Browse

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

ID PMID Title PublicationDate abstract
26224367 Immune system changes after sexual abuse in adolescents. 2016 Feb BACKGROUND: The immunological changes in diseases such as rheumatoid arthritis and multiple sclerosis have been found to be similar to the immunological changes in adults with post-traumatic stress disorder (PTSD). The biological consequences of and immunological disruptions associated with psychological trauma in sexually abused adolescents were investigated in this study. METHODS: Number of peripheral blood cells, intracellular cytokine level and cytotoxic activity of natural killer cells were measured on routine blood examination samples in adolescents aged 13-18 referred to the outpatient unit for forensic evaluation. Forty-three adolescents (patients with present/lifetime PTSD [PTSD-P/PTSD-L] associated with a history of childhood sexual abuse, n = 33; and 10 controls) were evaluated. RESULTS: Eosinophil percentage was high (P < 0.05), whereas stimulated intracellular interferon-γ was low (P < 0.05) in adolescents with PTSD-L compared with the control group. In PTSD-P patients exposed to repeated sexual abuse, CD3(+) HLA-DR(+) T-lymphocyte count was low (P < 0.05) compared with those with one-time sexual abuse. CONCLUSION: The increase in some immune system parameters and the decrease in several others, suggests a dysregulation of the immune system related to trauma in adolescents. Dysregulation of the immune system is known to cause autoimmune and chronic disease.
26155368 Relationship Between Serum Interleukin-17F Level and Severity of Atopic Dermatitis in Chil 2015 Jun 1 Background: Recent discovery of the Th17 pathway is providing new opportunities for understanding chronic immune-mediated diseases. The Th17 pathway has been historically associated with chronic inflammatory diseases such as psoriasis, multiple sclerosis, and rheumatoid arthritis. Among Th17 cytokines, pathogenic roles of IL-17A and IL-17F in asthma have been well described. Recently, the number of peripheral blood Th17 cells was found to correlate with disease severity in patients with atopic dermatitis (AD). This study aimed to investigate serum IL-17F levels in children with AD and to correlate this with severity of the disease. Methods: Enzyme-linked immunosorbent assay was used to measure IL-17F levels in the sera of 228 patients with AD and 62 control children. The SCORing Atopic Dermatitis (SCORAD) tool was used to determine the severity of disease. Results: The mean serum level of IL-17F in children with AD was significantly higher than that in the control group (p<0.05) Serum IL-17F levels were also higher in patients with severe AD than in those with mild AD (p<0.001), and IL-17F levels and SCORAD scores were positively correlated (p<0.05). Conclusions: Serum IL-17F level might be a useful marker in children with AD.
26131976 Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for A 2015 Jun 29 Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-κB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-κB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-κB signaling. NR4A receptors modulate NF-κB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A's receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-κB. Specifically, we will examine such NR4A/NF-κB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-κB interactions to limit hyper-inflammatory responses in vivo.
26131770 Therapeutic Effects of Bee Venom on Immunological and Neurological Diseases. 2015 Jun 29 Bee Venom (BV) has long been used in Korea to relieve pain symptoms and to treat inflammatory diseases, such as rheumatoid arthritis. The underlying mechanisms of the anti-inflammatory and analgesic actions of BV have been proved to some extent. Additionally, recent clinical and experimental studies have demonstrated that BV and BV-derived active components are applicable to a wide range of immunological and neurodegenerative diseases, including autoimmune diseases and Parkinson's disease. These effects of BV are known to be mediated by modulating immune cells in the periphery, and glial cells and neurons in the central nervous system. This review will introduce the scientific evidence of the therapeutic effects of BV and its components on several immunological and neurological diseases, and describe their detailed mechanisms involved in regulating various immune responses and pathological changes in glia and neurons.
26056507 Genetics of Interstitial Lung Disease: Vol de Nuit (Night Flight). 2015 Interstitial lung disease (ILD) is a chronic, progressive fibrotic lung disease with a dismal prognosis. ILD of unknown etiology is referred to as idiopathic interstitial pneumonia (IIP), which is sporadic in the majority of cases. ILD is frequently accompanied by rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), and other autoimmune diseases, and is referred to as collagen vascular disease-associated ILD (CVD-ILD). Susceptibility to ILD is influenced by genetic and environmental factors. Recent advances in radiographic imaging techniques such as high-resolution computed tomography (CT) scanning as well as high-throughput genomic analyses have provided insights into the genetics of ILD. These studies have repeatedly revealed an association between IIP (sporadic and familial) and a single nucleotide polymorphism (SNP) in the promoter region of the mucin 5B (MUC5B). HLA-DRB1*11 alleles have been reported to correlate with ILD in European patients with SSc, whereas in Japanese patients with RA, the HLA-DR2 serological group was identified. The aim of this review is to describe the genetic background of sporadic IIP, CVD-ILD, drug-induced-ILD (DI-ILD), pneumoconiosis, and hypersensitivity pneumonitis. The genetics of ILD is still in progress. However, this information will enhance the understanding of the pathogenesis of ILD and aid the identification of novel therapeutic targets for personalized medicine in future.
26040270 Synthesis and Biological Evaluation of N-Aryl-5-aryloxazol-2-amine Derivatives as 5-Lipoxy 2015 We describe the synthesis and biological evaluation of N-aryl-5-aryloxazol-2-amine derivatives that are able to inhibit 5-lipoxygenase (5-LOX), a key enzyme of leukotriene synthesis, for the treatment of inflammation-related diseases including asthma and rheumatoid arthritis. A novel structural moiety containing oxazole was initially identified from a chemical library using an in vitro enzymatic and cell-based assay, and its synthesized oxazole derivatives were further examined to develop a structure-activity relationship (SAR). SAR analysis demonstrated that a hydroxyl or amino group at the p-position on N-phenyl was essential for the 5-LOX-inhibitory activities of the derivatives, and that other halogen and methyl group-substituted derivatives affected the potency, positively or negatively. As a result, derivatives selected through first-round screening were further optimized using a cell-based assay and an in vivo assay to develop a potent, selective 5-LOX inhibitor. A final hit exhibited an improved efficacy in arachidonic acid-induced ear edema when applied topically but not orally. Moreover, it showed the additional advantage of sustainable antiinflammatory activity over a reference compound, zileuton. Taken together, chemical entities bearing an oxazole scaffold could be promising as therapeutic drugs for the treatment of chronic inflammatory skin disorders.
26017088 Biosimilars in inflammatory bowel diseases: an important moment for Brazilian gastroentero 2015 Jan Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohn's disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.
25943273 Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease a 2015 Jul Compromised intestinal barrier function is a prominent feature of inflammatory bowel disease (IBD). However, links between intestinal barrier loss and disease extend much further, including documented associations with celiac disease, type I diabetes, rheumatoid arthritis, and multiple sclerosis. Intestinal barrier loss has also been proposed to have a critical role in the pathogenesis of graft-versus-host disease (GVHD), a serious, potentially fatal consequence of hematopoietic stem cell transplantation. Experimental evidence has begun to support this view, as barrier loss and its role in initiating and establishing a pathogenic inflammatory cycle in GVHD is emerging. Here we discuss similarities between IBD and GVHD, mechanisms of intestinal barrier loss in these diseases, and the crosstalk between barrier loss and the immune system, with a special focus on natural killer (NK) cells. Unanswered questions and future research directions on the topic are discussed along with implications for treatment.
25883714 Iatrogenic aortic insufficiency following mitral valve replacement: case report and review 2015 Jun We report a 28-year-old white female who suffered significant aortic insufficiency (AI) following mitral valve (MV) replacement for endocarditis. The patient had history of rheumatoid arthritis and presented to our emergency department with a 3-month history of dyspnea, orthopnea, fevers and weight loss, worsening over 2 weeks, for which she took intermittent acetaminophen. On admission, vital signs revealed blood pressure of 99/70 mm Hg, heart rate of 120 beats/minute, and temperature of 98.8 °F; her weight was 100 lbs. Physical exam revealed a thin and pale female. Cardiac auscultation revealed regular tachycardic rhythm with a third heart sound, and a short early systolic murmur at the left lower sternal border without radiation. Lungs revealed right lower lobe rhonchi. Initial pertinent laboratory evaluation revealed hemoglobin 9.6 g/dL and white blood cell count 17,500/μL. Renal function was normal, and hepatic enzymes were mildly elevated. Chest radiogram revealed right lower lobe infiltrate. Blood cultures revealed Enterococcus faecalis. Two-dimensional echocardiogram revealed large multilobed vegetation attached to the anterior MV leaflet with severe mitral regurgitation (MR), otherwise normal left ventricular systolic function. She was started on appropriate antibiotics and underwent MV replacement with 25-mm On-X prosthesis. She was noted post-operatively to have prominent systolic and diastolic murmurs. Repeat echocardiogram revealed normal mitral prosthesis function, with new moderately severe AI. Transesophageal echocardiogram revealed AI originating from a tethered non-coronary cusp, due to a suture preventing proper cusp mobility. The patient declined further surgery. She recovered slowly and was discharged to inpatient rehabilitation 4 weeks later. This case highlights the importance of vigilance to this potential serious complication of valve surgery with regard to diagnosis and treatment to prevent long-term adverse consequences.
25878399 The inflammatory actions of coagulant and fibrinolytic proteases in disease. 2015 Aside from their role in hemostasis, coagulant and fibrinolytic proteases are important mediators of inflammation in diseases such as asthma, atherosclerosis, rheumatoid arthritis, and cancer. The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa), factor VIIa (FVIIa), tissue factor, and thrombin, also evoke cell-mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells) or inflammatory cells (e.g., macrophages) via the proteolytic activation of protease-activated receptors (PARs). Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll-like receptor-4 (TLR-4) activating fibrin degradation products (FDPs) and can release latent-matrix bound growth factors such as transforming growth factor-β (TGF-β). Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator) evoke plasmin-independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor-mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review.
25784694 Emerging translational approaches to target STAT3 signalling and its impact on vascular di 2015 Jun 1 Acute and chronic inflammation responses characterize the vascular remodelling processes in atherosclerosis, restenosis, pulmonary arterial hypertension, and angiogenesis. The functional and phenotypic changes in diverse vascular cell types are mediated by complex signalling cascades that initiate and control genetic reprogramming. The signalling molecule's signal transducer and activator of transcription 3 (STAT3) plays a key role in the initiation and continuation of these pathophysiological changes. This review highlights the pivotal involvement of STAT3 in pathological vascular remodelling processes and discusses potential translational therapies, which target STAT3 signalling, to prevent and treat cardiovascular diseases. Moreover, current clinical trials using highly effective and selective inhibitors of STAT3 signalling for distinct diseases, such as myelofibrosis and rheumatoid arthritis, are discussed with regard to their vascular (side-) effects and their potential to pave the way for a direct use of these molecules for the prevention or treatment of vascular diseases.
25738585 Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma p 2015 Mar 4 Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis, impinge on the performance of orthopaedic implants by impairing bone regeneration. For this reason, the development of effective surface modifications supporting the ingrowth of implants in morbid bone tissue is essential. Our study is designed to elucidate if cells with restricted cell-function limiting adhesion processes benefit from plasma polymer deposition on titanium. We used the actin filament disrupting agent cytochalasin D (CD) as an experimental model for cells with impaired actin cytoskeleton. Indeed, the cell's capacity to adhere and spread was drastically reduced due to shortened actin filaments and vinculin contacts that were smaller. The coating of titanium with a positively charged nanolayer of plasma polymerised allylamine (PPAAm) abrogated these disadvantages in cell adhesion and the CD-treated osteoblasts were able to spread significantly. Interestingly, PPAAm increased spreading by causing enhanced vinculin number and contact length, but without significantly reorganising actin filaments. PPAAm with the monomer allylamine was deposited in a microwave-excited low-pressure plasma-processing reactor. Cell physiology was monitored by flow cytometry and confocal laser scanning microscopy, and the length and number of actin filaments was quantified by mathematical image processing. We showed that biomaterial surface modification with PPAAm could be beneficial even for osteoblasts with impaired cytoskeleton components. These insights into in vitro conditions may be used for the evaluation of future strategies to design implants for morbid bone tissue.
25672799 Methotrexate induced apoptotic and necrotic chromatin changes in rat myeloid leukemia cell 2015 Apr OBJECTIVE: It was tested as to why low-dose methotrexate (MTX) effective against rheumatoid arthritis poses considerable health risk at higher doses. METHODS: The tumorigenic potential of My1/De blast cells was followed by cytology and by the kinetics of (18)FDG uptake. The toxicity of MTX on chromatin condensation was compared to predictive normal intermediates of chromosome condensation in control cells. RESULTS: MTX below 0.1 µg/ml did not cause visible changes in interphase chromatin structure. At its lowest toxic concentration (0.1 µg/ml) chromatin margination was confined to the outer edge of the nucleus. Between 0.1 and 5 µg/ml concentrations apoptotic chromatin shrinkage correlated with the dose of MTX. Apoptosis was exerted in early S phase excluding the mitotic effect. At higher MTX concentrations (>10 µg/ml) necrotic disruption and expansion took place. The lowest necrotic concentration (10 µg/ml) was close to highest apoptotic MTX concentration (5 µg/ml). CONCLUSIONS: The switch from apoptosis to inflammatory necrosis taking place within a narrow concentration range supports the notion of a narrow therapeutic spectrum. Chromatin changes are early markers of genotoxicity at much lower concentrations than citogenetic changes in properly chosen sensitive cells.
25294635 Risk of Venous Thromboembolic Events in Pregnant Patients With Autoimmune Diseases: A Popu 2016 Apr OBJECTIVE: The objective of this study is to evaluate the effect of autoimmune disease on the risk of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant women. METHODS: Using the Health Care Cost and Utilization Project, Nationwide Inpatient Sample database from 2003 to 2011, the risk of developing DVT, PE, and VTE among pregnant patients with selected autoimmune diseases was estimated using unconditional logistic regression analysis. RESULTS: Our study cohort consisted of 7 917 453 women of which 43 523 had underlying autoimmune diseases. Risk of VTE was high in pregnant women with systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, type 1 diabetes mellitus, ulcerative colitis, and Crohn's disease. CONCLUSION: Most autoimmune diseases considerably increase the risk of VTE. Thromboprophylaxis may be considered in pregnancies with autoimmune disease, particularly those with systemic lupus erythematosus and dermatomyositis.
25222660 Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: 2015 Jan : Primary nonresponse and primary nonremission are important limitations of tumor necrosis factor (TNF) antagonists, occurring in 10% to 40% and 50% to 80% of patients with inflammatory bowel disease, respectively. The magnitude of primary nonresponse differs between phase III clinical trials and cohort studies, indicating differences, e.g., in definition, patient population or blinding. The causes of nonresponse can be attributed to the drug (pharmacokinetics, immunogenicity), the patient (genetics, disease activity), the disease (type, location, severity), and/or the treatment strategy (dosing regimen, combination therapy). Primary nonresponse has been attributed to "non-TNF-driven disease" which is an overly simplified and potentially misleading approach to the problem. Many patients with primary nonresponse could successfully be treated with dose optimization during the induction phase or switching to another TNF antagonist. Therefore, primary nonresponse is frequently not a non-TNF-driven disease. Recent studies from rheumatoid arthritis and preliminary data from inflammatory bowel disease evaluating therapeutic drug monitoring have suggested that early measurement of drug and anti-drug antibody concentrations could help to define primary nonresponse and rationalize patient management of this problem. Moreover, a modeling approach including pharmacological parameters and patient-related covariants could potentially be predictive for response to the treatment. We describe an overview of this evolution in thinking, underpinned by previous findings, and assess the potential role of early measurement of drug and antidrug antibody concentrations in the definition and management of primary nonresponse.
25068998 Early effect of hydroxychloroquine therapy: relationship between cumulative dose and retin 2015 BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area. METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness. RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area. CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
27433031 Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis. 2016 We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.
26044543 Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflamma 2015 Oct OBJECTIVE: Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." METHODS: Extensive literature search in PubMed central. RESULTS: Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. CONCLUSIONS: The article highlights the complexity of interwoven pathways of osteopenia.
25860212 Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated w 2015 Apr The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2-20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3-55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure.
27392769 What Change in American Shoulder and Elbow Surgeons Score Represents a Clinically Importan 2016 Dec BACKGROUND: The American Shoulder and Elbow Surgeons (ASES) questionnaire was developed to provide a standardized method for evaluating shoulder function. Previous studies have determined the clinical responsiveness of this outcome measure for heterogenous populations or patients with nonoperatively treated rotator cuff disease. Currently, to our knowledge, no studies exist that establish the clinically relevant change in the ASES score after shoulder arthroplasty. QUESTIONS/PURPOSES: We asked: (1) What are the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for the ASES score after primary and reverse shoulder arthroplasties? (2) Are the MCID and SCB for the ASES score different between primary and reverse shoulder arthroplasties? (3) What patient-related factors are associated with achieving the MCID and SCB after total shoulder arthroplasty and reverse shoulder arthroplasty? METHODS: A longitudinally maintained institutional shoulder arthroplasty registry was retrospectively queried for patients who underwent primary shoulder arthroplasty, including anatomic or reverse total shoulder arthroplasty from 2007 to 2013, with a minimum 2-year followup. Seven hundred ninety-four patients were identified and eligible; 304 of these patients did not have 2 years of followup or complete datasets, resulting in a study cohort of 490 patients (62% of the 794 potentially eligible). The MCID and SCB of the ASES score for these patients was calculated using an anchor-based method, using four different anchors measuring satisfaction with work, activities, overall, and activity from the SF-36. The MCID (anchored to somewhat satisfied) and SCB (very satisfied) of the ASES score were calculated for the entire cohort and stratified by arthroplasty type. Multivariate logistic regression of patient-related factors that influence the MCID and SCB achievement was performed. RESULTS: The MCID for all patients combined ranged from 6.3 to 13.5; for the overall satisfaction anchor, the MCID was 13.5 ± 4.5 (95% CI, 4.8-22.3). The SCB for the overall cohort ranged from 12.0 to 36.6; for the overall satisfaction anchor, the SCB was 36.6 ± 3.8 (95% CI, 29.1-44.1). There were no differences in the MCID of the ASES score between anatomic and reverse shoulder arthroplasty for any of the anchors (p = 0.159-0.992) or the SCB for any of the anchors (p = 0.467-0.977). Combining anatomic and reverse shoulder arthroplasty in one group, higher preoperative ASES score (odds ratio [OR], 0.96; 95% CI, 0.94-0.98; p < 0.001), having a reverse shoulder arthroplasty (OR, 0.36; 95% CI, 0.16-0.85; p = 0.016), and having rheumatoid arthritis were independent predictors of not achieving an MCID for the ASES 2 years after surgery. Higher preoperative ASES score (OR, 0.91; 95% CI, 0.89-0.92; p < 0.001), a diagnosis of rotator cuff tear arthropathy (OR, 0.14; 95% CI, 0.07-0.30; p < 0.001), a diagnosis of back pain (OR, 0.42; 95% CI, 0.24-0.71); p = 0.002), and living alone (OR, 0.36; 95% CI, 0.19-0.69; p = 0.002) were all independent predictors of not achieving SCB after shoulder arthroplasty. CONCLUSIONS: Patients with glenohumeral arthritis or rotator cuff tear arthropathy who undergo primary conventional total or reverse shoulder arthroplasty and have at least a nine-point improvement in their ASES score experience a clinically important change, whereas those who have at least a 23-point improvement in their ASES score experience a substantial clinical benefit. High preoperative function was associated with a decreased likelihood of achieving clinically important change after total shoulder arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.