Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27579313 DHA and EPA Content and Fatty Acid Profile of 39 Food Fishes from India. 2016 Docosahexaenoic acid (DHA) is the principal constituent of a variety of cells especially the brain neurons and retinal cells and plays important role in fetal brain development, development of motor skills, and visual acuity in infants, lipid metabolism, and cognitive support and along with eicosapentaenoic acid (EPA) it plays important role in preventing atherosclerosis, dementia, rheumatoid arthritis, Alzheimer's disease, and so forth. Being an essential nutrient, it is to be obtained through diet and therefore searching for affordable sources of these ω-3 polyunsaturated fatty acids (PUFA) is important for consumer guidance and dietary counseling. Fish is an important source of PUFA and has unique advantage that there are many food fish species available and consumers have a wide choice owing to availability and affordability. The Indian subcontinent harbors a rich fish biodiversity which markedly varies in their nutrient composition. Here we report the DHA and EPA content and fatty acid profile of 39 important food fishes (including finfishes, shellfishes, and edible molluscs from both marine water and freshwater) from India. The study showed that fishes Tenualosa ilisha, Sardinella longiceps, Nemipterus japonicus, and Anabas testudineus are rich sources of DHA and EPA. Promotion of these species as DHA rich species would enhance their utility in public health nutrition.
27428445 Potentially severe drug-drug interactions among older people and associations in assisted 2016 Sep OBJECTIVE: This study aims to assess potentially severe class D drug-drug interactions (DDDIs) in residents 65 years or older in assisted living facilities with the use of a Swedish and Finnish drug-drug interaction database (SFINX). DESIGN: A cross-sectional study of residents in assisted living facilities in Helsinki, Finland. SETTING: A total of 1327 residents were assessed in this study. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and DDDIs were coded according to the SFINX. MAIN OUTCOME MEASURES: Prevalence of DDDIs, associated factors and 3-year mortality among residents. RESULTS: Of the participants (mean age was 82.7 years, 78.3% were females), 5.9% (N = 78) are at risk for DDDIs, with a total of 86 interactions. Participants with DDDIs had been prescribed a higher number of drugs (10.8 (SD 3.8) vs. 7.9 (SD 3.7), p < 0.001). A larger proportion of residents with DDDIs suffered from rheumatoid arthritis or osteoarthritis than those not exposed to DDDIs (24.7% vs. 15.4%, p = 0.030). The most frequent DDDIs were related to the concomitant use of potassium with amiloride (N = 12) or spironolactone (N = 12). Carbamazepine (N = 13) and methotrexate (N = 9) treatments were also frequently linked to DDDIs. During the follow-up, no differences in mortality emerged between the participants exposed to DDDIs and the participants not exposed to DDDIs. CONCLUSIONS: Of the residents in assisted living, 5.9% were exposed to DDDIs associated with the use of a higher number of drugs. Physicians should be trained to find safer alternatives to drugs associated with DDDIs. KEY POINTS   Potentially severe, class D drug-drug interactions (DDDIs) have been defined in the SFINX database as clinically relevant drug interactions that should be avoided.  • Of the residents in assisted living, 5.9% were exposed to DDDIs that were associated with the use of a higher number of drugs.  • The most frequent DDDIs were related to the concomitant use of potassium with amiloride or spironolactone. Carbamazepine and methotrexate were also linked to DDDIs.  • No difference in mortality was observed between residents exposed to DDDIs and residents not exposed to DDDIs.
27424477 Chronic immunosuppression does not potentiate the malignant progression of mucinous pancre 2016 Sep BACKGROUND: Premalignant mucinous pancreatic cystic lesions (mPCLs) are increasingly identified. AIMS: In this study, we aim to assess the effect of selected immunosuppressive therapies on the progression of mPCLs, including side-branch intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. METHODS: We performed a retrospective cohort study of patients with mPCLs diagnosed over a 24-year period who received chronic immunosuppression. Controls were matched on age at cyst diagnosis (±11 yrs) and cyst size (±8 mm). Measured outcomes included increase in cyst size, development of "worrisome features" as defined by consensus guidelines, progression to malignancy, and rate of surgical resection. RESULTS: 39 patients (mean age 60 yrs) with mPCLs were on immunosuppression. Leading indications for immunosuppression were solid organ transplant (n = 14), inflammatory bowel disease (n = 6), and rheumatoid arthritis (n = 5). 33% were on biologics, 77% on antimetabolites and 79% on multiple medications. Mean cyst size increased from 12.6 mm to 17.8 mm over a median of 16.5 months. 6 patients elected for surgical resection, and none ultimately developed malignancy. 26 cases with follow-up were matched to control subjects, with no significant differences among cases and controls in initial cyst size (12.8 mm vs 11.9 mm, P = 0.69), mean size increase (6.9 mm vs 5 mm, P = 0.47), follow-up interval (24.3 months vs 21.5 months, P = 0.44). No significant differences in the rate of worrisome features, malignancy, or surgical resection. CONCLUSIONS: Patients with mPCLs exposed to immunosuppressive medications did not have higher rates of malignancy or development worrisome features in the short term. This suggests that patients with mPCLs can be initiated or maintained on these agents without changes to surveillance practices.
27219305 Rheumatic Diseases in Chihuahua, México: A COPCORD Survey. 2016 Jun BACKGROUND: Rheumatic diseases (RDs) represent a global problem for health care systems and patients. Community Oriented Program for Control of Rheumatic Diseases (COPCORD) is a low-cost screening tool for detecting musculoskeletal (MSK) pain and RDs. OBJECTIVE: The aim of this study was to examine the pattern of MSK pain and RDs in clinic population in Chihuahua City, Mexico. METHODS: A cross-sectional study was conducted in 7 primary health clinics using the COPCORD methodology in subjects older than 18 years. People with MSK pain not induced by trauma (positive cases) were evaluated by primary care physicians and rheumatologists. RESULTS: The study included 1006 individuals with a mean age of 46.0 (SD, 15.8) years; 751 (74.7%) were women. Musculoskeletal pain in the previous 7 days was reported by 571 individuals (56.75%; 95% confidence interval [CI], 53.8%-60.1%), and 356 cases (35.4%; 95% CI, 32.5%-38.4%) were COPCORD positive. The mean pain intensity in visual analog scale was 6.62 (SD, 2.4). The most common painful joint was the knee (54.7%; 95% CI, 51.1%-59.0%). Two hundred eighty subjects with MSK pain (49.0%) previously sought medical attention, and 375 (65.7%) were under treatment. Functional impairment was reported by 69.8% of the COPCORD-positive subjects. The prevalence of RDs was 21.4% (95% CI, 18.9%-23.8%). The most prevalent disease was osteoarthritis (10.3%; 95% CI, 8.6%-12.4%), followed by regional pain syndromes (5.5%; 95% CI, 4.1%-7.0%), rheumatoid arthritis (1.4%; 95% CI, 0.8%-2.2%), and mechanical low-back pain (1.4%; 95% CI, 0.7%-2.2%). CONCLUSIONS: Musculoskeletal pain is an important problem that affects our community. The data provided in this study will be presented to the local authorities to help in the development of prevention strategies.
27216862 Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune dis 2016 Aug Recognition of self-antigen and its destruction by the immune system is the hallmark of autoimmune diseases. During the developmental stages, immune cells are introduced to the self-antigen, for which tolerance develops. The inflammatory insults that break the immune tolerance provoke immune system against self-antigen, progressively leading to autoimmune diseases. SH2 domain containing protein tyrosine phosphatase (PTP), SHP-1, was identified as hematopoietic cell-specific PTP that regulates immune function from developing immune tolerance to mediating cell signaling post-immunoreceptor activation. The extensive research on SHP-1-deficient mice elucidated the diversified role of SHP-1 in immune regulation, and inflammatory process and related disorders such as cancer, autoimmunity, and neurodegenerative diseases. The present review focalizes upon the implication of SHP-1 in the pathogenesis of autoimmune disorders, such as allergic asthma, neutrophilic dermatosis, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis, so as to lay the background in pursuance of developing therapeutic strategies targeting SHP-1. Also, new SHP-1 molecular targets have been suggested like SIRP-α, PIPKIγ, and RIP-1 that may prove to be the focal point for the development of therapeutic strategies.
26912511 Management of interstitial lung disease associated with connective tissue disease. 2016 Feb 24 The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because of other manifestations of CTD and comorbidities. Clinical trials of novel therapies including immunosuppressive therapies are needed to inform best treatment strategies.
26893020 The relationship between hypertension and health-related quality of life: adjusted by chro 2016 Jul OBJECTIVES: The aim of this study was to examine the relationship between hypertension and health-related quality of life (HRQoL) adjusted by chronic pain, other chronic diseases, and life habits in the general middle-aged population in Japan. METHODS: This study is a population-based cross-sectional study. In this study, 1117 participants aged 40-65 years and living in Shika Town completed a self-administered questionnaire including Short Form-36 (SF-36). The scores of SF-36 among hypertensives were compared with those of normotensives. The independent association of hypertension with each SF-36 subscale was analyzed using a multiple linear regression model adjusted by age, BMI, chronic pain, chronic diseases, sleep, exercise, and occupational status. We analyzed two groups; Group 1 which contained 846 participants completed the questionnaire without coronary heart disease and cerebral vascular disease, Group 2 which contained 686 participants without coronary heart disease, cerebral vascular disease, or diseases accompanied by chronic pain (gastroduodenal ulcer, fracture, osteoarthritis, osteoporosis, rheumatoid arthritis, and disc herniation). RESULTS: In Group 2, hypertensive women had a lower general health perception than normotensive women [unstandardized coefficients; B = -8.84, 95 % confidence interval (95 % CI) = -13.3 to -4.34, standardized coefficients; β = -0.200, p < 0.001], whereas hypertensive men had higher social functioning than normotensive men (B = 5.66, 95 % CI = 1.30-10.0, β = 0.149, p < 0.05) after adjusting by chronic pain and life habits. CONCLUSIONS: These results may be due to the sex difference in the light of the perception for health.
26054920 Autophagy in autoimmune disease. 2015 Jul Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. This process of cellular self-digestion is an essential stress response and is cytoprotective by removing damaged organelles and proteins that threaten the cell's survival. Key outcomes include energy generation and recycling of metabolic precursors. In the immune system, autophagy regulates processes such as antigen uptake and presentation, removal of pathogens, survival of short- and long-lived immune cells, and cytokine-dependent inflammation. In all cases, a window of optimal autophagic activity appears critical to balance catabolic, reparative, and inflammation-inducing processes. Dysregulation of autophagosome formation and autophagic flux can have deleterious consequences, ranging from a failure to "clean house" to the induction of autophagy-induced cell death. Abnormalities in the autophagic pathway have been implicated in numerous autoimmune diseases. Genome-wide association studies have linked polymorphisms in autophagy-related genes with predisposition for tissue-destructive inflammatory disease, specifically in inflammatory bowel disease and systemic lupus erythematosus. Although the precise mechanisms by which dysfunctional autophagy renders the host susceptible to continuous inflammation remain unclear, autophagy's role in regulating the long-term survival of adaptive immune cells has recently surfaced as a defect in multiple sclerosis and rheumatoid arthritis. Efforts are underway to identify autophagy-inducing and autophagy-suppressing pharmacologic interventions that can be added to immunosuppressive therapy to improve outcomes of patients with autoimmune disease.
25931626 Legionnaires' disease and associated comorbid conditions as causes of death in the U.S., 2 2015 May OBJECTIVE: Recent U.S. outbreaks of Legionnaires' disease (LD) underscore the virulent nature of this infectious pneumonia. To date, only a paucity of literature has described the mortality burden of LD. This study updates LD mortality using U.S. multiple-cause-of-death data from 2000-2010. METHODS: We calculated crude and age-adjusted rates for LD mortality for age, sex, race, state, Census region, and year. We conducted Poisson regression to assess seasonal and temporal trends. We generated matched odds ratios (MORs) to describe the association between LD-related deaths and other comorbid conditions listed on the death certificates. RESULTS: We identified a total of 1,171 LD-related deaths during 2000-2010. The age-adjusted mortality rate remained relatively static from 2000 (0.038 per 100,000 population, 95% confidence interval [CI] 0.031, 0.046) to 2010 (0.040 per 100,000 population, 95% CI 0.033, 0.047). The absolute number increased from 107 to 135 deaths during this period, with adults ≥45 years of age having the highest caseload. Overall, LD mortality rates were 2.2 times higher in men than in women. White people accounted for nearly 83.3% of all LD-related deaths, but the age-adjusted mortality rates for black and white people were similar. Comorbid conditions such as leukemia (MOR=4.8, 95% CI 3.5, 6.6) and rheumatoid arthritis (MOR=5.6, 95% CI 3.3, 9.4) were associated with LD diagnosis on death certificates. CONCLUSION: Comorbid conditions that could lead to an immunocompromised state were associated with fatal LD on U.S. death certificates. Characterization of LD mortality burden and related comorbidities has practice implications for clinical medicine and public health surveillance.
25900303 Fibroblastic synoviocytes secrete plasma proteins via α2 -macroglobulins serving as intra 2015 Nov Changes in plasma protein levels in synovial fluid (SF) have been implicated in osteoarthritis and rheumatoid arthritis. It was previously thought that the presence of plasma proteins in SF reflected ultrafiltration or extravasation from the vasculature, possibly due to retraction of inflamed endothelial cells. Recent proteomic analyses have confirmed the abundant presence of plasma proteins in SF from control and arthritic patients. Systematic depletion of high-abundance plasma proteins from SF and conditioned media from synoviocytes cultured in serum, and protein analysis under denaturing/reducing conditions have limited our understanding of sources and the native structures of "plasma protein" complexes in SF. Using Western blotting, qPCR, and mass spectrometry, we found that Hig-82 lapine fibroblastic synovicytes cultured under serum-free conditions expressed and secreted plasma proteins, including the cytokine-binding protein secreted phosphoprotein 24 kDa (Spp24) and many of the proteases and protease inhibitors found in SF. Treating synoviocytes with TGF-β1 or BMP-2 for 24 h upregulated the expression of plasma proteins, including Spp24, α2 -HS-glycoprotein, α1 -antitrypsin, IGF-1, and C-reactive protein. Furthermore, many of the plasma proteins of mass <151 kDa were secreted as disulfide-bound complexes with members of the α2 -macroglobulin (A2M) family, which serve as intracellular and extracellular chaperones, not protease inhibitors. Using brefeldin A to block vesicular traffic and protease inhibitors to inhibit endogenous activation of naïve A2M, we demonstrated that the complexes were formed in the endoplasmic reticulum lumen and that Ca(2+) cysteine protease-dependent processes are involved.
25889555 The influence of compatibility of processed radix Aconiti Kusnezoffii on the pharmacokinet 2015 Jul 1 ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis Fisch. and processed radix Aconiti kusnezoffii are the main components in many Chinese traditional patent medicines with the ratio of 1:1, which are used for treatment of rheumatoid arthritis, heart failure and so on. Glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin are the essential bioactive triterpenes and flavones in the extract of G. uralensis, which were analysis by a simple but accurate method. MATERIALS AND METHODS: In the present study, a specific HPLC method was developed and validated for simultaneous determination of pharmacokinetic parameters of glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin in G. uralensis after oral administration of single herb extract and a combination of two herbs extracts respectively. RESULTS: The calibration curves of the four components had good linearity higher than 0.9991 in the measured range. The intra-day and inter-day precisions (RSD) at different levels were both within 9.73%, and the accuracies (RE) were in the range of -7.9-8.0%. Compared with pharmacokinetic parameters of G. uralensis administered orally, values of AUC and Cmax of liquiritigenin and isoliquiritigenin decreased significantly (p<0.05), plasma concentrations of glycyrrhizic acid rose slightly and bimodal phenomenon of concentration-time of isoliquiritigenin and glycyrrhetinic acid disappeared after combined administration. DISCUSSION AND CONCLUSIONS: Some components in the extract of processed radix A. kusnezoffii showed different effects on the pharmacokinetics of the four ingredients in G. uralensis.
25645875 Autoimmune Disease in First-Degree Relatives and Spouses of Individuals With Celiac Diseas 2015 Jul BACKGROUND & AIMS: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. METHODS: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n = 29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n = 84,648) and controls (n = 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. RESULTS: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P = .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. CONCLUSIONS: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.
25571843 Celastrol prevents circulatory failure via induction of heme oxygenase-1 and heat shock pr 2015 Mar 13 ETHNOPHARMACOLOGICAL RELEVANCE: Celastrol, a quinone methide extracted from the root of Tripterygium wilfordii Hook, possesses anti-oxidant and anti-inflammatory effects. Tripterygium wilfordii Hook is officially listed in the Chinese Pharmacopoeia and is used traditionally against rheumatoid arthritis, ankylosing spondylitis, and cancer. Furthermore, the circulatory protective effect of celastrol on an in vivo animal model of sepsis was investigated. AIM OF THE STUDY: Sepsis is a systemic inflammatory disorder that increases tissue oxidative stress and leads to multiple organ injury. We evaluated the beneficial effects of celastrol on multiple organ failure induced by lipopolysaccharide (LPS) in rats. MATERIALS AND METHODS: Celastrol (0.5 and 1.0 mg/kg, i.v.) was administered to anaesthetized rats 2 h before and 30 min after LPS challenge (10 mg/kg, i.v.). Eight hours later, cardiac and aortic protein expressions related to inflammatory responses, superoxide anion production, and reduced glutathione (GSH) level were measured. RESULTS: Treatment with celastrol prevented circulatory failure (bradycardia and hypotension) 8h after LPS challenge. The plasma levels of ALT, LDH, TNF-α, and nitric oxide metabolites increased markedly during sepsis, which significantly reduced after celastrol treatments. Celastrol attenuated iNOS, TNF-α, NF-κB phospho-p65 expression, superoxide anion production, and caspase 3 activity in the cardiovascular system, all of which were markedly elevated after LPS challenge. Furthermore, celastrol induced HO-1 and HSP70 expressions increase in nuclear levels of Nrf2 and HSF-1, respectively, and increase cardiac GSH level 8h after LPS challenge. CONCLUSION: Anti-inflammatory and anti-oxidant effects of celastrol contribute to prevent circulatory failure in sepsis. Induction of HO-1 and HSP70 by celastrol participates in these beneficial effects.
25542985 Anti-inflammatory effects of a novel ricinoleic acid poloxamer gel system for transdermal 2015 Feb 1 Our previous study showed that the use of ricinoleic acid as an oil phase resulted in the formation of a stable pluronic lecithin organogel (PLO gel) with better thixotropic properties and higher permeation of ketoprofen than the isopropyl palmitate PLO gel. This study aims to evaluate and compare the in vitro and in vivo anti-inflammatory effects of the ricinoleic acid PLO gel system with isopropyl palmitate PLO gel. Ketoprofen was used as a model drug. In vitro anti-inflammatory activity and cell viability tests were performed in human rheumatoid arthritis synovial fibroblast cell line using a blank ricinoleic acid PLO gel and compared to that of the isopropyl palmitate PLO gel. In vivo anti-inflammatory activity of ricinoleic acid PLO gel containing 10% ketoprofen was evaluated and compared with the isopropyl palmitate PLO gel in a carrageenan-induced rat paw edema model. The results from the in vitro study showed that the blank ricinoleic acid PLO gel possessed significantly higher anti-inflammatory activity than isopropyl palmitate PLO gel at 1 mM concentration (p<0.05), while both the gel formulations had no significant cytotoxic activity. Further in vivo testing of the formulation showed that the ricinoleic acid PLO gel formulation was significantly more effective in reducing pain and edema when compared to the isopropyl palmitate PLO gel. In addition, the ricinoleic acid PLO gel formulation markedly inhibited the synthesis of prostaglandin E2. In conclusion, the efficacy of PLO gels used in pain management may be enhanced by using ricinoleic acid instead of isopropyl palmitate as an oil phase.
25318864 Diagnosis of latent tuberculosis infection with T-SPOT(®).TB in a predominantly immigrant 2015 Feb PURPOSE: The objective of this study is to compare how likely positive tuberculin skin test (TST) and T-SPOT(®).TB (TSPOT) results predict risk factors for tuberculosis in a predominantly immigrant patient population at risk of latent TB infection (LTBI) and with rheumatologic conditions requiring immunomodulatory therapy (IMT). METHODS: Prospective study conducted at a referral rheumatology clinic. Inclusion criteria included patients on various IMT, including immunosuppressive drugs that could predispose to TB progression. We studied risk factors associated with LTBI, test results, and tests' agreement. RESULTS: We studied 101 patients. Eighty (79.2 %) were from countries where TB is prevalent and Bacille Calmette-Guérin vaccination is placed routinely. Seventy-four (73.3 %) had rheumatoid arthritis and 92 (90.7 %) were on IMT. Among patients with both TST and TSPOT results, 25 (30.9 %) were TST(+) and 20 (24.7 %) had TSPOT(+) results. Fifteen patients (18.5 %) had TST(+)/TSPOT(+) results, and 51 (63.0 %) had TST(-)/TSPOT(-) results (agreement = 81.5 %; kappa = .54 [95 % CI, .34-.74; P < .001]). Each TSPOT(+) and TST(+) results were independently associated with immigrant status and prior residence in a TB prevalent country after adjustment for immunosuppressive therapy: Adjusted OR(TSPOT+)=6.6 (95 % CI, 1.2-123.3; P = .027); and adjusted OR(TST+)=11.2 (95 % CI, 2.0-209.5; P = .003). Seven out of 10 TST(+)/TSPOT(-) cases had a TST ≥15 mm induration, including three cases with history of TST conversion. CONCLUSIONS: TST(+) and TSPOT(+) results predict risk factors associated with LTBI independent of immunosuppressive IMT. Some TST(+)/TSPOT(-) results were unlikely to be false-negatives. The combined use of TST and TSPOT appears to be a reasonable diagnostic strategy to evaluate for LTBI in this population.
25267270 Rotator cuff fatty infiltration and atrophy are associated with functional outcomes in ana 2015 Feb BACKGROUND: Shoulder arthroplasty provides reliable pain relief and restoration of function. However, the effects of fatty infiltration and atrophy in the supraspinatus and infraspinatus muscles on functional outcomes are not well understood. QUESTIONS/PURPOSES: The purposes of this study were to (1) compare preoperative with postoperative fatty infiltration and atrophy of the supraspinatus and infraspinatus muscles after primary shoulder arthroplasty; and (2) identify any associations between these variables and outcome measures. METHODS: A retrospective analysis was undertaken of 62 patients with a mean age of 67 years (range, 34-90 years) who underwent shoulder arthroplasty. CT scans were conducted preoperatively and at 12 months postoperatively. Outcome variables included the degree of supraspinatus and infraspinatus fatty infiltration (percent fatty infiltration and Goutallier grade), muscle area (percent muscle area and Warner atrophy grade), shoulder strength, and the Western Ontario Osteoarthritis Score (WOOS), American Shoulder and Elbow Surgeons score, and Constant outcome score. RESULTS: Preoperatively, the mean percent fatty infiltration (FI) within the supraspinatus and infraspinatus was identical at 14%. One year after shoulder arthroplasty, both muscles had less fatty infiltration (6% and 7%, respectively; p<0.001). Similarly, the Goutallier grade significantly improved postoperatively for the supraspinatus (p=0.0037) and infraspinatus (p=0.0007). Conversely, measures of muscle atrophy remained unchanged postoperatively (p>0.251). Preoperatively, greater supraspinatus percent FI was negatively associated with preoperative shoulder strength (r=0.37, p=0.001) and Constant score (r=0.38, p=0.001). Postoperative infraspinatus percent FI was negatively associated with postoperative strength (r=0.3, p=0.021) and Constant score (r=0.3, p=0.04). Multivariable regression analysis of possible predictive factors demonstrated that preoperative supraspinatus percent muscle area (p=0.016) and the diagnosis of osteoarthritis (p=0.017) were associated with better followup WOOS scores, and preoperative supraspinatus strength was associated with postoperative strength (p=0.0024). Higher degrees of preoperative percent FI were not associated with worse patient-reported outcomes postoperatively. CONCLUSIONS: Supraspinatus and infraspinatus fatty infiltration improves after shoulder arthroplasty, whereas muscle area remains unchanged. Although further study of these variables is required, the negative associations identified between preoperative supraspinatus atrophy and the diagnosis of rheumatoid arthritis and postoperative quality-of-life outcome scores may aid the clinician in selecting the best treatment option for glenohumeral arthrosis and in the management of patient expectations. LEVEL OF EVIDENCE: Level III, prognostic study.
24812290 Lower etanercept levels are associated with high disease activity in ankylosing spondyliti 2015 Oct BACKGROUND: Previous data have shown that etanercept levels are associated with clinical response in rheumatoid arthritis. However, for ankylosing spondylitis (AS), data regarding this topic are inconclusive. OBJECTIVES: To investigate the relationship between etanercept levels and clinical response in patients with AS. METHODS: Observational prospective cohort study of 162 patients with AS =treated with etanercept, monitored during 24 weeks of treatment. Etanercept trough levels were determined, retrospectively, using an ELISA. Disease activity was measured using AS Disease Activity Score (ASDAS), including C-reactive protein (CRP) and Bath AS Disease Activity index (BASDAI). Active disease was defined as ASDAS≥2.1. Since etanercept is a drug administered at home there might have been some variation in trough level sampling. RESULTS: At 24 weeks etanercept levels were significantly higher in patients with ASDAS<2.1, (3.8 mg/L; IQR 2.5-5.2) compared with patients with ASDAS≥2.1 (2.3 mg/L; IQR 1.2-3.4; p≤0.001). Generalised estimating equation analysis demonstrated a statistically significant association between etanercept levels and ASDAS, BASDAI, CRP and erythrocyte sedimentation rate (all p<0.001). When patients were categorised into quartiles according to etanercept levels, the lowest quartile (etanercept<1.80 mg/L) comprised 35% of all patients with ASDAS≥2.1 while the highest quartile comprised only 14%. CONCLUSIONS: Disease activity and inflammation are associated with etanercept levels in patients with AS at 24 weeks of treatment. Measuring etanercept levels might help in identifying overtreatment and undertreatment and optimise etanercept therapy in AS.
27426420 The Unique Coexistence of Anti-SS-A/Ro Antibodies in a Neonate with Symptomatic Ischemic S 2016 Sep BACKGROUND: Neonatal cerebral infarction is a relatively common cause of neonatal seizures, with an incidence of at least 1:4000 live births and is associated with a high incidence of neurological sequelae. However, the pathophysiological mechanisms and predisposing factors responsible for neonatal infarction are not fully established. PATIENT DESCRIPTION: A full-term baby boy was transferred at two days of age for the treatment of a cluster of seizures. Cranial magnetic resonance imaging revealed multiple lesions compatible with acute cerebral infarction. The results of the blood tests performed to screen for thrombophilic diseases were normal for his age, and his perinatal history was unremarkable. A diagnosis of idiopathic cerebral infarction was made. Additional examination for autoimmune diseases showed that both the mother and the patient had the anti-SS-A/Ro antibody. The patient was treated with phenobarbital and has no neurological sequelae. CONCLUSIONS: This is the first report demonstrating the coexistence of neonatal cerebral infarction and neonatal lupus syndrome. Thus neonatal lupus syndrome may be an additional risk factor for neonatal stroke.
26268740 Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue of the Salivary Gla 2015 Oct BACKGROUND: The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). A large series of patients with long-term follow-up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. METHODS: Patients with biopsy-confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long-term outcomes were evaluated. RESULTS: A total of 247 patients were evaluated; 76% presented with limited-stage disease. There was a history of autoimmune disorder in 41%, with Sjögren disease being the most common (83%). Fifty-seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression-free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first-line management. On multivariate analysis, age <60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjögren disease was associated with improved OS. CONCLUSION: Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjögren disease have improved survival. Risks for long-term complications must be weighed when determining initial therapy.
27890169 Hepatitis C Virus Infection and Rheumatic Diseases: The Impact of Direct-Acting Antiviral 2017 Feb Chronic hepatitis C virus (HCV) infection is associated with liver and extrahepatic complications, including B-cell lymphoma, cardiovascular and kidney diseases, glucose metabolism impairment and rheumatic conditions ie, arthralgia, myalgia, cryoglobulinemia vasculitis, sicca syndrome and the production of autoantibodies. The treatment has long been based on interferon alpha (IFN) that was found poorly effective, and contraindicated in many autoimmune/inflammatory disorders because of possible exacerbation of rheumatic disorders. The recent emergence of new oral IFN-free combinations offers an opportunity for HCV infected patients with autoimmune/inflammatory disorders to be cured with a short treatment duration and low risk of side effects.