Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 28238882 | Rheumatic manifestations associated with Chikungunya virus infection: A study of 307 patie | 2018 Mar | OBJECTIVES: In the wake of the Chikungunya epidemic which struck Reunion Island in 2005 and 2006, we conducted a prospective, multicentre study (RHUMATOCHIK) whose main objective was analyse the characteristics and progression of rheumatic manifestations in patients with post-Chikungunya joint pain. METHODS: A cohort of 307 consecutively included patients underwent rheumatological examinations for pain secondary to Chikungunya virus infection. The long-term evaluation was conducted by telephone survey 1 and 2 years after the onset of the viral infection. RESULTS: At inclusion, mean age was 54 years (24-87) and 83.1% of the patients were female. Chronic joint pain was associated with synovitis in 64.2% of the patients, affecting primarily the wrists, the proximal interphalangeal joints of the fingers, and the ankles. Attempts to detect the viral genome in joint fluid (10 patients) and synovial tissue (6 patients) using the RT-PCR technique were repeatedly unsuccessful. With a mean follow-up of 32 months, joint pain persisted in 83.1% of the patients. Functional impairment, however, was moderate, with a HAQ score of 0.44±0.5. CONCLUSION: Chikungunya virus infection is frequently the cause of joint manifestations that can persist for several months, or even several years. In some cases, the clinical symptoms closely resemble those usually associated with rheumatoid arthritis. Further studies are necessary to improve the therapeutic management of these patients. | |
| 29277097 | Systemic review: agreement between the latent tuberculosis screening tests among patients | 2018 Nov | BACKGROUND/AIMS: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. METHODS: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. RESULTS: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). CONCLUSION: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient's country of origin and the precise nature of underlying diseases. | |
| 29245188 | Unmet Needs of Aboriginal Australians With Musculoskeletal Pain: A Mixed-Method Systematic | 2018 Sep | OBJECTIVE: Musculoskeletal pain (MSP) conditions are the biggest cause of disability, and internationally, indigenous peoples experience a higher burden. There are conflicting reports about Aboriginal Australians and MSP. We conducted a systematic review to describe the prevalence, associated factors, impacts, care access, health care experiences, and factors associated with MSP among Aboriginal Australians. METHODS: We used a systematic search of quantitative and qualitative scientific and grey literature (PROSPERO# CRD42016038342). Articles were appraised using the Mixed Methods Appraisal Tool. Due to study heterogeneity, a narrative synthesis was conducted. RESULTS: Of 536 articles identified, 18 were included (14 quantitative, 4 qualitative), of high (n = 11), medium (n = 2), and low (n = 5) quality. Prevalence of MSP in Aboriginal populations was similar to or slightly higher than the non-Aboriginal population (prevalence rate ratio 1.1 for back pain, 1.2-1.5 for osteoarthritis [OA], and 1.0-2.0 for rheumatoid arthritis). Aboriginal people accessed primary care for knee or hip OA at approximately half the rate of non-Aboriginal people, and were less than half as likely to have knee or hip replacement surgery. Communication difficulties with health practitioners were the main reason why Aboriginal people with MSP choose not to access care. No articles reported interventions. CONCLUSION: Findings provide preliminary evidence of an increased MSP burden among Aboriginal Australians, and particularly for OA, a mismatch between the disease burden and access to health care. To increase accessibility, health services should initially focus on improving Aboriginal patients' experiences of care, in particular by improving patient-practitioner communication. Implications for care and research are outlined. | |
| 30187679 | Is sonoelastography a helpful method of evaluation to diagnose Sjögren's syndrome? | 2019 Feb | OBJECTIVE: A new sonoelastography technique - virtual touch tissue quantification of acoustic radiation force impulses (ARFI) - offers a promising method for measuring tissue rigidity. The aim of this study was to assess the usefulness of ARFI for diagnosing Sjögren's syndrome (SS). METHODS: This transversal prospective study included 41 patients with SS according to American-European Consensus Group (AECG) criteria, and a control group without symptoms. All subjects underwent ARFI high-resolution ultrasound assessment of the parotid glands (PG) and submandibular glands (SMG). RESULTS: In patients with SS, parotid gland shear wave velocity (SWV) was 2.08 m/s ± 0.55, significantly higher than in control subjects (1.2 m/s ± 0.17) (P = 0.0001); submandibular gland SWV was higher in SS patients (2.12 m/s ± 0.44) than control subjects (1.56 m/s ± 0.16) (P = 0.001). CONCLUSIONS: Acoustic radiation force impulses sonoelastography can assist diagnosis of SS, and is a non-invasive and fast method of detecting pathological changes to the parotid and submandibular glands. | |
| 30039269 | Is it possible to apply the treat-to-target strategy in primary Sjögren's syndrome-associ | 2018 Nov | The treat-to-target (T2T) strategy improved long-term survival of patients with pulmonary arterial hypertension (PAH). Little was known about applying the T2T strategy in primary Sjogren's syndrome-associated PAH (pSS-PAH). We investigated how to identify patients who are more likely to reach the treatment goals in a cohort of pSS-PAH. In this way, we explored the possibility of implementing T2T in pSS-PAH. Data were retrospectively collected from patients visiting our center between 2007 and 2017. PAH was confirmed by right heart catheterization (RHC). Patients were treated following the T2T strategy. PAH treatment goals were defined by the 5th World Symposium on Pulmonary Hypertension. The primary end point was reaching the PAH treatment goals. Of the 62 patients enrolled, 98.4% were female, with a mean age of 38.9 ± 9.1 years at the diagnostic RHC. The median disease duration of pSS was 46 months (0-365), while the median disease duration of PAH was 12 months (0-149). Following the T2T strategy, 32 (50%) patients achieved the treatment goals. The 1-, 3-, and 5- year cumulative rates of reaching the goals were 40.6, 67.4, and 73.9%, respectively. Predictive factors included using immunosuppressants (HR 4.715, 95% CI 1.101-20.192, p = 0.037) and right ventricular anterior-posterior diameter (RV-APD) > 30 mm at baseline (HR 0.426, 95% CI 0.188-0.968, p = 0.042). The results provide strong evidence that patients who received immunosuppressants are more likely to reach the treatment goals. In contrast, impaired RV structure correlates to worse treatment response. The T2T strategy is effective in pSS-PAH. | |
| 29702976 | NUDT15 R139C variation increases the risk of azathioprine-induced toxicity in Chinese subj | 2018 Apr | INTRODUCTION: Azathioprine (AZA) is widely used as an immunosuppressive agent, and its efficacy has been recommended by many clinical studies. However, leukopenia, the most common toxicity, still restricts its clinical applications. Recent studies found that NUDT15 R139C polymorphism is strongly associated with AZA-induced leukopenia in Koreans. However, the follow-up studies available are all limited to inflammatory bowel disease (IBD). Here, we report a case of a Chinese patient with Sjögren syndrome (SS) with wild-type TPMT*3C who was diagnosed with AZA-induced severe toxicity due to NUDT15 mutation based on clinical and laboratory characteristics. CASE PRESENTATION: A 22-year-old Chinese woman with SS developed severe leukopenia after AZA administration for 21 days. Detection of 6-thioguanine nucleotides (6-TGN) showed that the erythrocyte concentration had beyond the monitoring range, indicating that severe leukopenia might be caused by AZA. Furthermore, gene sequencing showed that NUDT15 R139C (poor metabolizer) homozygosity might explain this adverse event. Based on the evidence, AZA administration was immediately stopped and supportive treatments provided, and the patient eventually recovered. CONCLUSION: In this report, we first provide detailed clinical and laboratory characteristics of AZA-induced leukopenia in a patient with SS with a mutant NUDT15 R139C genotype (TT allele) and normal TPMT activity. This case indicates that NUDT15 R139C and TPMT*3C genotypes, and more importantly, 6-TGN levels, should be routinely monitored for those administered with AZA to predict and prevent AZA-induced toxicity. | |
| 29073353 | Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients | 2018 Aug | OBJECTIVE: To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs. RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility criteria "targeted therapy history," "minimum required disease duration," "required negative rheumatoid factor," and "required Classification Criteria for Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time-point-of-retention reporting (adaptive trials). CONCLUSION: From this exploratory meta-epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials. | |
| 29519308 | Sjögren Syndrome With Associated Lymphocytic Interstitial Pneumonia Successfully Treated | 2018 Mar | Interstitial lung disease (ILD) is a significant complication of Sjögren syndrome (SS) associated with increased morbidity and mortality. The mainstay of treatment remains corticosteroid administration, with or without additional immunosuppressive therapies. Preliminary studies in SS have shown benefit in glandular and serologic parameters following treatment with the CTLA4 immunoglobulin fusion protein abatacept. Topical tacrolimus has been effective for ocular symptoms in SS, but systemic therapy has not been reported. We describe the first case, to our knowledge, of the successful use of a combination of systemic tacrolimus and abatacept in severe refractory SS and related ILD. | |
| 30120806 | Predictive value of ultrasound scoring in relation to clinical and histological parameters | 2019 Jan | BACKGROUND: Salivary gland dysfunction is one of the main clinical features of Sjögren's syndrome (SS), manifested by xerostomia with subsequent complications and well-established effects on the person's quality of life. OBJECTIVES: To determine firstly whether selected tests of salivary gland function and structure, unstimulated whole salivary flow rate (UWSFR), parotid flow rate (PFR), clinical oral dryness score (CODS) and ultrasound score (USS), can discriminate SS from non-SS sicca patients and secondly whether these tests can differentiate between patients in different subgroups of SS. METHOD: Unstimulated whole salivary flow rate, PFR, CODS and USS were determined in 244 patients comprised of SS patients (n = 118), SS patients at higher risk of lymphoma (n = 30) or with lymphoma (n = 26), and non-SS sicca disease controls (n = 70). RESULTS: All assessments showed a significant difference between the overall SS group and the disease control group, attributed mainly to the lymphoma subgroups of SS (p < 0.0001 for all parameters). There was a significant correlation (Spearman r = 0.7, p value <0.0001) and 87.3% agreement between USS and the histology focus scores of 119 patients. CONCLUSION: The results suggest that salivary gland tests including USS can aid in differentiating between SS and non-SS dry mouth, especially the subgroups of SS with lymphoma or at higher risk of developing lymphoma. | |
| 29558726 | Detection of salivary protein biomarkers of saliva secretion disorder in a primary Sjögre | 2018 May 30 | Saliva secretion disorder is one of the most common symptoms in primary Sjögren syndrome (pSS). Salivary biomarkers related to saliva secretion disorder were identified in a pSS murine model, NOD/ShiLtJ mouse, using differential proteomic analysis. Candidate biomarkers were screened with Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated in saliva and salivary glands by western blotting and immunohistochemistry (IHC). Biological functions were detected using ingenuity pathway analysis (IPA). We identified 1101 salivary proteins from NOD/ShiLtJ mice and BALB/c mice (control). Catenin alpha-3 (CTNNA3), tyrosine-protein phosphatase non-receptor type 6 (PTPN6), Ras-related C3 botulinum toxin substrate (RAC2), and intermediate conductance calcium-activated potassium channel protein 4 (KCNN4) were screened as candidate biomarkers from 225 significantly dysregulated salivary proteins. These proteins participated in adherens junction or saliva secretion pathway and may be related to saliva secretion disorder. Proteomic analysis revealed that CTNNA3, PTPN6, and RAC2 were dysregulated in saliva and salivary glands and showed satisfactory sensitivity and specificity in receiver-operating characteristic curve; KCNN4 showed no statistical difference. IHC and IPA indicated that CTNNA3 may regulate acinar cell morphology, while PTPN6 and RAC2 promoted lymphocyte adhesion in salivary glands. Thus, CTNNA3, PTPN6, and RAC2 may be related to saliva secretion disorder in pSS. | |
| 29775734 | Defining the osteoarthritis patient: back to the future. | 2018 Aug | The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-nineteenth century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'. A similar narrative applies to the concept of OA affecting the whole joint vs the 'wear-and-tear' hypothesis, inflammation and the role of the central nervous system (CNS). In the late nineteenth and early twentieth centuries, the Garrods (father and son) and Hermann Senator argued that OA was a whole joint disease, and that inflammation played a major role in its progression. Garrod Jnr and John Spender also linked OA to a neurogenic lesion 'outside the joint'. The remaining twentieth century was no less dynamic, with major advances in basic science, diagnostics, treatments, surgical interventions and technologies. Today, OA is characterized as a multi-disease with inflammation, immune and CNS dysfunction playing central roles in whole joint damage, injury progression, pain and disability. In the current 'omics' era (genomics, proteomics and metabolomics), we owe a great debt to past physicians and surgeons who dared to think 'outside-the-box' to explain and treat OA. Over 130 years later, despite these developments, we still don't fully understand the underlying complexities of OA, and we still don't have a cure. | |
| 29298069 | Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propan | 2018 Feb 8 | Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. Our efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, we discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by X-ray crystallographic analysis. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clinical candidate for the treatment of JAK1-mediated autoimmune diseases. | |
| 28320056 | Health-Related Quality of Life in an Inception Cohort of Children With Juvenile Idiopathic | 2018 Jan | OBJECTIVE: To describe changes in health-related quality of life (HRQoL) over time in children with juvenile idiopathic arthritis (JIA), relative to other outcomes, and to identify predictors of unfavorable HRQoL trajectories. METHODS: Children with JIA in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort were included. The Juvenile Arthritis Quality of Life Questionnaire (JAQQ, a standardized instrument), health-related Quality of My Life (HRQoML, an instrument based on personal valuations), and JIA core variables were completed serially. Analyses included median values, Kaplan-Meier survival curves, and latent trajectory analysis. RESULTS: A total of 1,249 patients enrolled at a median of 0.5 months after diagnosis were followed for a median of 34.2 months. The degree of initial HRQoL impairment and probabilities of reaching the best possible HRQoL scores varied across JIA categories (best for oligoarthritis, worst for rheumatoid factor-positive polyarthritis). Median times to attain best possible HRQoL scores (JAQQ 59.3 months, HRQoML 34.5 months), lagged behind those for disease activity, pain, and disability measures. Most patients followed trajectories with minimal or mild impairment; however, 7.6% and 13.8% of patients, respectively, followed JAQQ and HRQoML trajectories with persistent major impairment in HRQoL. JIA category, aboriginal ethnicity, and baseline disease activity measures distinguished between membership in trajectories with major and minimal impairments. CONCLUSION: Improvement in HRQoL is slower than for disease activity, pain, and disability. Improvement of a measure based on respondents' preferences (HRQoML) is more rapid than that of a standardized measure (JAQQ). Higher disease activity at diagnosis heralds an unfavorable HRQoL trajectory. | |
| 30013327 | Medication adherence and persistence in patients with autoimmune rheumatic diseases: a nar | 2018 | BACKGROUND: Several drugs are available for the treatment of autoimmune rheumatic diseases; however, their effectiveness may be negatively influenced by inappropriate adherence. Low adherence and persistence rates have a significant impact on patient quality of life and are associated with health-related expenses. PURPOSE: To provide an up-to-date narrative review on treatment adherence and persistence rates, and discuss the factors that influence them, in patients with autoimmune rheumatic diseases. MATERIALS AND METHODS: We searched the PubMed database for studies among patients with a diagnosis of rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), or psoriatic arthritis (PsA), published from January 2015 to February 2017. Only studies with a well-defined measurement of adherence/persistence and those that carried out an evaluation of the influencing factors were included. RESULTS: Fifteen relevant studies that evaluated adherence and/or persistence were included. Adherence rates varied between 9.3% and 94%, and persistence rates between 23% and 80%. Most of the studies used one method to evaluate adherence or persistence (different questionnaire scores, proportion of days covered, and mean treatment duration). A high concordance was found between the adherence measurements of the Medication Event Monitoring System and Visual Analog Scale. Factors of economic, demographic, and clinical nature were only moderately linked to treatment adherence or persistence. However, patient-related factors - such as positive and increased beliefs in medication necessity, strong views of the chronic nature of the diseases, and increased knowledge of the disease - were related to better treatment adherence. CONCLUSION: Owing to the heterogeneity of the study results, we consider that the use of more than one method to assess adherence/persistence should yield more comprehensive and accurate data about patient adherence behavior. Patient-related factors should be included and analyzed more often in adherence studies as the former may be modified to improve patient adherence. | |
| 30637206 | Clinical Significance of Serum Bilirubin in Behçet's Disease. | 2018 Dec | BACKGROUND AND OBJECTIVE: Bilirubin (Bb) is the product of the intravascular compartment of catabolic pathway. In a small number of clinical trials, it has been shown that Bb molecules are associated with cardiovascular diseases, diabetes, cancer, autoimmune (lupus, rheumatoid arthritis) diseases and schizophrenia. Behçet's disease is a chronic, multisystemic, inflammatory vasculitis that was first described by Hulusi Behçet in 1937, which affects almost all organs and systems without any known aetiology. Here, we investigated the clinical significance of serum Bb as a biomarker in the patients with Behçet's disease. METHODS: Seventy-one (N = 71) patients with Behcet's diagnosis within the last 1 year were included retrospectively. Control group consisted of 75 subjects with similar age and sex distribution. Serum Bb, indirect Bb, total Bb, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) data were recorded from the hospital records. RESULTS: In the Behçet group, direct Bb was significantly lower (P = 0.011), ESR and CRP were significantly higher (P = 0.00). No significant differences were observed in other parameters. In the whole group, total Bb and indirect Bb were negatively correlated with ESR (P = 0.025, P = 0.01). Direct Bb was negatively correlated with CRP (P = 0.002). For the diagnosis of Behçet, direct Bb with a threshold of < 0.14 can be used as a diagnostic test (P = 0.000) with 70% sensitivity, 68% specificity (area under the curve = 0.69; 95% confidence interval 0.59-0.80) in ROC curve analysis. CONCLUSION: According to our study, we found that inflammatory markers were high and direct Bb values were low in patients with Behcet's disease. In addition, Bb parameters were negatively associated with acute phase reactants. As a practical biomarker with anti-oxidative properties, the direct Bb can be used to diagnose and clinical follow-up in cases with Behçet's disease. | |
| 29463017 | Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and | 2018 Feb 18 | The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones. | |
| 29363290 | Brief Report: Cancer Immunotherapy in Patients With Preexisting Rheumatic Disease: The May | 2018 Mar | OBJECTIVE: To determine the risk of rheumatic disease flare and adverse effects in patients with preexisting rheumatic disease who were receiving immune checkpoint inhibitor (ICI) therapy. METHODS: A retrospective medical record review was performed to identify all patients who received ICI therapy at Mayo Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with a preexisting rheumatic disease were identified using specific diagnostic codes. RESULTS: Sixteen patients were identified (81% female, median age 68.5 years). The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia rheumatica (n = 5), Sjögren's syndrome (n = 2), and systemic lupus erythematosus (n = 2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatic disease at the time of initiation of the ICI. The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or hematologic (n = 2). In most cases, ICIs were offered only after failure of several other therapies. Immune-related adverse effects (IRAEs) occurred in 6 patients, and all were treated successfully with glucocorticoids and discontinuation of the ICI therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and those without IRAEs. CONCLUSION: To our knowledge, this represents the largest single-center cohort of patients with rheumatic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatic disease or any other IRAE. | |
| 28823732 | Mortality causes and outcomes in Indigenous populations of Canada, the United States, and | 2018 Feb | BACKGROUND: Indigenous populations of Canada, America, Australia, and New Zealand have increased rates and severity of rheumatic disease. Our objective was to summarize mortality outcomes and explore disease and social factors related to mortality. METHODS: A systematic search was performed in medical (Medline, EMBASE, and CINAHL), Indigenous and conference abstract databases (to June 2015) combining search terms for Indigenous populations and rheumatic diseases. Studies were included if they reported measures of mortality (crude frequency, mortality rate, survival, and potential years of life lost (PYLL)) in Indigenous populations from the four countries. RESULTS: Of 5269 titles and abstracts identified, 504 underwent full-text review and 12 were included. No studies from New Zealand were found. In five Canadian studies of systemic lupus erythematosus (SLE) patients, First Nations ethnicity was associated with lower survival after adjusting for disease and social factors, and an increased frequency of death from lupus and its complications compared to Caucasians was found. All-cause mortality was higher in Native Americans (n = 2 studies) relative to Whites with SLE after adjusting for disease and social factors, but not in those with lupus nephritis alone. Australian Aborigines with SLE frequently developed infection and lupus complications leading to death (n = 3 studies). Mortality rates were increased in Pima Indians in the United States with rheumatoid arthritis (RA) compared to those without RA. One study in Native Americans with scleroderma found nearly all deaths were related to progressive disease. CONCLUSIONS: Canadian and American Indigenous populations with SLE have increased mortality rates compared to Caucasian populations. Mortality in Canadian and Australian Indigenous populations with SLE, and in Native American populations with RA and scleroderma, is frequently attributed to disease progression or complications. The proportional attribution of rheumatic disease severity and social factors to mortality and complications leading to death between Indigenous and non-Indigenous populations has not been fully evaluated. | |
| 30562564 | Cytokine-targeted therapy for the management of solid organ transplant recipients. | 2019 Mar | INTRODUCTION: The number of solid organ transplants completed annually continues to trend upwards each year. Despite this, maintenance immunosuppression available on the market has remained relatively stagnant. Standard triple immunosuppression, composed typically of tacrolimus, mycophenolate, and steroids, lead to many side effects that limit the use of these medications. Tacrolimus, specifically, causes nephrotoxicity that can lead to renal dysfunction requiring a kidney transplant down the road. Alternative therapies for the management of immunosuppression need to be identified to try to mitigate these adverse effects. BODY: Cytokines are responsible for facilitating T cell differentiation and lead to the activation of inflammatory mediators that can contribute to graft damage and ultimately rejection. IL-4, IL-6, IL-12/23, and IL-15 are attractive targets for medications to try to ameliorate graft rejection. Various cytokine-targeted medications are currently available on the market for the treatment of inflammatory and autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, Crohn's, and multiple sclerosis. CONCLUSION: This article reviews cytokine involvement in alloimmunity and the potential role cytokine-targeted therapy may play in prevention of allograft rejection in solid organ transplant recipients. | |
| 30105062 | Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against Rheumatoid | 2018 | To compare efficacy of different extracts from Eucommia ulmoides Oliv. with both immune inflammation and joint destruction in collagen induced arthritis (CIA) rat model. Rats were divided into normal group (Nor), control group (CIA), TG group (treated with tripterygium glycoside), E70 group (treated with 70% ethanol extract from Eucommia ulmoides Oliv.), EA group (treated with ethyl acetate fraction from E70), and EN group (treated with n-butyl alcohol fraction from E70). All extracts from Eucommia ulmoides Oliv. could significantly inhibit ankle swelling, pathological manifestations, and cytokine levels in serum and spleen, by using foot volume measurement, H&E staining, ELISA, and RT-QPCR methods, respectively. All extracts could significantly inhibit rough joint surface and marginal osteophytes, improve RANKL/OPG ratio, and decrease MMP-9 expression, by using micro-CT and immunohistochemical staining. The activation of IKK/NF-κB signaling pathway was also inhibited by all extracts. In addition, ethyl acetate fraction from E70 presented better effect on RANKL/OPG system. This study identified effective extracts from Eucommia ulmoides Oliv. relieving immune inflammation and maintaining structural integrity of joints in CIA rats. |