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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27940398 Therapeutic role of nitric oxide as emerging molecule. 2017 Jan NO has many physiological roles; in inflammation, pain, rheumatoid arthritis, immune system, gastroprotection, as antioxidant and reported to be a free radical scavenger.Intensive research on the biological functions of NO and other reactive nitrogen oxide species demands exogenous sources of NO donors as research tools and pharmaceuticals. Since the mid-1980s, the development of new NO donors has offered several advantages over theprevious NO donors, such as spontaneous release of NO, donation of NO under controlled rates, and even the targeting of NO to certain tissues. Nitric oxide releasing derivatives of conventional NSAIDs have been synthesized not only to avoid gastrotoxicity, but also for making them fit for topical delivery, targeting them to brain and increase their analgesic and anti-inflammatory activity. "Hybrid nitrates" have vital role in different like NSAIDs, Anti-platelet, Antileukemic, Glaucoma, Antihypertensive, Antimalarial etc.
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.
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.
27417999 Adjuvants- and vaccines-induced autoimmunity: animal models. 2017 Feb The emergence of autoimmunity after vaccination has been described in many case reports and series. Everyday there is more evidence that this relationship is more than casual. In humans, adjuvants can induce non-specific constitutional, musculoskeletal or neurological clinical manifestations and in certain cases can lead to the appearance or acceleration of an autoimmune disease in a subject with genetic susceptibility. The fact that vaccines and adjuvants can trigger a pathogenic autoimmune response is corroborated by animal models. The use of animal models has enabled the study of the effects of application of adjuvants in a homogeneous population with certain genetic backgrounds. In some cases, adjuvants may trigger generalized autoimmune response, resulting in multiple auto-antibodies, but sometimes they can reproduce human autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, autoimmune thyroiditis and antiphospholipid syndrome and may provide insights about the potential adverse effects of adjuvants. Likewise, they give information about the clinical, immunological and histologic characteristics of autoimmune diseases in many organs, especially secondary lymphoid tissue. Through the description of the physiopathological characteristics of autoimmune diseases reproduced in animal models, new treatment targets can be described and maybe in the future, we will be able to recognize some high-risk population in whom the avoidance of certain adjuvants can reduce the incidence of autoimmune diseases, which typically results in high morbidity and mortality in young people. Herein, we describe the main animal models that can reproduce human autoimmune diseases with emphasis in how they are similar to human conditions.
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.
28711147 Future Directions of Genomics Research in Rheumatic Diseases. 2017 Aug Recent developments in human genome genotyping and sequencing technologies, such as genome-wide association studies and whole-genome sequencing analyses, have successfully identified several risk genes of rheumatic diseases. Fine-mapping studies using the HLA imputation method revealed that classical and non-classical HLA genes contribute to the risk of rheumatic diseases. Integration of human disease genomics with biological, medical, and clinical databases should contribute to the elucidation of disease pathogenicity and novel drug discovery. Disease risk genes identified by large-scale genetic studies are considered to be promising resources for novel drug discovery, including drug repositioning and biomarker microRNA screening for rheumatoid arthritis.
28692451 The value of musculoskeletal ultrasound in geriatric care and rehabilitation. 2017 Dec The WHO reports that one of the major chronic conditions affecting the elderly worldwide is musculoskeletal disorders that are associated with long-term pain and disability. Considering the healthcare needs of the elderly (i.e. comprehensive, accessible, efficient) and the advantages of ultrasound (US) use (patient-friendly, convenient, cost-effective, and does not require exposure to radiation or magnetic fields), there seems to be a 'gap' in the actual clinical practice. In this paper, we aimed to highlight the potential value of US imaging in the management of the elderly with a wide spectrum of musculoskeletal conditions (degenerative/rheumatic joint diseases, falls/trauma, nursing care, peripheral nerve problems, sarcopenia, and interventions). In this respect, electronic databases (ISI Web of Science, PubMed, Elsevier Science Direct) and reference lists of relevant articles/reviews were screened by two blinded investigators for each topic. The main medical subject heading terms selected to capture the most relevant papers on the topics in accordance with the literature were knee/hip/hand osteoarthritis, prevalence, rotator cuff injury, lateral epicondylitis, tendinopathy, rheumatoid arthritis, Sjogren's syndrome, polymyalgia rheumatica, crystal arthropathies, gout, pseudogout, carpal tunnel syndrome, fall, fractures, hematoma, pressure ulcer, ultrasonography, interventional, sarcopenia, body composition, rehabilitation, frail elderly, and aged. The search was limited to peer-reviewed full-text English journals starting from the earliest papers to May 2017. A study population (or part of the study population) of adults older than 65 years (if possible) was included. We especially underscore the use of US by clinicians as an extension of their physical examination or as a practical guide for an immediate intervention.
28524744 Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic p 2017 Jul Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast - osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis. Imbalances in the interplay of osteoblasts and osteoclasts might lead to bone-related diseases such as osteoporosis, rheumatoid arthritis, and bone metastases. Areas covered: We summarize and analyze the progress made in bone research in the context of the current knowledge of sphingolipid-related mechanisms regulating bone remodeling. Particular emphasis was given to bioactive sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs). Moreover, the mechanisms of how dysregulations of this machinery cause bone diseases, are covered. Expert opinion: In the context of bone diseases, pharmacological interference with sphingolipid machinery may lead to novel directions in therapeutic strategies. Implementation of knowledge derived from in vivo animal models and in vitro studies using pharmacological agents to manipulate the S1P/S1PRs axes suggests S1PR2 and S1PR3 as potential drug targets, particularly in conjunction with technology for local drug delivery.
28437887 Influence of sinomenine upon mesenchymal stem cells in osteoclastogenesis. 2017 Jun With the advent of aging, the morbidity rates of such diseases as osteoarthritis, rheumatoid arthritis, and osteoporosis has witnessed a significant increase. As a common rattan drug, sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-κ B ligand (RANKL) ratio, was investigated. Our results showed that, when compared with the untreated cells, treatment with 0.25mM SIN can down-regulate the mRNA and protein expression levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL, while the OPG was up-regulated. After being cultured with SIN treated MSC-conditioned medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts differentiated from RAW264.7 cells was reduced. Also, the expression levels of specific markers for active osteoclasts were decreased when incubated with stMSC-CM. Moreover, these changes were able to be recovered when the exogenous RANKL was added to the MSC-CM culture. This indicates that the increased OPG/RANKL ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results demonstrated that SIN has an inhibitory effect on osteoclast differentiation through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio. SIN can also serve as a proinflammatory mediator to regulate the MSC immunosuppressive effects. Our findings suggest that SIN can be useful for the treatment of bone diseases associated with over-activity of osteoclasts.
28324010 Separating the Anti-Inflammatory and Diabetogenic Effects of Glucocorticoids Through LXRβ 2017 Apr 1 Synthetic glucocorticoids (GCs), including dexamethasone (DEX), are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The GC receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX but still sensitive to its immunosuppressive actions. To determine whether this finding could be exploited for therapeutic intervention, we treated mice with GSK2033, a pan-LXR antagonist, alone or combined with DEX. GSK2033 suppressed GC-induced gluconeogenic gene expression without affecting immune-responsive GR target genes. The suppressive effect of GSK2033 on DEX-induced gluconeogenic genes was specific to LXRβ, was liver cell autonomous, and occurred in a target gene-specific manner. Compared with DEX treatment alone, the coadministration of GSK2033 with DEX decreased the recruitment of GR and its accessory factors MED1 and C/EBPβ to the phosphoenolpyruvate carboxykinase promoter. However, GSK2033 had no effect on DEX-mediated suppression of inflammatory genes expressed in the liver or in mouse primary macrophages stimulated with lipopolysaccharides. In conclusion, our study provides evidence that the gluconeogenic and immunosuppressive actions of GR activation can be mechanistically dissociated by pharmacological antagonism of LXRβ. Treatment with an LXRβ antagonist could allow the safer use of existing GC drugs in patients requiring chronic dosing of anti-inflammatory agents for the treatment of diseases such as rheumatoid arthritis and inflammatory bowel disease.
28209985 Ig-like domain 6 of VCAM-1 is a potential therapeutic target in TNFα-induced angiogenesis 2017 Feb 17 Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation. We demonstrated that a monoclonal antibody specific to VCAM-1-D6 suppressed TNFα-induced endothelial cell migration and tube formation and TNFα-induced vessel sprouting in rat aortas. We also found that the antibody insignificantly affected endothelial cell viability, morphology and activation. Finally, the antibody specifically blocked VCAM-1-mediated cell-cell contacts by directly inhibiting VCAM-1-D6-mediated interaction between VCAM-1 molecules. These findings suggest that VCAM-1-D6 may be a potential novel therapeutic target in TNFα-induced angiogenesis and that antibody-based modulation of VCAM-1-D6 may be an effective strategy to suppress TNFα-induced angiogenesis.
28103685 An Effective Bacterial Fucosidase for Glycoprotein Remodeling. 2017 Jan 20 Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages. Here, we report a highly efficient fucosidase, designated as BfFucH identified from a library of bacterial glycosidases expressed in E. coli from the CAZy database, which is capable of hydrolyzing the aforementioned fucosidic linkages, especially the α-1,6-linkage from the N-linked Fuc-α-1,6-GlcNAc residue on glycoproteins. Using BfFucH coupled with endoglycosidases and the emerging glycosynthases allows glycoengineering of IgG antibodies to provide homogeneous glycoforms with well-defined glycan structures and optimal effector functions.
28100077 Effects of M2000 (D-Mannuronic Acid) on Learning, Memory Retrieval, and Associated Determi 2017 Feb The d-mannuronic acid (M2000) is a novel nonsteroidal anti-inflammatory drug that has immunosuppressive effects together with antioxidant property. M2000 has shown a notable efficacy in experimental models of multiple sclerosis, rheumatoid arthritis, and nephrotic syndrome. In this work, the effect of M2000 on the treatment of Alzheimer's disease (AD) was performed by Morris water maze experiment, and the immunological assessments were carried out by Western blot, apoptosis (procaspase-3, Bax/Bcl(2), P53), enzymatic (superoxide dismutase [SOD]), and nonenzymatic oxidative stress (malondialdehyde [MDA]) tests. We found that pretreatment of AD in the rat model by M2000 had a potent efficacy on rat behavior and also it led to a significant inhibition of amyloid plaque production. Moreover, our data showed that M2000 can reduce the amount of Bax/Bcl(2), P53, MDA, and SOD, as well as it normalized the level of procaspase-3. Our results suggest M2000 is a potential therapeutic agent for the treatment of AD.
27733707 Systematic review of the efficacy and safety of biological therapy for inflammatory condit 2017 Feb Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies.
27708194 Effects of the Janus Kinase Inhibitor, Tofacitinib, on Testicular Leydig Cell Hyperplasia 2017 Jan Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis. Tofacitinib preferentially inhibits receptor signaling through JAK3 and JAK1, relative to JAK2. In the 2-year rat carcinogenicity study, there were tofacitinib, dose-related increases in the incidences of testicular Leydig cell hyperplasia and benign adenomas in male rats, and decreased incidences of mammary tumors and duct dilatation/galactocele in female rats. Such findings in rats are typical of agents, such as dopamine agonists, which decrease prolactin (PRL) activity. Since prolactin signals through the JAK2 pathway, we hypothesized that these findings were off-target effects due to inhibition of PRL signaling via JAK2. The studies reported here were designed to investigate the interruption of PRL signaling pathways in Leydig cells. In isolated primary rat Leydig cells, PRL increased phosphorylated Signal Transducer and Activator of Transcription-5 protein, and mRNA levels for luteinizing hormone receptor. Tofacitinib, at concentrations observed in the rat carcinogenicity study, dose-dependently inhibited these effects. These observations illustrate a novel mechanism, the inhibition of prolactin signaling by which modulation of JAK activity can modulate PRL signaling pathways to induce Leydig cell tumors in rats. Since human Leydig cells lack this PRL dependence for normal function, these rodent tumors do not indicate a health risk to human patients.
29563728 Aggressive Angioimmunoblastic T Cell Lymphomas (AITL) with Soft Tissue Extranodal Mass Var 2018 Mar Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells. On immunohistochemistry, the cells are positive for CD3, CD4, CD10, BCL2, and CXCL13. In this observational study, the clinicopathologic presentation and the immunohistochemical profile of five cases who initially presented with a soft tissue mass which is an extremely rare presentation of this rare type of non-Hodgkin lymphoma that was diagnosed at our center with peripheral blood and bone marrow involvement and the clinicopathologic presentation, immunohistochemical profile, and response to treatment on follow-up are correlated with the literature review. One case had a fulminant and aggressive course and was fatal within 2 months of diagnosis. The rest of the four cases are on regular chemotherapy and follow-up. Our five cases had presented with soft tissue masses, two in the axillary regio,n two in the hand, and one in the scapular region with an extranodal presentation, and there was associated lymphadenopathy which developed subsequently with classic histomorphology and immunohistochemical findings. The age range was 46-54 years and all five cases were males. Three cases were with anemia (hemoglobin range 6.5-8.0 mg/dl) and all five cases were having peripheral blood plasmacytosis. Histopathology was classic with paracortical involvement with polymorphous population of cells with neoplastic lymphocytes of small and large sizes with numerous arborizing blood vessels which correspond to high endothelial venules. Microscopically, three architectural patterns; pattern I was seen in three cases (60%) and then pattern II and III in one case each (20% each). Immunohistochemistry revealed CD4+, CD8-, CXCL13+, CD10+, BCL6+, CD19, CD20, CD1a, Tdt, CD21, and CD23+ in follicular dendritic cells. AITL is a rare and aggressive non-Hodgkin lymphoma with varied clinical presentation with classic histomorphology with various patterns which may cause diagnostic dilemma and immunophenotypic findings, and prompt and early diagnosis is mandatory for institution of therapy.
29351529 [Arthrodesis of the First Metatarsophalangeal Joint by Locking Plate]. 2017 PURPOSE OF THE STUDY The authors in their paper evaluate a group of patients who underwent arthrodesis of the first metatarsophalangeal joint using a locking plate. MATERIAL AND METHODS In the period 2010-2015, we performed surgery in 51 patients (56 forefeet), of which in 5 cases bilaterally and in 46 cases unilaterally, in 38 women and 13 men. The mean age was 57.8 years, the mean follow-up was 3.1 years. The indications for surgery were hallux rigidus in 23 patients, hallux valgus in 15 patients, hallux varus in 3 patients, and hallux erectus in 2 patients. In 4 patients the surgery was performed for valgus deformity associated with rheumatoid arthritis, 9 patients were indicated for a failure of the prior surgical intervention. In all 56 forefeet, the anatomic, low-profile titanium plate Variable Angle LCP 1st MTP Fusion Plate 2.4/2.7 was used. RESULTS According to Gainor s score the surgical outcomes were assessed as excellent in 46 patients who underwent surgery (90%), good in 4 patients (8%), fair in 1 patient (2%), and poor in 0 patient (0%). In 53 forefeet, the control radiographs showed solid bone union. In 2 patients and 3 forefeet, non-union of the arthrodesis occurred. In 2 forefeet, revision arthrodesis was performed, after which solid bone union followed. Malpositioned union was reported in 5 forefeet, of which in 4 cases into valgosity and in 1 case into dorsiflexion. DISCUSSION Numerous fixation materials can be used for arthrodesis of the first metatarsophalangeal joint. The use of the least stable Kirschner wires (cerclage) is being abandoned and substituted with a more stable fixation by screws, memory staples and locking plates. The achievement of excellent results requires proper positioning of the arthrodesis. Impingement syndrome between the big toe and the second toe can result in painful callosities formation, too large dorsiflexion can lead to a hallux hammertoe, with reduced big toe support function, to metatarsalgia. CONCLUSIONS The arthrodesis is indicated in patients with Grade III and IV hallux rigidus, with severe hallux valgus, hallux varus, and in patients in whom the previous surgeries failed. We tend to prefer stable arthrodesis. Fixation by anatomic LCP plate facilitates early rehabilitation, loading and early return to work and sports activities. Key words: arthrodesis, metatarsophalangeal joint, hallux rigidus, hallux valgus.
29292028 Effectiveness of interventions to improve therapy adherence in people with upper limb cond 2019 Apr STUDY DESIGN: Systematic review. INTRODUCTION: Patient adherence to orthosis wear and/or prescribed exercises improves functional outcome after acute injury and can prevent deformities, contractures, and reinjury of tissues. This is the first systematic review to review the evidence of the effectiveness of interventions to improve treatment adherence in children and adults with acute or chronic upper limb injuries or conditions. PURPOSE OF THE STUDY: The purpose of this study is to establish the effectiveness of interventions to improve hand therapy adherence in people with upper limb conditions and to report on outcome measures used when reporting adherence. METHODS: A literature search of MEDLINE (OVID), Embase (OVID), CENTRAL (OVID), CINAHL (EBSCO), and EmCare (OVID) (from inception to March 2017) was undertaken. Studies were selected if they met the following inclusion criteria: clinical trials; in adults or children with any injury or condition affecting the upper limb including acute trauma and injury; chronic and acquired musculoskeletal conditions; and neurological conditions. Two independent assessors rated the study quality and risk of bias using the Cochrane Collaboration tool for assessing the risk of bias. RESULTS: Eight studies met the inclusion criteria. Study quality ranged from 3 to 6 out of 7 points on the Cochrane risk of bias tool. There were 4 categories of intervention for improving adherence: orthosis/cast material/design; orthosis wear schedule; patient education mode for home exercise programs; and behavioral approaches. Due to heterogeneity of condition acuity, interventions, and outcomes reported, it was not possible to pool the results from all studies. Therefore, a narrative best evidence synthesis was undertaken. There is weak evidence from a very small number of trials that orthosis/cast material has no influence on treatment adherence in acute or chronic conditions and mode of patient education (audio-visual vs written) has no effect in acute conditions. There is low-to-moderate quality of evidence in support of behavioral interventions for achieving treatment adherence in chronic rheumatoid arthritis. CONCLUSION: Behavioral approaches that encourage self-efficacy are likely to be useful in achieving treatment adherence in populations with chronic upper limb conditions. There is insufficient evidence for other interventions aimed at improving adherence in acute upper limb injuries and conditions.
29257274 MicroRNA‑33 regulates the NLRP3 inflammasome signaling pathway in macrophages. 2018 Feb The nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome/interleukin (IL)-1β axis serves an essential role in regulating the development of rheumatoid arthritis (RA). The dysregulation of cellular metabolism, such as mitochondrial dysfunction, results in the activation of the NLRP3 inflammasome. microRNA (miR)‑33 has previously been identified to be a regulator of lipid metabolism and mitochondrial function. However, whether miR‑33 regulates the NLRP3 inflammasome/IL‑1β axis remains unknown. In the present study, it was observed that an miR‑33 mimic or anti‑miR‑33 markedly stimulated or inhibited, respectively, IL‑1β protein expression levels in mouse peritoneal macrophages. Mechanistically, miR‑33 upregulated the expression of NLRP3 mRNA and protein as well as caspase‑1 activity in primary macrophages. In addition, the results demonstrated that miR‑33 impaired mitochondrial oxygen consumption rates, resulting in the accumulation of cellular reactive oxygen species, which stimulated NLRP3 expression, caspase‑1 activity and IL‑1β secretion. The results of the present study demonstrated that miR‑33 levels and NLRP3 inflammasome activity were increased in peripheral blood monocytes from patients with RA patients compared with healthy donors. In conclusion, the present study identified miR‑33 to be a positive regulator of the NLRP3 inflammasome in macrophages. The miR‑33/NLRP3 inflammasome pathway may therefore be involved in RA development.
29255476 MPO-ANCA associated vasculitis with mononeuritis multiplex following influenza vaccination 2017 BACKGROUND: Although influenza vaccines are generally safe and effective, a variety of autoimmune phenomena have been reported after vaccination over the past years, such as Guillain-Barre syndrome, rheumatoid arthritis, pemphigus vulgaris, psoriasis, giant cell arteritis and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). CASE REPORT: We describe the case of a 67-year old man who presented with a myeloperoxidase-ANCA associated vasculitis with renal involvement and mononeuritis multiplex after seasonal influenza vaccination. He was initially treated with intravenous cyclophosphamide and high-dose prednisolone followed by maintenance treatment consisting of azathioprine and prednisolone. CONCLUSION: We hypothesize that seasonal influenza vaccination triggered a systemic immune response in a susceptible patient to develop AAV with renal involvement and vasculitic neuropathy. In general, seasonal influenza vaccinations are considered to be safe, however, clinicians should be aware of this rare phenomenon.