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

ID PMID Title PublicationDate abstract
25198369 Magnitude and clinical profile of juvenile idiopathic arthritis in a medical college hospi 2013 BACKGROUND: A number of children with Juvenile Idiopathic Arthritis (JIA) got admitted in the pediatrics ward of a medical college hospital. However, burden and clinical pattern of JIA have not been studied in our country. OBJECTIVES: To estimate the burden of JIA admitted in the pediatric department of medical college hospital of Bangladesh and to observe the status of active JIA in respect to magnitude, clinical profile and hematological changes. METHODS: A prospective study was carried out among the patients admitted in pediatric ward of a medical college hospital, Bangladesh from 2008 to 2010. All active JIA patients admitted during this period were included in this study. JIA was diagnosed according to the ILAR criteria. Male/Female ratio, age, Total Leukocyte Count (TLC), Differential count (D/C), Platelet count, Erythrocyte Sedimentation Rate (ESR), C Reactive Protein (CRP), Rheumatoid Factor (RF) of JIA patients were recorded. These were statistically analyzed with the help of SPSS programme using chi-square test. RESULTS: Twenty five cases of active JIA were diagnosed during this period. Magnitude was 3.75 per 1000 admitted cases. Male/Female ratio was 1.08:1. 10 (40%) cases were between the ages of 8 to 11 years. Polyarticular seronegative JIA was found in 10 (40%) cases and oligoarticular JIA in the next order 6 (24%). High ESR, TLC, platelet count was observed in 21 (84%) [p <.001], 19 (76%) [p <.009], 3 (12%) [p <.000] cases respectively. CONCLUSION: Burden of JIA was similar to all the areas of the world. Polyarticular seronegative JIA was commonly observed in our study. High ESR, increased TLC and Platelet count was the reliable predictor of active JIA.
25311252 Atypical focal forms of Whipple's disease seen by rheumatologists. 2015 Jan We report two atypical cases of focal Whipple's disease with rheumatic presenting symptoms. In one of these cases, the patient presented with chronic intermittent polyarthritis, systemic inflammation, and leukocytosis. Tests were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. There was no structural joint damage. Combined glucocorticoid and methotrexate therapy was only partially effective. Endocarditis requiring emergency valve replacement surgery occurred 4 years later. Evaluation of this event led to the diagnosis of Tropheryma whipplei infection responsible for both the endocarditis and the joint disease. The other patient presented with subacute inflammatory low back pain. His medical history was chiefly remarkable for intermittent inflammatory involvement of the wrists and right knee replacement surgery for osteoarthritis followed by a febrile effusion of the operated knee. Radiographs showed destructive lesions of the wrists. Magnetic resonance imaging findings suggested L2-L3 diskitis. A PCR assay on biopsy specimens from the disk lesions recovered T. whipplei, thus establishing the cause of the diskitis and previous joint manifestations. Combined doxycycline and hydroxychloroquine therapy was followed by full resolution of all clinical and laboratory abnormalities in both patients.
24020968 TNF receptor-associated factor 5 gene confers genetic predisposition to acute anterior uve 2013 INTRODUCTION: TNF Receptor-Associated Factor 5 (TRAF5) has been shown to be associated with autoimmune disease. The current study sought to investigate the potential association of TRAF5 with acute anterior uveitis (AAU) and pediatric uveitis in Han Chinese. METHODS: Three TRAF5 SNPs were analyzed in 450 AAU patients with or without ankylosing spondylitis (AS), 458 pediatric uveitis patients, and 1,601 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP Genotyping Assay. Numerous variables were evaluated, including age, sex distribution, and clinical and laboratory observations. RESULTS: Two SNPs (rs6540679, rs12569232) of TRAF5 were associated with pediatric uveitis, and rs12569232 also showed a relation with the presence of microvascular leakage. No significant associations were found when patients were subdivided according to their rheumatoid factor (RF) or anti-nuclear antibody (ANA) status or whether they had juvenile idiopathic arthritis (JIA). Rs12569232 predisposed to AAU and its subgroups (with ankylosing spondylitis (AS) or HLA-B27 positive). No association was found between rs10863888 and either pediatric uveitis or AAU. CONCLUSION: This study revealed that TRAF5 is involved in the development of AAU and pediatric uveitis. Further stratified analysis according to the clinical and laboratory observations suggested that rs12569232/TRAF5 may play a role in the development of retinal vasculitis.
24772147 Determination of Anti-nuclear Antibody Pattern Distribution and Clinical Relationship. 2014 Mar BACKGROUND AND OBJECTIVES: Autoantibodies are immunglobulins occurred directly against autoantigens that are known as endogen antigens. Autoimmune disease is an occasion that the body begins a fight against its own cells and tissues. The antibodies that are created by the body against its own cell nuclei are called as anti-nuclear antibodies (ANA), and one of the methods used for detection and pattern of ANA is indirect immunofluorescence test (IIF). In the present study, it was aimed to determine the rate of ANA positivity and patterns of the positive specimens, and to investigate the relationship between ANA positivity and diseases in patients. METHODS: ANA test results of a total of 3127 patients admitted during March 2010 to December 2012 were evaluated retrospectively. ANA test (HEp 20-10, EUROIMMUN, Germany) was used in dilution of 1:100 in IIF test. RESULTS: A total of 494 (15.8%) resulted as ANA positive. ANA positivity rate was significantly higher in female patients than the male ones (p<0.001). The most frequent ANA patterns were coarse speckled pattern (154 patients, 31.2%), nucleolar pattern (89 patients, 18.0%), fine speckled pattern (57 patients, 11.5%), and speckled pattern (48 patients, 9.7%). ANA positivity was most commonly determined in rheumatoid arthritis (RA) (42 patients, 8.5%), systemic lupus erythematosus (SLE) (29 patients, 5.9%), and rheumatoid vasculitis (RV) (28 patients, 5.7%). The most frequent symptoms or findings were joint pain (127 patients, 26.0%) and anemia (28 patients, 5.7%). ANA positivity rates were found to be significantly higher in patients with RA (p<0.001), with SLE (p<0.001), and with Raynaud phenomenon (p=0.001) in comparison to the controls. Amongst the most frequent diseases evaluated, no significant differences were found between the control groups and the groups of RV (p=0.089), multiple sclerosis (p=0.374), and Sjögren syndrome (p=0.311) in terms of ANA positivity rates. CONCLUSIONS: The present study is the first study reporting the positivity rate and distribution of ANA in Bolu located in northwestern Turkey. Information about the pattern types and the distribution of the patterns according to the diseases and symptoms contribute in diagnosis of autoimmune diseases. It is observed that clinical diagnosis has been supported significantly by ANA test according to data of our study.
23964148 Connective tissue diseases in primary biliary cirrhosis: a population-based cohort study. 2013 Aug 21 AIM: To establish the frequency and clinical features of connective tissue diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis (PBC). METHODS: Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD, and the systemic involvement was assessed. The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented. The diversity of incidence of CTDs in PBC of different countries and areas was discussed. For the comparison of normally distributed data, Student's t test was used, while non-parametric test (Wilcoxon test) for the non-normally distributed data and 2 × 2 χ(2) or Fisher's exact tests for the ratio. RESULTS: One-hundred and fifty (46.6%) PBC patients had one or more CTDs. The most common CTD was Sjögren's syndrome (SS, 121 cases, 36.2%). There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the PBC + SS patients were more likely to have fever and elevated erythrocyte sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences; PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower white blood cell (WBC) count, hemoglobin (Hb), platelet count, γ-glutamyl transpeptidase and immunoglobulin M levels, but higher frequency of renal involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients had higher WBC count and a tendency towards myocardial involvement. CONCLUSION: Besides the common liver manifestation of PBC, systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients. When overlapping with other CTDs, PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis.
25022061 [Comparison of tests for SS-A/Ro, Ro52 and Ro60 in predicting congenital heart block]. 2014 Apr Neonatal lupus erythematosus (NLE) is a rare syndrome caused by the transplacental passage of maternal autoantibodies. Anti SS-A antibodies of a mother with Sjögren syndrome are associated with congenital heart block (CHB) in the newborns with NLE. The purpose of this study was to investigate the utility of maternal antibody titers for SS-A, Ro52 and Ro60 in mothers of newborns with CHB. The study involved a total of 304 cases, 25 from mothers of newborns with CHB, 104 from mothers of newborns without and 175 from mothers suspected to have connective tissue diseases. All sera were tested with the EliA SS-A, EliA Ro52, EliA Ro60, MESACUP Ro52 and MESACUP Ro60. The concordance rate of Ro52 assays was 93.4%, whereas Ro60 assays showed a lower concordance rate (74.7%). The areas under the curve (AUC) of the EliA assays were higher than those of the MESACUP assays. The optimal cut-off values for EliA SS-A/Ro and EliA Ro60 as derived from the ROC analysis were 2027 U/mL and 2446 U/mL, respectively. The sensitivity and specificity for EliA SS-A using optimal cut-off values were 96.0% and 92.3%, respectively. A titer of 90% positive predictive value for EliA SS-A was reached at a cut-off of 9897.1 U/mL, corresponding to sensitivity and specificity values of 36.0% and 100%, respectively. In conclusion, the optimal cut-off value for EliA SS-A is likely to be useful for application in clinical practice for the EliA SS-A measurements in mothers to evaluate the risk of NLE for their newborns.
24661509 Facial nerve compression by the posterior inferior cerebellar artery causing facial pain a 2014 Mar 25 INTRODUCTION: We report an unusual case of facial pain and swelling caused by compression of the facial and vestibulocochlear cranial nerves due to the tortuous course of a branch of the posterior inferior cerebellar artery. Although anterior inferior cerebellar artery compression has been well documented in the literature, compression caused by the posterior inferior cerebellar artery is rare. This case provided a diagnostic dilemma, requiring expertise from a number of specialties, and proved to be a learning point to clinicians from a variety of backgrounds. We describe the case in detail and discuss the differential diagnoses. CASE PRESENTATION: A 57-year-old Caucasian woman with a background of mild connective tissue disease presented to our rheumatologist with intermittent left-sided facial pain and swelling, accompanied by hearing loss in her left ear. An autoimmune screen was negative and a Schirmer's test was normal. Her erythrocyte sedimentation rate was 6mm/h (normal range: 1 to 20mm/h) and her immunoglobulin G and A levels were mildly elevated. A vascular loop protocol magnetic resonance imaging scan showed a loop of her posterior inferior cerebellar artery taking a long course around the seventh and eighth cranial nerves into the meatus and back, resulting in compression of her seventh and eighth cranial nerves. Our patient underwent microvascular decompression, after which her symptoms completely resolved. CONCLUSION: Hemifacial spasm is characterized by unilateral clonic twitching, although our patient presented with more unusual symptoms of pain and swelling. Onset of symptoms is mostly in middle age and women are more commonly affected. Differential diagnoses include trigeminal neuralgia, temporomandibular joint dysfunction, salivary gland pathology and migrainous headache. Botulinum toxin injection is recognized as an effective treatment option for primary hemifacial spasm. Microvascular decompression is a relatively safe procedure with a high success rate. Although a rare pathology, posterior inferior cerebellar artery compression causing facial pain, swelling and hearing loss should be considered as a differential diagnosis in similar cases.
23830938 A current review of molecular mechanisms regarding osteoarthritis and pain. 2013 Sep 25 Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future.
24614117 Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European co 2014 BACKGROUND: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. AIM: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. METHODS: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. RESULTS: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively. CONCLUSIONS: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
25057265 Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idio 2014 BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged ≥2 to <18 years with rheumatoid-factor-positive or -negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. RESULTS: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. CONCLUSIONS: The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00688545.
25704907 Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systemati 2015 Jun OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection. METHODS: To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles. RESULTS: The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test. CONCLUSION: In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin.
24774505 Adalimumab in the treatment of immune-mediated diseases. 2014 Jan Tumour necrosis factor (TNF) plays an important role in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). TNF inhibition results in down-regulation of abnormal and progressive inflammatory processes, resulting in rapid and sustained clinical remission, improved quality of life and prevention of target organ damage. Adalimumab is the first fully human monoclonal antibody directed against TNF. In this article, we review the role and cost effectiveness of adalimumab in the treatment of IMIDs in adults and children. The efficacy and tolerability of adalimumab has been demonstrated in patients with a wide range of inflammatory conditions, leading to regulatory approval in rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, paediatric Crohn's disease, and intestinal Behçet's disease), ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and juvenile idiopathic arthritis. The major tolerability issues with adalimumab are class effects, such as injection site reactions and increased risk of infection and lymphoma. As with all anti-TNF agents, adalimumab is immunogenic, although less than infliximab, and some patients receiving long-term adalimumab will develop anti-drug antibodies, causing a loss of response. Comparisons of its clinical utility and cost effectiveness have shown it to be a valid treatment choice in a wide range of patients. Recent data from Italian economic studies show the cost effectiveness of adalimumab to be below the threshold value for health care interventions for most indications. In addition, analysis of indirect costs shows that adalimumab significantly reduces social costs associated with RA, PsA, AS, Crohn's disease and psoriasis. The fact that adalimumab has the widest range of approved indications, many often presenting together in the same patient due to the common pathogenesis, may further improve the utility of adalimumab. Current clinical evidence shows adalimumab to be a valuable resource in the management of IMIDs. Further research, designed to identify patients who may benefit most from this drug, will better highlight the role and cost-effectiveness of this versatile TNF inhibitor.
24147035 Innate immune signaling induces interleukin-7 production from salivary gland cells and acc 2013 Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren's syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues.
25674194 Spectrum of ultrasound pathologies of achilles tendon, plantar aponeurosis and flexor digi 2014 BACKGROUND: Enthesitis is considered a characteristic presentation of the second most common group of rheumatoid disorders, i.e. spondyloarthropathies (SpAs), particularly peripheral spondyloarthropathies. At the initial stages, enthesitis may be the only symptom of SpA, particularly in patients lacking the HLA-B27 receptor. MATERIAL/METHODS: In light of diagnostic difficulties with detecting enthesitis in clinical examinations and laboratory investigations, many studies point out the high specificity of imaging studies, and particularly ultrasonography. RESULTS: A total of 20% Achilles tendon entheses, 45% plantar aponeurosis entheses and 89.5% of flexor digiti brevis tendon entheses were unremarkable. In the remaining cases, the presentation of pathological lesions was not specific to enthesitis and might more likely correspond to degeneration or microinjuries of the entheses, beside the most obvious cases of achillobursitis or Kager's fat pad inflammation. CONCLUSIONS: The studies demonstrated that ultrasound scans rarely confirm the clinical diagnosis of enthesitis.
24331123 Aseptic loosening rate of the humeral stem in the Coonrad-Morrey total elbow arthroplasty. 2014 Jan BACKGROUND: Aseptic implant loosening is one of the most common complications leading to revision surgery in total elbow arthroplasty. Different humeral stem lengths are available with varying designs. In general, the decision of which stem length to use depends on the surgical diagnosis or simply the surgeon preference. Often, the longer stem is used for post-traumatic or revision cases while for rheumatoid patients the shorter stem is preferred. There are no data in the literature to favor one humeral stem size over the other according to the diagnosis. METHODS: We analyzed the total elbow joint database of the Coonrad-Morrey design at our institution for aseptic loosening leading to revision and compared the revision rate and the survival of the 4- and 6-inch humeral stems. RESULTS: Overall, revision for aseptic humeral loosening is infrequent and occurred in only 16 of 711 total elbow arthroplasties during a mean follow-up of 88 months. There was no significant difference in the revision rate between the 2 stem lengths (1.9% for the 4-inch stems and 2.6% for the 6-inch stem). CONCLUSION: Revision rate was correlated to the surgical diagnosis and was significantly higher for post-traumatic patients than for rheumatoid patients (5.1% vs 0.66%, P < .001). Of interest, and possibly not surprising, the mean time to revision was shorter for the 4-inch stems than it was for the 6-inch stems (37 vs 95 months, P = .034).
24976694 Oral manifestations of hepatitis C virus infection. 2014 Jun 28 Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV.
24792338 Longitudinally extensive transverse myelitis. 2014 Jun PURPOSE OF REVIEW: Longitudinally extensive transverse myelitis (LETM) is a frequently devastating clinical syndrome which has come into focus for its association with neuromyelitis optica (NMO). Recent advances in the diagnosis of NMO have led to very sensitive and specific tests and advances in therapy for this disorder. LETM is not pathognomonic of NMO, therefore it is important to investigate for other causes of myelopathy in these patients. This review aims to discuss recent advances in NMO diagnosis and treatment, and to discuss the differential diagnosis in patients presenting with LETM. RECENT FINDINGS: Fluorescence-activated cell sorting and cell binding assays for NMO-IgG are the most sensitive for detecting NMO spectrum disorders. Patients who have a clinical presentation of NMO, who have been tested with older ELISA or immunofluorescence assay and been found to be negative, should be retested with a fluorescence-activated cell sorting assay when available, particularly in the presence of recurrent LETM. Novel therapeutic strategies for LETM in the context of NMO include eculizumab, which could be considered in patients with active disease who have failed azathioprine and rituximab. Thorough investigation of patients with LETM who are negative for NMO-IgG may lead to an alternate cause for myelopathy. SUMMARY: LETM is a heterogeneous condition. Novel treatment strategies are available for NMO, but other causes need to be excluded in NMO-IgG-seronegative patients.
25519434 Increasing obesity and comorbidity in patients undergoing primary total hip arthroplasty i 2014 Dec 17 BACKGROUND: Few, if any data are available are available regarding the time-trends in characteristics of patients who have undergone primary THA. Our objective was to examine the time-trends in key demographic and clinical characteristics of patients undergoing primary total hip arthroplasty (THA). METHODS: We used the data from the Mayo Clinic Total Joint Registry from 1993-2005 to examine the time-trends in demographics (age, body mass index (BMI)), medical (Deyo-Charlson index) and psychological comorbidity (anxiety, depression) and underlying diagnosis of patients undergoing primary THA. Chi-square test and analysis for variance were used. Multivariable-adjusted logistic regression (age, sex, comorbidity-adjusted) compared 1993-95 to other study periods. Odds ratio (OR) and 95% confidence interval (CI) are presented. RESULTS: The primary THA cohort consisted of 6,168 patients with 52% women. In unadjusted analyses, compared to 1993-95, significantly more patients (by >2-times for most) in 2002-05 had: BMI ≥ 40, 2.3% vs. 6.3%; depression, 4.1% vs. 9.8%; and anxiety, 3.4% vs. 5.7%; and significantly fewer had an underlying diagnosis of rheumatoid/inflammatory arthritis, 3.7% vs. 1.5% (p ≤ 0.01 for all). In multivariable-adjusted models, compared to 1993-95, significantly more patients in 2003-05 had (all p-values ≤ 0.01): BMI ≥ 40, OR, 2.79 (95% CI: 1.85, 4.22); Deyo-Charlson Index ≥ 3, 1.32 (1.07, 1.63); depression, 2.25 (1.66, 3.05); and anxiety, 1.71 (1.19, 2.15). Respectively, fewer patients had a diagnosis of RA/inflammatory arthritis: 0.28 (0.17, 0.46; p < 0.01). Over the 13-year study period, Deyo-Charlson index increased by 22% (0.9 to 1.1) and the mean age decreased by 0.7 years (65.0 to 64.3) (p < 0.01 for both). CONCLUSIONS: Obesity, medical and psychological comorbidity increased and the underlying diagnosis of RA/inflammatory arthritis decreased rapidly in primary THA patients over 13-years. Our cohort characteristics are similar to previously described characteristics of national U.S. cohort, suggesting that these trends may be national rather than local trends. This is important information for policy makers to take into account for resource allocation. Studies of THA outcomes and utilization should take these rapidly changing patient characteristics into account.
24594001 A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade 2014 Feb Interleukin-6 (IL-6) is a cytokine with redundant and pleiotropic activities, and its synthesis is tightly regulated by transcriptional and posttranscriptional mechanisms. When infections and tissue injuries occur, IL-6 synthesis is promptly induced and provides an emergent signal that contributes to host defense through the stimulation of acute-phase responses, immune reactions, and hematopoiesis. After the environmental stress is removed from the host, the production of IL-6 is terminated. However, dysregulated continual synthesis of IL-6 is involved in the development of chronic inflammatory autoimmune diseases. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Worldwide clinical trials have demonstrated the outstanding efficacy of tocilizumab in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease; thus, a new era has come for the treatment of these diseases, which were previously considered intractable. Moreover, favorable results from off-label use of tocilizumab strongly suggest that it will be widely applicable for various refractory inflammatory autoimmune diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated in order to investigate the pathogenesis of specific diseases and to facilitate the development of more specific therapeutic strategies.
23945602 Anti-inflammatory components of the starfish Astropecten polyacanthus. 2013 Aug 13 Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively.