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ID PMID Title PublicationDate abstract
32613869 Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An ope 2021 Mar OBJECTIVES: To evaluate the efficacy and safety of iguratimod in patients with early primary Sjögren's syndrome (pSS). METHODS: Twenty-seven disease-modifying antirheumatic drug-naive female patients met the revised American-European Consensus Group criteria for pSS were enrolled in this open-label pilot study. Patients were treated with iguratimod 25 mg twice a day for 24 weeks. The disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at 12 and 24 weeks. Salivary and lacrimal gland function, laboratory, and subjective variables were also assessed. Generalized estimating equations were used to analyze parameters over time. RESULTS: ESSDAI (median, 5 versus 2 versus 2, p < .01), IgG (median, 26.6 versus 22.4 versus 21.4 g/L, p < .01) and rheumatoid factor (median, 119.9 versus 94.1 versus 83.8 lU/mL, p < .01) levels decreased significantly during iguratimod treatment. ESSPRI, salivary and lacrimal gland function, fatigue and health-related quality of life did not change during treatment. One patient experienced thrombocytopenia, and no other serious adverse effects were observed. CONCLUSION: In this study, iguratimod treatment is safe and effective for improving disease activity and laboratory parameters in early pSS patients.
34046419 Increased Incidence of Total Knee Replacement Surgery in Patients With Psoriasis: A Second 2021 Patients with rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, have increased risk of receiving total knee replacement surgery or total hip replacement surgery. We speculated that psoriasis could also attack the joints of the knees and hips, leading to an increased risk of receiving total knee replacement surgery or total hip replacement surgery. The aim of this study was to investigate the risk of total knee replacement or total hip replacement surgery in patients with psoriasis using a nationwide, population-based health claims database in Taiwan. Using the Taiwan's National Health Insurance Research Database, we identified 10,819 patients with psoriasis between 2000 and 2012. A comparison cohort consisting of five patients without psoriasis for each patient with psoriasis was assembled, based on frequency matching for sex, 10-year age interval, and index year. Both groups were followed until a diagnosis of the study outcomes (total knee replacement or total hip replacement surgery) or the end of the follow-up period. Incidence rate ratios (IRRs) for the outcome variables were calculated using multiple Poisson regression models. Female patients with psoriasis exhibited a significantly higher incidence of receiving total knee replacement surgery [adjusted IRR = 1.44, p = 0.014)]. Analyses stratified by age groups showed that the risk of receiving total knee replacement surgery was significantly higher older (adjusted IRR = 1.31, p = 0.047) patients with psoriasis. There were no significant differences in the risk of receiving total hip replacement surgery in patients with psoriasis compared with controls, either with or without stratification by sex or age groups. In conclusion, patients with psoriasis were associated with an increased risk of receiving total knee. Clinicians should be vigilant in assessing the presence of arthritis in these patients, and initiate strategies to delay or prevent the need for joint replacement.
34595847 Unique serum immune phenotypes stratify Oklahoma Native American rheumatic disease patient 2021 Oct 1 OBJECTIVE: Native American (NA) populations have higher rates of rheumatic disease and present with overlapping disease symptoms and nontraditional serological features, thus presenting an urgent need for better biomarkers in NA diagnostics. This study utilized a machine-learning approach to identify immune signatures that more effectively stratify NA rheumatic disease patients. METHODS: Adult NA patients with autoantibody-positive (AAB+) rheumatoid arthritis (RA) (n=28), autoantibody negative (AAB-) RA (n=18), systemic autoimmune rheumatic disease (n=28), arthralgia/osteoarthritis (n=28), polyarthritis/undifferentiated connective tissue disease (n=28), and controls (n=28) provided serum samples for cytokine, chemokine, and autoantibody assessment. Random Forest clustering and soluble mediator groups were used to identify patients and controls with similar biologic signatures. ACR criteria specific for systemic disease and RA identified differences in disease manifestations across clusters. RESULTS: Serum soluble mediators were not homogenous between different NA rheumatic disease diagnostic groups reflecting the heterogeneity of autoimmune diseases. Clustering by serum biomarkers created five analogous immune phenotypes. Soluble mediators and pathways associated with chronic inflammation and involvement of the innate, B cell, Tfh cell, and IFN-associated pathways, along with regulatory signatures, distinguished the five immune signatures among patients. Select clinical features were associated with individual immune profiles. Subjects with low inflammatory and higher regulatory signatures were more likely to have few clinical manifestations, whereas those with T cell pathway involvement had more arthritis. CONCLUSION: Serum protein signatures distinguished NA rheumatic disease patients into distinct immune subsets. Following these immune profiles over time may assist with earlier diagnoses and help guide more personalized treatment approaches.
34859176 Inequality of access to advanced therapies for patients with inflammatory arthritis: a pos 2021 OBJECTIVES: Advanced therapies (AT), including biologics, biosimilars and Janus kinase inhibitors, have dramatically improved the quality of life of patients with RA, PsA and axial spondyloarthritis (axSpA). Evidence-based criteria for prescribing these drugs in England and Wales is formulated by the National Institute for Health and Care Excellence (NICE) through health technology appraisals and guidelines, with the aim of providing equitable access to AT for patients with severe or resistant disease. Similar bodies exist in some, but not all European countries, with disparities in AT access between countries for RA. We examined whether this disparity was mirrored in England for RA, PsA and axSpA despite the National Health Service in England and Wales being legally obliged to provide funding for AT recommended by NICE's Health Technology Appraisal board, through the commissioning bodies, the clinical commissioning groups (CCGs). METHODS: We requested AT pathways from CCGs in England. Where these were not available, individual hospital Trusts were contacted using freedom of information requests. RESULTS: We found marked variability in the way that CCGs in England interpret NICE guidance. We found 41, 29 and 25 different pathways for RA, PsA and axSpA, respectively. Similar disparities existed with sequential prescribing where one AT did not work, with limits on the numbers of sequential AT in 54%, 59% and 59% of CCGs for RA, PsA and axSpA, respectively, and with these limits being different for the same condition between CCGs. CONCLUSION: Although patients at identical stages of their disease course should have access to the same NICE-approved AT, we found this is not the case for large parts of England. Inequality of access was found between regions, mirroring the variability that occurs between countries throughout Europe. Harmonization of access needs to be addressed by policymakers to ensure fairness in the way that clinicians and patients can access AT.
33837812 The histopathological synovitis score is influenced by biopsy location in patients with kn 2021 Apr 10 INTRODUCTION: Osteoarthritis (OA) and rheumatoid arthritis (RA) represent the most common forms of arthritis, which are mainly caused by mechanical and inflammatory components, respectively. Determination of synovial inflammation in synovial biopsies via the histopathological Krenn score may be crucial for correct diagnosis and treatment. Specifically, it remains unclear whether synovitis scores differ among multiple biopsy locations within a single joint. MATERIALS AND METHODS: Eighty synovial samples were taken from four standardized regions of the knee in 20 patients (ten primary OA, ten secondary OA) undergoing total knee arthroplasty (TKA) or total synovectomy. The Krenn synovitis score (grade 0-9) was determined in a blinded manner by two expert pathologists in all biopsies. Next to the inter-rater reliability, we evaluated the agreement of the determined scores among the four biopsy locations within each knee. RESULTS: The inter-rater reliability between the two pathologists was very high (Cohen's kappa = 0.712; r = 0.946; ICC = 0.972). The mean synovitis score was significantly higher in knees with secondary than in primary OA (p = 0.026). Importantly, we found clear differences between the scores of the four different biopsy locations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). CONCLUSIONS: While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score.
33692806 Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview. 2021 Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, IL-23A (p19) and IL-12/23B (p40), the latter shared with Interleukin-12 (IL-12). IL-23 is mainly produced by macrophages and dendritic cells, in response to exogenous or endogenous signals, and drives the differentiation and activation of T helper 17 (Th17) cells with subsequent production of IL-17A, IL-17F, IL-6, IL-22, and tumor necrosis factor α (TNF-α). Although IL-23 plays a pivotal role in the protective immune response to bacterial and fungal infections, its dysregulation has been shown to exacerbate chronic immune-mediated inflammation. Well-established experimental data support the concept that IL-23/IL-17 axis activation contributes to the development of several inflammatory diseases, such as PsA, Psoriasis, Psoriatic Arthritis; AS, Ankylosing Spondylitis; IBD, Inflammatory Bowel Disease; RA, Rheumatoid Arthritis; SS, Sjogren Syndrome; MS, Multiple Sclerosis. As a result, emerging clinical studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of IL-23 and Th17 cells in inflammatory rheumatic diseases.
33669367 Tissue-Resident Memory T Cells in Chronic Inflammation-Local Cells with Systemic Effects? 2021 Feb 16 Chronic inflammatory diseases such as rheumatoid arthritis (RA), Juvenile Idiopathic Arthritis (JIA), psoriasis, and inflammatory bowel disease (IBD) are characterized by systemic as well as local tissue inflammation, often with a relapsing-remitting course. Tissue-resident memory T cells (T(RM)) enter non-lymphoid tissue (NLT) as part of the anamnestic immune response, especially in barrier tissues, and have been proposed to fuel chronic inflammation. T(RM) display a distinct gene expression profile, including upregulation of CD69 and downregulation of CD62L, CCR7, and S1PR1. However, not all T(RM) are consistent with this profile, and it is now more evident that the T(RM) compartment comprises a heterogeneous population, with differences in their function and activation state. Interestingly, the paradigm of T(RM) remaining resident in NLT has also been challenged. T cells with T(RM) characteristics were identified in both lymph and circulation in murine and human studies, displaying similarities with circulating memory T cells. This suggests that re-activated T(RM) are capable of retrograde migration from NLT via differential gene expression, mediating tissue egress and circulation. Circulating 'ex-T(RM)' retain a propensity for return to NLT, especially to their tissue of origin. Additionally, memory T cells with T(RM) characteristics have been identified in blood from patients with chronic inflammatory disease, leading to the hypothesis that T(RM) egress from inflamed tissue as well. The presence of T(RM) in both tissue and circulation has important implications for the development of novel therapies targeting chronic inflammation, and circulating 'ex-T(RM)' may provide a vital diagnostic tool in the form of biomarkers. This review elaborates on the recent developments in the field of T(RM) in the context of chronic inflammatory diseases.
34423733 Extracellular vesicles in obesity and its associated inflammation. 2022 Obesity is characterized by low-grade, chronic inflammation, which promotes insulin resistance and diabetes. Obesity can lead to the development and progression of many autoimmune diseases, including inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, thyroid autoimmunity, and type 1 diabetes mellitus (T1DM). These diseases result from an alteration of self-tolerance by promoting pro-inflammatory immune response by lowering numbers of regulatory T cells (T(regs)), increasing Th1 and Th17 immune responses, and inflammatory cytokine production. Therefore, understanding the immunological changes that lead to this low-grade inflammatory milieu becomes crucial for the development of therapies that suppress the risk of autoimmune diseases and other immunological conditions. Cells generate extracellular vesicles (EVs) to eliminate cellular waste as well as communicating the adjacent and distant cells through exchanging the components (genetic material [DNA or RNA], lipids, and proteins) between them. Immune cells and adipocytes from individuals with obesity and a high basal metabolic index (BMI) produce also release exosomes (EXOs) and microvesicles (MVs), which are collectively called EVs. These EVs play a crucial role in the development of autoimmune diseases. The current review discusses the immunological dysregulation that leads to inflammation, inflammatory diseases associated with obesity, and the role played by EXOs and MVs in the induction and progression of this devastating conditi8on.
34331682 Turmeric and Curcumin: From Traditional to Modern Medicine. 2021 The rhizome of turmeric (Curcuma longa L.) has been used as an herbal medicine, coloring agent, spice, and food additive for thousands of years in different parts of the world particularly in Asian countries. It has been used for a range of diseases in many traditional medical schools, including Islamic traditional medicine, Chinese traditional medicine, and Ayurveda. It has been used mainly for digestive problems, as a cardio-, hepato-, and neuroprotective agent as well as in many inflammatory conditions such as arthritis and for enhancing immune system. Curcumin, a diarylheptanoid derivative found in turmeric, has anti-inflammatory, antioxidant, and anticancer properties; controls obesity and metabolic problems; and improves memory and mood disorders. Therapeutically, curcumin exhibits promising potential in preclinical and clinical studies and is currently in human trials for a variety of conditions, including metabolic syndrome, nonalcoholic fatty liver disease, rheumatoid arthritis, migraine, premenstrual syndrome, ulcerative colitis, knee osteoarthritis, polycystic ovarian syndrome, atherosclerosis, liver cirrhosis, amyotrophic lateral sclerosis, depression, psoriasis, and Alzheimer's disease. Among all beneficial activities reported for curcumin, the research toward the obesity and metabolic-preventing/suppressing aspects of curcumin is growing. These findings emphasize that most of the traditional applications of turmeric is due to the presence of its key constituent, curcumin. According to the traditional background of turmeric use and clinical values of curcumin, further preclinical studies for unstudied properties and clinical studies with larger sample sizes for confirmed activities are expected.
33190407 The necessity of patch testing in determining the causative drug of AGEP. 2021 Jul BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP)is a rare, severe skin reactionmainly caused by medications such as antibiotics, anti fungals, Calcium channel blockers and Anti malarias. Although it resolves spontaneously in most patients, systemic corticosteroids are neededin severe cases. AIMS: In order to determine the drug that is causing this condition, patch testing must be performed. Hydroxychloroquine is a medication that is used for the treatment of rheumatic and dermatologic conditions. And although it has been rarely seen to cause this reaction, we report a case of Hydroxychloroquine-induced (HCQ) AGEP which was confirmed by Patch testing. PATIENTS: A woman 49 years of age with an18 month history of mild, untreated Rheumatoid Arthritis experienced an acute episode of arthritis in her right elbow. Upon going to a rheumatologist, Prednisolone 5 mg BID and HCQ 200 mg daily were administered for a 30-day period. But after only 17 days of this treatment, the patient developed generalized erythema and painful pustular eruptions. Prednisolone dosage was changedto 7.5 mg per day andHCQ was discontinued one day afterthe appearance of eruptions. The diffuse erythema started improving a week after the patient's hospitalization.Considering the factthat our patient was receiving multiple potentially causative medications, patch testing was necessary to distinguish the drug responsible for this reaction. RESULTS: After the patch testing was done, HCQ-induced AGEP was confirmed. CONCLUSIONS: Patch testing is the gold standard of determining the responsible drug for an AGEP reaction. It should also be kept in mind that HCQ, although rarely, can cause this condition.
34931480 Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling 2021 Dec 20 OBJECTIVES: To investigate how psychosocial aspects affect the probability of achieving sustained remission in early RA, and to explore the directionality of this relationship. METHODS: Data were analyzed from the randomized controlled CareRA-trial. Sustained remission was defined as continued DAS28-CRP <2.6 from weeks 16 to 104. Patients completed the Short Form 36 (SF-36), Revised Illness Perception Questionnaire (IPQ-R) and Utrecht Coping List (UCL). These psychosocial variables were studied at baseline and week 16 as predictors of sustained remission with logistic regression. Next, subgroups of patients in remission at week 16 were identified by Latent Profile Analysis (LPA) based on these psychosocial indicators. Time to first loss of remission was then compared between groups by Cox-proportional-hazards regression. Finally, directionality of associations between psychosocial indicators and DAS28-CRP was explored with cross-lagged panel models (CLPM). RESULTS: Sustained DAS28-CRP-remission was associated with higher SF-36-scores and less passive coping at baseline, and with higher SF-36-scores and more positive IPQ-R-outcomes at week 16. Among patients in DAS28-CRP-remission at W16 (n=287), two subgroups were identified: a low-psychosocial-burden group (n=231/287) and high-psychosocial-burden group (n=56/287). The low-psychosocial-burden group retained remission longer (HR 0.51 [0.35-0.73]). In the CLPM, temporal relationships between psychosocial wellbeing and DAS28-CRP were complex, bidirectional and disease-phase dependent. CONCLUSION: Suboptimal psychosocial wellbeing and negative illness perceptions predicted lower probability of sustained remission in an early RA cohort. Illness perceptions appeared to become more clinically relevant with time. Finally, one-in-five patients showed worse psychosocial outcomes despite early remission, and these patients tended to lose remission earlier.
34554119 Hepatitis B (HBV) reactivation in patients receiving biologic therapy for chronic inflamma 2021 Jul INTRODUCTION AND AIM: Biologic treatment - particularly with the anti-TNF molecules - is frequently used in clinical practice to treat the severe form for both chronic rheumatic diseases and inflammatory bowel diseases. The immunosuppression induced by biologic therapies increases the risk of infections, including tuberculosis, as well as hepatitis B virus (HBV) reactivation may occur in inactive carriers or occult HBV infection (OBI) subjects during biologic therapy. This study aimed to update data on HBV prevalence and reactivation in patients receiving biologic therapy for either chronic rheumatic diseases or IBD, and to describe their management in clinical practice. MATERIALS AND METHODS: This study was performed in 6 Italian centers (3 Rheumatology Units and 3 Gastroenterology Units). Clinical, biochemical and virological data, as well as follow up information, were recorded and analyzed. RESULTS: 984 patients were considered, including 817 with rheumatic disease and 167 with IBD. A total of 43 showed HBV infection (38 OBI and 5 carriers) accounting for a prevalence of 4%. Among OBI patients, 1 (2.6%) case of HBV reactivation occurred in a male patient with Crohn disease. Among the 5 HBV carriers, two patients (1 with spondyloarthritis and 1 with rheumatoid arthritis) did not received HBV antiviral therapy, and both experienced flare of hepatitis at 47 and 49 months following biologic therapy starting. DISCUSSION: Data of our study highlight that guidelines on management of HBV patients treated with biologic therapies should be still implemented in clinical practice when considering that, although infrequent, HBV reactivation could be potentially life-threatening.
34253862 Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. 2021 Jul Interleukin-6 (IL-6) plays a crucial role in host defense against infection and tissue injuries and is a bioindicator of multiple distinct types of cytokine storms. In this review, we present the current understanding of the diverse roles of IL-6, its receptors, and its signaling during acute severe systemic inflammation. IL-6 directly affects vascular endothelial cells, which produce several types of cytokines and chemokines and activate the coagulation cascade. Endothelial cell dysregulation, characterized by abnormal coagulation and vascular leakage, is a common complication in cytokine storms. Emerging evidence indicates that a humanized anti-IL-6 receptor antibody, tocilizumab, can effectively block IL-6 signaling and has beneficial effects in rheumatoid arthritis, juvenile systemic idiopathic arthritis, and Castleman's disease. Recent work has also demonstrated the beneficial effect of tocilizumab in chimeric antigen receptor T-cell therapy-induced cytokine storms as well as coronavirus disease 2019 (COVID-19). Here, we highlight the distinct contributions of IL-6 signaling to the pathogenesis of several types of cytokine storms and discuss potential therapeutic strategies for the management of cytokine storms, including those associated with sepsis and COVID-19.
34017189 Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reductio 2021 It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.
33810460 Intra-Articular Administration of Cramp into Mouse Knee Joint Exacerbates Experimental Ost 2021 Mar 26 Osteoarthritis (OA) is the most common type of arthritis and is associated with wear and tear, aging, and inflammation. Previous studies revealed that several antimicrobial peptides are up-regulated in the knee synovium of patients with OA or rheumatoid arthritis. Here, we investigated the functional effects of cathelicidin-related antimicrobial peptide (Cramp) on OA pathogenesis. We found that Cramp is highly induced by IL-1β via the NF-κB signaling pathway in mouse primary chondrocytes. Elevated Cramp was also detected in the cartilage and synovium of mice suffering from OA cartilage destruction. The treatment of chondrocytes with Cramp stimulated the expression of catabolic factors, and the knockdown of Cramp by small interfering RNA reduced chondrocyte catabolism mediated by IL-1β. Moreover, intra-articular injection of Cramp into mouse knee joints at a low dose accelerated traumatic OA progression. At high doses, Cramp affected meniscal ossification and tears, leading to cartilage degeneration. These findings demonstrate that Cramp is associated with OA pathophysiology.
33635407 [Prescription of analgesics in patients with rheumatic diseases in Germany : A claims dat 2021 Apr OBJECTIVE: To investigate the prescription frequency of analgesics in persons diagnosed with rheumatoid arthritis (RA), axial spondylarthritis (axSpA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE) in 2019 using claims data. METHODS: Persons ≥ 18 years insured in 2019 with a diagnosis of RA (M05, M06), axSpA (M45), PsA (M07.0-3) or SLE (M32.1,8,9) were included. Analgesics were identified by the anatomic therapeutic classification (ATC) system. Reported is the percentage of individuals with ≥ 1 analgesics prescription for the respective rheumatic diagnosis in 2019 and for opioids age-standardized in each of the years 2005-2019. In addition, the proportion of long-term opioid use (prescriptions in ≥ 3 consecutive quarter years) in 2006 and 2019 is compared. RESULTS: Metamizole (29-33%) was the most commonly prescribed analgesic. Nonsteroidal anti-inflammatory drugs (NSAID)/coxibs were prescribed from 35% (SLE) to 50% (axSpA). Of the patients 11-13% were prescribed weak and 6-8% strong opioids. From 2005 to 2019, the proportion of persons with an opioid prescription remained stable, with similar or slightly decreasing proportions of weak opioids and more frequent prescriptions of strong opioids. The proportion of long-term opioid prescriptions increased from 2006 to 2019 from 8.9% to 11.0% (RA), from 6.9% to 9.1% (axSPA), from 7.8% to 9.5% (PsA), and from 7.5% to 8.8% (SLE), corresponding to a 17-24% increase. CONCLUSION: The prescription of opioids for persons with inflammatory rheumatic diagnoses is not as high in Germany as in other countries; however, the proportion of long-term prescriptions has considerably increased. The frequent prescription of metamizole is conspicuous.
33562074 Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Prote 2021 Feb 6 A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. Patients with autoimmune disorders have been reported with a variety of elevated cytokines and cytokines (such as rheumatoid arthritis); thus, we evaluated a limited number of cytokines/chemokines in POTS patients with elevated adrenergic and muscarinic receptor autoantibodies. We utilized the plasma of 34 patients from a previous study; all of the patients (100%) had autoantibodies against the A1 adrenergic receptor and 55.9% (19/34) had autoantibodies against the M4 muscarinic acetylcholine receptor. In particular, the plasma cytokine/chemokine levels were measured as biomarkers of inflammation by Quantibody(®) technology (Raybiotech, Peachtree Corners, GA, USA). We also evaluated the platelet dense granule numbers, as these patients frequently complain of symptoms related to platelet dysfunction. Patients were predominantly young females who displayed a multitude of co-morbidities but generally reported viral-like symptoms preceding episodes of syncope. Eighty five percent (29/34) had platelet storage pool deficiency. Patients had elevations in five of ten cytokine/chemokines biomarkers (IL1β, IL21, TNFα, INFγ, and CD30), whereas two biomarkers had decreased levels (CD40L and RANTES). Our observations demonstrate that POTS patients known to have autoantibodies against the G-protein-coupled adrenergic A1 receptor have abnormal plasma concentrations of inflammatory cytokines.
33108917 Small-molecule CSF1R kinase inhibitors; review of patents 2015-present. 2021 Feb INTRODUCTION: Colony stimulating factor 1 receptor (CSF-1R, also known as c-FMS kinase) is in the class III receptor tyrosine kinase family, along with c-Kit, Flt3 and PDGFRα. CSF-1/CSF-1R signaling promotes the differentiation and survival of myeloid progenitors into populations of monocytes, macrophages, dendritic cells and osteoclasts, as well as microglial cells and also recruits host macrophages to develop into tumor-associated macrophages (TAMs), which promote tumor progression and metastasis. AREAS COVERED: In the last 5 years, and recently stimulated by the approval of pexidartinib (Turalio™, Daiichi Sankyo) in 2019 for the treatment of tenosynovial giant cell tumors, there has been a large increase in activity (both journal articles and patent applications) around small molecule inhibitors of CSF1R. Features of this work have been the surprising diversity of chemical classes shown to be potent and selective inhibitors, and the breadth of disease states (cancer, arthritis, and 'cytokine storm' syndromes) covered by CSF1R inhibitors. All these aspects are covered in the following sections. EXPERT OPINION: The field has developed rapidly from 2014 to the present, with many different chemotypes proving to be potent inhibitors. The range of potential utilities of CSF1R inhibitors has also expanded to include dementia, ulcerative colitis/Crohn's disease, rheumatoid arthritis inflammation, and fibrosis.
33065756 Associations between pediatric asthma and adult non-communicable diseases. 2021 Feb BACKGROUND: To date, there is no comprehensive study examining how asthma diagnosed in childhood or adolescence is associated with diagnoses of subsequent non-communicable diseases (NCDs) during adulthood. Our study aimed to examine the associations between pediatric asthma and several adult NCDs, with temporality and long interval times between asthma and NCD diagnoses. METHODS: We used RAND Indonesian Family Life Survey Fifth Wave (IFLS5) fielded in 2014-2015, to study whether being diagnosed with pediatric asthma at 0-19 years of age was associated with increased risks of hypertension, diabetes, rheumatoid arthritis, stomach diseases, kidney diseases, and heart diseases or stroke diagnosed in adulthood. We used the weighted Poisson regression adjusting for age, sex, urbanicity, and insurance status to estimate risk ratios. Subgroup analyses were performed by sex and age of asthma and other NCD diagnoses. RESULTS: Pediatric asthma significantly increased risks of hypertension, diabetes, and stomach diseases diagnosed at 20 years of age or above. Males with pediatric asthma diagnosed at 0-10 years of age had significantly higher risk of hypertension, while females with pediatric asthma diagnosed at 0-10 years of age had significantly higher risks of diabetes and stomach diseases. Females with pediatric asthma diagnosed at 11-19 years of age had significantly higher risks of diabetes, arthritis, stomach diseases, and kidney diseases. We also found varying associations by age of NCD diagnosis. CONCLUSION: Our results suggest pediatric asthma is associated with increased risks of several adult NCDs, and these associations may vary by sex and age of asthma and other NCD diagnoses.
35236499 Short-term results of a novel management of supracondylar fracture with coexisting osteoar 2021 Dec 4 PURPOSE: Presence of supracondylar and periarticular femoral fracture with associated arthritis of knee poses a challenging situation to the orthopaedic surgeon. The results of fixation of fracture in osteoporosis are not very satisfactory and have complications. With fixation alone, they still cannot bear weight on affected leg due to severe disability of osteoarthritis. To make patient walk, conventionally three surgeries in the form of fracture fixation, removal of implant and total knee arthroplasty (TKA) needs to be done in staged manner. We propose a novel management in form of bifold fixation and simultaneous TKA. METHODS: Eight cases (6 females, 2 males) of supracondylar femoral fractures with severe osteoarthritis of the knee and osteoporosis were primarily fixed with bifold fixation using SIGN nail ( www.signfracturecare.org ) and locking plate together with simultaneous total knee arthroplasty. There were five cases (2 males and 3 females) of grade 4 (Kellgren-Lawrence grading) osteoarthritis (OA) and three cases (all females) of severe rheumatoid arthritis (RA). RESULTS: The mean age was 68 years and average time for full weight bearing was 6 days. Radiographic evidence of fracture union was achieved in 16.25 weeks. The mean Knee Society Score (KSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 months was 83.13 and 22.13 respectively. CONCLUSIONS: Single stage combined bifold osteosynthesis with interlocking nail and locking plate together with total knee arthroplasty helps in one time management of these difficult injuries. It is a cost-effective and economically sound option and gives excellent results with good patient satisfaction.