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ID PMID Title PublicationDate abstract
28661865 Health benefits of tai chi: What is the evidence? 2016 Nov OBJECTIVE: To summarize the evidence on the health benefits of tai chi. SOURCES OF INFORMATION: A literature review was conducted on the benefits of tai chi for 25 specific conditions, as well as for general health and fitness, to update a 2014 review of systematic reviews. Systematic reviews and recent clinical trials were assessed and organized into 5 different groups: evidence of benefit as excellent, good, fair, or preliminary, or evidence of no direct benefit. MAIN MESSAGE: During the past 45 years more than 500 trials and 120 systematic reviews have been published on the health benefits of tai chi. Systematic reviews of tai chi for specific conditions indicate excellent evidence of benefit for preventing falls, osteoarthritis, Parkinson disease, rehabilitation for chronic obstructive pulmonary disease, and improving cognitive capacity in older adults. There is good evidence of benefit for depression, cardiac and stroke rehabilitation, and dementia. There is fair evidence of benefit for improving quality of life for cancer patients, fibromyalgia, hypertension, and osteoporosis. Current evidence indicates no direct benefit for diabetes, rheumatoid arthritis, or chronic heart failure. Systematic reviews of general health and fitness benefits show excellent evidence of benefit for improving balance and aerobic capacity in those with poor fitness. There is good evidence for increased strength in the lower limbs. There is fair evidence for increased well-being and improved sleep. There were no studies that found tai chi worsened a condition. A recent systematic review on the safety of tai chi found adverse events were typically minor and primarily musculoskeletal; no intervention-related serious adverse events have been reported. CONCLUSION: There is abundant evidence on the health and fitness effects of tai chi. Based on this, physicians can now offer evidence-based recommendations to their patients, noting that tai chi is still an area of active research, and patients should continue to receive medical follow-up for any clinical conditions.
27965941 Health-related Quality of Life in Accordance with Fracture History and Comorbidities in Ko 2016 Nov BACKGROUND: The purpose of this study was to explore health-related quality of life (HRQOL) among Korean patients with osteoporosis and to measure the impact of fractures and comorbidity on their quality of life (QOL) using the Korean National Health and Nutrition Examination Survey (KNHANES) data with a nationwide representativeness. METHODS: This study was based on 4-year-data obtained from the KNHANES 2008 to 2011. Osteoporosis was diagnosed in 2,078 survey participants according to their bone mineral density measurements using dual energy X-ray absorptiometry. According to the World Health Organization study group, T-scores at or above -1.0 are considered normal, those between -1.0 and -2.5 as osteopenia, and those at or below -2.5 as osteoporosis The EuroQol five-dimensional questionnaire (EQ-5D) index score was used to assess the QOL. RESULTS: Of 2,078 patients diagnosed with osteoporosis, fractures were found to occur at 11.02%. Wrist fracture was the most frequent, affecting 4.52% of the patients, with a significantly different prevalence among men and women (P<0.001). The overall EQ-5D index score was 0.84±0.01 among patients with osteoporosis. With the exception of cancer, the EQ-5D index score were significantly lower for those having osteoarthritis, rheumatoid arthritis, hypertension, diabetes, chronic obstructive pulmonary disease and cardiovascular events compared to those without the related diseases. CONCLUSIONS: We found that low health utility was associated with previous spine fracture and comorbidities in patients with osteoporosis. In particular, the number of fracture experiences greatly deteriorated the HRQOL in patients with osteoporosis. Thus, prevention of secondary fractures and chronic care model for comorbidities should be a priority for osteoporosis management in order to improve HRQOL.
27896037 Functional Evaluation of Patients Undergoing Multiple Joint Replacements: A Retrospective 2016 Oct 15 INTRODUCTION:  Polyarthritis is a challenging condition that an orthopedic surgeon faces in day-to-day practice. Some of the conditions where multiple joints are affected are rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Multiple joint afflictions can cause severe impairment in the quality of life, which leads to a significant socioeconomic burden on the family and society. Joint replacement is considered as a treatment when severe joint pain or dysfunction is not alleviated by conservative management. Total joint arthroplasty remains one of the most commonly performed and universally accepted operative interventions for such patients. MATERIALS AND METHODS:  Fifty patients were invited into the study. All patients included in the study were 18 years of age and older and had undergone two or more joint replacements with a minimum of six months duration from the last surgery. The data was collected during the preoperative and postoperative periods through patient records and questionnaires. The Short Form 36 Health Survey Questionnaire (SF-36) scores were generated from an online application that is readily available on the official website SF-36 scoring system. The results were compared, analyzed, and tested for significance using the Wilcoxon signed rank test. RESULTS:  The highest incidence of multiple joint replacements appears to be in the age-group of 51 - 70 years (52%), the mean age of patients being 51.7 +/- 14.4 years. The ratio of female to male patients was 1.6:1. On comparison of preoperative and postoperative (six months) physical component and mental component scores, the differences were found to be significant (p-value: < 0.01). This finding is irrespective of the diagnosis, gender, or age of the patient. CONCLUSION:  In the study conducted on 50 patients, we found out that multiple joint arthroplasties are fruitful surgeries. The procedures are efficient in reducing the disabilities seen in patients with polyarthritis of various causes and improving the overall quality of life. We strongly recommend multiple joint arthroplasties to patients with severe disability. However, adequate medical management plays an equally important role to improve the overall results. Well-designed and larger studies are required to establish the treatment protocols and order of surgeries in patients with differing causes of polyarthritis.
27891180 The effect of foot orthoses with forefoot cushioning or metatarsal pad on forefoot peak pl 2016 BACKGROUND: Foot orthoses are frequently used in sports for the treatment of overuse complaints with sufficient evidence available for certain foot-related overuse pathologies like plantar fasciitis, rheumatoid arthritis and foot pain (e.g., metatarsalgia). One important aim is to reduce plantar pressure under prominent areas like metatarsal heads. For the forefoot region, mainly two common strategies exist: metatarsal pad (MP) and forefoot cushioning (FC). The aim of this study was to evaluate which of these orthosis concepts is superior in reducing plantar pressure in the forefoot during running. METHODS: Twenty-three (13 female, 10 male) asymptomatic runners participated in this cross-sectional experimental trial. Participants ran in a randomised order under the two experimental (MP, FC) conditions and a control (C) condition on a treadmill (2.78 ms(-1)) for 2 min, respectively. Plantar pressure was measured with the in-shoe plantar pressure measurement device pedar-x®-System and mean peak pressure averaged from ten steps in the forefoot (primary outcome) and total foot was analysed. Insole comfort was measured with the Insole Comfort Index (ICI, sum score 0-100) after each running trial. The primary outcome was tested using the Friedman test (α = 0.05). Secondary outcomes were analysed descriptively (mean ± SD, lower & upper 95%-CI, median and interquartile-range (IQR)). RESULTS: Peak pressure [kPa] in the forefoot was significantly lower wearing FC (281 ± 80, 95%-CI: 246-315) compared to both C (313 ± 69, 95%-CI: 283-343; p = .003) and MP (315 ± 80, 95%-CI: 280-350; p = .001). No significant difference was found between C and MP (p = .858). Peak pressures under the total foot were: C: 364 ± 82, 95%-CI: 328-399; MP: 357 ± 80, 95%-CI: 326-387; FC: 333 ± 81 95%-CI: 298-368. Median ICI sum scores were: C 50, MP 49, FC 64. CONCLUSIONS: In contrast to the metatarsal pad orthosis, the forefoot cushioning orthosis achieved a significant reduction of peak pressure in the forefoot of recreational runners. Consequently, the use of a prefabricated forefoot cushioning orthosis should be favoured over a prefabricated orthosis with an incorporated metatarsal pad in recreational runners with normal height arches.
27870974 Myocardial perfusion in peripheral Raynaud's phenomenon. Evaluation using stress cardiovas 2017 Feb 1 BACKGROUND: Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without any coexisting disease or secondary (SRP), due to connective tissue diseases (CTD). We hypothesized that adenosine stress cardiovascular magnetic resonance (CMR) can assess myocardial perfusion in a population of PRP and SRP. PATIENTS-METHODS: Twenty CTDs, aged 30.6±7.5yrs., 16F/4M, including 9 systemic sclerosis (SSc), 4 systemic lupus erythematosus (SLE), 3 mixed connective tissue disease (MCTD), 2 polymyositis (PM) and 2 rheumatoid arthritis (RA), with SRP, under treatment with calcium blockers, were evaluated by stress CMR and compared with age-sex matched PRP and controls. All RP patients were under treatment with calcium blockers. Stress perfusion CMR was performed by 1.5T system using 140mg/kg/min adenosine for 4min and 0.05mmol/kg Gd-DTPA for first-pass perfusion. A rest perfusion was performed with the same protocol. Late gadolinium enhanced (LGE) images were acquired after another dose of Gd-DTPA. RESULTS: In both PRP, SRP, the myocardial perfusion reserve index (MPRI) was significantly reduced compared with the controls (1.7±0.6 vs 3.5±0.4, p<0.001 and 0.7±0.2 vs 3.5±0.4, p<0.001, respectively). Furthermore, in SRP, MPRI was significantly reduced, compared with PRP (0.7±0.2 vs 1.7±0.6, p<0.001). Subendo-cardial LGE=8.2±1.7 of LV mass was revealed in 1 SLE, 1MCTD and 2 SSc, but in none of PR patients. CONCLUSIONS: MPRI reduction is common in both PRP and SRP, but it is more severe in SRP, even if RP patients are under treatment with calcium blockers. Occult fibrosis may coexist with the reduced MPRI in SRP but not in PRP.
27215364 Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation. 2016 Dec Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD.
27729945 Multiple Imputation of Missing Composite Outcomes in Longitudinal Data. 2016 In longitudinal randomised trials and observational studies within a medical context, a composite outcome-which is a function of several individual patient-specific outcomes-may be felt to best represent the outcome of interest. As in other contexts, missing data on patient outcome, due to patient drop-out or for other reasons, may pose a problem. Multiple imputation is a widely used method for handling missing data, but its use for composite outcomes has been seldom discussed. Whilst standard multiple imputation methodology can be used directly for the composite outcome, the distribution of a composite outcome may be of a complicated form and perhaps not amenable to statistical modelling. We compare direct multiple imputation of a composite outcome with separate imputation of the components of a composite outcome. We consider two imputation approaches. One approach involves modelling each component of a composite outcome using standard likelihood-based models. The other approach is to use linear increments methods. A linear increments approach can provide an appealing alternative as assumptions concerning both the missingness structure within the data and the imputation models are different from the standard likelihood-based approach. We compare both approaches using simulation studies and data from a randomised trial on early rheumatoid arthritis patients. Results suggest that both approaches are comparable and that for each, separate imputation offers some improvement on the direct imputation of a composite outcome.
27720274 Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical featur 2017 Feb BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis. OBJECTIVE: To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis. METHODS: Systematic review of published cases of TNF-α inhibitor-induced psoriasis. RESULTS: We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%). LIMITATIONS: Retrospective review that relies on case reports and series. CONCLUSION: While TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.
27659711 [Pulmonary manifestations in collagen vascular diseases]. 2016 Oct CLINICAL/METHODICAL ISSUE: Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. STANDARD RADIOLOGICAL METHODS: The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. PERFORMANCE: The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. ACHIEVEMENTS: Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. PRACTICAL RECOMMENDATIONS: At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management.
27520362 Cytoprotective pathways in the vascular endothelium. Do they represent a viable therapeuti 2016 Nov The vascular endothelium is a critical interface, which separates the organs from the blood and its contents. The endothelium has a wide variety of functions and maintenance of endothelial homeostasis is a multi-dimensional active process, disruption of which has potentially deleterious consequences if not reversed. Vascular injury predisposes to endothelial apoptosis, dysfunction and development of atherosclerosis. Endothelial dysfunction is an end-point, a central feature of which is increased ROS generation, a reduction in endothelial nitric oxide synthase and increased nitric oxide consumption. A dysfunctional endothelium is a common feature of diseases including rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus and chronic renal impairment. The endothelium is endowed with a variety of constitutive and inducible mechanisms that act to minimise injury and facilitate repair. Endothelial cytoprotection can be enhanced by exogenous factors such as vascular endothelial growth factor, prostacyclin and laminar shear stress. Target genes include endothelial nitric oxide synthase, heme oxygenase-1, A20 and anti-apoptotic members of the B cell lymphoma protein-2 family. In light of the importance of endothelial function, and the link between its disruption and the risk of atherothrombosis, interest has focused on therapeutic conditioning and reversal of endothelial dysfunction. A detailed understanding of cytoprotective signalling pathways, their regulation and target genes is now required to identify novel therapeutic targets. The ultimate aim is to add vasculoprotection to current therapeutic strategies for systemic inflammatory diseases, in an attempt to reduce vascular injury and prevent or retard atherogenesis.
27294919 Flavonoids as Cytokine Modulators: A Possible Therapy for Inflammation-Related Diseases. 2016 Jun 9 High levels of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6, are associated with chronic diseases like rheumatoid arthritis, asthma, atherosclerosis, Alzheimer's disease and cancer; therefore cytokine inhibition might be an important target for the treatment of these diseases. Most drugs used to alleviate some inflammation-related symptoms act by inhibiting cyclooxygenases activity or by blocking cytokine receptors. Nevertheless, these drugs have secondary effects when used on a long-term basis. It has been mentioned that flavonoids, namely quercetin, apigenin and luteolin, reduce cytokine expression and secretion. In this regard, flavonoids may have therapeutical potential in the treatment of inflammation-related diseases as cytokine modulators. This review is focused on current research about the effect of flavonoids on cytokine modulation and the description of the way these compounds exert their effect.
27214601 Autoantibodies against lamin C, NA14 and CK15 in primary vasculitides or autoimmune diseas 2016 May OBJECTIVES: Autoantibodies may play a role in the pathogenesis of primary vasculitides (PVs) like giant cell arteritis (GCA). We recently identified 3 cytoskeletal proteins (lamin C [laC], nuclear autoantigen of 14kD [NA14] and cytokeratin 15 [CK15]) as autoantigens in GCA and postulated a frequent autoantibody response against these antigens in PVs. METHODS: To test this hypothesis we studied a cohort of patients with PVs (n=61) and healthy individuals (n=27) for the presence of these autoantibodies using a recombinant cDNA expression library. To define their specifity for PV, we also examined patients with other autoimmune diseases such as rheumatoid arthritis (RA) and connective tissue diseases (CTD). RESULTS: We found no statistically significant differences in autoantibody responses between patients with PV and healthy controls, although there was a trend for an association between PVs and the occurrence of antibodies against laC and CK15. However, in patients with RA (n=33) or Sjögren's syndrome (SS, n=11) with vasculitides we observed more frequently autoantibodies against NA14, laC and CK15 compared to healthy controls. In patients with systemic lupus erythematosus (SLE, n=23) autoantibodies against laC were more frequent. The presence of autoantibodies in RA, SS and SLE was associated with systemic secondary vasculitis (SSV). In RA, laC- and NA14-seropositive patients were in a more advanced disease stage than seronegative patients with more frequent extraarticular manifestations (p=0.004). In SLE laC-autoantibody-positive patients had a higher SLE activity index (p<0.001). CONCLUSIONS: Serum autoantibodies against laC and NA14 are frequent in patients with RA and CTD and are associated with extensive disease and SSV. The potential pathogenic and prognostic role of these antibodies should be further investigated.
26987072 Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportun 2016 (R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models. The fact that (R)-roscovitine has undergone extensive preclinical safety/pharmacology studies, and phase I and II clinical trials in cancer patients, encourages its repurposing as a CF drug candidate.
26967224 Incidence and Duration of Cumulative Bisphosphonate Use among Community-Dwelling Persons w 2016 We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer's disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002-2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p <  0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD.
26612346 Toe resurfacing with a thin thoracodorsal artery perforator flap. 2017 May BACKGROUND: In toe reconstruction, amputation procedures are much more common than salvage procedures. However, toe resurfacing, rather than amputation, provides superior functional and aesthetic results. In this study, we report the clinical outcomes of toe resurfacing using a thin thoracodorsal artery perforator flap. PATIENTS AND METHODS: Between January 2004 and June 2013, a total of 15 patients underwent toe resurfacing using thoracodorsal artery perforator flaps. Thin flaps were harvested by discarding the deep adipose layer. Twelve cases involved a great toe defect, three, a second toe defect, three, a third toe defect, and one, a fourth toe defect. Patient ages ranged from 19 to 82 years (mean, 42.9 years). The mechanism of injury varied, including crushing injury, degloving injury, and diabetic foot infection. RESULTS: The size of thoracodorsal artery perforator flap ranged from 4 × 3 to 20 × 8 cm(2) and the thickness of the flap ranged from 4 to 9 mm (mean, 6.5 mm). All flap survived completely without complications. The mean follow-up period was 18.8 months (range, 12-60 months). Only one patient with rheumatoid arthritis had mild gait disturbance. All patients were satisfied with the aesthetic and functional results. CONCLUSION: Toe resurfacing with thin thoracodorsal artery perforator flaps appears to be a safer and more reliable option than amputation for preserving their function. © 2015 Wiley Periodicals, Inc. Microsurgery 37:312-318, 2017.
26526936 [Epidemiology and prevention of prosthetic joint infection]. 2015 Dec BACKGROUND: Prosthetic joint infection (PJI) is challenging for patients and orthopedic surgeons and represents a great economic burden to the health care system. The growing number of primary and revision arthroplasty procedures in an aging society with demographic changes will increase the number of PJIs in the future. AIM: This article presents an overview of the epidemiology and prevention of PJI. METHOD: A selective literature review was performed focusing on evidence-based epidemiology, risk factors, and prevention of PJI. RESULTS: The total number of primary arthroplasty and septic revision procedures is increasing. The incidence of PJI is constant, although surgical techniques have improved over the years, with a multitude of possible preventive procedures for use before surgical treatment. This is most likely due to the increasing comorbidities and individual risk factors of the patient. Both endogenous and exogenous risk factors are known to be associated with PJI. Endogenous risk factors include diabetes, obesity, immunosuppression, oncological diseases, rheumatoid arthritis, previous or chronic infections, and bacteriuria. Exogenous risk factors include the extended duration of the operation, blood transfusion, and hypothermia. However, the facilities in the operating theatre or the use of iodine-impregnated incision drape seem to have no influence on the incidence of PJI. PROSPECT: The increasing number of arthroplasty procedures and the static incidence of PJI will result in an increase in the total number of PJIs in the next few years. In particular, the costs to the health care system of the treatment of PJI will emphasize further the need for the prevention of PJI. Individual risk factors should be optimized before arthroplasty requiring a close cooperation between the general practitioner and the orthopedic specialist.
26376898 Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases. 2015 Dec Previous studies have identified the immunological functions of transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) in various adaptive immune cell types such as T and B lymphocytes. More recently, it has been shown that Blimp-1 extends its functional roles to dendritic cells (DCs) and macrophages, two cell types belonging to the innate immune system. The protein acts as a direct and indirect regulator of target genes by recruiting chromatin modification factors and by regulating microRNA expression, respectively. In DCs, Blimp-1 has been identified as one of the components involved in antigen presentation. Genome-wide association studies identified polymorphisms associated with multiple autoimmune diseases such as system lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease in PRDM1, the gene encoding Blimp-1 protein. In this review, we will discuss the immune regulatory functions of Blimp-1 in DCs with a main focus on the tolerogenic mechanisms of Blimp-1 required to protect against the development of autoimmune diseases.
26093043 Inhibition of the Immunoproteasome Subunit LMP7 with ONX 0914 Ameliorates Graft-versus-Ho 2015 Sep In the current study we evaluated the effects of immunoproteasome inhibition using ONX 0914 (formerly PR-957) to ameliorate graft-versus-host disease (GVHD). ONX 0914, an LMP7-selective epoxyketone inhibitor of the immunoproteasome, has been shown to reduce cytokine production in activated monocytes and T cells and attenuate disease progression in mouse models of rheumatoid arthritis, colitis, systemic lupus erythematosus, and, more recently, encephalomyelitis. Inhibition of LMP7 with ONX 0914 in the B10.BR→CBA MHC-matched/minor histocompatibility antigen (miHA)-disparate murine blood and marrow transplant (BMT) model caused a modest but significant improvement in the survival of mice experiencing GVHD. Concomitant with these results, in vitro mixed lymphocyte cultures revealed that stimulator splenocytes, but not responder T cells, treated with ONX 0914 resulted in decreased IFN-γ production by allogeneic T cells in both MHC-disparate (B10.BR anti-B6) and miHA-mismatched (B10.BR anti-CBA) settings. In addition, a reduction in the expression of the MHC class I-restricted SIINFEKL peptide was observed in splenocytes from transgenic C57BL/6-Tg(CAG-OVA)916Jen/J mice exposed to ONX 0914. Taken together, these data support that LMP7 inhibition in the context of BMT modulates allogeneic responses by decreasing endogenous miHA presentation and that the consequential reduction in allogeneic stimulation and cytokine production reduces GVHD development.
26020561 Second generation analysis of antinuclear antibody (ANA) by combination of screening and c 2015 Nov BACKGROUND: For the serological diagnosis of systemic autoimmune rheumatic diseases, a two-tier approach starting with sensitive antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) on HEp-2 cells followed by characterization of positive findings with different immunoassays is recommended. To overcome drawbacks of this approach, we developed a novel technique allowing the combination of screening and simultaneous confirmatory testing. For the first time, this creates the basis for second generation ANA testing. METHODS: ANA and autoantibodies (autoAbs) to double-stranded DNA (dsDNA), CENP-B, SS-A/Ro52, SS-A/Ro60, SS-B/La, RNP-Sm, Sm, and Scl-70 were determined by IIF and enzyme-linked immunosorbent assay (ELISA), respectively, and compared to simultaneous analysis thereof by second generation ANA analysis in patients with systemic lupus erythematosus (n=174), systemic sclerosis (n=103), Sjögren's syndrome (n=46), rheumatoid arthritis (n=36), mixed and undetermined connective tissue diseases (n=13), myositis (n=21), infectious disease (n=21), autoimmune liver disease (n=93), inflammatory bowel disease (n=78), paraproteinemia (n=11), and blood donors (n=101). RESULTS: There was very good agreement of second generation ANA testing with classical one by IIF and ELISA regarding testing for ANA and autoAbs to dsDNA, CENP-B, SS-B, RNP-Sm, Scl-70, SS-A/Ro52, and SS-A/Ro60 (Cohen's κ>0.8). The agreement for anti-Sm autoAb was good (κ=0.77). The differences of both approaches were not significant for autoAbs to SS-B/La, RNP-Sm, Scl-70, SS-A/Ro60, and SS-A/Ro52 (McNemar's test, p>0.05, respectively). CONCLUSIONS: Second generation ANA testing can replace the two-tier analysis by combining IIF screening with multiplex confirmative testing. This addresses shortcomings of classical ANA analysis like false-negative ANA findings and lack of laboratory efficiency and standardization.
25993132 An Improved Method for P2X7R Antagonist Screening. 2015 ATP physiologically activates the P2X7 receptor (P2X7R), a member of the P2X ionotropic receptor family. When activated by high concentrations of ATP (i.e., at inflammation sites), this receptor is capable of forming a pore that allows molecules of up to 900 Da to pass through. This receptor is upregulated in several diseases, particularly leukemia, rheumatoid arthritis and Alzheimer's disease. A selective antagonist of this receptor could be useful in the treatment of P2X7R activation-related diseases. In the present study, we have evaluated several parameters using in vitro protocols to validate a high-throughput screening (HTS) method to identify P2X7R antagonists. We generated dose-response curves to determine the EC50 value of the known agonist ATP and the ICs50 values for the known antagonists Brilliant Blue G (BBG) and oxidized ATP (OATP). The values obtained were consistent with those found in the literature (0.7 ± 0.07 mM, 1.3-2.6 μM and 173-285 μM for ATP, BBG and OATP, respectively) [corrected].The Z-factor, an important statistical tool that can be used to validate the robustness and suitability of an HTS assay, was 0.635 for PI uptake and 0.867 for LY uptake. No inter-operator variation was observed, and the results obtained using our improved method were reproducible. Our data indicate that our assay is suitable for the selective and reliable evaluation of P2X7 activity in multiwell plates using spectrophotometry-based methodology. This method might improve the high-throughput screening of conventional chemical or natural product libraries for possible candidate P2X7R antagonist or agonist.