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ID PMID Title PublicationDate abstract
22843791 Comparative effectiveness and predictors of response to tumour necrosis factor inhibitor t 2012 Nov OBJECTIVES: Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort. METHODS: Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified. RESULTS: The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response. CONCLUSION: Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.
21789498 Position of the prosthesis components in total ankle replacement and the effect on motion 2012 Mar PURPOSE: In some cases of total ankle replacement, perfect alignment of the prosthetic components is not achieved. This study analyses the extent to which component positioning is critical for the final range of motion. METHODS: Fourteen patients undergoing total ankle replacement were assessed preoperatively and postoperatively at seven and 13 months follow-up. X-ray pictures of the ankle were taken in static double leg stance, i.e. at neutral joint position, and in maximum plantarflexion and dorsiflexion. Measurements were obtained by a specially devised computer program based on anatomical reference points digitised on the radiograms. These allowed calculation of the position and orientation of the components in the sagittal and coronal planes, together with the joint range of motion. RESULTS: The mean range of motion was about 34 degrees at the first follow-up and maintained at the second. Tibial and talar components were more anterior than the mid-tibial shaft in 11 and nine patients, respectively. Mean inclination was about four degrees posterior for the tibial component and nearly one degree anterior for the talar component. A significantly larger range of motion was found in ankles both with the talar component located and inclined more anteriorly than the tibial. CONCLUSIONS: Correlation, though weak, was found between motion at the replaced ankle and possible residual subluxation and inclination of the components. However, a satisfactory range of motion was also achieved in those patients where recommended locations for the components could not be reached because of the size of the original joint deformity.
21600028 Use of tranexamic acid is a cost effective method in preventing blood loss during and afte 2011 May 21 BACKGROUND & PURPOSE: Allogenic blood transfusion in elective orthopaedic surgery is best avoided owing to its associated risks. Total knee replacement often requires blood transfusion, more so when bilateral surgery is performed. Many strategies are currently being employed to reduce the amount of peri-operative allogenic transfusions. Anti-fibrinolytic compounds such as aminocaproic acid and tranexamic acid have been used systemically in perioperative settings with promising results. This study aimed to evaluate the effectiveness of tranexamic acid in reducing allogenic blood transfusion in total knee replacement surgery. METHODOLOGY: This was a retrospective cohort study conducted on patients undergoing total knee replacement during the time period November 2005 to November 2008. Study population was 99 patients, of which 70 underwent unilateral and 29 bilateral knee replacement. Forty-seven patients with 62 (49.5%) knees (group-I) had received tranexamic acid (by surgeon preference) while the remaining fifty-two patients with 66 (51.5%) knees (group-II) had did not received any tranexamic acid either pre- or post-operatively. RESULTS: The mean drop in the post-operative haemoglobin concentration in Group-II for unilateral and bilateral cases was 1.79 gm/dl and 2.21 gm/dl, with a mean post-operative drainage of 1828 ml (unilateral) and 2695 ml (bilateral). In comparison, the mean drop in the post-op haemoglobin in Group-I was 1.49 gm/dl (unilateral) and 1.94 gm/dl (bilateral), with a mean drainage of 826 ml (unilateral) and 1288 ml (bilateral) (p-value < 0.001). INTERPRETATION: Tranexamic acid is effective in reducing post-operative drainage and requirement of blood transfusion after knee replacement.
21161534 Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheuma 2012 Mar The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.
21752492 Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: 2012 Nov BACKGROUND: Tumor necrosis factor (TNF)-α antagonists have been associated with the induction of de novo or worsening psoriasis. OBJECTIVE: We sought to retrospectively examine the clinical characteristics and outcomes of patients with psoriasis associated with anti-TNF-α therapy. METHODS: We performed a retrospective review of patients with new-onset or worsening psoriasis during TNF-α inhibitor therapy between 1998 and 2010. RESULTS: Of the 56 patients (mean age at psoriasis onset, 48.1 years), 41 (73%) were female. In all, 22 patients (39%) had Crohn's disease and 14 (25%) had rheumatoid arthritis. Thirty patients (54%) were treated with infliximab, 19 (34%) with adalimumab, and 7 (12%) with etanercept. New-onset or worsening psoriasis occurred after a mean treatment duration of 17.1 months. Plaque psoriasis (n = 27), palmoplantar pustulosis (n = 25), scalp psoriasis (n = 12), generalized pustular psoriasis (n = 7), erythrodermic psoriasis (n = 2), and inverse psoriasis (n = 2) were the cutaneous presentations. Among the 39 patients for whom full treatment response data were available, 33 (85%) had a complete or partial response; combined response rates (complete and partial) were slightly higher among those who discontinued anti-TNF-α therapy (16 of 17 patients [94%]) than among those who continued anti-TNF-α therapy (17 of 22 patients [77%]). LIMITATIONS: Retrospective nature, possible referral bias, and lack of complete follow-up for some patients are limitations. CONCLUSION: Although some patients sufficiently controlled their psoriasis while continuing anti-TNF-α therapy, those who discontinued therapy achieved higher rates of complete response. Further studies should explore the efficacy and safety of switching to an alternative anti-TNF-α agent.
22607256 Medical conditions, medication use, and their relationship with subsequent motor vehicle i 2012 PURPOSE: To examine the effects of various medical conditions and medications on subsequent motor vehicle injuries (MVIs). METHOD: The National Population Health Survey, a large, nationally representative, longitudinal study of Canadians, included self-reported medical conditions of asthma, arthritis/rheumatism, back problems excluding arthritis, high blood pressure, migraine headaches, diabetes, heart disease and distress, and medication use during the past month for asthma, high blood pressure, diabetes, heart, codeine/pethidine (Demerol)/morphine, other pain relievers, antidepressants, tranquilizers, and sleeping medication. Path analyses were used to examine the odds of subsequent MVI for different medical conditions and medication use reported prior to the MVI (in the previous wave of the survey) while controlling for age and sex. RESULTS: Increased odds of subsequent MVIs were found for asthma (odds ratio [OR]: 1.864, 95% confidence interval [CI]: 1.281, 2.713), arthritis/rheumatism (OR: 1.659, 95% CI: 1.163, 2.365), back problems (OR: 2.169, 95% CI: 1.624, 2.895), and migraines (OR: 1.631, 95% CI: 1.125, 2.364) but not for high blood pressure (OR: 1.435, 95% CI: 0.944, 2.181), diabetes (OR: 1.479, 95% CI: 0.743, 2.944), heart disease (OR: 2.627, 95% CI: 0.941, 7.334) or distress (OR: 1.153, 95% CI: 0.840, 1.581). Except for migraine with codeine/pethidine/morphine, this effect persisted regardless of whether medication was used to treat the condition. Respondents who reported using certain medications, namely, codeine/pethidine/morphine (OR: 2.215, 95% CI: 1.274, 3.850), other pain medication (OR: 1.630, 95% CI: 1.242, 2.139), antidepressants (OR: 2.664. 95% CI: 1.602, 4.429), and sleeping medication (OR: 2.059, 95% CI: 1.161, 3.651), had increased odds of subsequent MVI, independent of related medical condition, whereas tranquillizers showed no increased odds of subsequent MVIs. CONCLUSIONS: This study suggests that the relationship between medical conditions, medications, and MVIs is complex but consistent with other studies.
21148156 Registries in rheumatoid arthritis and autoimmune diseases: data from the French registrie 2011 Jan OBJECTIVES: Clinical registries have shown their effectiveness in capturing the long-term benefit of drugs in routine care. In France, two types of registry have been established to analyse the safety and efficacy of biological agents. METHODS: The Research Axed on Tolerance of Biotherapies (RATIO) registry was designed to prospectively collect all cases of lymphoma and opportunistic infections occurring in patients receiving anti-TNF blockers for any indication. We also examined the results from nationwide prospective cohorts in order to investigate the safety and efficacy of rituximab (RTX), abatacept (ABA) and tocilizumab in RA and other autoimmune diseases. RESULTS: Analysis of the RATIO registry demonstrated an increased risk of Legionella pneumophila infection in patients receiving anti-TNF therapy, a higher risk of tuberculosis [odds ratio (OR) (95% CI): 13.3 (2.6, 69.0) and 17.1 (3.6, 80.6) for infliximab and adalimumab vs etanercept, respectively], opportunistic infections and incidence of lymphoma, with mAb than with soluble-receptor anti-TNF. The characteristics of RA patients in RTX and ABA registries showed that some patients did not receive previous TNF blockers [20% in autoimmunity and RTX (AIR) and 13% in Orencia and RA (ORA)] and one-third of them were treated without concomitant DMARDs. Patients receiving RTX showed an increased proportion of severe infections (5.0/100 patient-years). Lung and cardiac comorbidities, extra-articular involvement and low immunoglobulin G before RTX were predictive factors of severe infections. In addition, the AIR registry suggested the effectiveness of RTX in patients with SLE. CONCLUSION: The establishment of biological registries in rheumatic diseases, in France, with their different methods, has already provided additional data to controlled trials, mainly on the risk of severe infections and lymphoma.
21644062 Outcomes of switching anti-TNF drugs in rheumatoid arthritis--a study based on observation 2011 Nov The aim of this study was to assess, based on observational data from the Finnish Register of Biological Treatment, the outcomes of switching an initial tumor necrosis factor (TNF) blocker to another in the treatment of rheumatoid arthritis (RA). RA patients, who started biological therapy with a TNF blocker between May 1999 and April 2009 and who switched to another TNF blocker, were studied (n=479). The outcomes were assessed according to the reason for and type of the switch. Outcome assessments included American College of Rheumatology 50 responder index (ACR50) response at 3 months after the switch, treatment duration of the second TNF blocker, and swollen joint counts, CRP and DAS28 score at the 3 months, best and last observations of the first and second TNF blocker, respectively. In those who switched due to lack of effectiveness (LOE), the disease activity parameters fell significantly from baseline upon use of infliximab or adalimumab, but had increased prior to the switch. Switching to another TNF blocker (etanercept or adalimumab) restored the response initially achieved with the first TNF blocker. The disease activity parameters fell significantly from baseline upon use of etanercept, and were maintained but not further improved after switching to adalimumab. TNF blocker switching seemed to be most beneficial in secondary LOE (defined as loss of ACR50 response). In those who switched due to adverse events (AE) or other reasons, a similar degree of response as had been achieved with the first agent was also achieved and maintained with the second agent. The results suggest that a second TNF blocker can restore the response in cases of secondary LOE and maintain it after switching due to an AE.
21255689 Management of autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus. 2011 May Autoimmune neutropenia, caused by neutrophil-specific autoantibodies is a common phenomenon in autoimmune disorders such as Felty's syndrome and systemic lupus erythematosus. Felty's syndrome is associated with neutropenia and splenomegaly in seropositive rheumatoid arthritis which can be severe and with recurrent bacterial infections. Neutropenia is also common in systemic lupus erythematosus and it is included in the current systemic lupus classification criteria. The pathobiology of the autoimmune neutropenia in Felty's syndrome and systemic lupus erythematosus is complex, and it could be a major cause of morbidity and mortality due to increased risk of sepsis. Treatment should be individualized on the basis of patient's clinical situation, and prevention or treatment of the infection. Recombinant human granulocyte colony-stimulating factor is a safe and effective therapeutic modality in management of autoimmune neutropenia associated with Felty's syndrome and systemic lupus erythematosus, which stimulates neutrophil production. There is a slight increased risk of exacerbation of the underlying autoimmune disorder, and recombinant human granulocyte colony-stimulating factor dose and frequency should be adjusted at the lowest effective dose.
22544263 Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received c 2012 Aug Studies that reported hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients have caused attention of disease-modifying antirheumatic drug (DMARD)-related HBV reactivation. Most of the studies were focused on HBV reactivation risk of biologic DMARDs; insufficient data are available to identify the exact risk of conventional DMARD (c-DMARD)-related HBV reactivation. This prospective study aimed to investigate the risk of HBV reactivation in HBV-infected RA patients who received c-DMARDs. A total of 476 RA patients were screened in this prospective non-randomized, non-controlled study. HBV-infected patients characterized by hepatitis B surface antigen (HBsAg) positive or HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive were analyzed for HBV DNA, followed with HBV DNA monitoring scheduled every 3 months, serum alanine aminotransferase test at 2-month intervals, or more frequently. Prevalence of HBsAg positive and HBsAg negative/anti-HBc positive was 6.51 and 51.1 %, respectively, among the 476 RA patients. Among 211 patients (23 patients were HBsAg positive and 188 patients were HBsAg negative/anti-HBc positive) who received c-DMARDs without antiviral prophylactic treatment, 4 patients developed HBV reactivation. Both HBsAg positive and HBsAg negative/anti-HBc positive patients have the possibility of developing HBV reactivation. There was no correlation between HBV reactivation and any specific c-DMARD. Glucocorticoid coadministration and negative anti-hepatitis B surface antigen (anti-HBs) at baseline showed correlation with reactivation. In conclusion, it would be rational to initiate antiviral prophylaxis according to risk stratification rather than universal prophylaxis for HBV-infected RA patients. Conventional DMARDs are relatively safe to HBV-infected patients with low reactivation risk (low HBV DNA level, no GCs administration, and anti-HB positive).
22082208 Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeut 2011 Dec Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the central nervous system, caused by the reactivation of the ubiquitous JC virus. PML usually occurs during severe immunosuppression, and the most common causes are represented by human immunodeficiency virus infection, lymphoproliferative disorders and other forms of cancer. Recently, the introduction of monoclonal antibodies (e.g. natalizumab, rituximab, efalizumab) in the treatment of several dysimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, has led to an increased incidence of PML. This phenomenon has had severe consequences, leading, for example, to the withdrawal from the market of Efalizumab, and important restrictions in the use of the other compounds, all of which are characterized by high efficacy in improving prognosis and quality of life. In this review we will discuss clinical, laboratory and imaging findings of PML. In addition, proposed pathogenetic mechanisms promoting the reactivation of JC virus in the context of treatment with monoclonal antibodies will be described.
22715356 ATP induced brain-derived neurotrophic factor expression and release from osteoarthritis s 2012 Brain-derived neurotrophic factor (BDNF), a neuromodulator involved in nociceptive hypersensitivity in the central nervous system, is also expressed in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We investigated the role of P2 purinoreceptors in the induction of BDNF expression in synovial fibroblasts (SF) of OA and RA patients. Cultured SF from patients with symptomatic knee OA and RA were stimulated with purinoreceptor agonists ATP, ADP, or UTP. The expression of BDNF mRNA was measured by quantitative TaqMan PCR. BDNF release into cell culture supernatants was monitored by ELISA. P2X4 expression in synovial tissue was detected by immunohistochemistry. Endogenous P2X4 expression was decreased by siRNA transfection before ATP stimulation. Kinase pathways were blocked before ATP stimulation. BDNF mRNA expression levels in OASF were increased 2 h and 5 h after ATP stimulation. Mean BDNF levels in cell culture supernatants of unstimulated OASF and RASF were 19 (±9) and 67 (±49) pg/ml, respectively. BDNF levels in SF supernatants were only elevated 5 h after ATP stimulation. BDNF mRNA expression in OASF was induced both by P2X receptor agonists ATP and ADP, but not by UTP, an agonist of P2Y purinergic receptors. The ATP-induced BDNF mRNA expression in OASF was decreased by siRNA-mediated reduction of endogenous P2X4 levels compared to scrambled controls. Inhibition of p38, but not p44/42 signalling reduced the ATP-mediated BDNF mRNA induction. Here we show a functional role of the purinergic receptor P2X4 and p38 kinase in the ATP-induced expression and release of the neurotrophin BDNF in SF.
22910222 The use of anti-COX2 siRNA coated onto PLGA nanoparticles loading dexamethasone in the tre 2012 Nov In drug delivery systems, some genes have the potential to interrupt unnecessary gene expression in specific target cells. In this study, two types of drug, glucocorticoids and siRNA, were co-delivered into conditioned cells to inhibit the expression of unnecessary genes and proteins involved in arthritis. To deliver the two factors into a human chondrocyte cell line (C28/I2), dexamethasone was first loaded into PLGA nanoparticles, and then drug-loaded PLGA nanoparticles were complexed with poly(ethyleneimine) (PEI)/siRNA. To test the co-delivery of siRNA and dexamethasone into chondrocytes, cells were transfected with green fluorescence protein siRNA (GFP siRNA) and drugs. After transfection with GFP siRNA, 70% reduction of C28/I2 cells demonstrated GFP expression, whereas MOCK carrying PLGA nanoparticles and PLGA nanoparticles without siRNA showed no differences of GFP expressions. COX-2 and iNOS productions in C28/I2 cells were examined after TNF-α pre-treatment to induce expression of arthritis-related molecules in vitro. The reduction of gene and protein expression associated with arthritis by transfection with dexamethasone-loaded and COX-2 siRNA-complexed PLGA nanoparticles was evaluated by RT-PCR, real time-qPCR, immunoblotting, immunohistochemistry, and immunofluorescence imaging.
20871129 Certolizumab pegol in the treatment of rheumatoid arthritis: a comprehensive review of its 2011 Feb Biological agents, including TNF inhibitors, have revolutionized the treatment of RA in recent years. Certolizumab pegol (CZP) is a novel pegylated anti-TNF approved for the treatment of adult patients with moderately to severely active RA. This article provides an overview of three published clinical trials of CZP in RA in patients with active disease who have shown an inadequate response to DMARDs, including MTX: RA prevention of structural damage (RAPID) 1 and 2, which evaluated the efficacy and safety of CZP added to MTX when dosed every 2 weeks, and efficacy and safety of CZP - 4 weekly dosage in rheumatoid arthritis (FAST4WARD), which evaluated CZP monotherapy when dosed every 4 weeks. In the trials, CZP plus MTX or as monotherapy significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage as early as Week 16 of the treatment. In addition, CZP treatment significantly improved patient-reported outcome measures, providing significant reductions in pain and fatigue and improvements in physical function as early as Week 1 of treatment; improvements in health-related quality of life were evident at the first assessment at Week 12. CZP treatment improved productivity at work, significantly reducing the number of days of missed work as well as the number of days with reduced productivity, and also increased productivity within the home and improved participation in family, social and leisure activities. CZP was generally well tolerated when used either as monotherapy or added to MTX; most adverse events were mild or moderate. Taken together, the results of these trials suggest that CZP is an effective new option for the treatment of RA.
21850283 Denosumab: an update. 2011 Aug Denosumab is a fully human monoclonal antibody that inhibits the formation, function and survival of osteoclasts, preventing the interaction of tumor necrosis factor ligand superfamily member 11 (receptor activator of nuclear factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator of NF-KB, RANK). This results in a reduction in bone resorption and an increase in bone mineral density. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. A number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab is a new alternative for the prevention and treatment of postmenopausal osteoporosis and a promising agent for the treatment of other bone diseases associated with bone loss.
22647228 [Merkel cell carcinoma during treatment with TNF-alpha inhibitors: coincidence or warning? 2012 BACKGROUND: Increasing numbers of patients are being treated with TNF-alpha inhibitors. Two patients in our outpatient clinic developed Merkel cell carcinoma during treatment with TNF alpha inhibitors. Since this is a very rare malignancy, this is a remarkable observation. CASE DESCRIPTION: A 70-year-old male with rheumatoid arthritis had been treated with etanercept for two years when he discovered a nodule on his elbow that started growing rapidly. It was diagnosed as Merkel cell carcinoma. Despite treatment, the patient died 2 years later. CONCLUSION: Merkel cell carcinoma is an aggressive malignancy with a clinically benign aspect. Patients treated with TNF-alpha inhibitors possibly have an increased risk of developing this malignancy.
21947375 Significant association between renal function and area of amyloid deposition in kidney bi 2012 Oct The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied by amyloid was <10% in 54 of them. Mesangial proliferative glomerulonephritis and membranous nephropathy were frequently combined with renal amyloidosis. For statistical analyses, the percentage of the area occupied by amyloid was transformed to a common logarithmic value (Log(10) % amyloid), as the histograms showed a log-normal distribution. Log(10) % amyloid was found to be correlated with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear regression analyses were then performed to examine the sex- and age-adjusted association between Log(10) % amyloid and each of the clinical variables. Cr, Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log(10) % amyloid, but urinary protein was not. There was a significant correlation between the area of amyloid deposition in renal tissue and parameters of renal function, especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or prevented, then it may be possible to maintain renal function at an acceptable level.
23143596 High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. 2012 Dec Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.
21158951 Value of the small cohort study including a physical examination for minor structural defe 2011 Mar Most known human teratogens are associated with a unique or characteristic pattern of major and minor malformations and this pattern helps to establish the causal link between the teratogenic exposure and the outcome. Although traditional case-control and cohort study designs can help identify potential teratogens, there is an important role for small cohort studies that include a dysmorphological examination of exposed and unexposed infants for minor structural defects. In combination with other study design approaches, the small cohort study with a specialized physical examination fulfills a necessary function in screening for new potential teratogens and can help to better delineate the spectrum and magnitude of risk for known teratogens.
21595599 The risk of tuberculosis in patients treated with TNF antagonists. 2011 May Over the last 12 years, TNF antagonists have been successfully used for the treatment of numerous patients afflicted by chronic inflammatory disorders. However, data from clinical trials and registries have shown that patients treated with these biologics have an increased risk of reactivating latent TB. The fact that TNF plays a role in the immune cell response and, more specifically, in maintenance of granuloma integrity is the accepted grounds for reactivation of TB following inhibition of TNF. Appropriate screening of latent TB and proper management of cases substantially reduces the incidence of active TB. Nevertheless, debate still remains regarding the value of the tuberculin skin test and IFN-γ-release assays as diagnostic tools, and treatment across guidelines and recommendations. This largely reflects differences in background population.