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ID PMID Title PublicationDate abstract
23335588 Systematic review of validation studies of the use of administrative data to identify seri 2013 Aug OBJECTIVE: To conduct a systematic review of the literature on the validation of algorithms identifying infections in administrative data for future use in populations with rheumatic diseases. METHODS: Medline and EMBase were searched using the themes "administrative data" and "infection" between 1950 and October 2012. Inclusion criteria consisted of validation studies of administrative data identifying infections in adult populations. Article quality was assessed using a validated tool. RESULTS: A total of 5,941 articles were identified, 90 articles underwent detailed review, and 24 studies were included. The majority (17 of 24) examined bacterial infections and 9 examined opportunistic infections. Eighteen studies were from the US and all but 4 studies used International Classification of Diseases, Ninth Revision codes. Rheumatoid arthritis patients were studied in 6 of 24 articles. The studies on bacterial infections in general reported highly variable sensitivity and positive predictive value (PPV) for the diagnosis of infections using administrative data (sensitivity range 4.4-100%, PPV range 21.7-100%). Algorithms to identify opportunistic infections similarly had a highly variable sensitivity (range 20-100%) and PPV (range 1.3-100%). Thirteen studies compared the diagnostic accuracy of different algorithms, which revealed that strategies including a comprehensive algorithm using a greater number of diagnostic codes or codes in any position had the highest sensitivity for the diagnosis of infection. Algorithms that incorporated microbiologic or pharmacy data in combination with diagnostic codes had improved PPV for identification of tuberculosis. CONCLUSION: Algorithms for identifying infections using administrative data should be selected based on the purpose of the study, with careful consideration as to whether a high sensitivity or PPV is required.
25190079 IL-6 in inflammation, immunity, and disease. 2014 Sep 4 Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
24764575 The biology and medical implications of interleukin-6. 2014 Apr Cytokines are soluble mediators, which aid cell-to-cell communication in immune responses, and interleukin-6 (IL-6) is a prototypical cytokine featuring redundant and pleiotropic activity. The complete elucidation of the IL-6-mediated signal transduction system has provided a molecular basis for the characteristic features of cytokines. When tissue damage or inflammation due to infections or injuries occurs, IL-6 synthesis is promptly induced, contributing to the host defense through the stimulation of acute-phase immune reactions and hematopoiesis. The production of IL-6 is terminated when tissue homeostasis is restored. The synthesis of IL-6 is tightly regulated transcriptionally and posttranscriptionally. However, the dysregulated continual synthesis of IL-6 has been implicated in the development of various diseases, including autoimmune and chronic inflammatory diseases and cancers. Clinical trials using the humanized anti-IL-6 receptor monoclonal antibody tocilizumab have demonstrated the efficacy of IL-6 blockade for the treatment of refractory inflammatory diseases, such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman disease. Moreover, favorable results from the off-label use of tocilizumab strongly suggest that it may be applicable for the treatment of other refractory immune-mediated diseases, including cancer. Therefore, the mechanisms for the dysregulated synthesis of IL-6 need to be elucidated to understand the pathogenesis of the resultant diseases and to facilitate the development of effective therapeutic strategies.
24217668 Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus. 2013 Aug The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.
24137247 Effects of an aqueous extract of Eucommia on articular cartilage in a rat model of osteoar 2013 Sep Osteoarthritis is a common chronic and progressively degenerative joint condition. The stem bark of Eucommia ulmoides Oliver (a member of the Eucommiaceae family), which is also known as Du-Zhong, is a traditional Chinese medicine commonly used for the treatment of rheumatoid arthritis. However, the mechanisms underlying the effects of Eucommia in the treatment of arthritis of the knee require further study. The present study investigated the effects of an aqueous extract of Eucommia on the articular cartilage (by Mankin's grade) and the levels of matrix metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 in the serum and synovial fluid in a rat model of osteoarthritis. The serum levels of MMP-1, -3 and -13 were measured by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) at weeks 1, 2 and 4. The levels of MMP-1, -3 and 13 were significantly decreased in the rats treated with Eucommia compared with those in the control rats (P<0.05). Histopathological examination results indicated a lower Mankin's grade in the Eucommia group compared with that of the control rats. Therefore, Eucommia was demonstrated to have a cartilage-protecting effect in rats with osteoarthritis, potentially by improving cartilage metabolism, regulating the degradation of the extracellular matrix of the articular cartilage, and inhibiting apoptosis in chondrocytes, thereby slowing down joint degeneration.
23687011 Readability and suitability assessment of patient education materials in rheumatic disease 2013 Oct OBJECTIVE: Web-based patient education materials and printed pamphlets are frequently used by providers to inform patients about their rheumatic disease. Little attention has been given to the readability and appropriateness of patient materials. The objective of this study was to examine the readability and suitability of commonly used patient education materials for osteoarthritis (OA), rheumatoid arthritis, systemic lupus erythematosus, and vasculitis. METHODS: Five or 6 popular patient resources for each disease were chosen for evaluation. Readability was measured using the Flesch-Kincaid reading grade level and suitability was determined by the Suitability Assessment of Materials (SAM), a score that considers characteristics such as content, graphics, layout/topography, and cultural appropriateness. Three different reviewers rated the SAM score and means were used in the analysis. RESULTS: Twenty-three resources written on the 4 diseases were evaluated. The education material for all 4 diseases studied had readability above the eighth-grade level and readability did not differ among the diseases. Only 5 of the 23 resources received superior suitability scores, and 3 of these 5 resources were written for OA. All 4 diseases received adequate suitability scores, with OA having the highest mean suitability score. CONCLUSION: Most patient education materials for rheumatic diseases are written at readability levels above the recommended sixth-grade reading level and have only adequate suitability. Developing more appropriate educational resources for patients with rheumatic diseases may improve patient comprehension.
25240432 Fixation of posterior process fractures of the olecranon using a modified suture bridge te 2014 Dec We encountered 2 patients with posterior process fractures of the olecranon and fixed the fragment using a modified suture bridge method without a metallic implant. The suture anchor was inserted distally through the fracture plane, and the small tip of proximal olecranon was reduced to the ulna. Computed tomography revealed bony union 4 and 5 months later. At the 1-year postoperative follow-up examination, the clinical outcomes were satisfactory in both patients. This suture bridge technique was reliable for small fragment fixation in posterior process fracture of the olecranon based on the tension band theory with no problems induced by metallic hardware.
24760746 Erythrovirus B19 and autoimmune thyroid diseases. Review of the literature and pathophysio 2015 Jan Erythrovirus B19 (EVB19) has been incriminated, over recent years, in the onset and/or pathogenesis of many diseases, especially autoimmune thyroid diseases. This review of the literature (published over the last 40 years using Pubmed and Science Direct search engines) was designed to define the role of EVB19, particularly in autoimmune thyroid diseases.Two cases of subacute thyroiditis, one case of Graves' disease (associated with type 1 diabetes and rheumatoid arthritis), and one case of Hashimoto's thyroiditis following acute EVB19 infection were reported. A retrospective case-control study in a pediatric population demonstrated the role of EVB19 in Hashimoto's thyroiditis. Four retrospective studies of pathology slides (including PCR, immunohistochemistry or in situ hybridization) and a prospective case-control study on pathology slides demonstrated the presence of EVB19 in thyroid tissue of patients with benign multinodular goiter, Graves' disease, autoimmune thyroiditis (including Hashimoto's thyroiditis), and thyroid cancer. EVB19 can be demonstrated in the thyroid gland in a wide range of diseases. Although acute EVB19 infection could theoretically trigger autoimmune thyroid disease, there is currently no evidence that EVB19 plays a specific role in the pathophysiology of autoimmune thyroid diseases.
24659150 [Trends in rehabilitation of patients with rheumatic diseases in Germany]. 2014 Mar Recent Deutsche Gesellschaft für Rheumatologie (DGRh, German Society of Rheumatology) guidelines emphasized the significance of coordinated multidisciplinary care and rehabilitation of patients with inflammatory rheumatic diseases. Nationwide data from the German pension insurance funds showed that inpatient rehabilitation due to rheumatoid arthritis (RA) varied by a factor of 2.6 between the different German states. From 2000 to 2012 rehabilitation measures were reduced by one third, most significantly in men with ankylosing spondylitis (AS). Rehabilitation measures because of RA or AS were provided up to 14 times more frequently by the German statutory pension insurance scheme compared with a large compulsory health insurance which is responsible for rehabilitation measures after retirement. In rehabilitation centers with high numbers of patients with inflammatory rheumatic diseases, higher structural and process quality were demonstrated. In 2011 a total of 40 % of RA patients in the national database of the collaborative arthritis centers showed medium or severe functional limitations. Among these disabled RA patients inpatient rehabilitation was reduced by about 50 % between 1995 and 2011. Out of all RA patients from outpatient rheumatology care with severe functional limitations 38 % had no functional restoration therapy within the previous 12 months with a high variation between rheumatologists. Experiences from other European countries may inspire German rheumatologists and other involved health professionals to initiate a wider range of rehabilitative interventions in the future.
23941291 Identification of three new cis-regulatory IRF5 polymorphisms: in vitro studies. 2013 Aug 13 BACKGROUND: Polymorphisms in the interferon regulatory factor 5 (IRF5) gene are associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis and other diseases through independent risk and protective haplotypes. Several functional polymorphisms are already known, but they do not account for the protective haplotypes that are tagged by the minor allele of rs729302. METHODS: Polymorphisms in linkage disequilibrium (LD) with rs729302 or particularly associated with IRF5 expression were selected for functional screening, which involved electrophoretic mobility shift assays (EMSAs) and reporter gene assays. RESULTS: A total of 54 single-nucleotide polymorphisms in the 5' region of IRF5 were genotyped. Twenty-four of them were selected for functional screening because of their high LD with rs729302 or protective haplotypes. In addition, two polymorphisms were selected for their prominent association with IRF5 expression. Seven of these twenty-six polymorphisms showed reproducible allele differences in EMSA. The seven were subsequently analyzed in gene reporter assays, and three of them showed significant differences between their two alleles: rs729302, rs13245639 and rs11269962. Haplotypes including the cis-regulatory polymorphisms correlated very well with IRF5 mRNA expression in an analysis based on previous data. CONCLUSION: We have found that three polymorphisms in LD with the protective haplotypes of IRF5 have differential allele effects in EMSA and in reporter gene assays. Identification of these cis-regulatory polymorphisms will allow more accurate analysis of transcriptional regulation of IRF5 expression, more powerful genetic association studies and deeper insight into the role of IRF5 in disease susceptibility.
23856014 Natural killer cells in human autoimmune disorders. 2013 Jul 11 Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases.
23253932 Effect of IL-17A blockade with secukinumab in autoimmune diseases. 2013 Apr Genetic studies and correlative expression data in diseased tissues have pointed to the role of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells are known to produce the proinflammatory cytokine IL-17A as well as other effector cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, γδ-T cells, macrophages and natural killer cells. It can thus be expected that the inhibition of IL-17A as a therapeutic target in autoimmune disease would exert different physiological effects than the suppression of Th17 cell activity. Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/κ isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases. Rapid and sustained symptom reductions in psoriasis, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have been observed in secukinumab-treated patients, with no overt safety signals. In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.
25584619 SARCOSPA - Sarcopenia in spondyloarthritis patients. 2014 Oct INTRODUCTION: The loss of muscle mass (MM) is a serious problem which has been demonstrated in patients with rheumatoid arthritis. There are few studies about the loss of MM in patients with spondyloarthritis (Spa). OBJECTIVE: To assess muscle mass index (MMI) in a cohort of patients with Spa and compare it with a control group of healthy individuals; to verify if a higher risk of sarcopenia is related with disease activity, functional impairment, duration of the illness and radiological damage. METHODS: Case control study. Muscle mass index (MMI) was determined, from the value of MM, using Lee's equation, in a cohort of patients with spondyloarthritis and in a control group. Bath Ankylosing Spondylitis Disease Activity and Function Indexes (BASDAI and BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) and Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were assessed in a cohort of patients with axial Spa, as well as Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 (DAS28) in patients with peripheral disease. Data were treated using SPSS version 17.0. Values of p<0,05 were considered with statistical significance. RESULTS: 60 patients were enrolled; 48.2% were males, mean age 45.5±13.4 years, mean disease duration 10.9±11.6 years; 36 had ankylosing spondylitis and 24 had psoriatic arthritis. 62% of patients had sarcopenia and there was a significant difference in mean MMI between patients and controls (7.65±0.98 vs 8.25±0.92; p=0.001, OR =5.23. In male patients, there was a statistically significant moderate negative correlation between MMI and BASDAI and BASFI (p=-0.536 and p=-0.445). No other significant correlations were identified. CONCLUSION: Our study supports the hypothesis of a greater prevalence of sarcopenia in patients with Spa compared to healthy controls. Some limitations included the sample size, potential confounding factor such the bias of measurement and the use of a non-validated equation to Portuguese population to calculate MM.
25220474 Updates on NSAIDs in patients with and without coronary artery disease: pitfalls, interact 2014 Oct NSAIDs are used worldwide by more than 30 million people everyday, given their anti-inflammatory, analgesic and antipyretic effects. NSAIDs are approved for several common adult diseases, including acute and chronic musculoskeletal or inflammatory disease, osteoarthritis, rheumatoid arthritis and other arthritic conditions, as well as for children with juvenile idiopathic arthritis. Importantly, the population commonly taking NSAIDs is that of older individuals who also represent the population with the highest risk for cardiovascular (CV) and gastrointestinal adverse effects. In recent years, a growing body of evidence regarding potential risks from chronic use of NSAIDs has emerged. The aim of this review is to update the available data concerning chronic use of NSAIDs in patients with and without CV disease by analyzing the mechanisms of action, the interference of specific NSAIDs with the established CV protective role of low-dose aspirin, and the potential increased risk of myocardial infarction, stroke, hypertension, heart failure and atrial fibrillation.
25436886 Humanized mouse models of epstein-barr virus infection and associated diseases. 2013 Mar 14 Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.
25086083 Determinants of vitamin D levels in children, adolescents, and young adults with juvenile 2014 Sep OBJECTIVE: Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA. METHODS: We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination. RESULTS: Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001). CONCLUSION: JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.
24968272 Endothelial dysfunction in chronic inflammatory diseases. 2014 Jun 25 Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.
24762269 With blood in the joint - what happens next? Could activation of a pro-inflammatory signal 2014 May One of the main complications of haemophilia A is haemophilic arthropathy (HA), a debilitating disease with a significant negative impact on motility and quality of life. Despite major advances in the treatment of haemophilia A, many patients still suffer from HA. We wish to develop new treatments for HA, but must first better understand its causes. Our laboratory studies molecular scissors that release the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) from cells. TNFα is considered the 'fire alarm' of the body - it helps to fight infections, but can also cause diseases such as inflammatory arthritis. We know that the molecular scissors, called TNFα convertase (TACE), and its newly discovered regulator termed iRhom2 can be rapidly activated by small amounts of cytokines, growth factors, and pro-inflammatory mediators present in the blood. We hypothesize that the rapid activation of TACE could help explain one of the unsolved mysteries regarding the development of HA, which is how even small amounts of blood can provoke a persistent inflammatory response. We propose that once blood enters the joint, iRhom2 and TACE are activated to release TNFα and that this could promote the development of HA in a similar manner to that in which it promotes rheumatoid arthritis (RA). We are currently using immune cells stimulated with blood degradation products, and mouse models of HA, to test this hypothesis. If successful, our study could provide the rationale for testing anti-TNF antibodies, which are already used to treat RA, for the treatment of HA. In addition, they might uncover iRhom2 and TACE as attractive new candidate targets for the treatment of HA.
23771559 Spondyloarthritis associated with acne conglobata, hidradenitis suppurativa and dissecting 2013 Aug To review and highlight the association of acne conglobata, hidradenitis suppurativa, and dissecting cellulitis of the scalp with inflammatory arthritic conditions, we report five illustrative patients with this association, and a review of the literature. All our patients were African-American males, and their skin disease present before the onset of arthritis. Both asymmetric peripheral arthritis and axial disease can occur. The arthritis is usually insidious and lacks association with rheumatoid factor and HLA-B27. Imaging of peripheral joints can reveal erosions, periosteal bone reaction and new bone formation. When the axial skeleton is involved, imaging can reveal sacroiliitis, syndesmophyte formation. NSAIDs, oral and intra-articular steroids, DMARDs and TNF alpha antagonists have all been used with success. Controlled trials with larger numbers of patients are needed to assess which treatment options are the most effective for this group of patients.
25156958 Factors affecting hospital charges after total shoulder arthroplasty: an evaluation of the 2014 Dec BACKGROUND: The number of total shoulder arthroplasties (TSA) performed in the United States increases yearly. At the same time, cost containment in health care continues to be a major concern. Therefore, it is imperative to identify specific variables that affect the cost of shoulder arthroplasty. METHODS: The U.S. National Inpatient Sample database was queried (1993-2010) to evaluate total hospital charges for shoulder arthroplasty. Etiology of arthritis, multiple medical comorbidities, and patient and hospital demographics were evaluated for their effect on total inpatient hospital charges by a multivariate analysis. RESULTS: Hospital charges for TSA increased from 1993 to 2010. Gender, race, and obesity were not associated with these differences in hospital charges. Post-traumatic and rheumatoid arthritis resulted in increased hospital charges; however, osteoarthritis resulted in decreased charges from the baseline. Multiple comorbidities (diabetes, lung disease, heart disease, and kidney disease) resulted in increased hospital charges after TSA. Regionally, the western and southern United States had the highest total charges above baseline. Larger hospitals and private urban hospitals also showed charges above baseline. CONCLUSIONS: The factors related to increased hospital charges after TSA are multifactorial and include medical comorbidities, patient demographics, and regionalization. As the future of health care continues to evolve, it is important for practitioners, legislators, insurance administrators, and hospitals to recognize factors that increase costs.