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ID PMID Title PublicationDate abstract
23163831 Economical aspect of biological therapy in inflammatory conditions in Hungary. 2013 Mar INTRODUCTION: There has been a burst in the use of biological therapies in the past decade resulting in increasing costs. In 2006 - 2010 the following biological agents were available in Hungary: adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab, and ustekinumab. All biological agents except rituximab were first line therapies; rituximab was a second line option in rheumatoid arthritis. AREAS COVERED: Data of the financing system related to health care services from the data warehouse of the Hungarian National Health Insurance Fund were in inflammatory conditions. Our analysis showed a constant increase in number of patients and overall cost of biological therapy as well as annual cost of biological agents. Distribution of first choice of biological therapy was compared in different diseases. Time from diagnosis to start of biological therapy showed relatively high deviations. EXPERT OPINION: In order to achieve both health benefit and cost-effectiveness it is crucial that biological therapy is initiated early enough in the course of the disease, after the failure of non-biological therapies. Health authorities in close collaboration with clinical decision-makers should ensure that early detection of the disease and early initiation of appropriate therapies-including non-biological and biological therapies-are carried out in the health care systems.
23006836 What is the prevalence of musculoskeletal problems in the elderly population in developed 2012 Sep 24 BACKGROUND: The proportion of older people will be tripled by the year 2050. In addition, the incidence of chronic musculoskeletal (MSK) conditions will also increase among the elderly people. Thus, in order to prepare for future health care demands, the magnitude and impact of MSK conditions from this growing population is needed. The objective of this literature review is to determine the current prevalence of MSK disorders in the elderly population. METHODS: A systematic literature search was conducted in Pubmed on articles in English, published between January 2000 and July 2011. Studies from developed countries with prevalence estimates on elderly people (60+) on the following MSK conditions were included: Non-specific extremity pain, rheumatoid arthritis, osteoarthritis, osteoporosis, and back pain. The included articles were extracted for information and assessed for risk of bias. RESULTS: A total of 85 articles were included with 173 different prevalence estimates. Musculoskeletal disorders are common in the elderly population, but due to heterogeneity of the studies, no general estimate on the prevalence of MSK can be determined. Women report more often MSK pain than men. Overall, prevalence estimates either remain fairly constant or increase slightly with increasing age, but with a tendency to decrease in the oldest (80+) people. CONCLUSIONS: Musculoskeletal disorders remain prevalent in the elderly population. Given the increasing proportion of elderly population in the world population and the burden of MSK diseases among the elderly people, efforts must be made to maintain their functional capacity for as long as possible through optimal primary and secondary health care.
22792085 Fenofibrate inhibited the differentiation of T helper 17 cells in vitro. 2012 Uncontrolled activity of T cells mediates autoimmune and inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, type 1 diabetes, and atherosclerosis. Recent findings suggest that enhanced activity of interleukin-17 (IL-17) producing T helper 17 cells (Th17 cells) plays an important role in autoimmune diseases and inflammatory diseases. Previous papers have revealed that a lipid-lowering synthetic ligand of peroxisome proliferator-activated receptor α (PPARα), fenofibrate, alleviates both atherosclerosis and a few nonlipid-associated autoimmune diseases such as autoimmune colitis and multiple sclerosis. However, the link between fenofibrate and Th17 cells is lacking. In the present study, we hypothesized that fenofibrate inhibited the differentiation of Th17 cells. Our results showed that fenofibrate inhibited transforming growth factor-β (TGF-β) and IL-6-induced differentiation of Th17 cells in vitro. However, other PPARα ligands such as WY14643, GW7647 and bezafibrate did not show any effect on Th17 differentiation, indicating that this effect of fenofibrate might be PPARα independent. Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. Thus, by ameliorating the differentiation of Th17 cells, fenofibrate might be beneficial for autoimmunity and inflammatory diseases.
22746153 Radiological signs indicating infection of dental origin in elderly Finns. 2013 May OBJECTIVE: The aim was to assess the prevalence and background factors of signs of infection of dental origin in elderly Finns. MATERIALS AND METHODS: Every third birth cohort between 60-78 years of age (n = 1733) in a southern and a northern region in Finland were invited. Altogether, 1069 subjects attended radiographic examination. Of those, 660 were dentate and formed the study sample. In the analysis an index as a sum of points (scale per lesion 0-3, range 0-420) indicating the severity of infection from periapical lesions, furcal lesions, vertical bone pockets, horizontal bone loss and severe dental caries was used. RESULTS: The index ranged individually from 0-91. Horizontal bone loss was found in 94%, vertical bone loss in 19%, periapical lesions in 46%, furcal lesions in 19% and carious lesions in 39% of the subjects. Only 3% of the subjects were free of dental infections, while 2% had mild, 17% moderate and 78% severe risk of dentogenic infection. Statistically significant background factors were region, level of education, number of regular drugs in use, drugs reducing salivation, alcohol consumption, cardiovascular disease, asthma and rheumatoid arthritis. CONCLUSIONS: Elderly Finns have high a prevalence of signs of infections of dental origin, which is associated with several socio-demographic and health-related factors.
22248635 Diffuse endocrine system, neuroendocrine tumors and immunity: what's new? 2012 During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment.
22236898 Radiologic review of total elbow, radial head, and capitellar resurfacing arthroplasty. 2012 Jan The use of metal and pyrolytic carbon radial head implants, capitellar resurfacing, and total elbow arthroplasty has become common in contemporary orthopedic surgery practice. The goal of total elbow arthroplasty is to decrease pain and restore an acceptable range of motion to the elbow joint. Rheumatoid arthritis is the primary indication for total elbow arthroplasty; newer indications include primary or posttraumatic osteoarthritis, fracture nonunion, acute comminuted fractures of the elbow, and postoperative resection of a neoplasm. Unlike total elbow arthroplasty, radial head replacement is most commonly performed in patients with trauma. Radial head fractures account for 33% of all elbow fractures in adults and are often associated with ligament disruption and valgus instability at the elbow. The goals of capitellar resurfacing arthroplasty include prevention of secondary osteoarthritis of the radiocapitellar joint and erosion in patients with radial head arthroplasty. Effective postoperative radiologic assessment of these different types of elbow reconstructions requires an understanding of their basic component design, physiologic purpose, and normal postoperative appearance, as well as the appearance of complications. Radiologists may have little training and experience with these new orthopedic devices.
21785694 Modelling cost-effectiveness of biologic treatments based on disease activity scores for t 2011 Background. The objective of this simulation model was to assess the cost-effectiveness of different biological treatment strategies based on levels of disease activity in Spain, in patients with moderate to severe active RA and an insufficient response to at least one anti-TNF agent. Methods. Clinically meaningful effectiveness criteria were defined using DAS28 scores: remission and Low Disease Activity State (LDAS) thresholds. Monte-Carlo simulations were conducted to assess cost-effectiveness over 2 years of four biological sequential strategies composed of anti-TNF agents (adalimumab, infliximab), abatacept or rituximab, in patients with moderate to severe active RA and an insufficient response to etanercept as first biological agent. Results. The sequential strategy including etanercept, abatacept and adalimumab appeared more efficacious over 2 years (102 days in LDAS) compared to the same sequence including rituximab as second biological option (82 days in LDAS). Cost-effectiveness ratios showed lower costs per day in LDAS with abatacept (427 €) compared to rituximab as second biological option (508 €). All comparisons were confirmed when using remission criteria. Conclusion. Model results suggest that in patients with an insufficient response to anti-TNF agents, the biological sequences including abatacept appear more efficacious and cost-effective than similar sequences including rituximab or cycled anti-TNF agents.
20179999 Fluorescent study of human blood plasma albumin alterations induced by ionizing radiation. 2011 May The use of hydrophobic fluorescent probe ABM (benzanthrone derivative) and albumin autofluorescence allowed show conformational alterations in Chernobyl clean-up workers blood plasma. Results obtained in 1996-1997 suggest that acidic expansion of plasma albumin takes place. Latest data (2006-2008) result in splitting of albumin alterations onto two stages - acidic expansion and N-F transition. The N-F transition is accompanied by the blue shift of fluorescence spectra and dehydration of tryptophanyl region of albumin molecule. In 2007 obtained.patterns of ABM spectra had never been previously seen in examined healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc. Patterns of ABM fluorescence spectra are associated with conformational changes of blood plasma albumin. The use of probe ABM and albumin auto-fluorescence allowed show conformational alterations in albumin of Chernobyl clean-up workers blood plasma. It is necessary to note that all investigated parameters significantly differ in observed groups of patients. These findings reinforce our understanding that the blood plasma albumin is a significant biological target of radiation. It may be concluded that fluorescence characteristics are representative of radiation induced albumin alterations and its carrier function.
20022196 Lewis lead enhances atrial activity detection in wide QRS tachycardia. 2012 Aug BACKGROUND: The differential diagnosis of wide QRS tachycardia is a challenge for the emergency physician. The major tool is the electrocardiogram (ECG), even though the sensitivity and specificity may be variable, depending on presentation. Additional leads could be used to improve the diagnostic accuracy of the ECG. OBJECTIVE: To document the use of the Lewis lead in improving the diagnostic accuracy of the ECG in wide QRS tachycardia. CASE REPORT: A 52-year-old woman with rheumatoid arthritis, in treatment with methotrexate, was admitted with progressive dyspnea that evolved to acute respiratory distress and shock at arrival. Pneumonia was diagnosed as the infection and she received antibiotics, and respiratory and inotropic support. She was also using amiodarone for more than 10 years, but she couldn't state the reason. On cardiac monitoring, wide QRS tachycardia was detected and ventricular tachycardia was considered on the differential diagnosis. The standard 12-lead ECG was complemented with the Lewis lead, obtained with higher speed and amplitude, demonstrating atrioventricular concordance and excluding ventricular tachycardia. The patient was treated for septic shock, and she died 2 days later. CONCLUSION: The Lewis lead is a simple and easy strategy to enhance atrial activity detection in wide QRS tachycardia.
23112137 Gold nanoparticles downregulate interleukin-1β-induced pro-inflammatory responses. 2013 Feb 11 Interleukin 1 beta (IL-1β)-dependent inflammatory disorders, such as rheumatoid arthritis and psoriasis, pose a serious medical burden worldwide, where patients face a lifetime of illness and treatment. Organogold compounds have been used since the 1930s to treat rheumatic and other IL-1β-dependent diseases and, though their mechanisms of action are still unclear, there is evidence that gold interferes with the transmission of inflammatory signalling. Here we show for the first time that citrate-stabilized gold nanoparticles, in a size dependent manner, specifically downregulate cellular responses induced by IL-1β both in vitro and in vivo. Our results indicate that the anti-inflammatory activity of gold nanoparticles is associated with an extracellular interaction with IL-1β, thus opening potentially novel options for further therapeutic applications.
23075877 New drug therapies on the horizon for IBD. 2012 IBD are diseases of the GI tract causing important morbidity. Several anti-TNF-α agents are currently used to treat Crohn's disease and ulcerative colitis. Although these molecules have dramatically improved the treatment of IBD, up to half of the patients have no sustained benefit due to nonresponse, loss of response or intolerance. New anti-TNF strategies are under development. Novel therapies targeting other immune pathways are under study, such as antibodies targeting the IL-12/IL-23 pathway, and have shown interesting preliminary results. In parallel, antiadhesion therapies limiting the recruitment of cells to the gut will reach the clinic in the coming years. Small molecules inhibiting the production of proinflammatory cytokines are already used in the clinic for rheumatoid arthritis, and Tofacitinib, a Janus kinase inhibitor, seems to have great potential to treat ulcerative colitis. In this review we focus on the novel molecules that are likely to reach the clinic in the near future for the treatment of IBD.
22833242 The incidence and associations of malignancy in a large cohort of patients with biopsy-det 2013 Apr The South Australian (SA) myositis database has registered all patients with biopsy-proven inflammatory myositis in SA from 1980 to 2009. We determined the incidence and associations of malignancy in myositis by linking this database with the SA cancer registry. Standardized incidence ratios (SIR) for malignancy were determined using the total SA population over the same time period, stratified by age and gender. The SIR for cancer in the myositis population (n = 373) was 1.39, p = 0.047. There was a trend towards an increased SIR in dermatomyositis but no increased risk of malignancy in polymyositis or inclusion body myositis. Malignancies of the lung and prostate were the commonest and 28 % of malignancies occurred within one year of IIM diagnosis. The odds of developing cancer were significantly raised in the presence of a shawl sign, male gender, and in patients with overlap syndrome or rheumatoid arthritis whilst myalgia was a significant protective factor. HLA-A28 allele was overrepresented in patients with malignancy (11 vs 2 %, p = 0.006). Patients in SA with myositis are at modestly increased risk for malignancy. We report clinical and genetic risk factors allowing the identification of patients at greatest risk for malignancy.
22737386 Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concep 2012 Jan Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to have a role in the pathogenesis of inflammatory, edematous, neovascular and neurodegenerative disorders. Several TNF-blocking drugs have been developed and approved, and are in clinical use for inflammatory diseases such as rheumatoid arthritis, psoriasis and ankylosing spondylitis. TNF-α blockers are widely used in ophthalmology as an off-label alternative to "traditional" immunosuppressive and immune-modulatory treatments in noninfectious uveitis. Preliminary studies suggest a positive effect of intravenously administered TNF-α blockers, mainly infliximab, for treating refractory diabetic macular edema and neovascular age-related macular degeneration. Unfortunately, much of the current data raises considerable safety concerns for intravitreal use of TNF-α inhibitors, in particular, intraocular inflammatory responses have been reported after intravitreal injection of infliximab. Results of dose-finding studies and humanized antibody or antibody fragments (e.g. adalimumab) are anticipated in the coming years; these will shed light on potential benefits and risks of local and systemic TNF-α blockers used for treatment of diseases of the retina and choroid.
22701454 Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is Th 2012 There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.
22678997 Non-invasive identification of proteoglycans and chondrocyte differentiation state by Rama 2013 Feb Proteoglycans (PGs) are crucial extracellular matrix (ECM) components that are present in all tissues and organs. Pathological remodeling of these macromolecules can lead to severe diseases such as osteoarthritis or rheumatoid arthritis. To date, PG-associated ECM alterations are routinely diagnosed by invasive analytical methods. Here, we employed Raman microspectroscopy, a laser-based, marker-free and non-destructive technique that allows the generation of spectra with peaks originating from molecular vibrations within a sample, to identify specific Raman bands that can be assigned to PGs within human and porcine cartilage samples and chondrocytes. Based on the non-invasively acquired Raman spectra, we further revealed that a prolonged in vitro culture leads to phenotypic alterations of chondrocytes, resulting in a decreased PG synthesis rate and loss of lipid contents. Our results are the first to demonstrate the applicability of Raman microspectroscopy as an analytical and potential diagnostic tool for non-invasive cell and tissue state monitoring of cartilage in biomedical research.
22488076 Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory? 2012 Jul PURPOSE OF REVIEW: Spondyloarthritis (SpA) is a chronic immune-mediated inflammatory disease of unknown origin. Here we aim to review whether SpA is driven by T-cell and/or B-cell autoreactivity or by abnormal innate immune responses. RECENT FINDINGS: SpA does not share genetic risk factors, female predominance, presence of disease-specific autoantibodies and response to T-cell or B-cell-targeted therapies with prototypical autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Growing evidence indicates that increased responsiveness of innate immune cells such as macrophages, mast cells and neutrophils drives inflammation in SpA. The altered innate immune response may be related to nonantigen-presenting functions of HLA-B27, including the induction of an unfolded protein response, and can be triggered by bacterial and mechanical stress. Innate immune cells appear to be the main producers of both pro-inflammatory (tumor necrosis factor, IL-1, IL-23, IL-17) and anti-inflammatory (IL-10) cytokines in SpA. SUMMARY: The predominance of myeloid above lymphoid alterations suggests an autoinflammatory rather than autoimmune origin of inflammation in SpA. Therefore, targeting innate cells or their inflammatory mediators may be more effective than T-cell or B-cell-directed therapies.
22328279 A B cell explanation for autoimmune disease: the forbidden clone returns. 2012 Apr More than 60 years ago, Burnet first proposed the 'forbidden clone' hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral self-antigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate B-T cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.
23788906 Mechanisms of psychological resiliency in women after mastectomy. 2012 AIM OF THE STUDY: To investigate into the mechanisms of resiliency in women after mastectomy. We hypothesized that the mechanism of resiliency in women with breast cancer would involve facilitation of adaptive coping strategies and inhibition of maladaptive strategies. We tested a mediational model in which resiliency was related to satisfaction with life through coping strategies. MATERIAL AND METHODS: Thirty women after mastectomy aged 28-69 years (M = 53.23, SD = 9.00) completed the Ego Resiliency Scale, Mental Adjustment to Cancer Scale, and Satisfaction with Life Scale. RESULTS: The bootstrapping technique revealed that there were significant indirect effects for positive reframing (95% CI: 0.01-0.36), hopelessness/helplessness (95% CI: 0.18-0.83) and anxious preoccupation (95% CI: 0.001-0.55) but not for fighting spirit. The models explained up to 33% of the variance in satisfaction with life. CONCLUSIONS: Coping strategies fully explain the effect of resiliency on satisfaction with life in women after mastectomy. This finding provides additional evidence of the fundamental role of coping strategies in the mechanisms of resiliency. We obtained similar results in patients with type II diabetes and rheumatoid arthritis. The lack of significant associations of fighting spirit with resiliency suggests that this coping strategy may be beneficial for somatic health but its contribution to the mechanisms of psychological resiliency is complex.
22113499 Influence of dietary components on regulatory T cells. 2012 Feb 10 Common dietary components including vitamins A and D, omega-3 and probiotics are now widely accepted to be essential to protect against many diseases with an inflammatory nature. On the other hand, high-fat diets are documented to exert multiple deleterious effects, including fatty liver diseases. Here we discuss the effect of dietary components on regulatory T cell (Treg) homeostasis, a central element of the immune system to prevent chronic tissue inflammation. Accordingly, evidence on the impact of dietary components on diseases in which Tregs play an influential role will be discussed. We will review chronic tissue-specific autoimmune and inflammatory conditions such as inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis and allergies among chronic diseases where dietary factors could have a direct influence via modulation of Tregs homeostasis and functions.
21703910 Role of microRNA-155 in autoimmunity. 2011 Jun MicroRNAs (miRNAs) have recently emerged as a major class of gene expression regulators linked to most biological functions. MiR-155 is encoded within a region known as B cell integration cluster (Bic) gene, identified originally as a frequent integration site for the avian leukosis virus. Disregulation of endogenous miR-155 has been implicated in the pathogenesis of human cancers. Recently, aberrant expression of miR-155 was observed in many autoimmune conditions, including rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Moreover, functional analysis demonstrated that miR-155 has powerful regulatory potential in a wide variety of immune cells through targeting specific mRNAs. Since pathogenic immune cells play a pivotal role in pathogenesis of human autoimmune diseases, miR-155 might be a versatile therapeutic target. This review will discuss the current understandings for the role of miR-155 in autoimmunity.