed that their functions were mainly related to cytokine active metal ion binding, enzyme binding and DNA binding, and enriched in TNF signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, RA pathway and other signaling pathways that are closely related to RA. The molecular docking results show that the effector components of GGD bind better to the core targets of RA, and some are even better than methotrexate. The therapeutic effect of GGD for RA is achieved by affecting the core targets such as VEGFA, IL-1β, IL6, CXCL8, CCL2, and JUN, which together interfere with the tumor necrosis factor signaling pathway and RA pathway to treat RA. The above study provides new ideas for further exploration of this classic formula in the future.

Access to biologics and Janus kinase inhibitors for treatment of rheumatic diseases in the biosimilars era in Poland: a nation-level study.

By reducing treatment costs, biosimilars provide an opportunity to improve accessibility to highly effective drugs. This study aimed to evaluate access to biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) among patients with rheumatic musculoskeletal diseases within a 10 year timeframe in Poland. We performed a retrospective analysis using a nationwide public payer database. By 2022, 11 102, 6602, and 4400 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were treated with bDMARDs or JAKis. Peak drug utilization was observed for adalimumab, followed by etanercept and tocilizumab. Within the study timeframe, the estimated access to innovative drugs increased from 0.8%, 1.4%, and 0.8% to 3.2%, 8.7%, and 3.5% for RA, PsA, and axSpA patients, respectively. Affordable tumor necrosis factor inhibitors (TNFis) still predominate among innovative therapeutics, but their market share declined from 87% to 46%. The number of patients treated with other bDMARDs/JAKis almost doubled within the prespecified timeframe. Overall, the average annual treatment cost per patient decreased by 60%, from 7315 EUR to 2886 EUR. Despite recent safety warnings, JAKis appear to be increasingly utilized. Additional analyses regarding the COVID‑19 pandemic showed impaired access to intravenous therapies, but not subcutaneous or oral formulations. In Poland, biosimilars‑related savings improved availability of higher‑priced innovative drugs rather than less costly TNFis. Data‑driven resource allocation and dedicated policy solutions facilitating access to affordable biologics are recommended.

Evidence of the interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and Chinese herbal medicine: A scoping review

ObjectivesChinese herbal medicine (CHM) has been shown to be effective in autoimmune rheumatic diseases, but harmful herb-drug interactions might be inherent. We aim to review the evidence regarding herb-drug interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and CHM. MethodsWe searched PubMed, EMBASE and CINAHL from inception till 30 April 2023 using keywords that encompassed ‘herb-drug interactions’, ‘herbs’ and ‘immunosuppressants’. Articles were included if they contained reports about interactions between immunosuppressive drugs used in the treatment of rheumatic diseases with CHM. Level of evidence for each pair of interaction was graded using the algorithm developed by Colalto. ResultsA total of 65 articles and 44 unique pairs of interactions were identified. HDIs were reported for cyclophosphamide, cyclosporine, tacrolimus, methotrexate, mycophenolic acid, glucocorticoids, sulfasalazine, tofacitinib and biologic disease-modifying antirheumatic drugs. Among these, cyclosporine (n = 27, 41.5%) and tacrolimus (n = 19, 29.2%) had the highest number of documented interactions. Hypericum perforatum had the highest level of evidence of interaction with cyclosporine and tacrolimus. Consumption reduced the bioavailability and therapeutic effects of the drugs. Schisandra sphenanthera had the highest level of evidence of interaction with tacrolimus and increased the bioavailability of the drug. Majority of the articles were animal studies. ConclusionOverall level of evidence for the included studies were low, though interactions between cyclosporine, tacrolimus, Hypericum perforatum and Schisandra sphenanthera were the most and well-documented. Healthcare professionals should actively enquire about the concurrent use of CHM in patients, especially when drugs with a narrow therapeutic index are consumed.

Why most (but perhaps not all) DMARDs work equally well

Biological- or targeted-synthetic DMARD-responses reported in randomized clinical trials, placebo-controlled or head-to-head, in patients with rheumatoid arthritis, psoriatic arthritis or spondyloarthritis are unbelievably similar, when looking across trials performed in the same disease and applying the same primary outcome measures. The exception to this rule may be the response to Janus-kinase-inhibitors, which seem to work 10 % better in all trials (JAK-bonus) This article provides a potential explanation for this remarkable phenomenon, including an explanation for the JAK-bonus. It seems as if JAK-inhibitors exert some inflammation-independent effects on pain, fatigue and wellbeing, and that drug treatment of rheumatic diseases is more than the inhibition of inflammation alone.

Malic Acid for the Treatment of Rheumatic Diseases.

Malic Acid for the Treatment of Rheumatic Diseases.

Niosomes based formulation containing tenoxicam: A newer solution for the rheumatic diseases

This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of rheumatic diseases. Mechanical dispersion technique with controlled pressure was employed to prepare different niosomal formulations. The effects of different ratios of surfactant (span-60), lipid, and sodium deoxycholate on noisome's physicochemical properties have been examined. Moreover, inhibition of TNF-α in lipopolysaccharide-activated cultured Human leukemia monocytic (THP-1) cells were demonstrated to assess the in vitro inflammation profile. Finally, the optimized niosomal formulation (TN3) was prepared in gel matrix consist of carbopol 934 (termed as TN34) and stability was also tested at 4±2̊C, 25±2̊C, 37±2̊C and 45±2̊C for 6months. The optimized niosomal formulation exhibited a small vesicle size (165±14nm) and high drug encapsulation (79.64±1.5%). Niosomal gel formulation TN34 showed pH (6.7), viscosity (6810±3.34cps), spreadability (19.11±1.87gm.cm/sec) and also displayed sustained release pattern of drug release (98.16±0.07% TN released from gel matrix in 24h) in vitro release study. TN34 exhibited substantial anti-inflammatory response, with ∼75% inhibition of TNF-α in 48h. Stability investigation revealed that refrigerator temperature is most suitable for the storage of niosomal gel. Transdermal niosomal formulation displayed promising potential in the treatment of rheumatic diseases.

Long-term golimumab persistence: Five-year treatment retention data pooled from pivotal Phase III clinical trials in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis

IntroductionGolimumab, a monoclonal antibody against tumor necrosis factor–α (TNF-α), is used widely for treatment of rheumatic diseases. Long-term persistence is an important factor influencing therapeutic benefit and is a surrogate measure of efficacy. We compared five-year golimumab treatment persistence across studies, indications, and lines of therapy using pooled data from pivotal golimumab Phase III clinical trials.MethodsThis post-hoc analysis evaluated use of golimumab administered subcutaneously (50 or 100 mg every four weeks) for up to five years in 2228 adult participants with rheumatoid arthritis (RA; GO-BEFORE, GO-AFTER, and GO-FORWARD studies), psoriatic arthritis (PsA; GO-REVEAL study), or ankylosing spondylitis (AS; GO-RAISE study). Retention rate differences were evaluated by study, indication, and line of therapy using log-rank tests, and probability of treatment persistence was estimated by Kaplan–Meier analysis.ResultsGolimumab retention rates at Year 5 were consistently high when used as 1st-line therapy (69.8%) and did not differ significantly across the three indications tested (p = 0.5106) or across 1st-line studies (p = 0.2327). Retention at Year 5 was better in participants using golimumab as 1st-line than in those using it as 2nd-line (41.6%) therapy. Participants on 2nd-line golimumab therapy had a longer disease duration (median 9.2 years versus 3.7 years) than those on 1st-line golimumab therapy.ConclusionsThese data support the value of long-term golimumab therapy in patients with chronic, immune-mediated rheumatic diseases when used as 1st-line (RA, PsA, AS) or 2nd-line (RA) therapy.Key Points• Golimumab is a human monoclonal antibody directed against tumor necrosis factor–α (TNF-α) and is approved widely for the treatment of rheumatic autoimmune diseases.• We compared the probability of treatment persistence, or the time of continuous drug use, for golimumab across five Phase III studies spanning multiple rheumatic indications over five years.• Treatment persistence was favorable and did not differ significantly for participants with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, but persistence was greater when golimumab was used as 1st-line than as 2nd-line biologic therapy.

Cone Density Distribution and Related Factors in Patients Receiving Hydroxychloroquine Treatment.

Hydroxychloroquine is an effective treatment for rheumatic diseases; however, retinal damage is a possible side effect. We aimed to identify the retinal area and related risk factors associated with cone density reduction caused by hydroxychloroquine. We recorded the retinal images of patients with rheumatic diseases taking hydroxychloroquine (n = 44) and compared them with images of healthy controls (n = 107). Cone density was obtained in vertical and horizontal axes. Regions of decreased cone density and associations between age, rheumatic disease type, dosage for ideal body weight, and cone density were evaluated. Cone densities were significantly lower in hydroxychloroquine-treated patients than in sex- and age-matched controls in the vertical axis (P < 0.001), with no significant difference in the horizontal axis (P = 0.120); in healthy elderly than in healthy young people in the horizontal axis (P < 0.001), with no significant difference in the vertical axis (P = 0.100); in hydroxychloroquine-treated elderly than in hydroxychloroquine-treated young patients in both axes (both P < 0.05); among patients with different rheumatic disease types, with no significant difference in the vertical axis (P = 0.294). The daily dose was negatively correlated with cone density in the vertical axis and inferior quadrant. Hydroxychloroquine reduces retinal cone cell density in the vertical axis. Cone density loss in the horizontal axis increases with age; further, hydroxychloroquine dosage is negatively correlated with cone density in the vertical axis and inferior quadrant. Early screening of hydroxychloroquine-related retinal injury should consider changes in cone density in the vertical axis.

Therapeutic antibodies in rheumatology

Emil von Behring's serum therapy for diphtheria was the first therapeutic use of antibodies. More than 100 years later, anew era in the treatment of rheumatic diseases began in 1998 with the approval of infliximab, an antibody directed against tumor necrosis factor alpha (TNF alpha). The special feature of antibody therapy is the ability to bind and neutralize antigens in ahighly specific manner. In addition, target cells can be eliminated by activation of the immune system. These properties of the immune system are exploited in rheumatology to eliminate inflammatory cytokines or antibody-producing Blymphocytes. The tolerability is usually good but potential side effects, such as reactivation of tuberculosis with anti-TNF alpha treatment must be considered. Currently, 20different antibodies and fusion proteins have been approved in Germany for the treatment of various inflammatory rheumatic diseases. Biosimilars can contribute to aprice reduction after the patent protection expires. Many additional target antigens are being investigated and further structural innovations (e.g., bispecific antibodies, nanobodies or coupling with small molecules) are being developed.

Dehydroepiandrosterone (DHEA) Supplementation in Rheumatic Diseases: A Systematic Review.

Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA) with controversial results. To review the results of DHEA use in rheumatic diseases. PubMed, Scielo, Scopus, and Embase databases were systematically searched for articles on the treatment of rheumatic diseases with DHEA between 1966 and April 2023. Twenty-one studies were identified: 13 in SLE, 5 in SS, 2 in RA, and 1 in fibromyalgia. DHEA use in SLE has shown a mild to moderate effect on disease activity, a positive effect on bone mineral density (BMD), and improved fatigue. The studies on SS showed a decrease in symptoms of dry mouth, but its performance did not differ from placebo in disease activity. In RA, a questionable effect on disease activity was noted. The only study on fibromyalgia failed to show any improvement. The drug was well tolerated; mild androgenic effects were the most common complaints. DHEA seems to have a place in SLE treatment, where it improves BMD and disease activity. The use in RA, SS, and FM is questionable.

Clinical characteristics of patients with rheumatic diseases and abnormal liver function

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Hydroxychloroquine, QTc prolongation and risk of torsades de pointes

Hydroxychloroquine (HCQ) is a common medication used for the treatment of rheumatic diseases. As a result of its widespread use during COVID-19, there are increasing concerns about its cardiotoxicity. HCQ is known to cause QTc prolongation, and its long-term use has been associated with cardiomyopathy and conduction abnormalities. Despite reports of ventricular arrhythmia in COVID-19 patients taking HCQ, there have been reassuring data in approved indications. HCQ has been in use for several decades with a good safety profile. In addition to better disease control and prevention of flares, it is associated with decreased risk of cardiovascular diseases. But given its small risk of cardiotoxicity, clinicians should be aware of this effect and monitor patients for developing cardiac symptoms.

Current State of Platelet-rich Plasma in the Treatment of Rheumatic Disease: A Retrospective Review of the Literature.

Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.

Hydroxychloroquine as ‘Potential Treatment Option’ for Persistent Immune Dysregulation in Long COVID: Revisiting Its New Use as a ‘Versatile’ Molecule!

COVID-19 pandemic is over now and we are in great peace of relief after three years of first case reported in China. This pandemic has observed a significant impact on quality of life globally and this puts unforgettable imprints on the history of mankind. Reason for more havoc in this pandemic was less studied virus before this ‘unpredicted or surprise pandemic’ by medical scientists regarding its pathophysiology, available treatment options and lack of effective vaccine to tackle this dragon. Rationale would be COVID-19 is the first observed and reported pandemic of corona virus related global disease apart from its previously occurring SARS and MERS Epidemics. Fast track developments in medical treatment options with use of ultrafast digital and artificial intelligence techniques have curtailed mortality on a large scale globally. Although mortality is significantly reduced, morbidity is documented in significant number of cases worldwide after this Dragon related pandemic. Morbidity due to COVID-19 now called as ‘Long COVID’, which is underreported &amp; half-heartedly evaluated globally. Long COVID is related to persistent immune dysregulation which occurred during evolution of COVID-19 as a natural trend of disease &amp; documented during the course of active viremia, during recovery of viral illness and after the post viral phase. Immune dysregulation occurs in a ‘selected group’ of cases irrespective of disease severity and vaccination status, and observed in cases irrespective of severity of illness as with negligible illness resulted into brainstorming effect on medical scientists and researchers as of today to advanced and mandates further global research. Globally, one third of recovered or affected cases of COVID-19 are facing long covid and need prompt treatment options to tackle this dragon related long term effect on body. ‘Immunomodulatory’ or immunity modifying agents are the primary targets to curtail immune dysregulation and long covid. Some experts recommend ‘disease modifying agents’ to treat long covid cases. Still, many miles to go to reach effective treatment options for long covid and we don’t have effective options as of now for this ‘health issue of global concern’ related to Dragon. Hydroxychloroquine is initially used as an antimalarial and as an anti-inflammatory molecule for decades in various rheumatic conditions with satisfactory results. Despite decades of dependable use and predictable results in the treatment of rheumatic disease, HCQ remains a drug with an ever-expanding number of underlying mechanisms. HCQ was tried initially for prophylaxis treatment of COVID-19 due to its anti-inflammatory properties but has not shown any dramatic results. WHO has removed HCQ from the treatment plan after many trial results with disappointing outcomes. HCQ is a drug with multiple beneficial pleiotropic effects such as immunomodulatory effects which regulates immunological responses that inhibit dysregulated immune system. These Immunomodulatory and or diseases modifying effects of HCQ makes it the future candidate with ‘game changer’ role for management of Long covid resulting from immune dysregulation as a core pathophysiologic pathway of this Dragon Pandemic. Revisiting this old drug with ‘versatile effects’ can be used as treatment option for short time as frontline molecule for Long covid when no definitive options are available after consideration of risk benefit ratio which is a cost-effective treatment option.

Choosing Wisely: The Canadian Rheumatology Association Pediatric Committee's List of Items Physicians and Patients Should Question.

To develop a list of tests or treatments frequently used in pediatric rheumatology practice which may be unnecessary based on existing evidence. A Choosing Wisely (CW) Working Group composed of 16 pediatric rheumatologists, one allied health practitioner, one parent, and one patient used the Delphi method to generate, rank, and refine a list of tests and treatments that may be unnecessary or harmful. The items with the highest content agreement and perceived impact were presented in a survey to all Canadian Rheumatology Association (CRA) physicians who practice pediatric rheumatology. Respondents were asked to rate their agreement, impact, and rank the items. Five items with the highest composite scores and two additional items selected by the CW Working Group were put forward for literature review. The initial Delphi procedure generated 80 items. After three rounds, the list was narrowed to 13 items. The survey was completed by 41/81 (51%) CRA pediatric members across Canada. Respondent characteristics were similar to the CRA pediatric membership for gender, geographical location, and career stage. The highest composite score items were anti-nuclear antibody testing, drug toxicity monitoring, human leukocyte antigen-B27 testing, rheumatoid factor/anti-cyclic citrullinated peptide testing, and Lyme serology testing. Two additional items (numerous or repeated intra-articular corticosteroid injections, and autoinflammatory diseases genetic testing) were also selected. Literature review was performed for these seven highest priority items. We have identified areas for quality improvement in the evaluation and treatment of rheumatic diseases in Canadian children.

Safety and efficacy of mesenchymal stem cells therapy in the treatment of rheumatoid arthritis disease: A systematic review and meta-analysis of clinical trials.

Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques. A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration. This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.

Beliefs, Experiences, and Openness Regarding Dietary Interventions: Data From an Urban Hispanic Population With Rheumatic Disease in the US.

To obtain descriptive data on the beliefs, behaviors, and openness regarding dietary changes for rheumatic diseases in an urban US Hispanic patient population with rheumatic disease as foundational data for future intervention design. We distributed a voluntary survey to our primarily Hispanic population at an outpatient rheumatology clinic for 19 weeks. This survey queried individuals' behaviors as they related to dietary intake used for the treatment of rheumatic disease, perceptions of the effect of food groups on rheumatic disease activity, barriers to physician-recommended diets, and willingness to try future interventions. We used descriptive statistics and Pearson's chi-square test to evaluate associations. More than 40% of survey respondents from our primarily (88%) Hispanic population noted a link between what they ate and their underlying rheumatic disease activity. More than one-third of patients had, at some point, modified dietary intake to affect their rheumatic disease. Vegetables, fruit, and white meats were commonly reported to improve disease, while red meat and processed foods were reported to worsen disease. Barriers to following a prespecified diet included cost and lack of knowledge. More than 70% of respondents indicated willingness to attempt certain eating patterns should it help their underlying rheumatic disease. In this primarily Hispanic rheumatic disease patient population, many have not only noted a correlation between dietary intake and rheumatic disease activity but are also open to future nutrition-related interventions. As this population experiences poor rheumatic disease outcomes and a high rate of lifestyle-related comorbidities, an intervention to optimize healthy eating patterns would likely be beneficial as well as acceptable.