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21693740 Association between disease-modifying antirheumatic drugs and diabetes risk in patients wi 2011 Jun 22 CONTEXT: Rheumatoid arthritis (RA) and psoriasis have been linked with insulin resistance and diabetes mellitus (DM). Prior investigations suggest that systemic immunosuppressive drugs may improve insulin resistance and reduce the risk of DM. OBJECTIVE: To compare the risk of newly recorded DM among participants diagnosed with RA or psoriasis based on use of a variety of disease-modifying antirheumatic drugs (DMARDs). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study among 121,280 patients with a diagnosis of either RA or psoriasis on at least 2 visits. The analyses were conducted in the context of 2 large health insurance programs, 1 in Canada and 1 in the United States, using administrative data. The mean follow-up was 5.8 months and began with the first prescription for a DMARD after study eligibility was met. Drug regimens were categorized into 4 mutually exclusive groups: (1) tumor necrosis factor (TNF) inhibitors with or without other DMARDs; (2) methotrexate without TNF inhibitors or hydroxychloroquine; (3) hydroxychloroquine without TNF inhibitors or methotrexate; or (4) other nonbiologic DMARDs without TNF inhibitors, methotrexate, or hydroxychloroquine (reference exposure). MAIN OUTCOME MEASURE: Newly recorded DM as evidenced by a new diagnosis of DM with use of a DM-specific medication. RESULTS: The study cohort consisted of 13,905 participants with 22,493 treatment episodes starting 1 of the categories of DMARD regimens between January 1996 and June 2008. New diabetes cases and respective incidence rates per 1000 person-years were: other nonbiologic DMARDs (55 cases among 3993 treatment episodes; rate, 50.2; 95% confidence interval [CI], 47.3-53.2); TNF inhibitors (80 cases among 4623 treatment episodes; rate, 19.7; 95% CI, 19.1-20.3); methotrexate (82 cases among 8195 treatment episodes; rate, 23.8; 95% CI, 23.0-24.6); and hydroxychloroquine (50 cases among 5682 treatment episodes; rate, 22.2; 95% CI, 21.3-23.1). The multivariate adjusted hazard ratios for DM were 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, 0.77 (95% CI, 0.53-1.13) for methotrexate, and 0.54 (95% CI, 0.36-0.80) for hydroxychloroquine compared with other nonbiologic DMARDS. CONCLUSION: Among patients with RA or psoriasis, the adjusted risk of DM was lower for individuals starting a TNF inhibitor or hydroxychloroquine compared with initiation of other nonbiologic DMARDs.
20020139 A case of cellulitis causing tissue defect during etanercept therapy. 2012 Jan Tumor necrosis factor-alpha (TNF-α) antagonists are employed increasingly during recent years in patients with active rheumatoid arthritis who do not respond to disease-modifying anti-rheumatic drugs. Contraindications such as infections, auto-antibody formation and hypersensitive reactions can be observed during the treatment with TNF-α antagonist drugs. Our case was a 52-year-old woman, followed by several centers for a period of 21 years with a seropositive, erosive and nodular RA diagnosis. Anti TNF-α treatment was commenced due to the failure to control the disease. During the treatment, a serious cellulite developed, which required hospitalization and surgical debridement as well as intravenous antibiotics treatment. Through the present case, we aimed to draw attention to the skin infection during the use of etanercept in a patient with RA.
21078627 Risk of adverse events including serious infections in rheumatoid arthritis patients treat 2011 Mar OBJECTIVE: To assess the risk of adverse events (AEs) in patients with RA treated with tocilizumab, an IL-6 receptor antibody, in published randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted using the Cochrane library, PUBMED and EMBASE for all RCTs (of the use of tocilizumab for RA) until September 2009. Fixed effect meta-analyses were conducted to compare the incidence of AEs after treatment with tocilizumab 8 and 4 mg/kg in combination with MTX, and 8 mg/kg tocilizumab monotherapy, with controls. Pooled summary odds ratios (ORs) were calculated using the Mantel-Haenszel method. RESULTS: Six trials were analysed (four trials included 8 mg/kg tocilizumab and MTX combination therapy, three of which also assessed the 4 mg/kg dose). Three studies assessed tocilizumab monotherapy at 8 mg/kg. Pooled ORs revealed statistical significance for an increased risk of AEs in the 8 mg/kg combination group compared with controls (OR = 1.53; 95% CI 1.26, 1.86). The risk of infection was significantly higher in the 8 mg/kg combination group compared with controls (OR = 1.30; 95% CI 1.07, 1.58). No increased incidence of malignancy, tuberculosis reactivation or hepatitis was seen. CONCLUSION: Tocilizumab in combination with MTX as a treatment for RA is associated with a small but significantly increased risk of AEs, which is comparable with that of other biologics. Vigilance for untoward effects is, therefore, imperative in any patient treated with these immuno-suppressive agents.
22146214 Bisphosphonate fractures as a cause of painful total hip arthroplasty. 2011 Dec 6 Osteoporotic fractures pose a significant health concern for postmenopausal women. Bisphosphonate therapy has been shown to decrease the risk of these fractures. The bisphosphonate alendronate was approved by the US Food and Drug Administration for use in the United States in 1995, but questions have recently arisen concerning low-energy subtrochanteric femur fractures sustained by chronic users. Although no definitive association or causality between bisphosphonates and these fractures has been established, numerous cautionary reports exist concerning the duration of use and safety of alendronate in osteoporotic patients. This article reports 3 occurrences of bisphosphonate-associated atypical femur fractures as an etiology of periprosthetic hip pain in the total hip arthroplasty (THA) patient. These fractures are particularly concerning because these patients are often not advised to protect their weight bearing simply due to a painful THA and may sustain a catastrophic failure if not followed closely. Several theories have been suggested concerning the pathophysiology of atypical low-energy subtrochanteric fractures following bisphosphonate use. Each patient described in this article carried a diagnosis of rheumatoid arthritis and underwent chronic medical therapy; each patient experienced a delay in the diagnosis and onset of therapy due to low suspicion for bisphosphonate-associated fracture. This problem may become more common in the clinical setting; therefore, one must be vigilant and aware of this etiology of periprosthetic hip pain.
21708014 Potential role and mechanism of IFN-gamma inducible protein-10 on receptor activator of nu 2011 Jun 27 INTRODUCTION: IFN-gamma inducible protein-10 (CXCL10), a member of the CXC chemokine family, and its receptor CXCR3 contribute to the recruitment of T cells from the blood stream into the inflamed joints and have a crucial role in perpetuating inflammation in rheumatoid arthritis (RA) synovial joints. Recently we showed the role of CXCL10 on receptor activator of nuclear factor kappa-B ligand (RANKL) expression in an animal model of RA and suggested the contribution to osteoclastogenesis. We tested the effects of CXCL10 on the expression of RANKL in RA synoviocytes and T cells, and we investigated which subunit of CXCR3 contributes to RANKL expression by CXCL10. METHODS: Synoviocytes derived from RA patients were kept in culture for 24 hours in the presence or absence of TNF-α. CXCL10 expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of cultured synoviocytes. Expression of RANKL was measured by RT-PCR and western blot in cultured synoviocytes with or without CXCL10 and also measured in Jurkat/Hut 78 T cells and CD4+ T cells in the presence of CXCL10 or dexamethasone. CXCL10 induced RANKL expression in Jurkat T cells was tested upon the pertussis toxin (PTX), an inhibitor of Gi subunit of G protein coupled receptor (GPCR). The synthetic siRNA for Gαi(2) was used to knock down gene expression of respective proteins. RESULTS: CXCL10 expression in RA synoviocytes was increased by TNF-α. CXCL10 slightly increased RANKL expression in RA synoviocytes, but markedly increased RANKL expression in Jurkat/Hut 78 T cell or CD4+ T cell. CXCL10 augmented the expression of RANKL by 62.6%, and PTX inhibited both basal level of RANKL (from 37.4 ± 16.0 to 18.9 ± 13.0%) and CXCL10-induced RANKL expression in Jurkat T cells (from 100% to 48.6 ± 27.3%). Knock down of Gα(i2) by siRNA transfection, which suppressed the basal level of RANKL (from 61.8 ± 17.9% to 31.1 ± 15.9%) and CXCL10-induced RANKL expression (from 100% to 53.1 ± 27.1%) in Jurkat T cells, is consistent with PTX, which inhibited RANKL expression. CONCLUSIONS: CXCL10 increased RANKL expression in CD4+ T cells and it was mediated by Gα(i) subunits of CXCR3. These results indicate that CXCL10 may have a potential role in osteoclastogenesis of RA synovial tissue and subsequent joint erosion.
21749686 The expression of the receptor for advanced glycation end-products (RAGE) in RA-FLS is ind 2011 Jul 12 INTRODUCTION: The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of arthritis. We conducted this study to determine the effect of interleukin (IL)-17 on the expression and production of RAGE in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). The role of nuclear factor-κB (NF-κB) activator 1 (Act1) in IL-17-induced RAGE expression in RA-FLS was also evaluated. METHODS: RAGE expression in synovial tissues was assessed by immunohistochemical staining. RAGE mRNA production was determined by real-time polymerase chain reaction. Act-1 short hairpin RNA (shRNA) was produced and treated to evaluate the role of Act-1 on RAGE production. RESULTS: RAGE, IL-17, and Act-1 expression increased in RA synovium compared to osteoarthritis synovium. RAGE expression and production increased by IL-17 and IL-1β (*P <0.05 vs. untreated cells) treatment but not by tumor necrosis factor (TNF)-α in RA-FLS. The combined stimuli of both IL-17 and IL-1β significantly increased RAGE production compared to a single stimulus with IL-17 or IL-1β alone (P <0.05 vs. 10 ng/ml IL-17). Act-1 shRNA added to the RA-FLS culture supernatant completely suppressed the enhanced production of RAGE induced by IL-17. CONCLUSIONS: RAGE was overexpressed in RA synovial tissues, and RAGE production was stimulated by IL-17 and IL-1β. Act-1 contributed to the stimulatory effect of IL-17 on RAGE production, suggesting a possible inhibitory target for RA treatment.
21702012 Cytosolic phospholipase A2 induction and prostaglandin E2 release by interleukin-1β via t 2011 Oct OBJECTIVE: Cytosolic phospholipase A2 (cPLA2) is a rate-limiting enzyme that plays a critical role in the biosynthesis of eicosanoids. The aim of this study was to investigate the mechanisms underlying interleukin-1β (IL-1β)-induced cPLA2 expression in human rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. In a mouse model of IL-1β-mediated inflammatory arthritis, neutrophil infiltration, bone erosion, and cPLA2 expression in ankle synovium were analyzed by immunohistochemistry. IL-1β-induced cPLA2 expression was determined by Western blotting, real-time polymerase chain reaction, and gene promoter assay using pharmacologic inhibitors and transfection with short hairpin RNAs or small interfering RNAs. The recruitment of NF-κB and p300 to the cPLA2 promoter was determined by chromatin immunoprecipitation assay. Prostaglandin E2 (PGE2) biosynthesis was evaluated by enzyme-linked immunosorbent assay. RESULTS: IL-1β-induced cPLA2 expression and PGE2 release were mediated through a myeloid differentiation factor 88 (MyD88)/c-Src-dependent matrix metalloproteinase (MMP)/heparin-binding epidermal growth factor (HB-EGF) cascade linking to transactivation of the EGF receptor (EGFR)/phosphatidylinositol 3-kinase (PI 3-kinase)/Akt, p300, and NF-κB p65 pathways. IL-1β also stimulated Akt phosphorylation and nuclear translocation. Activation of Akt eventually led to the acetylation of histone residues by phosphorylation and recruitment of p300 and enhanced its histone acetyltransferase activity on the NF-κB elements of the cPLA2 promoter. IL-1β-induced NF-κB transcriptional activity was mediated through a PI 3-kinase/Akt-dependent cascade. Up-regulation of cPLA2 by IL-1β increased PGE(2) biosynthesis in RASFs. CONCLUSION: IL-1β-induced cPLA2 expression is mediated through activation of the MyD88/c-Src, MMP/HB-EGF, EGFR/PI 3-kinase/Akt, p300, and NF-κB pathways. These results provide insights into the mechanisms underlying IL-1β-enhanced joint inflammatory responses in RA and may inspire new targeted therapeutic approaches.
22873531 Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. 2012 Aug 9 BACKGROUND: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. METHODS: In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). RESULTS: At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts. CONCLUSIONS: In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.).
20033415 Vitamin D level: is it related to disease activity in inflammatory joint disease? 2011 Apr The objectives of this study are to assess the vitamin D status in patients (pts) with inflammatory joint diseases (IJD), and its correlation with disease activity. 121 consecutive pts (85 rheumatoid arthritis (RA), 22 psoriatic arthritis (PSA), 14 ankylosing spondylitis (AS)) underwent clinical and laboratory evaluation which included kidney and liver function tests, serum calcium and phosphor levels, 25(OH)D and parathyroid hormone (PTH). Disease activity was assessed by DAS 28 in RA and PSA pts and by BASDAI in AS pts, sedimentation rate (ESR) and CRP. According to activity indexes, pts were divided into subgroups with low (DAS28 < 3.2 and BASDAI < 4), and moderate-to-high disease activity (DAS28 > 3.2 and BASDAI > 4). Associations between serum levels of 25(OH)D and age, gender, ethnicity, type and disease duration, treatment, (anti-tumor necrosis factorα (TNFα) agents or DMARDs), seasonal variations, and disease activity were assessed. Vitamin D deficiency was found in 51 pts (42.1%). The incidence was higher among Arab pts (76.7%) compared to Jews (23%). The difference of 25(OH)D levels between Arabs (mean 9.4 ± 4.2 ng/ml) and Jews (mean 17.8 ± 8.4 ng/ml) was statistically significant (p < 0.0001). We did not find correlation between vitamin D levels and the other evaluated factors. A surprisingly high incidence of vitamin D deficiency was found in IJD patients in a sunny Mediterranean country. This finding justifies the inclusion of vitamin D in the routine lab work-up of pts with IJD. The only statistical significant correlation was found between vitamin D level and ethnic origin. Further studies are needed to look for genetic polymorphism of vitamin D receptors.
23075431 Prevalence and severity of periodontitis in Indonesian patients with rheumatoid arthritis. 2013 Aug BACKGROUND: Patients with rheumatoid arthritis (RA) may have more prevalent and severe periodontitis than healthy controls. Periodontitis may increase the systemic inflammation in RA. The aim of this study is to assess periodontitis prevalence and severity and its potential association with systemic inflammation in Indonesian patients with RA. METHODS: A full-mouth periodontal examination including probing depth, gingival recession, plaque index, and bleeding on probing was performed in 75 Indonesians with RA and 75 age-, sex-, and smoking-matched Indonesian controls. A validated questionnaire was used to assess smoking, body mass index, education, and medical conditions. In addition, in all participants, the use of drugs was noted, and erythrocyte sedimentation rates and serum levels of high-sensitivity C-reactive protein (hsCRP), rheumatoid factor, and anti-citrullinated protein antibodies were measured. Differences in periodontitis prevalence and 12 measures of periodontitis severity between patients with RA and controls were analyzed using univariate analyses. RESULTS: No significant differences in periodontitis prevalence and 11 measures of periodontitis severity between patients with RA and controls were observed. Conversely, patients with RA had a significantly lower surface area of healthy pocket epithelium versus controls (P = 0.008), and a tendency toward higher hsCRP levels was observed in patients with RA with severe periodontitis compared with patients with RA with no mild or moderate periodontitis (P = 0.063). It has to be noted that all patients with RA were on anti-inflammatory drugs, whereas none of the controls used such drugs. CONCLUSION: Prevalence and severity of periodontitis in Indonesian patients with RA is comparable to controls but with less healthy pocket epithelium than in controls and a tendency toward a higher inflammatory state in patients with RA and severe periodontitis.
23138447 Evaluation of the efficacy and safety of etanercept 50 mg once weekly in Japanese patient 2013 Sep OBJECTIVE: Tumor necrosis factor-α inhibitors have been available in recent years for treating early and established rheumatoid arthritis (RA). Twice-weekly administration of 25 mg etanercept (ETN) has demonstrated efficacy and safety. The objective of this study was to evaluate the efficacy of once-weekly administration of 50 mg ETN (ETN50), and to compare it with that of twice-weekly administration of 25 mg ETN (ETN25). METHODS: The ETN50 group comprised 29 patients and the ETN25 group 26. The analysis compared changes from baseline in Disease Activity Score in 28 joints (DAS28)-C reactive protein (CRP) and DAS28-erythrocyte sedimentation rate (ESR) between the ETN50 and ETN25 groups. RESULTS: Overall, 42.3 % of ETN50 patients achieved DAS28-ESR remission (<2.6), and 76.9 % experienced low disease activity at 24 weeks. Patients in the ETN50 group also experienced more significant improvement in DAS28-ESR at 4 weeks, higher DAS28-ESR remission rates, and lower disease activity rates than ETN25 group patients. No serious adverse events were experienced in the safety analysis set (ETN50 group). CONCLUSION: These results suggest that ETN50 can lead to earlier remission and higher remission rates compared with ETN25 in patients with RA.
21892671 Study protocol of a multicenter registry of patients with rheumatoid arthritis starting bi 2012 Jun Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.
20171051 Total hip arthroplasty with an uncemented tapered femoral component in patients younger th 2011 Jan The purpose of the present study was to evaluate the outcome of primary uncemented total hip arthroplasty in patients younger than 50 years using the Taperloc (Biomet, Warsaw, Ind) femoral component. We evaluated 94 hips in 79 patients at a mean follow-up of 16 years (range, 11-18.5 years). The average age of the patients at the time of surgery was 36 years (range, 20-49 years). Three femoral components had been revised, none for aseptic loosening. Complete clinical and radiographic follow-up was obtained on the 91 hips that had not undergone femoral component revision. The mean Harris hip score increased from 54 points (range, 20-72) before surgery to 93 points (range, 68-100) at the time of this review. Radiographically, 89 stems (98%) were determined to have fixation by bone ingrowth, 2 (2%) demonstrated stable fibrous ingrowth, and no femoral component was loose. Distal femoral osteolysis was identified in 1 hip (1%). These findings indicate that excellent clinical and radiographic results can be achieved in young patients with the Taperloc femoral component at a mean follow-up of 16 years.
23213270 Increased toll-like receptor 2 expression in peptidoglycan-treated blood monocytes is asso 2012 The close relationship between increased TLR-2 expression in blood monocytes and insulin resistance in RA patients is shown in this study. Traditional risk factors for metabolic disorders, including the waist circumstance, body mass index (BMI), triglyceride (TG), and ratio of TG to high density lipoprotein (HDL) cholesterol, were closely correlated with HOMA (homoeostasis model assessment) index in patients with nondiabetic RA. Expressions of TLR2 in peripheral blood monocytes, following stimulation with peptidoglycan which is known as a TLR2 agonist, were closely correlated with the HOMA index, TNF-α, and IL-6 concentrations. Accordingly, TLR-2 receptor and its related inflammatory cytokines could be potential therapeutic targets in managing insulin resistance in RA patients.
20701456 Could antibodies against serum amyloid A function as physiological regulators in humans? 2011 Mar The natural structuring of the immune system is responsible for the functional physiological state of the body. The development of natural autoantibodies involved in homeostasis relies on the ability to distinguish between exposed/masked and altered/non-altered self antigens. The objectives of this article were to address the relationships between antigen and autoantibodies against serum amyloid A (SAA), define SAA protein concentrations in 219 blood donor (BD) sera and determine their autoantibody levels and search for possible clinical associations with autoimmune and thrombotic diseases. Just recently, an increasing number of reports have indicated significantly decreased levels of autoantibodies against pro-inflammatory molecules, such as anti-TNF-alpha, anti-IL-6, or anti-CRP found in diseased conditions, as compared to healthy donors, or even to less severe disease conditions. In accord with this line of thought, our data indicate a predominant presence of anti-SAA autoantibodies in healthy BDs (above 95% as tested by the immunoblot analysis, n = 41). Using ELISA, high levels of anti-SAA antibodies were confirmed with a median OD = 0.996 for the BD group (n = 219). This suggests that anti-SAA antibodies might have a physiological role in homeostasis and/or the innate immune system and could actually be a part of the natural antibody repertoire. Significantly, lower median levels were found in patients with arterial thrombosis. Based on 219 BD sera, we could establish a new median value of 20 μg/ml for SAA antigen and a cut-off value of 114.7 μg/ml (97.5th percentile). Significantly, higher concentrations of SAA were observed for antiphospholipid syndrome, rheumatoid arthritic, and SLE patients.
21698373 Cemented fixed-bearing PFC total knee arthroplasty: survival and failure analysis at 12-17 2011 Sep BACKGROUND: Total knee arthroplasty (TKA) is the appropriate treatment for degenerative pathology of the knee. Implant surveillance is mandatory to improve clinical results. We present the long-term results of a series of consecutive TKA Press Fit Condylar (J&J), cemented fixed bearing with selective patellar resurfacing in nonselected patients. MATERIALS AND METHODS: In this prospective case series, 223 TKA were clinically and radiographically evaluated using the Hospital for Special Surgery (HSS) knee score and the Knee Society Roentgenographic Evaluation and Scoring System. RESULTS: There were 197 patients, with an average age of 68.4 years [95% confidence interval (CI) 52.7-84.1 years]; 49 arthroplasties were implanted in men (21.1%) and 184 (78.9%) in women. The average follow-up was approximately 13.5 years (162.1 months; 95% CI 132.3-191.9), and it was possible to evaluate 179 implants (76.8% of the implanted prosthesis) in 176 patients. The average HSS score increased from 61.5 (95% CI 60.4-62.7) to 89.4 (95% CI 87.7-.93.5) points. The cumulative average survival rate at 15 years (the endpoint being failure with revision) was 90.6%  ± 2% standard deviation. Resurfacing the patella did not make a difference in terms of implant survival. Progressive radiolucent lines were observed around 20 implants (14.3%); all were revised. CONCLUSIONS: The PFC system is an excellent prosthetic solution. Early clinical complications, mechanical axis and patellar resurfacing do not correlate with implant failure, whereas progressive radiolucent lines do.
21423632 Design of glycopeptides used to investigate class II MHC binding and T-cell responses asso 2011 Mar 15 The glycopeptide fragment CII259-273 from type II collagen (CII) binds to the murine A(q) and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259-273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259-273 glycopeptide library in which two anchor positions crucial for binding in pockets of A(q) and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to A(q) and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.
21114589 Salivary flow rate and periodontal infection - a study among subjects aged 75 years or old 2011 May OBJECTIVE: To analyse the relation of stimulated and unstimulated salivary flow rates to periodontal infection in home-dwelling elderly people aged 75 years or older. SUBJECTS AND METHODS: This study was based on a subpopulation of 157 (111 women, 46 men) home-dwelling, dentate, non-smoking elderly people (mean age 79.8, SD 3.6 years) from the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly Study). The data were collected by interview and oral clinical examination. RESULTS: Persons with very low (< 0.7 ml min⁻¹) and low stimulated salivary flow rates (0.7- < 1.0 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR: 0.7, CI: 0.5-0.9 and RR: 0.7, CI: 0.5-0.9, respectively, when compared with those with normal stimulated salivary flow. Persons with a very low unstimulated salivary flow rate (< 0.1 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR 0.8, CI: 0.6-1.0, when compared with subjects with low/normal unstimulated salivary flow. CONCLUSIONS: In a population of dentate, home-dwelling non-smokers, aged 75 years or older, low stimulated and unstimulated salivary flow rates were weakly associated with a decreased likelihood of having teeth with deep periodontal pockets.
22209041 The minimum 10-year results of a second-generation cementless acetabular shell with a poli 2012 Aug The purpose of this prospective study was to evaluate the minimum 10-year outcomes and survivorship of the Reflection shell with a polished inner surface and an improved locking mechanism. Three hundred sixty-three total hip replacements with a mean follow-up of 11.6 years (range, 10.0-15.1) were evaluated. The mean Harris Hip and WOMAC scores at last follow-up were 87 and 77, respectively. Four cups were revised: 2 for infection and 2 for aseptic loosening. Thirteen cases underwent liner exchange for wear. Radiographic review of remaining cups identified 8.8% with identifiable peri-acetabular osteolysis and no cases of loosening. The overall 10- and 15-year Kaplan-Meier survivorship was 94% and 90% for the total hip arthroplasty system while the survivorship of the shell remained 99.4% at 15 years.
21332746 Temporomandibular joint reconstruction with total alloplastic joint replacement. 2011 Mar This paper is a preliminary paper which presents the early findings of an ongoing prospective trial on the use of the TMJ Concepts and Biomet Lorenz total joint replacement systems for the reconstruction of the temporomandibular joint (TMJ). Total alloplastic replacement of the TMJ has become a viable option for many people who suffer from TMJ disease where surgical reconstruction is indicated. Degenerative joint diseases such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, TMJ ankylosis, malunited condylar fractures and tumours can be successfully treated using this technique. There are a number of TMJ prostheses available. Two of the joint replacement products, which have been found to be most reliable and have FDA approval in the United States, are the TMJ Concepts system and the Biomet Lorenz system, and for this reason they are being investigated in this study. This study presents the findings of seven patients with a total of 12 joint replacements using either the TMJ Concepts system or the Biomet Lorenz joint system. Two patients (3 joints) had the TMJ Concepts system and five patients (9 joints) had the Biomet Lorenz system. Although still early, the results were generally pleasing, with the longest replacement having been in position for three years and the most recent six months. The average postoperative mouth opening was 29.7 mm (range 25-35 mm) with an average pain score of 1.7 (range 0-3, minimum score of 0 and maximum 10). Complications were minimal and related to sensory disturbance to the lip in one patient and joint dislocation in two patients.