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ID PMID Title PublicationDate abstract
30371923 Intramedullary Antibiotic Delivery for Emphysematous Osteomyelitis of the Femur. 2019 Jan 1 The authors present a case of bilateral femoral emphysematous osteomyelitis caused by Escherichia coli in a 60-year-old woman with rheumatoid arthritis who was receiving long-term prednisone therapy. The infection in both femoral shafts was eradicated with surgical debridement, followed by insertion of intramedullary rods composed of culture-specific antibiotic cement into the femoral canals in conjunction with 6 weeks of intravenous antibiotics. The rods were subsequently removed, and no signs of further osteomyelitis were recognized at follow-up. To the authors' knowledge, this is the first case of its kind reported in the orthopedic literature. Emphysematous osteomyelitis, a rare and dangerous entity, can be successfully managed by intramedullary antibiotic delivery in the subacute setting. [Orthopedics. 2019; 42(1):e128-e130.].
30046842 Correction to: The beliefs of rheumatoid arthritis patients in their subcutaneous biologic 2018 Sep In the original publication, the family name of the last author was incorrect. The correct name should read as Jaime Calvo-Alén.
29427206 Neuromodulation in Inflammatory Skin Disease. 2018 Mar Inflammatory skin diseases are difficult to treat because of a lack of available treatment options for severe disease. However, recent advances have shown that vagus nerve stimulation can be used to decrease inflammation and reduce disease severity in rheumatoid arthritis and inflammatory bowel disease. Changes in cytokine profiles observed in these studies are similar to those seen with use of biologics in inflammatory skin disease, suggesting that they act along similar pathways to disrupt chronic inflammation and treat inflammatory disease. This commentary explores the existing evidence demonstrating the efficacy of neuromodulation in inflammatory disease, and outlines reasons why these findings could translate to the dermatology setting to treat inflammatory skin disease.
29665605 [Shoulder Arthroplasty]. 2018 Apr Shoulder arthroplasty has been performed increasingly during the last years. The concept of modern anatomic shoulder arthroplasty is based on C. S. Neer's first shoulder prosthesis in the 1950s which was originally designed for the treatment of fractures of the proximal humerus. Since then, this monoblock prosthesis has undergone many changes and improvements. By now, an anatomic reconstruction of the joint is possible. Hence, the indications for anatomic shoulder arthroplasty have been added amongst others by osteoarthritis, necrosis, rheumatoid arthritis or posttraumatic arthritis. For years stemmed shoulder arthroplasty has been state of the art with a good clinical and radiological outcome. Nevertheless, stem-related problems occurred leading to the invention of short-stem and stem-free shoulder prosthesis. Stem-free shoulder arthroplasty allows an even better anatomic reconstruction and therefore offers more opportunities, e.g. in a severe posttraumatic status. Only short- to midterm results are published so far but those are very convincing indicating that stem-free shoulder arthroplasty is the future. Reverse shoulder arthroplasty has its origin in the 1980s. Paul Grammont invented a reversed shoulder prosthesis for patients suffering from cuff arthropathy. The center of rotation is medialised and inferiorised using the pre-loading of the deltoid muscle to move the shoulder joint. The initial prosthesis had undergone many variations as well but in contrast to anatomic shoulder arthroplasty biomechanics is still discussed a lot in reverse shoulder arthroplasty; especially in terms of finding the right inclination angle or how to prevent instability or scapular notching. This article gives a review about indications, concepts and complications of shoulder arthroplasty.
27598847 Ophthalmic Manifestations in Chronic Inflammatory Rheumatic Diseases at a Referral Hospita 2018 PURPOSE: To determine the profile of ophthalmic manifestations in chronic inflammatory rheumatic diseases (CIRD). METHODS: Observational study at the Yaounde Central Hospital and Innel Medical Centre (2004 to 2012). RESULTS: The study population (n = 36) consisted of 14 men and 22 women with average age of 47.9 ± 17.2 years. Cases of CIRD were rheumatoid arthritis (n = 16), systemic lupus erythematosus (n = 8), ankylosing spondylitis (n = 8), mixed connective tissue disease (n = 2), scleroderma (n = 1), and juvenile idiopathic arthritis (n = 1). Ophthalmic manifestations found in 22 (61.1%) patients were dry eye syndrome (n = 7), cataract (n = 6), anterior uveitis (n = 6), glaucoma (n = 4), and suspected maculopathy (n = 1). No association was found between steroids used and supcapsular cataract (p = 0.06) or glaucoma (p = 0.06). CONCLUSION: Ocular manifestations occurred in 61.1% of CIRD. Dry eye syndrome and anterior uveitis were commonly observed.
30391024 Identification of novel susceptibility genes associated with seven autoimmune disorders us 2019 Feb Convergent evidence from multiple and independent genetics studies implicate a small number of genes that predispose individuals to multiple autoimmune disorders (AuD). These intersecting loci reinforced the hypothesis that disorders with overlapping etiology group into a cluster of closely related genes within a whole genome molecular interaction network. We tested the hypothesis that "biological network proximity" within a whole genome molecular interaction network can be used to inform the search for multigene inheritance. Using a set of nine previously published genome wide association studies (GWAS) of AuD genes, we generated AuD-specific molecular interaction networks to identify networks of associated genes. We show that all nine "seed genes" can be connected within a 35-member network via interactions with 26 connecting genes. We show that this network is more connected than expected by chance, and 13 of the connecting genes showed association with multiple AuD upon GWAS reanalysis. Furthermore, we report association of SNPs in five new genes (IL10RA, DGKA, GRB2, STAT5A, and NFATC2) which were not previously considered as AuD candidates, and show significant association in novel disease samples of Crohn's disease and systemic lupus erythematosus. Furthermore, we show that the connecting genes show no association in four non-AuD GWAS. Finally, we test the connecting genes in psoriasis GWAS, and show association to previously identified loci and report new loci. These findings support the hypothesis that molecular interaction networks can be used to inform the search for multigene disease etiology, especially for disorders with overlapping etiology.
30302309 IgG4-related disease presenting with combined pulmonary fibrosis and emphysema (CPFE). 2018 A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The patient was a current-smoker and had a past illness of autoimmune pancreatitis with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema, and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4-RD may be an underlying condition in patient with CPFE.
29927712 Case series: rheumatological manifestations attributed to exposure to Libby Asbestiform Am 2018 An increased risk for Systemic Autoimmune Diseases (SAID) has been reported in Libby, Montana, where extensive exposures to fibrous amphiboles occurred due to mining and use of asbestos-laden vermiculite. In addition, positive antinuclear autoantibody tests are associated with exposure to Libby Asbestiform Amphiboles (LAA) in both humans and mice. Among 6603 subjects who underwent health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), 13.8% were diagnosed with an autoimmune disease, with prevalence values for the most common SAID being significantly higher than expected in the United States. Among the CARD screening population, serological and clinical profiles are diverse, representing symptoms and autoantibodies reflective of systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis, and other rheumatic syndromes, including undifferentiated connective tissue disease (UCTD). Based upon screening of medical records by physicians with rheumatology expertise, the evolving nature of rheumatological disease in these patients is often atypical, with mixed diagnostic criteria and with a 1:1 male-to-female ratio. Through the Libby Epidemiology Research Program, cases were identified that illustrate clinical autoimmune outcomes with LAA exposure. Our goal was to better characterize SAID in Libby, MT in order to improve recognition of autoimmune outcomes associated with this exposure. In view of recent discoveries of widespread exposure to fibrous minerals in several areas of the U.S. and globally, it is critical to evaluate rheumatologic manifestations in other cohorts so that screening, surveillance, and diagnostic procedures are able to detect and recognize potential autoimmune outcomes of asbestos exposure. ABBREVIATIONS: ANA, antinuclear autoantibody; ARD, Asbestos-Related Diseases; ATSDR, Agency for Toxic Substances & Disease Registry; CARD, Center for Asbestos Related Diseases; CCP, Cyclic citrullinated peptide antibody; CREST, limited cutaneous form of scleroderma; CT, computed tomography; DIP, Distal Interphalangeal Joint; DLCO, Diffusing Capacity of the Lung for CO(2); DMARD, Disease Modifying Anti-Rheumatic Drugs; ENA, Extractable Nuclear Antigen antibodies; FVC, Forced Vital Capacity; LAA, Libby Asbestiform Amphiboles; LERP, Libby Epidemiology Research Program; MCP, Metacarpal Phalangeal Joint; PIP, Proximal Interphalangeal Joint; PIP, rheumatoid arthritis; RV, Residual Volume; SAID, Systemic autoimmune diseases; SLE, systemic lupus erythematosus; SSc, Systemic Sclerosis; TLC, Total Lung Capacity.
29740473 Empirical Bayes Estimation of Semi-parametric Hierarchical Mixture Models for Unbiased Cha 2018 Genome-wide association studies (GWAS) suggest that the genetic architecture of complex diseases consists of unexpectedly numerous variants with small effect sizes. However, the polygenic architectures of many diseases have not been well characterized due to lack of simple and fast methods for unbiased estimation of the underlying proportion of disease-associated variants and their effect-size distribution. Applying empirical Bayes estimation of semi-parametric hierarchical mixture models to GWAS summary statistics, we confirmed that schizophrenia was extremely polygenic [~40% of independent genome-wide SNPs are risk variants, most within odds ratio (OR = 1.03)], whereas rheumatoid arthritis was less polygenic (~4 to 8% risk variants, significant portion reaching OR = 1.05 to 1.1). For rheumatoid arthritis, stratified estimations revealed that expression quantitative loci in blood explained large genetic variance, and low- and high-frequency derived alleles were prone to be risk and protective, respectively, suggesting a predominance of deleterious-risk and advantageous-protective mutations. Despite genetic correlation, effect-size distributions for schizophrenia and bipolar disorder differed across allele frequency. These analyses distinguished disease polygenic architectures and provided clues for etiological differences in complex diseases.
29686666 Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. 2018 Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.
29593881 Clinical characteristics and patient-reported outcomes in patients with inadequately contr 2018 BACKGROUND: Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. METHODS: Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. RESULTS: Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. CONCLUSION: RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.
28778870 Interleukin (IL-6) Immunotherapy. 2018 Aug 1 Interleukin 6 (IL-6) is a prototypical cytokine for maintaining homeostasis. When homeostasis is disrupted by infections or tissue injuries, IL-6 is produced immediately and contributes to host defense against such emergent stress through activation of acute-phase and immune responses. However, dysregulated excessive and persistent synthesis of IL-6 has a pathological effect on, respectively, acute systemic inflammatory response syndrome and chronic immune-mediated diseases. The IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor antibody, is currently being used for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman disease. Lines of recent evidence strongly suggest IL-6 blockade can provide broader therapeutic strategy for various diseases included in acute systemic and chronic inflammatory diseases.
29576708 Further Study of Influence of Panax notoginseng on Intestinal Absorption Characteristics o 2018 Jan BACKGROUND: Tripterygium wilfordii (TW) is widely employed to treat rheumatoid arthritis and autoimmune disorders clinically, which, however, accompany with disturbing hepatotoxicity and nephrotoxicity. The previous research showed that Panax notoginseng (PN) compatibly and significantly reduces the TW-induced hepatotoxicity. OBJECTIVE: To explore the underlying mechanism, the present study was designed to reveal the influence of PN on the intestinal absorption process of TW-derived active components in rat. MATERIALS AND METHODS: An in situ single-pass intestinal perfusion technique was established and preformed to obtain the perfusate samples of triptolide (TP), tripterine (TE), TW extract, and TW-PN extract. A rapid and sensitive ultra-performance liquid-chromatography tandem mass spectrometry method was subsequently developed and validated to determine the concentrations of TP and TE in the perfusate samples. Then, the absorption parameters, effective permeability, absorption rate constant, and percentage of 10 cm intestinal absorption were calculated strictly. RESULTS: The final data indicated that both TP and TE have no special absorption site in the intestine and are primarily absorbed in a passive manner. Otherwise, the absorption of TP was decreased from compatibility of PN, but the absorption of TE was enhanced. CONCLUSION: The absorption reduction of TP and absorption elevation of TE from TW initiated by the combination of PN are contributed to attenuate the toxicity and reinforce the therapeutic efficacy of TW. It is practically reasonable of usage of TW compatibility with PN clinically. SUMMARY: Panax notoginseng (PN) regulated the absorption process of Tripterygium wilfordii (TW) in intestineBoth triptolide (TP) and tripterine (TE), two typical components of TW, have no special absorption site in the intestine and are primarily absorbed in a passive mannerPN decreased the absorption of TP and enhanced the absorption of TE in the intestine. Abbreviations used: 10 cm% ABS: percentage of 10 cm intestinal absorption, DMARDs: Disease-modifying antirheumatic drugs, GU: Glycyrrhiza uralensis, K(a): Absorption rate constant, NSAIDs: Nonsteroidal anti-inflammatory drugs, P(eff): Effective permeability, PN: Panax notoginseng, QC: Quality control, RA: Rheumatoid arthritis, RG: Rehmannia glutinosa, SPIP: Single-pass intestinal perfusion, TE: Tripterine, TP: Triptolide, TW: Tripterygium wilfordii, UPLC-MS/MS: Ultra-performance liquid-chromatography tandem mass spectrometry.
30389556 Natural joints: Boundary lubrication and antiphospholipid syndrome (APS). 2019 Mar The paper shows that osteoporosis (OA) changes the SF content and the lipid profile substantially. To estimate the implication of the lipid environment in case the articular cartilage (AC) changes, we measured friction coefficient normal samples, with early and late stages of (OA). During joint inflammation and osteoarthritis, enzymatically activated β(2)-Glycoprotein I is transformed into antibody conformation. Our hypothesis about cartilage degradation of PL bilayers by antibodies (β(2)-Glycoprotein I) is considering antiphospholipid syndrome (APS), which was not discussed in the literature before. Deactivated PL molecule has no ability to form bilayers, lamellar phases, and liposomes. The phospholipid content in synovial fluid (SF) during joint inflammation, osteoarthritis, and rheumatoid arthritis is significantly higher (2-3 times) above the normal concentration of PL, and has a poor boundary-lubricating ability is deactivated.
30214149 Focus on biosimilar etanercept - bioequivalence and interchangeability. 2018 BACKGROUND: The recent approval of reference etanercept (re-ETN) biosimilars SB4, GP2015, and HD203 produced relevant changes in the management of rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis due to the considerably lower cost of these products and the consequent savings. AIMS: To review the pharmacodynamics, pharmacokinetics, efficacy, and safety of ETN biosimilars when employed as first-line therapy or after transition from re-ETN. Patients' acceptability was also addressed. EVIDENCE REVIEW: The available literature was reviewed through a search of PubMed database, and abstract books of the American College for Rheumatology and European League Against Rheumatism annual meetings. SB4, GP2015, and HD203 were licensed by the US, European and South Korea regulatory agencies after the bioequivalence to re-ETN was demonstrated through pharmacodynamic and pharmacokinetic studies, and randomized, head to head, controlled trials. Based on the evidence of efficacy and safety of SB4 and HD203 in RA, and of GP2015 in psoriasis, by the extrapolation principle, the three biosimilars were approved for all indications licensed for re-ETN, and the regulatory agencies introduced the interchangeability from the originator to the biosimilar. Extrapolation of indications, and particularly interchangeability raised relevant concerns among the rheumatologists due to the low level of evidence supporting the switching strategy (or transition). Rheumatologists' concerns are oriented toward the relevant number of biosimilar discontinuations after the transition ranging from 7%-17% over a short-term follow-up period. As resulted from two studies, at least 20%-30% of the patients claimed more exhaustive information on the switching procedure. CONCLUSION: Based on the available evidence, re-ETN biosimilars may be a good option as first-line therapy, while further data are needed to definitively establish the efficacy, safety, and the economic reflexes of transitioning from re-ETN.
29884803 Cannabinoids for the treatment of rheumatic diseases - where do we stand? 2018 Aug As medical use of cannabis is increasingly legalized worldwide, a better understanding of the medical and hazardous effects of this drug is imperative. The pain associated with rheumatic diseases is considered a prevalent indication for medicinal cannabis in various countries. Thus far, preliminary clinical trials have explored the effects of cannabis on rheumatoid arthritis, osteoarthritis and fibromyalgia; preliminary evidence has also found an association between the cannabinoid system and other rheumatic conditions, including systemic sclerosis and juvenile idiopathic arthritis. The potential medicinal effects of cannabis could be attributable to its influence on the immune system, as it exerts an immunomodulatory effect on various immune cells, including T cells, B cells and macrophages. However, the available evidence is not yet sufficient to support the recommendation of cannabinoid treatment for rheumatic diseases.
30226016 High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes from the He 2019 Apr BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS: Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS: The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS: Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.
29848120 Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with bi 2018 Jun Latent tuberculosis infection (LTBI) accounts for almost a quarter of the world population, and, in 5-10% of the subjects with impaired immune-response against M. tuberculosis growth, it may progress to active tuberculosis (TB). In this review, we focus on the need to propose a screening for LTBI including preventive therapy offer in rheumatic patients undergoing therapy with biological drugs. Areas covered: We report on evidence that biologics are associated with an increased risk of active TB reactivation. This effect seems to be mainly limited to treatment with anti-tumor necrosis factor (TNF) agents, while non-anti-TNF-targeted biologics are not likely associated to any increased risk. We introduce the concept that the patients' coexisting host-related risk factors, such as comorbidities, are crucial to identify those at higher risk to reactivate TB. We report that preventive TB therapy is well tolerated in patients treated with biological drugs. Expert commentary: Availability of non-anti-TNF targeted biologics, that are not associated with an increased risk of TB reactivation, offers a great opportunity to tailor a therapeutic intervention at low/absent TB risk. After proper LTBI screening investigations, preventive TB therapy has been demonstrated to be effective and well-tolerated to reduce the risk of TB reactivation in rheumatic patients requiring biological drugs.
33730773 TNFR signalling and its clinical implications. 2018 Jan Tumour necrosis factor-α (TNF-α) is a highly pleiotropic cytokine with effects on multiple pathological and physiological functions via two distinct receptors, TNFR1 and TNFR2. Much of the pro- inflammatory action of TNF-α is mediated by TNFR1 whereas TNFR2 is thought to play an immunoregulatory and tissue protective role. Anti-TNF- α biologics have been extremely successful in treating a number of immune mediated pathologies, including rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis and inflammatory bowel disease. However, anti-TNF therapy has been shown to induce systemic lupus erythematosus and psoriasis in some patients, and to be deleterious in multiple sclerosis. It is hypothesized that these paradoxical effects of anti-TNF-α are due to inhibition of TNFR2 signalling. In this review, we will focus on the biology and pathophysiologic role of TNF-α and on the therapeutic implications of targeting TNF-α receptor signalling.
29995544 Outcome measures of disease activity for rare autoimmune rheumatic diseases. 2018 Jul 2 Systemic lupus erythematosus, scleroderma, myositis and Sjögren's syndrome are rare, complex, multi-systemic rheumatic diseases associated with significant morbidity and mortality. Thorough assessments of disease activity are required to guide clinical management and assess response to new therapies in clinical trials. This article reviews the commonly used outcome measures to assess this group of diseases and discusses the limitations of their use.