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

ID PMID Title PublicationDate abstract
31712033 Effect of stopping hydroxychloroquine therapy on the multifocal electroretinogram in patie 2020 Feb OBJECTIVE: To report the effect of hydroxychloroquine therapy cessation on the multifocal electroretinogram (mfERG) in a case series of patients with rheumatic disease suspected to have retinopathy. METHODS: Comprehensive data were retrospectively reviewed on 14 patients from a total of 50 cases who discontinued hydroxychloroquine due to suspected toxicity. Patients were followed for 4 years after the cessation of therapy. mfERG testing had been part of original screening for hydroxychloroquine retinopathy and was continued after therapy cessation at 6-month intervals. Descriptive statistics, independent sample t test, and one-way analysis of variance with repeated measures and post hoc analysis were conducted to determine patients' clinical characteristics and changes in the mfERG after therapy cessation, respectively. RESULTS: All 14 patients were female; 12 were treated for rheumatoid arthritis and 2 for systemic lupus erythematosus. Three groups were identified: (i) 9 patients in whom the responses of the mfERG recovered to within normative values after cessation of hydroxychloroquine therapy, (ii) 3 who experienced limited recoveries, and (iii) 1 patient whose mfERG response was unchanged. There was no significant difference (p > 0.05) in the clinical characteristics of these patients. However, the proportional reduction of mfERG ring 1, 2, and 3 amplitudes from age normal responses at the time of discontinuation of drug use for the first and second groups of patients was significantly different, with more reduction in group 2 (p < 0.05). CONCLUSION: Early detection of hydroxychloroquine retinopathy through screening and subsequent therapy discontinuation could result in recovery of the mfERG ring amplitude response and preservation of visual function.
31632402 Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation. 2019 Neutrophils are the most abundant type of white blood cells. Upon stimulation, they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) is part of immune defense mechanisms but also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes, and cancer. For this reason, much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well-understood. Here, we studied how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide (PAA) gels with distinctly defined elasticities (Young's modulus E) within the physiologically relevant range from 1 to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen). Neutrophils were cultured on these substrates and stimulated with potent inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 kPa). LPS-induced NETosis increased with increasing cell contact area, while PMA-induced NETosis did not require adhesion at all. Furthermore, inhibition of phosphatidylinositide 3 kinase (PI3K), which is involved in adhesion signaling, completely abolished LPS-induced NETosis but only slightly decreased PMA-induced NETosis. In summary, we show that LPS-induced NETosis depends on adhesion and substrate elasticity while PMA-induced NETosis is completely independent of adhesion.
31416441 A case of pleural effusion caused by Mycobacterium fortuitum and Mycobacterium mageritense 2019 Aug 15 BACKGROUND: Non-tuberculous mycobacteria cause chronic pulmonary infection, but pleuritis and pleural effusion are rarely associated with infection with non-tuberculous mycobacteria, especially rapid-growing mycobacteria. CASE PRESENTATION: A 68-year-old woman with rheumatoid arthritis who was using prednisone, azathioprine, and certolizumab pegol presented complaining of fever, dry cough, and night sweats for the past 2 weeks. Chest examination revealed bilateral opacity that was more pronounced on her right side. Bronchoalveolar lavage fluid and pleural effusion fluid were obtained, and revealed coinfection with Mycobacterium fortuitum and Mycobacterium mageritense. Imipenem/cilastatin, levofloxacin, and minocycline were prescribed for 6 months, and the patient was well and asymptomatic for the subsequent 6 months. CONCLUSIONS: This is the first case report describing pleural effusion associated with coinfection with two different mycobacterial species. If the species cannot be identified, the possibility of mycobacterial coinfection should be considered.
31414971 Systematic Review: Immunoglobulin G N-Glycans as Next-Generation Diagnostic Biomarkers for 2019 Dec Glycomics is a new subspecialty in omics systems sciences that offers significant promise for next-generation biomarkers on disease susceptibility, drug target discovery, and precision medicine. In this context, alternative immunoglobulin G (IgG) N-glycosylation has been reportedly implicated in several common chronic diseases, although systematic assessment is currently lacking in the literature. We conducted a systematic review of observational studies on IgG N-glycan variability and susceptibility to common chronic diseases. Observational studies reporting an association between diseases (such as colorectal cancer, dyslipidemia, ischemic stroke, rheumatoid arthritis, and systemic lupus erythematosus) and IgG N-glycans quantified by ultraperformance liquid chromatography were included. The glycans were categorized into 24 initial IgG glycan peaks (GPs). Notably, aging positively correlated with GP1, GP2, GP4-7, GP10, GP11, GP19, and GP24, while negatively correlated with GP8, GP12-15, GP17, GP18, GP20, GP21, and GP23 (p < 0.05). The absolute value of significant correlation coefficients of age and IgG glycans ranged from 0.043 to 0.645. We found that the high levels of GP1-4, GP6, GP7, and GP24 and low levels of GP9, GP13-15, GP18, and GP23 could potentially increase the risk of disease. In conclusion, the present systematic review suggests that the field of glycomics, and GP1-4, GP6, GP7, GP9, GP13-15, GP18, GP23, and GP24 in particular, holds promise for further candidate biomarker research on susceptibility to common chronic diseases.
31412748 Decreased Expression of Semaphorin 3A and Semaphorin 7A Levels and Its Association with Sy 2020 Feb A growing body of data suggests that semaphorins are involved in both normal and pathological immune responses, as well as autoimmune pathologies. To investigate the plasma semaphorin 3A (Sema3A) and semaphorin 7A (Sema7A) levels in systemic lupus erythematosus (SLE) patients and their correlation with clinical manifestations and laboratory indexes, a two-step method was applied. First, 80 SLE patients and 80 healthy controls were recruited for comparing serum Sema3A and Sema7A concentrations. Second, 40 rheumatoid arthritis (RA) patients and 40 sjögren's syndrome (SS) patients were then included as disease controls. Plasma Sema3A and Sema7A concentrations were detected by ELISA. There were significant differences in Sema3A and Sema7A among four groups. When compared to healthy controls, both Sema3A and Sema7A levels were decreased in SLE and increased in RA; increased Sema3A level and decreased Sema7A level were found in SS. There were significant differences in Sema3A concentration between SLE and RA, SLE and SS. Moreover, there were significant differences in Sema7A level between SLE and RA, SS and RA. However, no significant differences in Sema3A between SS and RA and no significant differences in Sema7A between SS and SLE were observed. Both plasma Sema3A and Sema7A levels were correlated with anti-SSA and IgM. Area under curve (AUC) of the receiver operating characteristic (ROC) curve for Sema3A and Sema7A were 0.535 (0.455-0.613) and 0.671 (0.594-0.742), respectively. Aberrant Sema3A and Sema7A expression and their clinical associations in SLE suggest their important role in this disease.
31356910 Roles of chitinase 3-like 1 in the development of cancer, neurodegenerative diseases, and 2019 Nov Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly increased by various inflammatory and immunological conditions, including rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, and several cancers. However, its physiological and pathophysiological roles in the development of cancer and neurodegenerative and inflammatory diseases remain unclear. Several studies have reported that CHI3L1 promotes cancer proliferation, inflammatory cytokine production, and microglial activation, and that multiple receptors, such as advanced glycation end product, syndecan-1/αVβ3, and IL-13Rα2, are involved. In addition, the pro-inflammatory action of CHI3L1 may be mediated via the protein kinase B and phosphoinositide-3 signaling pathways and responses to various pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 could contribute to a vast array of inflammatory diseases. In this article, we review recent findings regarding the roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of cancers, neurodegenerative diseases, and inflammatory diseases.
31338169 Tolerance and safety of rapid 2-hour infusion of rituximab in patients with kidney-affecti 2019 Jul OBJECTIVE: According to the manufacturer's documentation, rituximab (RTX) should be administered with slow infusion rates to prevent infusion-related adverse events (AEs). Nevertheless, slow infusions are time-consuming and uncomfortable for patients and medical staff. Therefore, faster infusion rates have been studied and proven safe and well tolerated in lymphomas and rheumatoid arthritis (RA). A small amount of data is available for rapid RTX infusions in non-RA autoimmune diseases. METHODS: Beginning in September 2015, all RTX-reated patients in our centre and willing to participate, were switched from slow RTX infusions (4.25 hours, given at least once to all patients) to fast infusions (2 hours). A total of 85 RTX 2-hour infusions was administered to 53 patients with autoimmune diseases with renal involvement and selected primary glomerulonephritides (26 ANCA-associated vasculitis, nine systemic lupus erythematodes, seven membranous nephropathy, five IgM nephropathy and six other autoimmune disease). Most of the patients received chronic corticosteroid therapy. The prednisone equivalent dose median (IQR) was 0.1 (0.0-0.2) mg/kg/day. RESULTS: Rapid RTX infusions were generally well tolerated. Only two infusion-related AEs were recorded: one Common Terminology Criteria for Adverse Events, grade 3, (lower back pain and hypotension followed by chills necessitating methylprednisolone and dipyrone administration) and one grade 1 (subjective intolerance). The AEs frequency does not differ from other studies with rapid RTX infusions in patients with lymphomas and RA. CONCLUSIONS: Our experience supported other published data and provides evidence concerning the safety of non-initial RTX 2-hour infusion which can be administered without raising the infusion-related AEs rate in patients with kidney-affecting autoimmune diseases and glomerulonephritides.
31231388 Divergent Roles for the IL-1 Family in Gastrointestinal Homeostasis and Inflammation. 2019 Inflammatory disorders of the gastro-intestinal tract are a major cause of morbidity and significant burden from a health and economic perspective in industrialized countries. While the incidence of such conditions has a strong environmental component, in particular dietary composition, epidemiological studies have identified specific hereditary mutations which result in disequilibrium between pro- and anti-inflammatory factors. The IL-1 super-family of cytokines and receptors is highly pleiotropic and plays a fundamental role in the pathogenesis of several auto-inflammatory conditions including rheumatoid arthritis, multiple sclerosis and psoriasis. However, the role of this super-family in the etiology of inflammatory bowel diseases remains incompletely resolved despite extensive research. Herein, we highlight the currently accepted paradigms as they pertain to specific IL-1 family members and focus on some recently described non-classical roles for these pathways in the gastrointestinal tract. Finally, we address some of the shortcomings and sources of variance in the field which to date have yielded several conflicting results from similar studies and discuss the potential effect of these factors on data interpretation.
31213874 Release of active peptidylarginine deiminase into the circulation during acute inflammatio 2019 Purpose: Peptidylarginine deiminase (PAD) catalyzes citrullination, a post-translational modification that can alter structure, function and antigenicity of proteins. Citrullination in the lungs due to smoking is believed to initiate an anti-citrulline immune response in rheumatoid arthritis. Citrullination in other inflamed organs has also been demonstrated, but it is not known whether smoking or inflammatory processes in general result in release of relevant amounts of PAD into the circulation with potential to cause citrullination of proteins at various anatomical sites. Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) induces an acute systemic inflammation response. In the present study, we investigate whether smoking or acute systemic inflammation causes release of PAD into the circulation. Patients and methods: This study included 36 patients with coronary heart disease (16 smokers and 20 non-smokers) undergoing CABG surgery with CPB. Circulating levels of PAD2 and PAD4, PAD activity, the neutrophil activation markers MPO, MMP-9 and lipocalin-2, the cytokines IL-6 and IL-10, and the chemokine CXCL8 were measured 2 hrs preoperatively and 2 hrs postoperatively. Results: At baseline, serum PAD2 and PAD4 concentration did not differ between smokers and non-smokers. However, serum from non-smokers contained higher PAD activity than serum from smokers. Circulating PAD2 levels and PAD activity increased markedly in both groups after surgery, as did all neutrophil activation markers, cytokines and chemokine. PAD2 levels correlated with neutrophil activation markers, but not with cytokine and chemokine levels. Conclusion: Blood levels of PAD2 did not differ significantly between smokers and non-smokers, but smokers had decreased PAD activity in the circulation. PAD2 levels and PAD activity increased in blood during inflammation induced by CABG with CPB. This suggests that acute inflammation, ischemia or reperfusion, or a combination of these, leads to systemic spreading of enzymatically active PAD, which may affect protein function and induce generation of citrullinated self-antigens.
31105565 Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal 2019 Pelvic and abdominal radiotherapy plays an important role in eradication of malignant cells; however, it also results in slight intestinal injury. The apoptosis of cells in the intestinal epithelium is a primary pathological factor that initiates radiation-induced intestinal injury. Auranofin, a gold-containing triethylphosphine, was approved for the treatment of rheumatoid arthritis, and its therapeutic application has been expanded to a number of other diseases, such as parasitic infections, neurodegenerative disorders, AIDS, and bacterial infections. Recently, a treatment strategy combining the use of auranofin and ionizing radiation aimed at increasing the radiosensitivity of cancer cells was proposed for improving the control of local cancers. In this study, we evaluated the effect of auranofin on the radiosensitivity of intestinal epithelial cells. The treatment with a combination of 1 μM auranofin and 5 Gy ionizing radiation showed clear additive effects on caspase 3 cleavage and apoptotic DNA fragmentation in IEC-6 cells, and auranofin administration significantly aggravated the radiation-induced intestinal injury in mice. Auranofin treatment also resulted in the activation of the unfolded protein response and in the inhibition of thioredoxin reductase, which is a key component of the cellular antioxidant system. Pre-treatment with N-acetyl cysteine, a well-known scavenger of reactive oxygen species, but not with a chemical chaperone, which inhibits endoplasmic reticulum stress and the ensuing unfolded protein response, significantly reduced the radiosensitizing effects of auranofin in the IEC-6 cells. In addition, transfection of IEC-6 cells with a small interfering RNA targeted against thioredoxin reductase significantly enhanced the radiosensitivity of these cells. These results suggest that auranofin-induced radiosensitization of intestinal epithelial cells is mediated through oxidative stress caused by the deregulation of thioredoxin redox system, and auranofin treatment can be an independent risk factor for the development of acute pelvic radiation disease.
31068930 In the Right Place, at the Right Time: Spatiotemporal Conditions Determining Plasma Cell S 2019 Plasma cells (PCs), the B lineage cells responsible for producing and secreting antibodies (Abs), are critical cellular components of the humoral immune system. While most of the antibody-secreting cells in the body have a rather short lifetime of a few days, some of them can become long-lived and persist in the body over the entire life span of an individual. The majority of these long-lived plasma cells secretes protective antibodies against pathogens, and are thereby crucial for the humoral component of immunological memory. The generation of these protective antibody-secreting cells can be triggered by an exposure to pathogens, and also by vaccination. Although the majority of plasma cells are protective, sometimes long-lived plasma cells produce autoreactive antibodies, which contribute to the pathogenesis and perpetuation of chronic autoimmune diseases, including lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. In order to promote the formation of protective antibody-secreting cells and to target pathogenic plasma cells, it is crucial to understand the signals which promote their longevity and allow them to exert their function. In recent years, it has become clear that plasma cells depend on extrinsic factors for their survival, leading to the concept that certain tissue microenvironments promote plasma cell retention and longevity. However, these niches are not static structures, but also have dynamic features with respect to their cellular composition. Here, we review what is known about the molecular and cellular composition of the niches, and discuss the impact of dynamic changes within these microenvironments on plasma cell function. As plasma cell metabolism is tightly linked to their function, we present new tools, which will allow us to analyze metabolic parameters in the plasma cell niches in vivo over time.
30906135 High-performance liquid chromatographic analysis explores the potential antioxidative agen 2019 Jan BACKGROUND: Antioxidative properties of medicinal plants play the key role in plant defense mechanism. Argyreia argentea is an evergreen shrub which is used in the treatment of boils, gastric ulcers, tumor, marasmus, paralysis and spermatorrhea, rheumatoid arthritis, cold, painful sensation, and fever. AIMS: This research investigates the phytochemical contents and antioxidative effects of optimized crude methanol extract of A. argentea. MATERIALS AND METHODS: Crude methanol extract of A. argentea prepared in an optimized procedure has been analyzed by high-performance liquid chromatography to quantitatively determine the phytochemical contents. Tannin content of the extract was determined by established method. The extract was also analyzed for in vitro antioxidative actions by spectrophotometric analysis using 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) method, N, N-dimethyl-1,4-diaminobenzene (DMPD) free radical scavenging method, superoxide radical scavenging method, and nitric oxide scavenging method. RESULTS: The experimental results showed a high amount of catechin hydrate (348.62 mg/100 g of dry extract) and moderate amount of gallic acid, p-coumaric acid, and rutin hydrate in the methanol extract of A. argentea. Tannin content was found to be 29.66 mg/g tannic acid equivalent. Scavenging effects expressed as inhibition concentrations (IC(50)) for ABTS assay, DMPD assay, superoxide assay, and NO assay were 1148.3 µg/mL ± 7.32 µmol ascorbic acid/g, 1017.68 µg/mL, 1116.89 µg/mL, 1835.23 µg/mL, respectively. All the values were compared with their respective standards. No β-carotene was detected in the extract. CONCLUSIONS: Use of A. argentea extract as a source of functional food as well as an antioxidative agent could be considered with further confirmation.
30858306 Cardiac phenotype in mouse models of systemic autoimmunity. 2019 Mar 8 Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.
30825593 Genetic variation of matrix metalloproteinase enzyme in HIV-associated neurocognitive diso 2019 May 25 Matrix metalloproteinases (MMPs) play a key role in several diseases such as rheumatoid arthritis, HIV-associated neurological diseases (HAND), multiple sclerosis, osteoporosis, stroke, Alzheimer's disease, certain viral infections of the central nervous system, cancer, and hepatitis C virus. MMPs have been explained with regards to extracellular matrix remodeling, which occurs throughout life and ranges from tissue morphogenesis to wound healing in various processes. MMP are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). Matrix metalloproteases act as an interface between host's attack by Tat protein of HIV-1 virus and extracellular matrix, which causes breaches in the endothelial barriers by degrading ECM. This process initiates the dissemination of virus in tissues which can lead to an increase HIV-1 infection. MMPs are diverse and are highly polymorphic in nature, hence associated with many diseases. The main objective of this review is to study the gene expression of MMPs in HIV-related diseases and whether TIMPs and MMPs could be related with disease progression, HIV vulnerability and HAND. In this review, a brief description on the classification, regulation of MMP and TIMP, the effect of different MMPs and TIMPs gene polymorphisms and its expression on HIV-associated diseases have been provided. Previous studies have shown that MMPs polymorphism (MMP-1, MMP-2 MMP3, and MMP9) plays an important role in HIV vulnerability, disease progression and HAND. Further research is required to explore their role in pathogenesis and therapeutic perspective.
29570171 Factors Associated With Health Care Utilization of Recurrent Clostridium difficile Infecti 2019 Apr BACKGROUND: The incidence of infection due to Clostridium difficile infection (CDI) and subsequent economic burden are substantial. GOALS: The impact of changing practice patterns on demographics at risk and utilization of health care resources for recurrence of CDI remains unclear. STUDY: A total of 291,163 patients hospitalized for CDI were identified from 1995 to 2014 from the New York SPARCS database. The χ test, the Welch t test, and multivariable logistic regression analysis were performed to evaluate factors related to readmission. RESULTS: Hospital admissions and readmissions for CDI peaked in 2008 at 20,487 and 13,795, respectively, and have since decreased (linear trend, 0.9706 and 0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required ≥2 admissions. Risk factors for readmission included: age 55 to 74, government insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165 and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830 (0.63%) patients with CDI underwent surgery, with emergent being more common than elective (71% vs. 29%). CONCLUSIONS: Hospital admissions and readmissions for CDI peaked in 2008 and have since been steadily declining. These trends may be secondary to improved diagnostic capabilities and evolving antibiotic regimens. More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk factors for these patients have been identified. Although <1% of all patients with CDI undergo surgery, these rates have also been declining.
29249121 Matrix metalloproteinase 1: a better biomarker for squamous cell carcinoma by multiple mic 2019 Jun BACKGROUND: The present study aimed to validate MMP1 role in the development of squamous cell carcinoma (SCC) by bioinformatics methods. METHODS: Gene expression data of 10 GSE series (5 HNSCCs and 5 cSCCs) were obtained from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs). RESULTS: Higher expression of MMP1 was found rank number one in 9/10 GSE series of SCC. MMP1 was mainly focused on Gene Ontology (GO) terms of collagen catabolic process, extracellular matrix disassembly. The analysis results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways mainly involved Rheumatoid arthritis, Bladder cancer and Pathways in cancer. Also, MMP1 was identified as a hub protein in the PPI network by using Cytoscape software. In addition, others MMPs members of family were analyzed. CONCLUSIONS: These results suggested that MMP1 may be pivotal to the transition from normal skin to premalignant lesions to SCC, thus representing a potential therapeutic target gene of diagnosis and prevention in SCC.
31552141 A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-relate 2019 Growing evidence suggests that inflammation is a significant contributor to different cardiovascular diseases (CVDs). Mendelian randomization (MR) was performed to assess the causal inference between plasma soluble IL6 receptor (sIL6R), a negative regulator of IL6 signaling, and different cardiovascular and immune-related disorders. Cis-MR with multiple instrumental variables showed an inverse association of sIL6R with rheumatoid arthritis, atrial fibrillation, stroke, coronary artery disease, and abdominal aortic aneurysm. However, genetically-determined sIL6R level was positively associated with atopic dermatitis and asthma. Also, sIL6R level was associated with longevity, as evaluated by parental age at death, a heritable trait. Gene-based association analysis with S-PrediXcan by using tissues from GTExV7 showed that IL6R tissue expression-disease pair associations were consistent with the directional effect of IL6 signaling identified in MR. Genetically-determined reduced IL6 signaling lowers the risk of multiple CVDs and is associated with increased longevity, but at the expense of higher atopic risk.
31050974 [Contraction of the tensor fasciae latae muscle of the fascia of the broad thigh and flexi 2019 OBJECTIVE: Introduction: The illustration of the ranges of bending the limb during the outflow allowed to divide the study group into two parts. In the majority of respondents, the initial flexion prevailed over the final one. The researchers focused on finding the reasons for the advantage of the final bend over the initial one in 30% of the subjects. The aim: The analysis of the dynamic stride under the control of the MVN Biomech system in the bending of the knee joint of the lateral limb, comparing the preparation to the leg (initial bending) and its ending (final). PATIENTS AND METHODS: Materials and Methods: 18 right-handed 25 to 35 year old runners were selected after the following exclusion criteria were applied: polyarticular hypermobility, systemic diseases, Rheumatoid arthritis, osteoarthritis, post-traumatic instability. The MVN Biomech system assessed the three-dimensional movements of the joints of the free part of the lower limb and pelvis, and the flexibility of the muscles was subject to physiotherapeutic assessment. RESULTS: Results: In 55% of respondents dominated the pattern in which the initial flexion exceeded by min. 10⁰ final bend in both limbs (decreasing type). The researchers focused on finding the reasons for the smaller difference or the advantage of the final bending on both sides in 30% of respondents (mixed type). The comparison of physiotherapeutic examination results and measurements of MVN Biomech showed functional contractures of the tensor fasciae latea muscles in 5 subjects with a mixed type (83% of subjects with a mixed type). CONCLUSION: Conclusions: Contraction of the tensor fasciae latae constrained the initial flexion of the knee joint of the lateral limb, and also increased bilateral visitation of the hip joints during the dynamic mixed-type twitch. The remaining muscles of the lower limbs show no statistically significant differences in elasticity compared to the type of the leg.
31988667 Biosimilar biological drugs in the treatment of inflammatory bowel diseases. 2019 Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.
31879497 Partial thickness rotator cuff tears: Patient demographics and surgical trends within a la 2020 Jan INTRODUCTION: Partial thickness rotator cuff tears (PTRCT) are a common injury reported in 13-32% of the population, yet most of the current literature focuses on full thickness rotator cuff tears. Therefore, the purpose of this study was to analyze trends among patients with PTRCT including: (1) demographics; (2) comorbidities; (3) cost of care; (4) setting of initial diagnosis; and (5) change in incidence of PTRCT or surgical approach over time. METHODS: A Medicare patient-population consisting of 44 million lives was retrospectively analyzed from 2007 to 2017 using International Classification of Disease, 9th Revision (ICD-9) codes. Patients were identified for PTRCT using ICD-9 code: 726.13. The query yielded a total of 44,978 patients all of which had been previously diagnosed with PTRCT. Primary trends analyzed included: demographics, comorbidities, cost of care, initial setting of diagnosis, and change in incidence of PTRCT or surgical approach over time. RESULTS: PTRCTs and surgical repair of PTRCTs were most common in patients ages 65 to 69 and least common in patients who were 85 and older. Incidence of PTRCT was greater in females (54.12%) than males (45.88%). Comorbidities found within the population included hypertension, hyperlipidemia, diabetes mellitus, tobacco use, obesity, rheumatoid arthritis, and osteoarthritis of the shoulder. The average cost per episode of care totaled $9,923.26. PTRCTs were most commonly diagnosed in patients who resided in assisted living facilities (n = 27,106), making up 60% of the patient population. Reported incidence of PTRCT has increased substantially along with the surgical repair of PTRCT. CONCLUSION: Reported cases of PTRCT and its surgical repair have both increased substantially over time. Approximately 11.70% of patients with PTRCT undergo either open or arthroscopic procedure as a means of surgical repair. With the growing popularity of arthroscopic procedures for rotator cuff repair, further investigation should be performed to analyze trends and risk factors for PTRCT, a seemingly underrepresented orthopedic condition.