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ID PMID Title PublicationDate abstract
26998377 The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review. 2016 Purpose. Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn's disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis. Methods. A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement. Results. After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP). Conclusion. Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker.
26997007 Postural & striatal deformities in Parkinson`s disease: Are these rare? 2016 Jan Parkinson`s disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.
26264940 Insights into IL-37, the role in autoimmune diseases. 2015 Dec Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders.
26236331 Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. 2015 In recent years, IL-17A (IL-17), a pro-inflammatory cytokine, has received intense attention of researchers and clinicians alike with documented effects in inflammation and autoimmune diseases. IL-17 mobilizes, recruits and activates different cells to increase inflammation. Although protective in infections, overproduction of IL-17 promotes inflammation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, among others. Regulating IL-17 levels or action by using IL-17-blocking antibodies or IL-17R antagonist has shown to attenuate experimental autoimmune diseases. It is now known that in addition to IL-17-specific transcription factor, RORγt, several other transcription factors and select microRNAs (miRNA) regulate IL-17. Given that miRNAs are dysregulated in autoimmune diseases, a better understanding of transcriptional factors and miRNA regulation of IL-17 expression and function will be essential for devising potential new therapies. In this review, we will overview IL-17 induction and function in relation to autoimmune diseases. In addition, current findings on transcriptional regulation of IL-17 induction and plausible interplay between IL-17 and miRNA in autoimmune diseases are highlighted.
26109829 Risk factors associated with sacral stress fractures: a systematic review. 2015 May OBJECTIVES: The objective of this study was to examine and identify risk factors associated with the development of sacral stress fractures in order to improve diagnosis in clinical practice. METHODS: Electronic search strategies in PubMed, CINAHL, Scopus, and SPORTDiscus were combined with a hand search to identify articles for inclusion. Studies were considered if they described patient cases in which imaging confirmed diagnosis of a sacral stress fracture, and the diagnosis included whether the fracture was a sacral insufficiency or sacral fatigue stress fracture. RESULTS: In those that developed sacral insufficiency fractures, the risk factors that were most prevalent included osteoporosis, pelvic radiation therapy, rheumatoid arthritis, long-term corticosteroid therapy, and postmenopausal, each with a prevalence of 100%. Risk factors with 100% prevalence in those diagnosed with sacral fatigue fractures included recent increase in training intensity and deficient diet. DISCUSSION: A pattern of signs and symptoms are consistent among subjects with sacral stress fractures. Patients being unsuccessfully treated for low-back and buttock pain who fit the risk factor profiles for sacral stress fractures should be referred to a physician for further diagnostic workup.
26072724 Multiple visceral artery aneurysms. 2015 Aug A 63-year-old woman patient was presented with 3 visceral artery aneurysms, which were identified accidentally at nuclear magnetic resonance imaging carried out because of small mass in the left adrenal gland, which was suspected by ultrasound. Computed tomography (CT) examination was indicated and showed fusiform aneurysm on splenic artery, saccular aneurysm of right renal artery, and saccular aneurysm of left segmental renal artery. Also, she experienced hypertension, cardiomyopathy, thyroid gland strum with normal hormone levels, osteoporosis, and rheumatoid arthritis. The patient was treated by open conventional surgery followed by end-to-end anastomosis reconstructions firstly of the right renal and then splenic artery. In 5 days, the patient was released from hospital in good condition. Control CT examination in 9 months did not show enlargement of remaining aneurysm. Histopathology confirmed just typical aneurysm degeneration based on atherosclerosis.
25676126 [Fibroblasts as pathogenic cells in rheumatic inflammation]. 2015 Feb Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis, synovial hyperplasia and progressive degeneration of affected joints. These processes are mediated by cells of the immune system as well as by synovial fibroblasts (RASF) originating from the lining layer of the synovium. In this scenario RASFs display an activated phenotype: they show an altered expression of adhesion molecules which allows attachment to articular cartilage and by synthesis of proteases they mediate progressive cartilage and bone destruction. Furthermore, they produce various cytokines and chemokines, which are essential for promoting the inflammatory response. In recent years it has become evident that RASFs not only passively respond to the proinflammatory milieu in the joints of RA patients but also actively contribute by the overproduction of several cytokines and chemokines. These proinflammatory cytokines trigger the transformation of RASFs into an aggressive and invasive phenotype. Additionally, the primarily altered genuine RASFs are actively involved in the recruitment and activation of immune cells. Taken together, they are key players in the development of the well-known chronic, destructive inflammatory response in joints affected by RA.
25669996 Application of metabolomics in autoimmune diseases: insight into biomarkers and pathology. 2015 Feb 15 Metabolomics has recently become a new technology using mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (NMR) to access metabolite profiles in biofluids or tissue extracts for the detection of biomarker molecules and biochemical effects induced by a disease or its therapeutic intervention. This review outlines recent advances in the use of metabolomic techniques to study autoimmune diseases (ADs), including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), autoimmune diabetes et al. Many studies have demonstrated that AD patients including subtypes of some diseases, and healthy individuals can be distinguished using metabolic profiling accompanied with well-established data analysis tools including principal component analysis (PCA) and partial least squares (PLS). These metabolites not only affect glucose, amino acid and lipid metabolism, but also involve alteration of neurotransmitters, nucleotides, immune responses and anti-inflammatory responses. Knowledge of unique metabolomic fingerprint in ADs could be useful for diagnosis, treatment, and detection mechanisms of diseases.
25525953 Molecular hydrogen in sports medicine: new therapeutic perspectives. 2015 Apr In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine.
26343270 Involvement of Interleukin 6 in Hepatitis B Viral Infection. 2015 Hepatitis B is a major global health problem and a potentially life-threatening liver infection caused by hepatitis B virus (HBV). Many cytokines including interleukin 6 (IL-6) have been shown to be involved in the HBV infection process. IL-6 is a typical cytokine made up of 184 amino acids, and the gene is located in chromosome 7p21. For healthy people, serum IL-6 levels are usually too low to be detected. However, dysregulated synthesis of IL-6 has been discovered in chronic inflammatory diseases such as hepatitis B, Crohn's disease and rheumatoid arthritis. IL-6 also plays an important role in HBV replication and in the development of hepatitis B disease. This review aims to present the latest discoveries concerning the role of IL-6 in hepatitis B disease progression, and HBV entry and replication, and evaluate polymorphisms that are associated with the development of hepatitis B disease.
25354465 Risk of ischemic stroke in patients with polymyositis and dermatomyositis: a systematic re 2015 May Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, have been demonstrated to increase ischemic stroke risk, but the data on polymyositis (PM) and dermatomyositis (DM) remain unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing ischemic risk in patients with PM/DM versus non-PM/DM participants. Pooled risk ratio and 95 % confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Three cohort studies were identified and included in our data analysis. The pooled risk ratio of ischemic stroke in patients with PM/DM was 1.61 (95 % CI 1.28-2.02). The statistical heterogeneity of this meta-analysis was insignificant with an I (2) of 0 %. Our study demonstrated a statistically significant increased ischemic stroke risk among patients with PM/DM.
28032700 Management of Acute Hematogenous Infection Following Total Knee Arthroplasty: A Case Serie 2016 Nov OBJECTIVE: Acute hematogenous infection is a devastating complication that can occur after total knee arthroplasty (TKA). The best strategies for management of this infection remain controversial. Two-stage revision has been well described as the gold standard for the management of chronic late infections. However, there is a paucity of information presently available on the management and outcomes of patients treated for acute hematogenous infections. The purpose of the present study was to report the outcome of acute hematogenous infections following TKA with the treatment of irrigation, debridement, and retention of the prosthetic components. METHODS: Eleven patients who had been diagnosed with acute hematogenous infection of the knee following TKA underwent irrigation and debridement between 2002 and 2012. To improve the efficiency of irrigation, a vacuum constriction device was used and the most sensitive antibiotics were injected into the irrigation saline. The mean age of the 11 patients was 56.3 ± 11.8 years (range, 35-73 years), with 2 male patients (18.2%) and 9 female patients (81.8%). The diagnosis at primary operation was osteoarthritis in three cases, rheumatoid arthritis in seven and osteoarthritis (OA) secondary to fracture in 1. They had pain and swell with the acute onset of pain after a previously well-functioning TKA, and met the Musculoskeletal Infection Society (MSIS) criteria for prosthetic joint infection. Before the onset of symptoms in the operated knees, patients had a history of bacteriaemia, and blood culture was consistent with the culture result of local infection. Failure was defined as: (i) death before the end of antibiotic treatment; (ii) a further surgical intervention for treatment of infection was needed; and (iii) life-long antibiotic treatment, or chronic infection. The prosthesis survivorship, Knee Society Score (KSS) and the factors that may lead to the infection recurrence, such as type of bacteria, age, sex, rheumatoid arthritis, history of diabetes, and interval surgery time, were analyzed. RESULTS: Among the 11 patients, the most common infecting organisms were staphylococcal and streptococcus species. The 2 staphylococcal species cases included: Staphylococcus epidermidis (1) and Staphylococcus aureus (1); The 7 Streptococcus species cases included: Streptococcus agalactiae (1), β-Hemolytic Streptococcus (1), Streptococcus pneumonia (3), Streptococcus dysgalactiae (1), Viridans streptococci (1) and Enterobacter cloacae (1). The survivorship at the endpoint was 9 in 2 years. The survival rate for patients with a staphylococcal infection was 0%, and 100% for patients infected with non-staphylococcus species, with a mean KSS of 72.6 points. The duration of symptoms prior to operation and the type of pathogen affected the outcome (P = 0.00). CONCLUSIONS: Patients who developed an acute hematogenous infection with non-staphylococcus species following operative debridement and continuous irrigation with prosthetic retention had satisfactory outcomes, but patients infected with staphylococcal had poor results. To improve the success rate of treatment, patients should be treated as soon as possible and individually according to the bacterial culture results.
27859438 Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar ther 2017 Apr WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.
27369644 Collection and management of selected comorbidities and their risk factors in chronic infl 2016 Oct INTRODUCTION: In chronic inflammatory rheumatic diseases (CIRDs), comorbidities such as cardiovascular disease and infections are sub-optimally managed. EULAR recently developed points to consider to collect and report comorbidities. The objective of this present study was to develop a pragmatic guide to collect, report and propose management recommendations for comorbidities, from a rheumatologist perspective. METHODS: The collection and reporting of comorbidities and risk factors was adapted from the EULAR points to consider. To develop management recommendations, the process comprised (1) systematic literature reviews by 3 fellows and (2) a 2-day consensus process involving 110 experts (rheumatologists and health professionals). Votes of agreement (Likert 1-5 where 5 indicates full agreement) were obtained. RESULTS: The six selected comorbidities were ischemic cardiovascular diseases, malignancies, infections, diverticulitis, osteoporosis and depression. The literature review retrieved 97 articles or websites, mostly developed for the general population. The consensus process led to reporting presence of comorbidities, current treatment, risk factors (e.g. hypertension), screening (e.g. mammography) and prevention (e.g. vaccination). Management recommendations include physical examination (e.g. blood pressure or lymph node examination), prescribing screening procedures, and interpreting results to refer in a timely manner to appropriate other health professionals. Agreement was high (mean±standard deviation, 4.37±0.33). CONCLUSIONS: Using an evidence-based approach followed by expert consensus, this initiative furthers the dissemination in France of the EULAR points to consider, and clearly defines what part of the management of comorbidities is potentially within the remit of rheumatologists. This initiative should facilitate systematic management of patients with CIRDs.
26385063 The effects of RelB deficiency on lymphocyte development and function. 2015 Dec Multiple receptors that control cell growth and inflammation activate the NFκB pathway that comprises of two pathways. Dysfunction of the classical pathway leads to impaired adaptive and innate immunity in humans. In contrast the exact role of the alternative NFκB pathway mediated by RelB in humans remains largely elusive. We have recently identified deleterious mutations in RelB in patients with combined immunodeficiency and autoimmunity. We studied here the biological effects of RelB deficiency on the immune system. We show that the thymus in this patient is dysplastic and consequently new thymus emigrants are rare and there is an accumulation of CD45 RO(+) T cells with an increase in CD62L(+) central memory cells. The TCR repertoire of these cells appears skewed with selective clonal expansion. In vitro responses to T cell mitogens were markedly depressed and so were PHA induced IL2 and IFNγ production. In addition, the TH1 promoting T bet and STAT1 were reduced. In contrast, hyper-activation was seen in response to anti-CD3 and CD28. T cell dependent antibody responses were low to absent in all patients. We found that BAFF-R was reduced and CD40 signaling aberrant. Critically, CD27(+) memory cells were absent. We have shown here for the first time the role of RelB on lymphocyte development in humans. In the absence of RelB, B cells development is arrested, resulting in poor production of immunoglobulins and specific antibodies. T cell maturation in the thymus appears altered with reduced output and production of a skewed T cell repertoire with expansion of clones which are likely the cause of the autoimmune features observed in these patients.
27305810 Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic D 2016 May Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far.
27294954 Isoflavones: Anti-Inflammatory Benefit and Possible Caveats. 2016 Jun 10 Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks.
27228629 Quality of Life, Coping and Depression in Systemic Lupus Erythematosus. 2016 Mar Physical, mental and social well-being are important outcomes in patients with chronic rheumatic diseases, including systemic lupus erythematosus (SLE). The MOS SF-36 and the WHO QoL Bref are appropriate for assessing quality of life (QoL) in patients with SLE. The QoL of patients with SLE is impaired compared with that of controls. Fibromyalgia adversely affects the QoL of SLE patients. Women with SLE had significantly lower scores on subscales of the sense of coherence (SoC) compared with matched controls. This reduced SoC in SLE women represents impaired adaptive coping and is independently associated with reduced QoL in women with SLE. Depression and anxiety are common among SLE patients, and the frequency is similar to that in patients with rheumatoid arthritis. A reciprocal longitudinal relationship between depression and illness intrusiveness was found in patients with SLE. Disease activity and damage are not associated with depression. The subjective experience, not the illness per se, causes depression.
26525344 ASICs Mediate Pain and Inflammation in Musculoskeletal Diseases. 2015 Nov Chronic musculoskeletal pain is debilitating and affects ∼ 20% of adults. Tissue acidosis is present in painful musculoskeletal diseases like rheumatoid arthritis. ASICs are located on skeletal muscle and joint nociceptors as well as on nonneuronal cells in the muscles and joints, where they mediate nociception. This review discusses the properties of different types of ASICs, factors affecting their pH sensitivity, and their role in musculoskeletal hyperalgesia and inflammation.
26234519 Glycoxidation of histone proteins in autoimmune disorders. 2015 Oct 23 Post translational modifications (PTMs) alter the characteristic properties of proteins by influencing the spatial orientation of amino acid residues leading to a variety of pathological complications. Among the large number of PTMs, much attention has focused on non-enzymatic glycation and oxidation of proteins that form advanced glycation end products and generate autoantibodies. Histone proteins are essential components of chromatin structure and have role in its higher order structural formation. They have abundance of lysine and arginine residues and thus are prone to glyoxidation reactions. Glyoxidation causes structural alterations in histones and consequently leads to a variety of modifications in their amino acid sequence and the secondary and tertiary structure producing new antigenic determinants that may result in cause an aggressive autoimmune response. Here we review and evaluate the field of histone glyoxidation and its role in autoimmune disorders. We explore their structural alterations and immunogenicity of histones after glycation and oxidation reactions, and their role in autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis and diabetes.