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ID PMID Title PublicationDate abstract
24324915 Cost Effectiveness of TNF-α Inhibitors in Rheumatoid Arthritis. 2013 Background. TNF-α inhibitors have shown to be effective in reducing disease activity and improving the quality of life. Due to the high costs associated with acquisition of this treatment, this study was undertaken to evaluate the ICER of TNF-α antagonists (etanercept, adalimumab, and infliximab) in improving the quality of life. Methods. The HAQ and SF-36 were administered at phases 1, 2, and 3, in order to assess the improvement in the QOL. Suppression of disease activity was assessed through the DAS-28. Results. Statistically significant improvements (P < 0.05) were noted for the SF-36 and HAQ after 3 months and for the DAS-28 after 6 months of TNF-α inhibitor therapy. The mean ICER per 10% improvement in the HAQ, DAS-28, and SF-6D were €1976.5, €2086.5, and €2316.4, respectively, following 6 months of TNF-α intervention. Most favorable ICERs were reported from a patient who had to undergo surgical intervention whilst on DMARD therapy. Conclusion. Significant improvement was observed in patients' quality of life, after a short timeframe of 6 months. Such data is useful information in the light of convincing policy makers, in terms of providing access to the medications to individual patients on national health service schemes.
24219035 Mechanisms of action of methotrexate. 2013 As one of the most utilized disease-modifying anti-rheumatic drugs, methotrexate (MTX) has revolutionized the treatment of rheumatoid arthritis as well as many other non-rheumatic chronic inflammatory diseases. Far from a simple anti- proliferative agent as was once thought, our understanding of how it exerts its anti-inflammatory effects has grown over the years. The mechanisms of action of MTX are reviewed here, and we look at how this knowledge helps to explain some of its most common side effects.
24139501 [Glycosylation of autoantibodies in autoimmunes diseases]. 2013 Dec Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target.
23905401 [Tramadol/acetaminophen combination tablets]. 2013 Jul Tramadol/acetaminophen fixed-dose combination tablets (Tramse) combine tramadol, a centrally acting week opioid analgesic, with low-dose acetaminophen. The action of tramadol may be described as a weak agonist at the mu-opioid receptor, inhibition of serotonin reuptake, and inhibition of noradrenaline reuptake. The second component in these tablets, acetaminophen mainly appears to act through central mechanism. Chronic pain may be broadly classified into nociceptive, neuropathic and mixed. Tramset may exert additive or synergic benefits in treating the multiple mechanism of pain. Clinical studies have revealed its efficacy and safety for a variety of pain condition such as chronic low back pain, rheumatoid arthritis, fibromyalgia and painful diabetic peripheral neuropathy. It is expected that Tramset is going to induce pain relief and to improve disturbance of daily life in patients with intractable chronic pain. However overuse of Tramset may induce severe adverse effects such as addiction, abuse and hepatotoxicity. Therefore clinician should continuously assess pain intensity, activity of daily life, mode of its consumption, and adverse effects after prescription.
23853619 Non-contraceptive benefits of oral hormonal contraceptives. 2013 Winter It is becoming evident that oral hormonal contraceptives-besides being well established contraceptives-seem to become important medications for many functional or organic disturbances. So far, clinical effectiveness has been shown for treatment as well as prevention of menstrual bleeding disorders and menstrual-related pain symptoms. Also this is true for premenstrual syndrome (PMS) and premenstrual disphoric disorder (PMDD). Particular oral contraceptives (OCs) containing anti-androgenic progestogens were shown to be effective medications for treatment of androgenisation symptoms (seborrhea, acne, hirsutism, alopecia). Through perfect suppression of the hypothalamic-pituitary-ovarian axis OCs have proven to be effective in elimination of persistent follicular cysts. Endometriosis/adenomyosis related pain symptoms are well handled similar to other drugs like Gonadotropine Releasing Hormone agonists but are less expensive, with less side effects, and possibility to be used for longer periods of time. This is also true for myoma. Pelvic inflammatory disease, rheumatoid arthritis, menstrual migraine, and onset of multiple sclerosis are prevented or delayed. Bone density is preserved and asthma symptoms improved. Endometrial hyperplasia and benign breast disease can be controlled. There is definitely a significant impact on risk reduction regarding endometrial, ovarian, and colon cancers. In conclusion, it needs to be recognized that oral combined hormonal contraceptives (estrogen/ progestogen combination) are - besides being reliable forms of contraception - are cost-effective medications for many medical disorders in women. Therefore, these contraceptives drugs are important for female and global health and should be used in clinical practice.
23777821 Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving 2014 Jan Reports of autoimmune diseases, including psoriasis- and dermatitis-like skin reactions with anti-tumor necrosis factor-α (TNF-α), are increasing, likely a reflection of the growing use of these agents. This paradoxical phenomenon can no longer be considered rare, with some studies providing incidence estimates of greater than 10%. This paradoxical inflammation has been reported in patients receiving treatment with anti-TNF-α agents for a variety of inflammatory conditions, including inflammatory bowel disease, psoriasis and rheumatoid arthritis and appears to be a class effect. Moreover, there have recently been reports of autoimmune arthralgia occurring in patients receiving anti-TNF-α agents. Further studies are necessary to determine the true incidence of this phenomenon and to identify those patients most likely to be at risk.
23719673 Azastilbenes: a cut-off to p38 MAPK inhibitors. 2013 Jul 21 Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.
28509217 Scleroderma renal crisis in a newly diagnosed mixed connective tissue disease resulting in 2013 May Mixed connective tissue disease (MCTD) is a rheumatic disease with a combination of multiple connective tissue disorders, which includes dermatomyositis or polymyositis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. It affects various organs of the body, which includes the lungs, heart, kidneys, joints, muscles and the haematological system. Here, we report a case of MCTD consisting of scleroderma, Sjögren's syndrome and polymyositis complicated by scleroderma renal crisis (SRC) but with negative anti-nuclear antibody (ANA), anti-Scl 70 and anti-centromere antibodies. The patient was started on captopril for the treatment of SRC but developed chronic kidney disease despite adequate blood pressure control with angiotensin-converting enzyme inhibitor (ACEi).
23438723 Oxidative stress in patients with cardiovascular disease and chronic renal failure. 2013 May Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients. In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.
23020579 TRPA1: A gatekeeper for inflammation. 2013 Tissue damage evokes an inflammatory response that promotes the removal of harmful stimuli, tissue repair, and protective behaviors to prevent further damage and encourage healing. However, inflammation may outlive its usefulness and become chronic. Chronic inflammation can lead to a host of diseases, including asthma, itch, rheumatoid arthritis, and colitis. Primary afferent sensory neurons that innervate target organs release inflammatory neuropeptides in the local area of tissue damage to promote vascular leakage, the recruitment of immune cells, and hypersensitivity to mechanical and thermal stimuli. TRPA1 channels are required for neuronal excitation, the release of inflammatory neuropeptides, and subsequent pain hypersensitivity. TRPA1 is also activated by the release of inflammatory agents from nonneuronal cells in the area of tissue injury or disease. This dual function of TRPA1 as a detector and instigator of inflammatory agents makes TRPA1 a gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract.
23000633 Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases. 2013 Jun Rituximab is a monoclonal antibody to the CD20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin's B-cell lymphoma in 1997. In the last 15years, it has emerged as a potent immunosuppressant for many immune-mediated diseases, beginning initially with rheumatoid arthritis, and now extending into several other fields, including clinical nephrology. Based on recent large clinical trials, it is FDA-approved for the treatment of ANCA-associated vasculitis and continues to be studied in off-label usage for many glomerular diseases, including membranous nephropathy, lupus nephritis, and mixed cryoglobulinemia. It has been used as a treatment in nephrotic syndrome in children and adults, including both minimal change disease and focal segmental glomerulosclerosis. Given its efficacy, tolerability and safety profile in comparison to more conventional treatment regimens, RTX is rapidly emerging as a critical treatment modality in glomerular disease.
25381966 Detection of adalimumab and anti-adalimumab levels by ELISA: clinical considerations. 2014 Nov Psoriasis (Ps) is a common and stigmatizing chronic inflammatory skin disease that may cause other chronic inflammatory conditions with overlapping pathology, such as rheumatoid arthritis (RA). Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a pivotal role in chronic inflammatory and autoimmune diseases such as uveitis, multiple sclerosis, systemic lupus, arthritis, Ps, and Crohn's disease. The TNF superfamily and receptors represent active targets for drug development. Anti-TNF biological therapies, such as infliximab, adalimumab (ADL), and etanercept, are effective in treating RA, spondyloarthritis, Ps, and inflammatory bowel diseases, but long-term treatment can induce anti-drug antibody (ADA) formation associated with lower drug levels and clinical nonresponse. An investigation of the relationship between serum ADL/anti-adalimumab antibody (AAA) concentration, and clinical response in moderate to severe Ps, confirmed an association between ADL and AAA levels and response. Although the detection of ADAs can be used to determine the cause of nonresponse and aid therapy decisions, the contrary observation of long-term responders with low drug levels and detectable ADA suggests that another mechanism is also involved.
25069739 In human basophils, IL-3 selectively induces RANKL expression that is modulated by IgER-de 2014 Nov BACKGROUND: Receptor activator of NF-κB ligand (RANKL) is expressed as either surface (hRANKL1, hRANKL2) or soluble (hRANKL3) form. RANKL is involved in multifaceted processes of immunoregulation and bone resorption such as they occur in rheumatoid arthritis (RA). Interestingly, activated basophils, which are effector cells in allergic inflammation, contribute to the progress of collagen-induced arthritis (CIA), a mouse model for RA. Here, we investigate under which conditions human basophils express RANKL. METHODS: Among other stimuli, basophils were cultured with IL-3 alone. Alternatively, as a secondary stimulus, IgER-dependent or IgER-independent agents were added simultaneously either with IL-3 or after prolonged IL-3 culturing. Expression of RANKL protein and mRNA was analyzed by flow cytometry, ELISA, and real-time PCR. A coculture system was applied to investigate biological activity of basophil-derived RANKL. RESULTS: We show that in human basophils, IL-3 but no other stimulus induces de novo expression of soluble and surface RANKL, of which the latter enhances survival of MoDC. Upon simultaneous stimulation, IgER cross-linking reduces surface RANKL expression, while IgER-independent stimuli have no effect. This is in contrast to consecutive stimulation, as triggering with both IgER-dependent and IgER-independent stimuli enhances RANKL expression, particularly in its soluble form. Real-time PCR analysis shows that RANKL expression is mainly regulated at the mRNA level. CONCLUSION: This study identifies IL-3 as a potent inducer of RANKL expression in human basophils, suggesting them to interact with bone physiology and activation of immune cells. IgER-dependent and IgER-independent stimuli modulate the IL-3-mediated RANKL expression in a time- and stimulus-dependent fashion.
24987496 Complication rates in diabetics with first metatarsophalangeal joint arthrodesis. 2014 BACKGROUND: First metatarsophalangeal joint (MTPJ) arthrodesis has been an effective surgical entity when indicated, but a range of severe to mild complications can occur from this procedure. Patients with diabetes mellitus have an increased risk in surgical complications, most commonly associated with soft tissue and bone healing, when compared to non-diabetic patients. The purpose of this study was to evaluate the complication rates of first MTPJ arthrodesis in diabetic patients and compare them to the existing complication rates for the procedure. METHODS: A retrospective chart review was done on 76 diabetic patients, from June 2002 to August 2012. Thirty-two males and 44 females were included in the study. The authors evaluated many variables that could impact postoperative complications, including age, gender, bone graft incorporation, hemoglobin A1c, tobacco use, body mass index, peripheral neuropathy, hallux extensus, hallux interphalangeal arthritis, and rheumatoid arthritis, and compared them with the complication findings. Patient follow-up was no less than 24 months. RESULTS: Overall, approximately two-thirds of the patients had no complications and 35.5% of patients had at least one mild or moderate complication. Of the non-union and mal-union complications, 80 and 70% had peripheral neuropathy, respectively. One hundred percent of the patients that had mal-positions or hardware failure also had peripheral neuropathy. No severe complications were seen during follow-up. Only two of the moderate complications needed revisions, and the rest of those with moderate complications were asymptomatic. CONCLUSION: In conclusion, first MTPJ arthrodesis is overall an effective and beneficial procedure in patients with diabetes mellitus. Diabetic patients with peripheral neuropathy have an increased risk for mild and moderate complications.
24936253 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? 2014 Jun 15 Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells (like erythrocytosis and myeloproliferative disease), autoimmune disorders (like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology (like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions (like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), and finally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia (acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.
24692552 Linker length matters, fynomer-Fc fusion with an optimized linker displaying picomolar IL- 2014 May 16 Fynomers are small binding proteins derived from the human Fyn SH3 domain. Using phage display technology, Fynomers were generated inhibiting the activity of the proinflammatory cytokine interleukin-17A (IL-17A). One specific Fynomer called 2C1 inhibited human IL-17A in vitro with an IC50 value of 2.2 nm. Interestingly, when 2C1 was genetically fused to the Fc part of a human antibody via four different amino acid linkers to yield bivalent IL-17A binding proteins (each linker differed in length), the 2C1-Fc fusion protein with the longest linker displayed the most potent inhibitory activity. It blocked homodimeric IL-17A with an IC50 value of 21 pm, which corresponds to a hundredfold improved IC50 value as compared to the value obtained with monovalent Fynomer 2C1. In contrast, the 2C1-Fc fusion with the shortest linker showed only an ∼8-fold improved IC50 value of 260 pm. Furthermore, in a mouse model of acute inflammation, we have shown that the most potent 2C1-Fc fusion protein is able to efficiently inhibit IL-17A in vivo. With their suitable biophysical properties, Fynomer-Fc fusion proteins represent new drug candidates for the treatment of IL-17A mediated inflammatory conditions such as psoriasis, psoriatic arthritis, or rheumatoid arthritis.
23474514 A new podiatry service for patients with arthritis. 2013 Mar 1 AIM: The aims of this study were to identify the impact of a new podiatric rheumatology service on reducing foot pain, impairment and disability in patients with foot problems associated with rheumatic disease, and to report on patient satisfaction with the service. METHOD: A retrospective study of 245 patients with rheumatic disease at Counties Manukau DHB was conducted. Foot pain, impairment and disability were measured using a self-reporting patient outcome measure, the Foot Function Index. A range of podiatric interventions were reported. A self-administered, postal patient satisfaction questionnaire was sent to 148 patients. RESULTS: Over two-thirds of patients were observed with hallux valgus (bunions). The results demonstrate a significant reduction in foot pain (p<0.001) from initial visit to second visit (18% reduction in pain). A significant decrease in foot disability (p=0.04) was found from initial visit to second visit. No significant differences were seen with foot impairment (p=0.78). A variety of intervention measures were used with 24% of patients being prescribed foot orthoses and 28% of patients given footwear advice. The patient satisfaction survey found 84% of patients reported they were satisfied with the new service and 80% of patients reported that the service helped with their foot problems. CONCLUSION: The current service meets the needs of patients who suffer from rheumatological foot conditions such as rheumatoid arthritis and gout. The need for good foot education, provision of foot orthoses and advice on footwear are crucial to reduce the burden on patients with rheumatological foot conditions.
24353850 Lumbar disc degenerative disease: disc degeneration symptoms and magnetic resonance image 2013 Dec STUDY DESIGN: Cross sectional and observational. PURPOSE: To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. OVERVIEW OF LITERATURE: Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. METHODS: This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. RESULTS: During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). CONCLUSIONS: Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life.
24302706 Discordance of global estimates by patients and their physicians in usual care of many rhe 2014 Jun OBJECTIVE: To analyze discordance between global estimates by patients (PATGL) and their physicians (DOCGL) according to demographic and self-report variables on a Multidimensional Health Assessment Questionnaire (MDHAQ) in patients with many rheumatic diseases seen in usual care. METHODS: Each patient completed an MDHAQ at each visit, which includes scores for physical function, pain, and PATGL, each found on the traditional Health Assessment Questionnaire (HAQ), and scores for sleep quality, anxiety, depression, self-report joint count, and fatigue, which are not found on the HAQ. A random visit of 980 patients with any rheumatic diagnosis was analyzed in 3 categories: PATGL=DOCGL (within 2 of 10 units), PATGL>DOCGL (by ≥2 of 10 units), and DOCGL>PATGL (by ≥2 of 10 units), using descriptive statistics and multinomial logistic regression models. RESULTS: Patients included 145 with rheumatoid arthritis, 57 with systemic lupus erythematosus, 173 with osteoarthritis, 348 with other inflammatory diseases, and 257 with other noninflammatory diseases. Overall, PATGL=DOCGL in 509 (52%), PATGL>DOCGL in 371 (38%), and DOCGL>PATGL in 100 (10%). PATGL>DOCGL was associated significantly with older age, female sex, low formal education, Hispanic ethnicity, not working, high MDHAQ physical function and pain scores, and high scores for fatigue, poor sleep, anxiety, depression, and self-report joint count, which are not available on the HAQ. Pain and fatigue were significant in a final multinomial logistic regression; the other variables may raise awareness of discordance to clinicians. CONCLUSION: Global estimates of patients indicated significantly poorer status than estimates of their physicians in 38% of 980 patients with rheumatic conditions, and were associated with demographic and MDHAQ scores, 5 of which are not available on the HAQ.
23183379 Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in ther 2013 May In this review we report the recent progresses, available in the literature, concerning the biology and the potential therapeutic role of both mesenchymal stem cells (MSCs) and hematopoietic stem cells in autoimmune diseases. Mesenchymal stem cells (MSCs) are responsible for the normal turnover and maintenance of adult mesenchymal tissues and their pleiotropic nature allows them to sense and respond to an event in the local environment, be it injury or inflammation. Recently, MSCs have been shown to have immune-modulatory properties and immunosuppressive capacities, acting on different immune cells both in vitro and in vivo, in addition to an immunologically privileged phenotype. Moreover, several works suggest that MSCs are defective in autoimmune diseases. These aspects are now considered the most intriguing aspect of their biology, introducing the possibility that these cells might be used as effective therapy in autoimmune diseases. Autoimmune diseases represent a failure of normal immune regulatory processes as they are characterized by activation and expansion of immune cell subsets in response to non-pathogenic stimuli. As autoimmune diseases can be transferred, or alternatively, cured, by stem cell transplantation, a defect in the hemopoietic stem cell as a cause of autoimmune diseases may be postulated. The rationale for autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases is the ablation of an aberrant or self-reactive immune system by chemotherapy and regeneration of a new and hopefully self-tolerant immune system from hematopoietic stem cells. In the past 15years, more than 1500 patients worldwide have received HSCT, mostly autologous, as treatment for a severe autoimmune disease and the majority were affected by multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis and idiopathic cytopenic purpura.