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ID PMID Title PublicationDate abstract
30489710 2017 May Sarilumab (Kevzara) for subcutaneous (SC) injection is a fully human immunoglobulin G1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin-6 receptors inhibiting interleukin-6 mediated signalling. It is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more biologic or non-biologic disease-modifying antirheumatic drugs (DMARDs). Sarilumab is available in 150 mg and 200 mg single-use pre-filled syringes for SC injection. The recommended dose of sarilumab is 200 mg SC injection every two weeks, with a reduction to 150 mg every two weeks for management of neutropenia, thrombocytopenia, and elevated liver enzymes. Sarilumab should be given in combination with methotrexate or other conventional DMARD but may be used as monotherapy in cases of intolerance or contraindication to methotrexate or DMARDs. The manufacturer has submitted a price of $700 per pre-filled syringe (for both 150 mg and 200 mg doses) resulting in an annual cost of $18,200 per patient. [Table: see text]
29348754 The Impact of Different Classification Criteria Sets on the Estimated Prevalence and Assoc 2017 This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e', lateral and septal e'), and left atrial volume index in 176 RA patients. Relationships of traditional cardiovascular risk factors and RA characteristics with LV diastolic function and dysfunction according to previous and current criteria were determined in multivariate regression models. Waist-hip ratio was associated with E/A (standardised β (SE) = -0.28 ± 0.09, p = 0.0002) and lateral e' (standardised β (SE) = 0.26 ± 0.09, p = 0.01); low diastolic blood pressure was related to E/e' (standardised β (SE) = -0.16 ± 0.08, p = 0.04). Diastolic dysfunction prevalence differed upon applying previous (59%) compared to current (22%) criteria (p < 0.0001). One SD increase in waist-hip ratio was associated with diastolic dysfunction when applying current criteria (OR = 2.61 (95% CI = 1.51-4.52), p = 0.0006), whereas one SD increase in diastolic blood pressure was inversely related to diastolic dysfunction upon using previous criteria (OR = 0.57 (95% CI = 0.40-0.81), p = 0.002). In conclusion, application of current and previous diastolic dysfunction criteria markedly alters the prevalence and risk factors associated with diastolic dysfunction in RA.
28814890 Clinical and economic analysis of outcomes of dose tapering or withdrawal of tumor necrosi 2017 OBJECTIVE: To compare the real-world, 5-year clinical and cost impact of maintaining treatment with the tumor necrosis factor-α inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab vs dose tapering or withdrawal in rheumatoid arthritis (RA) patients who have achieved remission (defined as a 28-joint count Disease Activity Score [DAS28] < 2.6) or low disease activity (LDA; DAS28 < 3.2). METHODS: Using a 5-year Markov model with 1-month cycle length, we examined the clinical and cost impact of three treatment strategies: withdrawal, tapering, or maintenance of anti-TNFs among RA patients in remission or who have achieved LDA. This model assessed the time to loss of disease control, time to regaining control after treatment reinitiation, and associated medical and anti-TNF costs. To determine the risk of losing disease control, 14 studies (2309 patients) were meta-analyzed, adjusted for treatment strategy, anti-TNF, RA patient type (early or established RA), and model entry criterion (remission or LDA). RESULTS: Anti-TNF withdrawal and tapering incurred comparable 5-year total costs (€37,900-€59,700 vs €47,500-€59,200), which were lower than those incurred by anti-TNF maintenance (€67,100-€72,100). Established RA patients had higher total costs than early RA patients (€45,900-€72,100 vs €37,900-€71,700). Maintenance was associated with the longest time to loss of disease control (range, 27.3-47.1 months), while withdrawal had the shortest (range, 6.9-30.5 months). CONCLUSION: Dose tapering or withdrawal of anti-TNFs results in similar reduction of health care costs but less time in sustained disease control compared to maintaining therapy. Future research is needed to understand the long-term clinical consequences of these strategies and patient preferences for treatment withdrawal.
28810523 Reactive oxygen species mediated NF-κB/p38 feedback loop implicated in proliferation inhi 2017 Oct 1,7-Dihydroxy-3,4-dimethoxyxanthone (XAN) is a bioactive compound isolated from Securidaca inappendiculata Hassk. and exerts the inhibitory effects on fibroblast-like synoviocytes by targeting NF-κB and p38. This study was designed to elucidate mechanisms underlying the divergent regulation on the two pathways in HFLS-RA cells by XAN. Expressions of hallmark proteins and transcription of GADD45α mRNA were determined by Western-blot and RT-qPCR methods, respectively. Fluorescence staining was employed to evaluate intracellular oxidative stress. Effects of XAN and N-acetyl-l-cysteine (NAC) on the proliferation of cells were investigated by MTT assay, and pro-apoptotic effects of XAN were assessed by Annexin V-FITC/PI method. It was found XAN blocked NF-κB signaling in HFLS-RA cells shortly after treatment. Moreover, it up-regulated both transcription and expression of GADD45α, and subsequently activated p38 pathway. As time went on, XAN significantly promoted the generation of reactive oxygen species (ROS), which accompanied with sustained up-regulation of p-p38 and increased apoptosis. 48H later, dual-effects of XAN on NF-κB and p38 were reversed. As activation of p38 and increased apoptosis induced by XAN were antagonized by NAC, they were deemed as ROS mediated effects. Furthermore, the accumulated ROS should also account for the activation of NF-κB in the late stage of treatments via interfering in p38/MSK1/NF-κB feedback. Altogether, these findings suggested XAN-induced ROS contributed great importance to the proliferation inhibition of HFLS-RA cells by mediating NF-κB/p38 feedback loop and apoptosis, which provided us a panoramic view of potential target in the therapy of RA by XAN.
28719897 Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without 2017 INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. OBJECTIVE AND METHODS: To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. RESULTS: A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). CONCLUSION: We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome.
28108251 Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives 2017 Feb 15 As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model.
28752263 Photobiomodulation therapy by NIR laser in persistent pain: an analytical study in the rat 2017 Nov Over the past three decades, physicians have used laser sources for the management of different pain conditions obtaining controversial results that call for further investigations. In order to evaluate the pain relieving possibilities of photobiomodulation therapy (PBMT), we tested two near infrared (NIR) laser systems, with different power, against various kinds of persistent hyperalgesia animal models. In rats, articular pain was reproduced by the intra-articular injection of sodium monoiodoacetate (MIA) and complete Freund's adjuvant (CFA), while compressive neuropathy was modelled by the chronic constriction injury of the sciatic nerve (CCI). In MIA and CFA models, (NIR) laser (MLS-Mphi, ASA S.r.l., Vicenza, Italy) application was started 14 days after injury and was performed once a day for a total of 13 applications. In MIA-treated animals, the anti-hyperalgesic effect of laser began 5 min after treatment and vanished after 60 min. The subsequent applications evoked similar effects. In CFA-treated rats, laser efficacy started 5 min after treatment and disappeared after 180 min. In rats that underwent CCI, two treatment protocols with similar fluence but different power output were tested using a new experimental device called Multiwave Locked System laser (MLS-HPP). Treatments began 7 days after injury and were performed during 3 weeks for a total of 10 applications. Both protocols reduced mechanical hyperalgesia and hindlimb weight bearing alterations until 60 min after treatment with a higher efficacy recorded for the animals treated using the higher power output. In conclusion, this study supports laser therapy as a potential treatment for immediate relief of chronic articular or neuropathic pain.
27550296 Transforming growth factor β activated kinase 1: a potential therapeutic target for rheum 2017 Jul 1 Pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α are central regulators of autoinflammatory diseases. While targeting these cytokines has proven to be a successful clinical strategy, the long-term challenges such as drug resistance, lack of efficacy and poor clinical outcomes in some patients are some of the limitations faced by these therapies. This has ignited strategies to reduce inflammation by potentially targeting a variety of molecules, including cell surface receptors, signalling proteins and/or transcription factors to minimize cytokine-induced inflammation and tissue injury. In this regard, transforming growth factor β activated kinase 1 (TAK1) is activated in the inflammatory signal transduction pathways in response to IL-1β, TNF-α or toll-like receptor stimulation. Because of its ideal position upstream of mitogen-activated protein kinases and the IκB kinase complex in signalling cascades, targeting TAK1 may be an attractive strategy for treating diseases characterized by chronic inflammation. Here, we discuss the emerging role of TAK1 in mediating the IL-1β, TNF-α and toll-like receptor mediated inflammatory responses in diseases such as RA, OA, gout and SS. We also review evidence suggesting that TAK1 inhibition may have potential therapeutic value. Finally, we focus on the current status of the development of TAK1 inhibitors and suggest further opportunities for testing TAK1 inhibitors in rheumatic diseases.
30207563 Fibromyalgia Syndrome and Vitiligo: A Novel Association. 2018 Jun OBJECTIVES: This study aims to assess the relationship between fibromyalgia syndrome (FMS) and vitiligo in Iraqi patients and evaluate the predictors of this relationship, if present. PATIENTS AND METHODS: The case-control study included 100 Iraqi patients (46 males, 54 females; mean age 30.4±14 years; range 15 to 65 years) with vitiligo and 200 age- and sex-matched healthy controls (74 males, 126 females; mean age 30.3±9.4 years; range 15 to 62 years). Baseline characteristics of patients and controls were recorded. The 2012 Canadian Guidelines criteria were used for the diagnosis of FMS and applied to all patients and controls. RESULTS: Prevalence of FMS in vitiligo patients and controls was 12% and 7%, respectively (p=0.15, odds ratio=1.8, 95% confidence interval=0.8-4.08). FMS symptoms in vitiligo patients were fatigue (46%), diffuse body pain (34%), sleep disturbance (33%), cognitive dysfunction (30%), and mood disorders (23%), while visceral involvements were central nervous system (52%), skin (35%), gastrointestinal tract (32%), cardiovascular system- respiratory system (16%), genitourinary tract (8%), and ear nose throat (7%). Of vitiligo patients, FMS was significantly more common among females (22.2%) compared to none among males (0%) (p<0.05). Prevalence of FMS was restricted to female sex only and a significantly higher prevalence rate of FMS was found among female vitiligo patients (22.2%) compared to controls (9.5%). Receiving phototherapy significantly increased the risk of having FMS by 5 times compared to female patients not receiving phototherapy. Use of any steroid reduced the risk of having FMS by 2.5 times (inverse of odds ratio=0.4) among females patients (p>0/05). No significant association was found between FMS in vitiligo patients and age, disease duration, type of vitiligo, use of any immunosuppressant and body mass index (p>0.05). CONCLUSION: Fibromyalgia syndrome was more prevalent in vitiligo patients compared to controls, which was clinically important but statistically not significant. There was a significant association between FMS in vitiligo patients and female sex, severe form of vitiligo, and receiving phototherapy. This may suggest that early diagnosis of FMS in vitiligo patients may help in early treatment and subsequently improve patients' quality of life.
29085766 Exploration of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one derivatives as JAK 2017 This study focuses on understanding the structural features of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one (dpp) derivatives to computationally identify new JAK inhibiting compounds. For the purpose, a novel virtual screening strategy, with 2D and 3D-QSAR (CoMFA and CoMSIA), data mining, pharmacophore modeling, ADMET prediction, multi-targeted protein-based docking and inverse QSAR, was employed. The 2D-QSAR equations developed for the JAK3, JAK2 and JAK1 involved five physicochemical descriptors. These descriptors correlate with the anti-RA activity with R(2) values for JAK3, JAK2 and JAK1 are 0.9811, 0.8620 and 0.9740, respectively. The 3D-QSAR studies such as CoMFA and CoMSIA carried out through PLS analysis of the training set of JAK3, JAK2 and JAK1, gave Q(2) values as 0.369, 0.476 and 0.490; [Formula: see text] values as 0.863, 0.684 and 0.724 and, F values as 23.098, 28.139 and 31.438, respectively. The contour maps produced by the CoMFA and CoMSIA models were used to understand the importance of hydrogen bond donor, acceptor, hydrophobic, steric and electrostatic interactions. The molecular docking studies of these selected compounds with various JAK proteins were carried out and the protein-ligand interactions were also studied. The study concluded that dpp15(s) is a highly potent JAK inhibitor with a very good predicted IC(50) value.
28967053 Multifaceted aseptic protocol decreases surgical site infections following hip arthroplast 2018 Mar INTRODUCTION: We investigate the effectiveness of a comprehensive aseptic protocol in reducing surgical site infection (SSI) after hip arthroplasty in a single medical centre with a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA). METHODS: A prospectively collected database of all patients undergoing hip arthroplasty in a single centre between 2005 and 2011 was reviewed for SSI using Centers for Disease Control (CDC) criteria and AAOS guidelines. All patients were administered an aseptic protocol consisting of: preoperative 2% mupirocin nasal ointment and 0.4% chlorhexidine surgical-site wipes; modified instrument care; perioperative prophylactic vancomycin and cefazolin; and surgical-site skin preparation with chlorhexidine, alcohol and iodophor. We compare our protocol hip arthroplasty SSI rate to our institutional historical control and to contemporary literature. RESULTS: Among 774 patients, 69% were ASA>2, 45% had BMI≥30 and 10.3% had rheumatoid arthritis. We found an overall 0.39% infection rate; significantly lower than our institutional historical control (0.39% vs. 2.60%, p<0.001, OR 0.15, NNT 200) and significantly lower than 6 published reports (p<0.001-0.022, OR 0.16-0.22). Compared to these cohorts, significantly more of our patients were ASA>2, had BMI≥30 or had rheumatoid arthritis. Patients with 3 or more identifiable risk factors were at an increased risk of SSI compared to those with 2 or fewer risk factors. CONCLUSIONS: Our aseptic protocol decreases SSI in a high-risk population undergoing hip arthroplasty in a medical centre and community with a high prevalence of MRSA.
28400234 Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prost 2017 Jun 1 A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE(2) release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F=33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.
29175662 Comorbidities in relation to fatality of first myocardial infarction. 2018 Jan INTRODUCTION: Present knowledge concerning potential associations between comorbidities and the fatality of a first myocardial infarction (MI) is limited. AIM: To identify comorbidities in 45-70-year-old individuals who suffered a first MI and died within 7 days in Stockholm County from 1992-1994. In addition, to assess how each of the comorbidities identified, as well as the number of hospitalizations during the 10-year period prior to the MI, was associated with MI fatality. METHODS: The data collected on our inception cohort of 1984 first MI, of which 524 were fatal within 7 days, were primarily self-reported, proxy-reported by questionnaire and/or extracted from comprehensive national registers. Comorbidities among fatal cases with a prevalence >2% were identified. Risk ratios (with 95% confidence intervals) for the association of MI fatality with number of prior hospitalizations and specific comorbidities were calculated using binomial regression with log link. A structured review of autopsy reports on fatal cases was performed in order to identify additional indicators of comorbidities. RESULTS: After adjusting for sex, age and disposable income, the number of previous hospitalizations was associated with 7-day MI fatality. Of the comorbidities identified as prevalent in fatal cases, the following were associated with 7-day fatality in crude analysis: epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes, and rheumatoid arthritis. Indicators of comorbidities identified from autopsy data included a silent MI, severe atherosclerosis of the abdominal aorta, and hepatic steatosis. Adjustments for sex and age (although not possible for epilepsy and alcoholism), did not substantially alter results. CONCLUSIONS: Our current findings indicate that in connection with a first MI, particular attention should be paid to those with repeated prior hospitalizations and/or epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes and rheumatoid arthritis.
28440350 High frequency ultrasonography of the hand versus anti-RA33 evaluation in early rheumatoid 2017 Apr 22 AIM: Accurate diagnosis and early treatment in rheumatoid arthritis (RA) can lead to a good outcome and a correct management of the disease. We aimed toinvestigate the prognostic value of anti-RA33 antibodies, by evaluating the relationship with ultrasonographic (US) findings in patients with early RA. MATERIAL AND METHODS: We performed a prospective study which included 29 patients, diagnosed with early RA according to the ACR/EULAR 2010 criteria and 21 sex and age-matched control subjects. All patients underwent clinical and biological assessment, followed by US examination in grayscale (GS) and power Doppler (PD) at baseline and after 12 months [from the second to the fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and wrists (RCC), in dorsal aspect]. The second and fifth MCP joints were scanned also in lateral aspects. RESULTS: The initial GS evaluation revealed the presence of synovitis in all 29 patients; PD found at least one joint with a PD grade higher than 1 in 23 patients, higher than 2 in 20 patients, and grade 3 in 6 patients; at 12 months, we revealed the presence of GSUS synovitis in 25 patients and PDUS examination found active synovitis in 12 subjects. In those patients, the anti-RA33 titre was significantly lower compared to those without PDUS active synovitis (p=0.031), with a moderately negative correlation (r=-0.519, p=0.0039). CONCLUSIONS: The current study shows that anti-RA33 antibodies might constitute an additional tool for diagnosing early RA patients and can help identify patients with mild disease and a low level of activesynovitis.
28872085 [Manifestations of the connective tissue associated interstitial lung disease under high r 2017 Aug 28 To analyze the features of the connective tissue associated interstitial lung disease (CTD-ILD) by high resolution computed tomography (HRCT).
 Methods: A total of 127 patients with CTD-ILD, who were diagnosed by clinic laboratory examination and pathology in Xiangya Hospital of Central South University form September 2013 to September 2015, were enrolled for this study. Their lung features of HRCT imaging were retrospectively analyzed.
 Results: The classifications for 127 patients were as follows: 36 cases of rheumatoid arthritis (28.3%), 34 cases of dermatomyositis and polymyositis (26.8%), 31 cases of systemic sclerosis (24.4%), 18 cases of Sjögren syndrome (14.2%), 7 cases of mixed connective tissue disease (5.5%), and 1 cases of systemic lupus erythematosus (0.8%). According to the features of HRCT imaging, the patients were divided as follows: 77 cases (60.6%) of nonspecific interstitial pneumonia (NSIP), 46 cases (36.2%) of usual interstitial pneumonia (UIP), 2 cases (1.6%) of lymphocytic interstitial pneumonia (LIP), 1 case (0.8%) of cryptogenic interstitial pneumonia (COP), and 1 case (0.8%) of acute interstitial pneumonia (AIP). The HRCT findings for 36 cases of rheumatoid arthritis associated interstitial lung disease were UIP (24 cases, 66.7%) and NSIP (12 cases, 33.3%); the HRCT findings for 34 cases of dermatomyositis and polymyositis associated interstitial lung disease were NSIP (32 cases, 94.1%), UIP (1 case, 2.9%) and COP (1 case, 2.9%); the HRCT findings for 31 cases of systemic sclerosis associated interstitial lung disease were NSIP (21 cases, 67.8%), UIP (9 cases, 29%), LIP(1 case, 3.2%); the HRCT findings for 18 cases of Sjögren syndrome associated interstitial lung disease were NSIP (9 cases, 50.0%), UIP (8 cases, 44.4%), LIP (1 case, 5.6%); the HRCT findings for 7 cases of mixed connective tissue disease associated interstitial lung disease were UIP (4 cases, 57.1%), NSIP (3 cases, 42.9%). SLE-ILD was rare, with only 1 case of AIP.
 Conclusion: Different types of CTD-ILD patients display relatively unique manifestation of HRCT.
28941123 Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-prov 2018 Jan AIM: To retrospectively investigate the features of renal involvements in patients with primary Sjögren's syndrome (pSS) with biopsy results. METHODS: A total of 2096 pSS inpatients at Peking Union Medical College Hospital in China from 2005 to 2015 were identified. Patients with biopsy-proven renal involvement (SS-renal) and matched controls (SS-only) were recruited. The clinical and pathologic features as well as treatments and outcomes were systematically analyzed. RESULTS: One hundred and three pSS nephritis (inpatients had biopsy-proven renal involvement. Tubulointerstitial 53, 51.5%) was the prominent pathologic pattern with glomerulonephritis (GN) present in 50 (48.5%) of the renal lesions. The patterns of GN lesions included membranous nephropathy (37, 35.9%), mesangial proliferative glomerulonephritis (six, 5.8%) or immunoglobulin A nephropathy (three, 2.9%), minimal change disease (four, 3.9%) and focal segmental glomerulosclerosis (three, 2.9%). Compared to SS-only patients, SS-renal patients had fewer dry eyes and positive objective xerostomia (P < 0.05). They presented with a significantly lower incidence of interstitial lung disease (ILD), leukocytopenia and elevated immunoglobulin G levels (P < 0.05). They received a larger initial dosage of corticosteroid and had a higher mortality rate (P < 0.05). CONCLUSION: This Chinese SS-renal population with biopsy results has diverse pathologic patterns and distinct clinical features. They are characterized with prominent renal-associated and mild SS-associated features. They received more vigorous treatment but had poorer prognosis.
28951424 Myd88 is required for disease development in a primary Sjögren's syndrome mouse model. 2017 Dec Sjögren's syndrome (SS) is an autoimmune disease that often results in diminished exocrine gland function. SS patients also experience systemic disease manifestations, including hypergammaglobulinemia and pulmonary and renal pathoses. MyD88 is a ubiquitously expressed adaptor molecule used by all immune cells that is required for IL-1 receptor (IL-1R), IL-18R, and most TLR signaling. The precise role of MyD88 in SS has not been evaluated, although this adaptor is critical for development of lupus, a related autoimmune disease. This study tested the hypothesis that Myd88-mediated signaling is required for local and systemic SS manifestations. To this end, we generated NOD.B10Sn-H2(b) /J (NOD.B10) mice that are deficient in Myd88 (NOD.B10 (Myd88-/-) ). We found that NOD.B10 animals that lack Myd88 show reduced exocrine and extraglandular inflammation. Moreover, these animals are protected from loss of salivary flow. Splenocytes from NOD.B10 (Myd88-/-) mice did not up-regulate activation markers or secrete IL-6 in response to a Myd88-dependent agonist, although BCR signaling remained intact. Finally, IgM, IgG, and anti-nuclear autoantibodies were reduced in NOD.B10 (Myd88-/-) mice compared with the parental strain. These data demonstrate that Myd88 is a crucial mediator of local and systemic SS disease manifestations.
29237605 Association between rainfall and diagnoses of joint or back pain: retrospective claims ana 2017 Dec 13 OBJECTIVE: To study the relation between rainfall and outpatient visits for joint or back pain in a large patient population. DESIGN: Observational study. SETTING: US Medicare insurance claims data linked to rainfall data from US weather stations. PARTICIPANTS: 1 552 842 adults aged ≥65 years attending a total of 11 673 392 outpatient visits with a general internist during 2008-12. MAIN OUTCOME MEASURES: The proportion of outpatient visits for joint or back pain related conditions (rheumatoid arthritis, osteoarthritis, spondylosis, intervertebral disc disorders, and other non-traumatic joint disorders) was compared between rainy days and non-rainy days, adjusting for patient characteristics, chronic conditions, and geographic fixed effects (thereby comparing rates of joint or back pain related outpatient visits on rainy days versus non-rainy days within the same area). RESULTS: Of the 11 673 392 outpatient visits by Medicare beneficiaries, 2 095 761 (18.0%) occurred on rainy days. In unadjusted and adjusted analyses, the difference in the proportion of patients with joint or back pain between rainy days and non-rainy days was significant (unadjusted, 6.23% v 6.42% of visits, P<0.001; adjusted, 6.35% v 6.39%, P=0.05), but the difference was in the opposite anticipated direction and was so small that it is unlikely to be clinically meaningful. No statistically significant relation was found between the proportion of claims for joint or back pain and the number of rainy days in the week of the outpatient visit. No relation was found among a subgroup of patients with rheumatoid arthritis. CONCLUSION: In a large analysis of older Americans insured by Medicare, no relation was found between rainfall and outpatient visits for joint or back pain. A relation may still exist, and therefore larger, more detailed data on disease severity and pain would be useful to support the validity of this commonly held belief.
28371797 Real-life effectiveness of Golimumab in biologic-naïve patients with rheumatoid arthritis 2017 Jun OBJECTIVES: To assess the effectiveness of subcutaneous Golimumab 50 mg/monthly combined with methotrexate (SC GLM + MTX) over 52 weeks of treatment, in biologic-naïve RA patients, in a multicentre nationwide cohort from the Rheumatic Diseases Portuguese Register (Reuma.pt). METHODS: Data for this observational study was collected from March 2011 to August 2015. Disease activity (DAS28), functional capacity (HAQ) and Patient Global Disease Assessment (PGDA) were measured at baseline and weeks 12, 24 and 52 of treatment. The primary objective was clinical remission over 52 weeks (1 year) and secondary objectives were: functional response and functional remission over 52 weeks, variation of individual components of DAS over time and treatment persistence at week 52. Comparison between baseline variables of subjects with and without clinical remission was performed. The SC GLM + MTX persistence rate was estimated by the Kaplan-Meier analysis. Cox proportional hazard model approach was used to evaluate predictive factors of persistence, response and remission. RESULTS: A total of 109 patients were enrolled in the study: 94 (86.2%) female, mean age 55.5±13.2 years, mean age at diagnosis 45.5±13.5 years, mean age at beginning of treatment with biologic agents 53.1±13.1 years; 78.1% positive for serum rheumatoid factor. All patients were biologic-naïve and had active disease, despite previous treatment with conventional DMARDs. At the time of this analysis, 93 patients had a follow-up time of at least 52 weeks (i.e. started treatment before August 2014). Of this group, 38.3% achieved clinical remission, 91.9% functional response and 35.2% functional remission, over 52 weeks. Treatment persistence was 75.3% at 1 year. Disease activity indices were all statistically significantly lower at 12, 24 and 52 weeks when compared to baseline. Older age at diagnosis was associated to a lower probability of clinical remission (HR= 0.96, p= 0.031) whereas higher C-reactive protein baseline levels were associated with a lower probability of functional response (HR= 0.54; p= 0.026). CONCLUSIONS: Golimumab 50 mg + MTX showed effectiveness in the treatment of patients with active RA, in accordance to what previously observed in clinical trials. A consistent and significant decrease in RA disease activity through 52 weeks of treatment and a significant functional improvement were observed, as well as a high persistence on treatment.
27937009 The anti-arthritic activity of total glycosides from Pterocephalus hookeri, a traditional 2017 Dec CONTEXT: Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis. OBJECTIVE: To evaluate the anti-arthritic activity of total glycosides from P. hookeri, and its possible mechanisms of action. MATERIALS AND METHODS: Anti-arthritic activity of total glycosides from P. hookeri (oral administration for 30 days at 14-56 mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively. RESULTS: Total glycosides (56 mg/kg) decreased the paw swelling (38.0%, p < 0.01), arthritis scores (25.3%, p < 0.01) and synovial inflammation in AA rats. The glycosides significantly (p < 0.05-0.01) attenuated the inflammation induced by xylene, carrageenan, acetic acid and agar, increased the pain threshold in acetic acid-induced writhing in mice and mechanical stimuli-induced hyperalgia in AA rats. The glycosides (14, 28, 56 mg/kg) also suppressed the NF-κB p65 expression (33.1-78.2%, p < 0.05-0.01), reduced MDA (21.3-35.9%, p < 0.01) and NO (20.3-32.4%, p < 0.05-0.01) levels, respectively, enhanced the SOD activity (7.8%, p < 0.05) at 56 mg/kg in AA rats. DISCUSSION AND CONCLUSION: Our findings confirmed the anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress.