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ID PMID Title PublicationDate abstract
23379925 Sensory neuropathy associated with aggressive cauterization using a bipolar radiofrequency 2013 Feb Because significant postoperative blood loss can result in many complications, hemostasis remains a critical part of successful joint replacement outcomes. Advanced techniques, such as electrocautery use after optimally timed tourniquet release, focus on desired patient blood loss outcomes. The purposes of this study were to report the incidence of nerve injury, identify associated risk factors following the use of bipolar electrocautery for hemostasis in the posterior knee during primary total knee arthroplasty, and compare that rate with the rate seen using a standard electrocautery device. Clinical and operative data were retrospectively reviewed for an association with postoperative nerve injury in 241 consecutive patients when using bipolar electrocautery between July 2007 and October 2008. A comparison group of 192 demographically similar consecutive patients between November 2008 and October 2009 was also evaluated to establish a surgeon-specific benchmark when using standard electrocautery. Seven (2.9%) of 241 patients in the bipolar electrocautery group reported documented neuropathies compared with 1 (0.52%) of 192 patients using standard electrocautery. In addition, female sex and rheumatoid arthritis were associated with postoperative nerve injury following bipolar electrocautery. Although the bipolar radiofrequency device is effective in achieving hemostasis, the authors recommend judicious use of this procedure in women or patients with rheumatoid arthritis and cautious, nonaggressive use of posterior compartment bipolar radiofrequency ablation in the remaining patient populations.
24324327 Effects of 6 months of abatacept treatment on aortic stiffness in patients with rheumatoid 2013 BACKGROUND: Systemic inflammation plays an important role in the increased cardiac risk observed in rheumatoid arthritis (RA). Effective control of inflammation and disease activity may be of benefit in reducing cardiovascular risk in RA patients. OBJECTIVE: Our study was conducted in patients with active RA to investigate the effects of 24-week abatacept treatment on aortic stiffness measured by pulse wave velocity (PWV). RESULTS: The study included 21 patients, of whom 17 were females, with a mean age of 65.2±13.7 years. Ten patients had positive rheumatoid factors, 16 positive anti-citrullinated protein antibodies, and 19 presented an erosive form of RA. Sixteen patients were nonresponders to anti-tumor necrosis factor-alpha treatments. After 6 months of abatacept treatment, there was a significant increase in PWV levels (9.8±2.9 versus 8.5±3.9 m/second; P=0.02). A nonsignificant increase in total cholesterol and low-density lipoprotein cholesterol was observed. There was also a significant increase in high-density lipoprotein cholesterol levels, which led to a nonsignificant decrease in atherogenic index. The improvement in disease activity was significant, and there was a decrease of systemic inflammatory parameters, but without reaching statistical significancy. Changes in PWV were significantly correlated with changes in Disease Activity Score on 28 joints based on erythrocyte sedimentation rate (r=0.46; P=0.035) and in high-density lipoprotein cholesterol (r=-0.38; P=0.046). No correlation was observed with changes in C-reactive protein and in other parameters of lipid profile or in steroid dose. CONCLUSION: The worsening of aortic stiffness found after 6 months of abatacept therapy might be due to an insufficient decrease in systemic inflammation.
25419237 Expression profiles of long non-coding RNAs located in autoimmune disease-associated regio 2014 BACKGROUND: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes. METHODS: We aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4(+) and naive CD8(+) T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells). RESULTS: We show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (α <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (α <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8(+) T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. CONCLUSIONS: The observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways.
25027606 Novel treatments with small molecules in psoriatic arthritis. 2014 Current treatment options for patients with active psoriatic arthritis (PsA) include synthetic disease-modifying antirheumatic drugs and biologic agents. Propelled by increased understanding of immunopathogenesis of PsA, new therapeutic agents targeting different biologic pathways have been evaluated. This article discusses novel small-molecule, orally available treatments that are currently in clinical development for the treatment of psoriasis and PsA. This includes the phosphodiesterase 4 inhibitor apremilast and Janus kinase (JAK) inhibitors. Apremilast has demonstrated significant improvements in patients with moderate to severe psoriasis and PsA in phase II and III clinical trials and has recently been approved for the treatment of PsA. Tofacitinib, an oral inhibitor of JAK3, JAK1, and, to a lesser degree, JAK2, approved for the treatment of rheumatoid arthritis in several countries, has demonstrated positive results in psoriasis in phase II studies. Studies in PsA are ongoing. With these new developments, treatment options will continue to improve in the future.
22867272 Alteration in plasma protein binding properties of propranolol and flurbiprofen during dev 2013 Mar Adjuvant-induced arthritis (AA) in the rat is used as a model for rheumatoid arthritis. In AA rats, the pharmacokinetics of various drugs is affected due to the alterations of plasma protein binding of drugs. We choose propranolol (PL) and flurbiprofen (FP) as model basic and acidic drugs, respectively, and investigated the effect of AA induction on their plasma protein binding at each developing stage of inflammation. The plasma protein binding of PL and FP was dramatically changed due to reduced albumin and increased α₁-acid glycoprotein levels for at least 21 days after adjuvant treatment. Moreover, we illustrated the differences in protein binding in AA between both the drugs in each developing stage of inflammation. These results suggest that the changed plasma protein levels in AA rats accompanying the altered protein binding of drugs affect the pharmacokinetics of drugs which extensively bind to plasma protein under inflammatory condition.
23695883 Arthritis severity locus Cia4 is an early regulator of IL-6, IL-1β, and NF-κB activators 2013 Jul 2 Cia4 is a locus on rat chromosome 7 that regulates disease severity and joint damage in models of rheumatoid arthritis, including pristane-induced arthritis (PIA). To identify molecular processes regulated by Cia4, synovial tissues from MHC-identical DA (severe erosive) and DA.F344(Cia4) congenics (mild nonerosive) rats were collected at preclinical and recent onset stages following the induction of PIA and analyzed for gene expression levels. Il6 levels were significantly higher in DA compared with congenics on day 10 (135-fold) after PIA induction (preclinical stage) and remained increased on days 14 (47.7-fold) and 18 (29.41-fold). Il6 increased before Il1b suggesting that Il6 could be driving Il1b expression and early synovial inflammation; 187 genes had significantly different expression levels and included inflammatory mediators increased in DA such Slpi (10.94-fold), Ccl7 (5.17-fold), and Litaf (2.09-fold). Syk or NF-κB activating and interacting genes, including Cd74 Ccl21, were increased in DA; 59 genes implicated in cancer-related phenotypes were increased in DA. Genes involved in cell metabolism, transport across membranes, and tissue protection such as Dgat1, Dhcr7, and Slc1a1 were increased in DA.F344(Cia4) congenics; 21 genes differentially expressed or expressed in only one of the strains were located within the Cia4 interval and could be the gene accounting for the arthritis effect. In conclusion, the Cia4 interval contains at least one new arthritis gene that regulates early Il6, Il1b expression, and other inflammatory mediators. This gene regulates the expression of cancer genes that could mediate the development of synovial hyperplasia and invasion, and cartilage and bone destruction.
25394970 [Molecular pathological diagnostics of infections in orthopedic pathology]. 2014 Nov The diagnosis of infections in patients with arthritis and/or in joint prostheses requires interdisciplinary cooperation and the application of up-to-date methods. The histological investigation of the synovial membrane allows the differentiation of acute, chronic and granulomatous synovialitis. Detection of conserved regions of the microbial genome by PCR, especially 16S rRNA for bacteria and 18S rRNA for fungi, is a broad approach for the classification of pathogens which cannot be cultured. Acute infectious arthritis and periprosthetic infections share the spectrum of pathogens with sepsis, therefore multiplex PCR-based methods for the detection of sepsis can be employed. Molecular diagnostics can detect minimal infections in periprosthetic tissues even after antibiotic therapy. The anamnesis (enteral or urogenital infection), clinical picture (oligoarthritis) and further parameters (e.g. HLA B27 status) are important for the diagnosis of reactive arthritis. In many cases of reactive arthritis, molecular methods allow the detection of bacterial DNA or RNA in synovial fluid or tissue samples. The low sensitivity of histopathological methods may be compensated by application of PCR techniques, especially in the differential diagnosis of granulomatous synovitis including mycobacterial infections. Molecular methods can be used to support the differential diagnosis of septic and reactive arthritis. MicroRNA techniques combined with PCR for detection of pathogens support the differential diagnosis of rheumatoid arthritis with severe inflammatory activity compared to infectious arthritis. Proteomic methods could expand the methodological spectrum for the diagnosis of infections.
24218541 Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoi 2014 Jan A critical piece in the translation of preclinical studies to clinical trials is the determination of dosing regimens that allow maximum therapeutic benefit with minimum toxicity. The preclinical pharmacokinetic (PK)/pharmacodynamic (PD) profile of tofacitinib, an oral Janus kinase (JAK) inhibitor, in a mouse collagen-induced arthritis (mCIA) model was compared with clinical PK/PD data from patients with rheumatoid arthritis (RA). Preclinical evaluations included target modulation and PK/PD modeling based on continuous subcutaneous infusion or oral once- or twice-daily (BID) dosing paradigms in mice. The human PK/PD profile was obtained from pooled data from four phase 2 studies in patients with RA, and maximal effect models were used to evaluate efficacy after 12 weeks of tofacitinib treatment (1-15 mg BID). In mCIA, the main driver of efficacy was inhibition of cytokine receptor signaling mediated by JAK1 heterodimers, but not JAK2 homodimers, and continuous daily inhibition was not required to maintain efficacy. Projected efficacy could be predicted from total daily exposure irrespective of the oral dosing paradigm, with a total steady-state plasma concentration achieving 50% of the maximal response (Cave50) of ~100 nM. Tofacitinib potency (ED50) in clinical studies was ~3.5 mg BID (90% confidence interval: 2.3, 5.5) or total Cave50 of ~40 nM, derived using Disease Activity Scores from patients with RA. The collective clinical and preclinical data indicated the importance of Cave as a driver of efficacy, rather than maximum or minimum plasma concentration (Cmax or Cmin), where Cave50 values were within ~2-fold of each other.
24381766 Disease Activity and Bone Mineral Density of MCP Joints in Patients with Rheumatoid and Ps 2013 Background. Bone damage in rheumatoid arthritis (RA) and in psoriatic arthritis (PsA) includes an accelerated bone mineral density (BMD) reduction. The objective was to evaluate BMD variations of the metacarpophalangeal joints (MCPs) in patients starting treatment with methotrexate (MTX) or etanercept. Methods. Patients affected by RA or PsA with hand joints involvement and with moderate or high disease activity, were enrolled in this study. All patients underwent clinical examination, laboratory exams, and a DXA scan of the most affected hand, as assessed with an ultrasound examination at the baseline, at the time of enrolment and after 1, 3, 6, and 12 months. Patients non-responders to MTX received combination therapy, while patients with no previous treatment initiated MTX. Results. 22 patients were enrolled. In both RA and PsA groups, BMD increased independently of the treatment. However, in the patients affected by RA, a slight BMD decrease was observed at the last checkup. Globally, the BMD variations of the MCPs were strongly correlated with the disease activity. At the reduction of DAS28, the scores corresponded an increase of BMD. Conclusions. MCPs BMD is inversely correlated to disease activity. BMD increase seems to be correlated with the response to treatment and not with the drug itself.
25117161 A case of abatacept associated neutrophilic dermatosis and a review of the literature. 2014 Aug Abatacept is a novel biological agent that dampens the immune response by blocking the co-stimulation of T-cells, thus downregulating T-cell activation. It is currently approved for the treatment of rheumatoid arthritis (RA). The group of novel immunomodulatory agents, referred to as biologics, have now been used extensively, with established safety and side-effect profiles. There are, however, increasing reports of adverse paradoxical reactions, most notably resulting from anti-tumour necrosis factor (TNF) therapy. While cutaneous adverse reactions to abatacept are rare, there are a few reports of such paradoxical reactions. We report a case of an idiosyncratic paradoxical neutrophilic dermatosis associated with the use of abatacept.
23943297 The rheumatoid forefoot. 2013 Dec Rheumatoid arthritis (RA) manifests itself in a variety of ways, with its effect being seen in around 90 % of sufferers' feet. The foot has been found to be the most common reason for incapacity in patients with RA, with the forefoot the most common area. The foot is second, behind only the hand, as the most common place for manifestation of RA. Pain in the foot is commonly the most debilitating condition, which causes the patient to seek specialist help. As well as pain, foot deformities such as hallux valgus and claw toes are common complaints. These symptoms often arise as a result of continued walking on an unstable foot, leading to painful callosities and dislocation of the metatarsophalangeal joints. Other conditions, such as pannus formation and Morton's neuroma, can be related to RA. This review sets out what we believe to be a successful approach to the rheumatoid forefoot, which aims at the relief of pain and the preservation of ambulation. Key to a successful outcome is appropriate medical control with a multidisciplinary approach that enables close liaison between orthopaedic surgeons, orthotists, and rheumatologists. Combined clinics provide this multidisciplinary care. Those treating RA need to be aware of the high incidence of foot involvement and how early intervention may benefit the patient. The aim of this article is to present current evidence to enable people to develop a treatment algorithm for this condition.
24467766 Comparison of plasma vitamin D levels in patients with Sjögren's syndrome and healthy sub 2015 Jan AIM: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands. There is increasing evidence indicating that vitamin D is important in the initiation and propogation of a range of autoimmune diseases which may include SS. The aim of the present study was to evaluate plasma vitamin D (vit D) levels in patients with SS and to compare this with a control group. METHOD: One hundred and seven SS patients (97 [90.7%] female and 10 [9.3%] male) and 74 healthy controls (64 [86.5%] female and 10 [13.5%] male) were included into the study. Plasma baseline 25-hydroxy-vit D levels were measured by high-powered liquid chromatography method using an Agilent 1100 liquid chromatograph. RESULTS: Plasma vit D levels in SS patients (20.5 ± 10.5 μg/L) were significantly lower than in the control group (28.4 ± 15.2 μg/L) (P < 0.001). Female SS patients had significanly lower vit D levels (19.3 ± 9.3 μg/L) than controls (28.3 ± 15.8 μg/L) (P < 0.001) but this difference was not present among the male patients and controls. There was no correlation between plasma vit D levels and erythrocyte sedimentation rate and C-reactive protein in SS patients. CONCLUSION: Vit D deficiency was frequent in patients with SS. In particular, female SS patients had the risk of vit D deficiency. It may be convenient to look for vit D deficiency and to correct vit D nutritional status in SS patients.
24967971 Activation of HIF-1α (hypoxia inducible factor-1α) prevents dry eye-induced acinar cell 2014 Jun 26 The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sjögren's syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sjögren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1α. Interestingly, the areas of stable HIF-1α expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1α conditional knockout (CKO) mice in which HIF-1α expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sjögren's syndrome, CD3(+) and CD11b(+) cells infiltrated HIF-1α CKO LGs. Our results show that DE induced the expression of HIF-1α that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.
24623563 Patient involvement in outcome measures for psoriatic arthritis. 2014 May Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthritis with a varied clinical phenotype. There has been considerable international collaboration over recent years to develop and prioritise appropriate disease domains and outcome measures to capture all aspects of this complex disease. It has been recognised that patient-reported measures and physician assessments are complementary and, when used together, allow an improved reflection of disease burden. Taking this concept one step further, the experience in rheumatoid arthritis has demonstrated benefits of incorporating the patient perspective in the development of outcome measures. We report a systematic review demonstrating (1) that there has been little incorporation of the patient perspective in the development of outcome measures and domains in PsA, (2) the proceedings from the preliminary patient involvement in outcome measures for PsA (PIOMPSA) meetings, and (3) a proposed roadmap for improving patient involvement.
24411527 [Pathophysiology of primary Sjögren's syndrome]. 2014 Aug Primary Sgögren's syndrome (SSP) is one of the most common connective tissue disorder with an estimated prevalence between 0.6 and 1.7% of the general population. Lymphocytic infiltration of salivary gland is easily accessible favoring the diagnosis, and clinical and fundamental research. However, while many advances have been obtained in the recent decades, the pathophysiology of SSP remains unclear combining environmental factors with genetic predisposition. A central role tends to be attributed to salivary gland epithelial cells, originally designated as "innocent bystanders" and to B cells through the intervention of survey factors like BAFF. New T cells subsets are also carefully studied, particularly natural T regulatory and Th17 cells. They could indeed represent new therapeutic targets.
24044622 Nijmegen breakage syndrome and chronic polyarthritis. 2013 Sep 17 We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur. In our patient microbiologic cultures of synovial fluid including Mycoplasma spp. were negative. At first, because of suspected mycoplasmal arthritis we used macrolides and doxycycline combined with hydroxychloroquine but without therapeutic response. However, the use of rituximab led to remission of her polyarthritis lasting for 9 months. Autoimmune features were rarely reported in NBS. An occurrence of JIA-like, chronic polyarthritis in NBS, a DNA repair disorder characterized by decreased tolerance of immunosuppressive drugs such as methotrexate and a high natural risk for lymphomas, makes therapeutic approach even more complex.
25530283 Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) ac 2015 Oct BACKGROUND: Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. METHODS: An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. RESULTS: Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. CONCLUSIONS: At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions.
24176737 Infection of the sigmoid colon during TNFα antagonist therapy for chronic inflammatory jo 2014 May We report 7 cases of sigmoid colon infection in patients taking TNFα antagonist therapy to treat chronic inflammatory joint disease. There were 5 women and 2 men with a mean age of 57.5 years (range, 21-77 years). The presenting symptoms were abdominal pain, bowel habit changes, and a fever. These symptoms developed within 6 months after starting TNFα antagonist therapy in 5 of the 7 patients. Empirical antibiotic therapy was used in all 7 patients. Surgical colectomy was performed in 4 patients, including 1 who required a temporary Hartmann's procedure. The risk of infection associated with TNFα antagonist therapy is well documented. However, few cases of colon infection have been reported and little is known about this potentially severe complication. Glucocorticoids or non-steroidal anti-inflammatory drugs may worsen the infection, particularly as they can attenuate the clinical symptoms, thereby delaying the diagnosis. A history of sigmoid colon infection, diverticulosis, and/or diverticulitis must be sought before starting treatment with a biological agent. Prophylactic treatment may be considered if such a history is found. Diagnostic investigations are in order to develop a standardized management strategy in patients with a history of intestinal tract infection.
24379468 Primary total elbow arthroplasty. 2013 Nov BACKGROUND: Primary total elbow arthroplasty (TEA) is a challenging procedure for orthopedic surgeons. It is not performed as frequently as compared to hip or knee arthroplasty. The elbow is a nonweight-bearing joint; however, static loading can create forces up to three times the body weight and dynamic loading up to six times. For elderly patients with deformity and ankylosis of the elbow due to posttraumatic arthritis or rheumatoid arthritis or comminuted fracture distal humerus, arthroplasty is one of the option. The aim of this study is to analyze the role of primary total elbow arthroplasty in cases of crippling deformity of elbow. MATERIALS AND METHODS: We analyzed 11 cases of TEA, between December 2002 and September 2012. There were 8 females and 3 males. The average age was 40 years (range 30-69 years). The indications for TEA were rheumatoid arthritis, comminuted fracture distal humerus with intraarticular extension, and posttraumatic bony ankylosis of elbow joint. The Baksi sloppy (semi constrained) hinge elbow prosthesis was used. Clinico-radiological followup was done at 1 month, 3 months, 6 months, 1 year, and then yearly basis. RESULTS: In the present study, average supination was 70° (range 60-80°) and average pronation was 70° (range 60-80°). Average flexion was 135° (range 130-135°). However, in 5 cases, there was loss of 15 to 35° (average 25°) of extension (45°) out of 11 cases. The mean Mayo elbow performance score was 95.4 points (range 70-100). Arm length discrepancy was only in four patients which was 36% out of 11 cases. Clinico-radiologically all the elbows were stable except in one case and no immediate postoperative complication was noted. Radiolucency or loosening of ulnar stem was seen in 2 cases (18%) out of 11 cases, in 1 case it was noted after 5 years and in another after 10 years. In second case, revision arthroplasty was done, in which only ulnar hinge section, hinge screw and lock screw with hexagonal head were replaced. CONCLUSION: Elbow arthroplasty remains a valuable option for deformed and ankylosed elbows especially in the demanding patients with crippling deformity of the elbow.
23903812 Trajectory of intensive treat-to-target disease modifying drug regimen in an observational 2013 Jul 31 OBJECTIVES: Studies of early rheumatoid arthritis (RA) cohorts have analysed treatment response and prognostic factors at fixed time points. However, in treat-to-target protocols, therapeutic decision-making is dynamic and responsive to disease activity over time. To determine when a minimal residual disease response target should be expected, our primary objective was to identify the time-dependent therapeutic response to combination disease modifying antirheumatic drugs (DMARDs) for 12 months. Our secondary objective determined factors affecting this response trajectory. DESIGN: Observational cohort. SETTING: Treat-to-target early RA clinic in Australian tertiary referral hospital. PARTICIPANTS: We enrolled consecutive patients attending an early arthritis clinic with symptom duration less than 12 months, who were diagnosed with RA for the first time between 2004 and 2008. 101 met these eligibility criteria and data were available at baseline through 12 months. INTERVENTIONS: intensive DMARDs according to a treat-to-target protocol. PRIMARY AND SECONDARY OUTCOME MEASURES: We measured disease activity scores (DAS) at each visit, then analysed therapeutic response and associated factors in a time-dependent fashion over 12 months. RESULTS: The median DAS4vESR of 4.46 at baseline decreased 12 weeks later by 24%, while the proportion with DAS4v ≤ 2.6 increased (p<0.01). DAS4v continued to decrease over 52 weeks. DAS4v reduction of at least -0.45 at 4 weeks was predictive of DAS4v at 28 and 52 weeks. Female gender, current smoking, primary education and an interaction between baseline weight and C reactive protein (CRP) negatively impacted DAS4v reduction over 4 and 52 weeks. Time-varying effects of blood pressure, neutrophils, erythrocyte sedimentation rate and CRP also significantly influenced DAS4v over 52 weeks. CONCLUSIONS: Time-dependent data suggest that the largest reduction of DAS4v to combination DMARDs occurs in the first month of therapy, and this predicts subsequent response. Variables known to impact long-term treatment response in RA also impacted early DAS4v response to combination DMARDs.