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ID PMID Title PublicationDate abstract
29624512 Gastrointestinal Tract Vasculopathy: Clinicopathology and Description of a Possible "New E 2018 Jul Noninfectious gastrointestinal (GI) vasculopathic disorders are rare and are often overlooked in histopathologic examination or when forming differential diagnoses due to their rarity. However, involvement of the GI tract may lead to serious complications, including ischemia and perforation. Since awareness of the types of vasculopathy that may involve the GI tract is central to arriving at a correct diagnosis, we reviewed our institutional experience with GI tract vasculopathy in order to enhance diagnostic accuracy of these rare lesions. We report the clinical and histologic features of 16 cases (excluding 16 cases of immunoglobulin A vasculitis) diagnosed over a 20-year period. Of the 16 patients, 14 presented with symptoms related to the GI vasculopathy (including 2 presenting with a mass on endoscopic examination). The remaining 2 patients presented with incarcerated hernia and invasive adenocarcinoma. The vasculopathy was not associated with systemic disease and appeared limited to the GI tract in 8 patients. Eight had associated systemic disease, but only 6 had a prior diagnosis. The underlying diagnoses in these 6 patients included systemic lupus erythematosus (1), dermatomyositis (2), rheumatoid arthritis (1), eosinophilic granulomatosis with polyangiitis (1), and Crohn disease (1). One patient with granulomatous polyangiitis and 1 patient with systemic lupus erythematosus initially presented with GI symptoms. The 8 cases of isolated GI tract vasculopathy consisted of enterocolic lymphocytic phlebitis (4), idiopathic myointimal hyperplasia of the sigmoid colon (1), idiopathic myointimal hyperplasia of the ileum (1), granulomatous vasculitis (1), and polyarteritis nodosa-like arteritis (1). Isolated GI tract vasculopathy is rare, but appears to be almost as common as that associated with systemic disease. The chief primary vasculopathies are enterocolic lymphocytic colitis and idiopathic myointimal hyperplasia. Although the latter occurs predominantly in the left colon, rare examples occur in the small bowel and likely represent a complex, more protean disorder.
29621153 Linkage of Infection to Adverse Systemic Complications: Periodontal Disease, Toll-Like Rec 2018 Apr 5 Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others. The overlapping participation of TLRs in the control of infection, and pathogenesis of systemic diseases, has served as a starting point for research delving into the poorly defined area of infection leading to increased risk of various systemic diseases. Although conflicting studies exist, cardiovascular disease, diabetes, cancer, rheumatoid arthritis, and obesity/metabolic dysfunction have been associated with differing degrees of strength to infectious diseases. Here we will discuss elements of these connections focusing on the contributions of TLR signaling as a consequence of bacterial exposure in the context of the oral infections leading to periodontal disease, and associations with metabolic diseases including atherosclerosis and type 2 diabetes.
29455258 Effects of capsaicin on ovarian granulosa cell proliferation and apoptosis. 2018 Jun Capsaicin is the pungent ingredient in red peppers. Due to the effects on the sensory nerve fibers, capsaicin has been used to treat pain and inflammation associated with a variety of diseases including rheumatoid arthritis and diabetic neuropathy, obesity, and cardiovascular and gastrointestinal conditions. Despite the extensive publications on different systems, the studies of the effects on the ovary are very limited. The present study was conducted to examine the possible proliferative and/or apoptotic effects of various doses of capsaicin on primarily derived granulosa cells. In accordance with this purpose, ovarian granulosa cells were exposed to different doses of capsaicin for 24 and 48 h. The proliferative effects of capsaicin were examined by immunocytochemistry, immunofluorescence, and western blot using an antibody against proliferating cell nuclear antigen (PCNA) and cell viability assay (MTT). The effects on apoptosis were determined by immunocytochemistry and immunofluorescence using antibodies against cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). We showed that the number of apoptotic cells increased in a capsaicin dose and time-dependent manners. We found that a low dose of CAP in 24 h administration was more effective on granulosa cell proliferation. Our results suggest that low-dose and short-term administration of CAP may have a positive effect on ovarian folliculogenesis.
29323344 Updating osteoimmunology: regulation of bone cells by innate and adaptive immunity. 2018 Mar Osteoimmunology encompasses all aspects of the cross-regulation of bone and the immune system, including various cell types, signalling pathways, cytokines and chemokines, under both homeostatic and pathogenic conditions. A number of key areas are of increasing interest and relevance to osteoimmunology researchers. Although rheumatoid arthritis has long been recognized as one of the most common autoimmune diseases to affect bone integrity, researchers have focused increased attention on understanding how molecular triggers and innate signalling pathways (such as Toll-like receptors and purinergic signalling pathways) related to pathogenic and/or commensal microbiota are relevant to bone biology and rheumatic diseases. Additionally, although most discussions relating to osteoimmune regulation of homeostasis and disease have focused on the effects of adaptive immune responses on bone, evidence exists of the regulation of immune cells by bone cells, a concept that is consistent with the established role of the bone marrow in the development and homeostasis of the immune system. The active regulation of immune cells by bone cells is an interesting emerging component of investigations that seek to understand how to control immune-associated diseases of the bone and joints.
29243407 Rheumatic diseases are associated with a higher risk of dementia: A nation-wide, populatio 2018 Feb AIM: Previous research demonstrated the possible relevance of dementia and rheumatic diseases. This population-based study aims to investigate the association of rheumatic diseases and dementia. METHODS: The data of this case-control study was extracted from the Taiwan National Health Insurance Research Database. Diagnosis of dementia and rheumatic diseases mentioned in this study were retrieved by the International Classification of Diseases-9 code. We recruited cases (n = 10 180) with dementia and controls (n = 61 080) during 2000-2010, by matching on age, gender and index date with a match ratio 1 : 6. The Chi-square test was used to calculate the baseline characteristics of the cases and controls for categorical variables such as age and gender. Simple conditional and multivariable conditional logistic regression models were used to estimate crude and adjusted odds ratios. RESULTS: Statistical significance was observed in Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and osteoarthritis (OA) among females (P < 0.05 for SS and SLE; P < 0.01 for OA), and in SS, psoriatic arthritis (PsA) and OA among males (P < 0.01 for SS; P < 0.05 for PsA and OA). Further, we also demonstrated a significant difference in SLE and OA among the younger group (age = 40-64) (P < 0.01 for SLE and OA), and in SS and OA among the older group (age ≧ 65) (P < 0.01 for SS and OA). CONCLUSION: In this population-based case-control study, we found that patients with rheumatoid arthritis, SS, SLE, PsA and OA are significantly associated with a higher risk of dementia than those without rheumatic diseases. We hypothesized that inflammation and medications are two possible mechanisms.
30398010 Musculoskeletal symptoms and disorders among 350 garment workers in Bangladesh: A cross-se 2018 Dec OBJECTIVE: To study the prevalence of musculoskeletal (MSK) symptoms and disorders among garment workers in Bangladesh, to look for possible relationships between pain location and type of work performed and to estimate the prevalence of rheumatological diagnoses. METHODS: A cross-sectional pilot study among 350 garment workers using the COPCORD (Community Oriented Program for Control of Rheumatic Disorders) methodology. Subjects with musculoskeletal pain were examined by rheumatologists for rheumatological diagnosis. The workers were classified into cutting, sewing, finishing and quality control operators. RESULTS: Most of the workers were aged below 35 years (88%) and females (82.9%) and the majority had only primary education (74.6%). The prevalence of MSK pain within 7 days of the interview was 77.1%, a much higher figure than in the general population. The most affected sites were: shoulder (17.9%), lower back (15.2%), neck (13.8%) and knee (10.8%). Multiple regional pain was the commonest finding in 173 of 350 workers. In this pilot study rheumatoid arthritis was diagnosed in 0.9%, undifferentiated arthritis in 1.1%, nonspecific low back pain in 4.6%, soft tissue rheumatism in 3.7%, osteoarthritis in 0.9% and lumbar spondylosis in 1.1%, figures comparable with those observed in the general population; spondyloarthropathy was seen more often, in 1.42%, possibly explained by the small numbers. CONCLUSIONS: Musculoskeletal pains are common among garment workers of Bangladesh and may cause morbidity, disability, and work loss. Our findings may be important to plan ergonomic measures preventing complaints and may be of interest for international companies ordering garments in Bangladesh.
29621248 Adherence to rivaroxaban versus apixaban among patients with non-valvular atrial fibrillat 2018 BACKGROUND: Medication non-adherence can result in poor health outcomes. Understanding differences in adherence rates to non-vitamin K oral anticoagulants (NOACs) could guide treatment decisions and improve clinical outcomes among patients with non-valvular atrial fibrillation (NVAF). OBJECTIVE: To compare adherence to rivaroxaban and apixaban among the overall NVAF population and subgroups of prior oral anticoagulant (OAC) users (e.g., multiple comorbidities, non-adherence risk factors). METHODS: Using healthcare claims from the Truven Health Analytics MarketScan (7/2012-7/2015), adult patients with ≥2 dispensings of rivaroxaban or apixaban ≥ 180 days apart with > 60 days of supply, ≥ 6 months of pre- and post-index eligibility, ≥ 1 atrial fibrillation diagnosis pre- or on the index date, and without valvular involvement were identified. Propensity-score methods adjusting for potential baseline confounders were used to create matched cohorts of rivaroxaban and apixaban patients. Adherence was assessed during the implementation phase using the percentage of patients with proportion of days covered (PDC) ≥0.8 at 6 months. Subgroups of patients with prior OAC use were evaluated; additional subgroups were identified and evaluated by Quan-Charlson Comorbidity index ≥2 and presence of non-adherence risk factors (i.e., mental disorders, stress, isolation, and rheumatoid arthritis). RESULTS: A total of 13,890 NVAF subjects were included in each of the 2 matched cohorts. All baseline characteristics were balanced between cohorts. At 6 months, significantly more rivaroxaban users were adherent to treatment compared to apixaban users (81.8% vs. 78.0%; absolute difference of 3.8%; p<.001). Rivaroxaban users had significantly higher adherence rates in all subgroups examined. CONCLUSION: Rivaroxaban users had consistently higher adherence rates than apixaban users overall and among all NVAF subgroups examined.
29037536 Open reduction and internal fixation for nonunion of extra-articular distal humeral fractu 2018 Jan HYPOTHESIS: The study purpose was to report the clinical and radiologic outcomes of osteosynthesis by open reduction and internal fixation for nonunion of extra-articular distal humeral fractures in patients aged 70 years or older. MATERIALS AND METHODS: This retrospective study included 28 patients who received osteosynthesis treatment between March 2010 and December 2015. Primary conservative treatment had failed in all patients. All surgical procedures were performed via the posterior approach without olecranon osteotomy and with the use of double-locking plates for each column. RESULTS: The mean patient age was 72 years, and surgical procedures were performed a mean of 7.6 months after injury. Preoperatively, extension-flexion was 32° to 101° and forearm pronation-supination was 74° to 47°. The mean visual analog scale score was 4; the mean Mayo Elbow Performance Score was 50; and the mean Disabilities of the Arm, Shoulder and Hand score was 58. All cases showed proper union after a mean of 5.2 months. At the final follow-up examination, the extension-flexion and rotation arcs had improved significantly (to 20° to 124° and to 80° to 66°, respectively; both P < .001), and all clinical scores were satisfactory (visual analog scale score, 1; Mayo Elbow Performance Score, 65; and Disabilities of the Arm, Shoulder and Hand score, 24; all P < .001). Ulnar nerve transposition was performed in 7 patients, and no distinct ulnar nerve symptom was observed in any patient at the final follow-up examination. CONCLUSIONS: We consider osteosynthesis by open reduction and internal fixation as a recommended option for extra-articular distal humeral fractures in elderly patients aged 70 years or older in whom conservative treatment has failed.
29998369 Decreased serum thrombospondin-1 and elevation of its autoantibody are associated with mul 2018 Oct The pathological effects of thrombospondin-1 (TSP-1) have been studied in many preclinical tumor models and rheumatoid arthritis. However, the role of TSP-1 and anti-thrombospondin-1 autoantibodies (ATSA) in systemic lupus erythematosus (SLE) has not been specifically defined. In this study, we investigated the clinical relevance and functional significance of TSP-1 and ATSA in SLE patients. Serum levels of TSP-1 and ATSA were measured by ELISA in 138 adult SLE patients and 60 healthy controls. Blood cell counts, rheumatoid factor (RF), immunoglobulins, erythrocyte sedimentation rate (ESR), complements, and SLE-related autoantibodies were measured by standard laboratory techniques. Disease activity was assessed by systemic lupus erythematosus disease activity index (SLEDAI). TSP-1 concentrations were significantly lower in SLE patients compared with those in healthy controls. A significant difference of TSP-1 was observed in the patients with serositis, C3 decrease, RF positive, leukocytopenia, and thrombocytopenia. The levels of TSP-1 showed a positive correlation with the number of leukocyte and thrombocyte, while a negative correlation with anti-dsDNA antibody, IgG, ESR, and SLEDAI. ATSA was observed in 58.7% (81/138) of SLE patients, which was significantly higher than that in healthy controls (7/60, p < 0.05). Patients with active SLE showed higher ATSA positivity (67.1%) than those with inactive disease (47.1%, p < 0.05). ATSA was positively correlated with anti-rRNP antibody, IgG, total protein, and C4. This study revealed the opposite clinical relevance of TSP-1 and its autoantibody in SLE for the first time. TSP-1 may play an anti-inflammatory and immunoregulatory role in SLE autoimmunity. ATSA increased more frequently in disease-active patients and was associated with more severe clinical manifestations, which implicated its antagonistic role on TSP-1 and its involvement in the pathogenesis of SLE.
30154020 "Island-shape" Fractures of Lister's tubercle have an increased risk of delayed extensor p 2018 Oct PURPOSE: Weperformed a retrospective case-control study to explore the hypothesis that conditions adjacent to Lister's tubercle (LT) in patients with distal radial fractures (DRFs) exhibiting dorsal comminution would influence the extent of the delayed extensor pollicis longus (EPL) rupture. METHODS: Among patients treated by volar locking plates (VLPs) were placed between March 2011 and December 2015, 314 met inclusion/exclusion criteria and were analyzed. We designated group 1 as the "EPL rupture" and group 2 as the "no EPL rupture". Basic demographic data, radiological findings, and operative variables were evaluated. The fracture patterns around LT were classified as follows: type I, no fracture line/fragment in LT or the EPL groove (third compartment); type IIA, a fracture of LT or the EPL groove with displacement <2 mm; type IIB, a fracture of LT or the EPL groove with displacement >2 mm; and type III, the presence of an island-shaped fracture fragment of LT (isolated free fragment of LT). RESULTS: EPL ruptures were found in 18 patients (5.7%). The basic demographic parameters did not differ significantly among the groups. Clinically, neither the time to surgery nor the type of VLP used (of three different types) was not significantly associated with EPL rupture, nor was arthroscopically assisted reduction. In terms of radiological variables, the overall ratio of intra-to-extra-articular fractures did not differ among the groups. However, the fracture type significantly affected the extent of the rupture (P < 0.001), the odds ratio of which increased significantly in the fracture order IIA, IIB, and III, compared to type I (91.9, 220.1, and 342.06, respectively). CONCLUSIONS: The extent of delayed EPL rupture after treatment of DRFs by VLPs was associated with the fracture pattern around the LT. Especially, an island-shaped LT fracture was associated with a high rupture risk because callus formation narrowed the EPL groove. LEVEL OF EVIDENCE: Therapeutic Level III.
30275259 Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatr 2019 Feb OBJECTIVE: To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases. METHODS: The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria. RESULTS: In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities. CONCLUSION: An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term JIA. These preliminary criteria will be formally validated with a dedicated project.
29953670 Comparison of Methods for Improving Fracture Risk Assessment in Diabetes: The Manitoba BMD 2018 Nov Type 2 diabetes is a risk factor for fracture independent of FRAX (fracture risk assessment) probability. We directly compared four proposed methods to improve the performance of FRAX for type 2 diabetes by: (1) including the rheumatoid arthritis (RA) input to FRAX; (2) making a trabecular bone score (TBS) adjustment to FRAX; (3) reducing the femoral neck T-score input to FRAX by 0.5 SD; and (4) increasing the age input to FRAX by 10 years. We examined major osteoporotic fractures (MOFs) and hip fractures (HFs) over a mean of 8.3 years observation among 44,543 women and men 40 years of age or older (4136 with diabetes) with baseline lumbar spine and hip DXA from 1999 through 2016. Controlled for unadjusted FRAX probability, diabetes was associated with an increased risk for MOFs and HFs. All four FRAX adjustments attenuated the effect of diabetes, but a residual effect of diabetes was seen on MOF risk after TBS adjustment, and on HF risk after the RA and TBS adjustments. Among those with diabetes, unadjusted FRAX risk underestimated MOF (observed/predicted ratio 1.15; 95% CI, 1.03 to 1.28), but this was no longer significant after applying the diabetes adjustments. HF risk was more severely underestimated (observed/predicted ratio 1.85; 95% CI, 1.51 to 2.20) and was only partially corrected with the diabetes adjustments (still significant for the RA and TBS adjustments). Among those with diabetes, there was moderate reclassification based upon a fixed MOF cut-off of 20% (4.1% to 7.1%) or fixed HF cut-off of 3% (5.7% to 16.5%). Net reclassification improvement increased for MOF with each of the diabetes adjustments (range 3.9% to 5.6% in the diabetes subgroup). In conclusion, each of the proposed methods for addressing limitations in the ability of FRAX to assess fracture risk in individuals with diabetes was found to improve performance, though no single method was optimal in all settings. © 2018 American Society for Bone and Mineral Research.
29045077 Subjective Complaints as the Main Reason for Biosimilar Discontinuation After Open-Label T 2018 Jan OBJECTIVE: To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity, and safety in daily practice after transitioning treatment from original reference infliximab (Remicade [REM]) to a biosimilar infliximab (CT-P13 [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Of the initial 222 REM-treated patients, 192 agreed to transition to CT-P13 and were included in this multicenter prospective cohort study. Changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and changes in the CRP levels, infliximab trough levels, and anti-infliximab antibody levels were assessed after 6 months, and adverse events (AEs) were documented. Drug survival and prognostic factors were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS: During 6 months follow-up, 24% of the patients (n = 47) discontinued CT-P13. Thirty-seven patients restarted REM, 7 switched to another biologic drug, and 3 continued without a biologic drug. The DAS28-CRP remained stable from baseline to month 6, with a mean ± SD score of 2.2 ± 0.9 at baseline to 2.2 ± 0.8 at 6 months (difference of 0.0 [95% confidence interval (95% CI) -0.1, 0.2]). The BASDAI increased from a mean ± SD of 3.8 ± 2.0 at baseline to 4.3 ± 2.1 at 6 months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough levels, and anti-infliximab antibody levels did not change. Just prior to CT-P13 discontinuation, the DAS28-CRP components tender joint count and patient's global assessment of disease activity, as well as the BASDAI were increased compared to baseline. The most frequently reported AEs were arthralgia, fatigue, pruritus, and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62, 0.95]) at baseline was predictive of discontinuing CT-P13. CONCLUSION: In our cohort, one-fourth of patients discontinued CT-P13 during 6 months of follow-up, mainly due to an increase in the subjective features of the tender joint count and the patient's global assessment of disease activity and/or subjective AEs, possibly explained by nocebo effects and/or incorrect causal attribution effects.
29398155 [Interstitial lung disease and pancreatic cancer: Series of two cases]. 2018 Jan INTRODUCTION: Pancreatic cancer is often not diagnosed until at a metastatic stage at which point the prognosis is very poor. Pulmonary metastases are pleomorphic, often present at the time of diagnosis and can lead to the discovery of an asymptomatic primary disease. CASE REPORT: We describe two cases aged 60 and 74 years, where imaging identified what was thought to be an interstitial lung disease but which was actually metastasis from pancreatic cancer. In the first case, CT showed multiple excavated pulmonary nodules but the presentation with medullary compression led rapidly to pathological diagnosis on bone lesions. In the second patient, a history of rheumatoid arthritis and the lack of abdominal symptoms led to an initial search for disease related to the rheumatoid disease. Histopathology, from lung and bone biopsies, enabled a correct diagnosis to be achieved. CONCLUSION: Where atypical interstitial lung disease occurs, biopsy should be considered in order not to delay a diagnosis of cancer, especially pancreatic cancer.
28916716 Deregulation of microRNA expression in purified T and B lymphocytes from patients with pri 2018 Jan OBJECTIVE: MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren's syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. METHODS: Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays. RESULTS: A major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155-5 p, hsa-miR-222-3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28-5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222-3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p. CONCLUSIONS: This study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS.
29602451 [Autologous serum tears: Long-term treatment in dry eye syndrome]. 2018 Mar INTRODUCTION: Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid. PATIENTS AND METHODS: This is a monocentric retrospective observational study conducted on 47 patients, with 83 eyes treated with autologous serum eye drops for isolated or secondary dry eye disease at the Marseille Public Hospitals between April 2014 and April 2017. The patients' subjective symptoms (ocular surface disease index [OSDI] score), their degree of satisfaction and the side effects were collected using questionnaires. Tear Break Up Time (BUT) and Schirmer scores were noted. A clinical evaluation based on fluorescein staining (Oxford score) was carried out prior to treatment with AST at P0 followed by 5 periods: P1 (between 1 and 3 months), P2 (3 to 9 months), P3 (9 to 15 months), P4 (15 months to 24 months), and P5 (>24 months). RESULTS: Out of the 83 eyes treated, the mean age was 54.39±21.56. There were 20 males (42.55 %) and 27 females (57.44 %); treatment indications consisted mainly of 25.53 % GVH, 21.27 % severe dry eye disease and 19.14 % Sjögren syndrome. The mean duration of follow-up was 9.82 months±15.50. The OSDI score decreased by 19.32 points±29.37 (P<0.05) between P0 and P1 and by 23.06 points±18.41 (P<0.05) between P0 and P4. The Oxford clinical score showed a significant decrease by the third month of treatment, between P0 and P2, by 1.32 points±1.76 (P<0.05). The Schirmer test and the BUT also showed an improvement in dry eye symptoms over time with AST, significantly at P1 (P<0.05). DISCUSSION: Complementary biological analyzes on the composition of AST are under way in order to identify predictive factors of effectiveness; patients not responding to AST treatment might respond to allogeneic serum from healthy donor cord blood. CONCLUSION: On this first series of 83 eyes treated with ASD, clinical efficacy was noted in most of the patients. No infectious complications were reported, and the satisfaction rate was very high.
29033144 Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's synd 2018 Jan Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important anti-inflammatory activities in epithelial cells. Herein, the comparative analysis of SG biopsies and SGEC lines obtained from SS patients and controls had revealed constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function in the ductal epithelia of SS patients that were associated with cell-autonomously activated NF-κB and IL-1β pathways. Transcriptome profiling analysis revealed several differentially expressed proinflammatory and metabolism-related gene sets in SS-SGEC lines. These aberrations largely correlated with the severity of histopathologic lesions, the disease activity and the occurrence of adverse manifestations in SS patients studied, a fact which corroborates the key role of the persistently-activated epithelia in the pathogenesis of both local and systemic features of this disease. The treatment of control SGEC lines with PPARγ agonists was found to diminish the NF-κB activation and apoptosis induced by proinflammatory agents. In addition, the in-vitro application of PPARγ agonists and pharmacologic inhibitors of IL-1β and NF-κB had significant beneficial effects on SS-SGEC lines, such as the restoration of PPARγ functions and the reduction of their intrinsic activation, a fact which may advocate the future clinical study of the above agents as therapeutic modalities for SS.
30111639 Effect of the Inclusion of the Metacarpophalangeal Joints on the Wrist Magnetic Resonance 2018 Nov OBJECTIVE: To extend the magnetic resonance imaging (MRI) score for assessment of wrist synovitis in juvenile idiopathic arthritis (JIA) by inclusion of the metacarpophalangeal (MCP) joints, and to compare the metric properties of the original and the extended score. METHODS: Wrist MRI of 70 patients with JIA were scored by 3 independent readers according to (1) the wrist component of the rheumatoid arthritis MRI synovitis score (comprising distal radioulnar, radiocarpal, and combined midcarpal and carpometacarpal joints); and (2) an extended score including the MCP joints. Thirty-eight patients had a 1-year MRI followup. The concordance between the readers [intraclass correlation coefficient (ICC), 95% limits of agreement (LOA), and weighted Cohen's κ], correlations with clinical variables (Spearman's ϱ), and the sensitivity to change [standardized response mean (SRM)] were calculated for both scores. RESULTS: The interreader agreement was moderate for the original score (ICC 0.77; 95% CI 0.68-0.84) and good for the extended score (ICC 0.86; 95% CI 0.80-0.91). Using 95% LOA, the aggregate score variability was less favorable with relatively wide LOA. Weighted Cohen's κ of the individual joints indicated good agreement for the original score and good to excellent agreement for the extended score. Correlations with clinical variables reflecting disease activity improved for the extended score and its SRM was higher compared to that of the original score. CONCLUSION: The extended score showed better reliability, construct validity, and sensitivity to change than the original. Inclusion of the MCP joints should be considered for a more accurate assessment of disease activity and treatment efficacy in JIA.
29415763 Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytok 2018 Feb 7 BACKGROUND: The anti-inflammatory effect of abatacept is most pronounced in patients with high-titer autoantibodies (including anticitrullinated protein antibodies [ACPA] and rheumatoid factor [RF]). Considering that autoantibodies trigger inflammatory cytokine production by monocytes and that abatacept binds to monocytes, influencing their functional state, we hypothesized that abatacept may effectively inhibit the production of several different cytokines by ACPA- or RF-challenged monocytes. METHODS: Peripheral blood CD68(+) monocytes stimulated with macrophage colony-stimulating factor for 24 h were exposed to random immunoglobulin G alone (negative control), purified ACPA, purified RF, or lipopolysaccharide (positive control) in cell culture plates coated with citrullinated vimentin (to allow ACPA immune complex formation). Stimulations were done in the presence or absence of abatacept or tumor necrosis factor (TNF) antibody (adalimumab) with or without indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan. Supernatants were analyzed for key proinflammatory cytokines TNF-α, interleukin (IL)-1β, IL-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) after 24 h. RESULTS: Exposure to ACPA or RF significantly induced the production of TNF-α (20-fold and 27-fold, respectively), IL-1β (each 4-fold), IL-6 (12-fold and 11-fold, respectively), IL-8 (43-fold and 30-fold, respectively), and CCL2 (each 4-fold) in human monocytes. Abatacept inhibited this autoantibody-mediated upregulation of cytokines, reducing TNF-α by > 75%, IL-1β by > 65%, IL-6 and IL-8 by > 80%, and CCL2 by > 60%. In contrast, a TNF inhibitor did not influence autoantibody-induced proinflammatory cytokine production. IDO inhibition reversed the effect of abatacept and again permitted the induction of cytokine production by ACPA and RF. CONCLUSIONS: These data show that abatacept interferes with autoantibody-mediated cytokine production by monocytes through induction of IDO. This inhibitory effect on the production of several effector cytokines in RA may explain the fast anti-inflammatory effect of abatacept as well as its preferential efficacy in patients with high-titer ACPA and RF.
30340338 Probiotics in Autoimmune and Inflammatory Disorders. 2018 Oct 18 Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro. This interaction is linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on mechanistic studies in animal models. Microbial⁻immune system crosstalk has been linked to: short-chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multiorgan inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.