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

ID PMID Title PublicationDate abstract
31272097 Association of HLA Alleles with Primary Sjögren Syndrome in the South Tunisian Population 2020 OBJECTIVE: In order to investigate human leukocyte antigen (HLA) genes predisposing to primary Sjögren syndrome (pSS), we conducted an association study using HLA loci (A, B, and DRB1) and 9 polymorphic microsatellite markers spanning the HLA region in pSS patients as compared to healthy individuals. SUBJECTS AND METHODS: Forty-four patients fitting the European criteria of pSS and 123 healthy controls were analyzed for their HLA class I and class II alleles. HLA class I typing was performed using a standard microlymphocytotoxicity method followed by PCR-SSP. HLA-DRB1 genotyping was performed using PCR-SSP. We studied the polymorphism of 9 microsatellite markers for both groups. Microsatellite genotyping was performed using the PCR fluorescent technique. RESULTS: We observed a positive association between HLA-B15 and pSS in the Tunisian population (p = 0.004, OR 7.57). The comparison of the frequencies of DRB1 alleles in pSS patients and controls confirmed the association of the DRB1*03 allele with pSS (p = 0.02, OR 2.36). On the other hand, the association study of microsatellite markers showed that the a9 allele of D6S265 marker and the a20 of C1.2.C were found to be positively associated with pSS as compared to controls (p =0.0003, OR 10.29, and p =0.001, OR 4.79, respectively). Using the "Haplo.stats" software analysis, we found that the most associated region was located in the HLA class I region and limited by HLA-A and D6S265 loci (p = 0.00056). CONCLUSION: The results of this study support the hypothesis of the existence of a susceptibility gene for pSS located in the HLA class I and III regions.
32721173 Ultra-High Frequency Ultrasound, A Promising Diagnostic Technique: Review of the Literatur 2021 Aug OBJECTIVES: Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique which finds several applications in diverse clinical fields. The range of frequencies between 30 and 100 MHz allows for high spatial resolution imaging of superficial structures, making this technique suitable for the imaging of skin, blood vessels, musculoskeletal anatomy, oral mucosa, and small parts. However, the current clinical applications of UHFUS have never been analyzed in a consistent multidisciplinary manner. The aim of this study is to revise and discuss the current applications of UHFUS in different aspects of research and clinical practice, as well as to provide some examples of the current work-in-progress carried out in our center. MATERIALS AND METHODS: A literature search was performed in order to retrieve articles reporting the applications of UHFUS both in research and in clinical settings. Inclusion criteria were the use of frequencies above 30 MHz and study design conducted in vivo on human subjects. RESULTS: In total 66 articles were retrieved. The majority of the articles focused on dermatological and vascular applications, although musculoskeletal and intraoral applications are emerging fields of use. We also describe our experience in the use of UHFUS as a valuable diagnostic support in the fields of dermatology, rheumatology, oral medicine, and musculoskeletal anatomy. CONCLUSION: Ultra-high frequency ultrasonography application involves an increasing number of medical fields. The high spatial resolution and the superb image quality achievable allow to foresee a wider use of this novel technique, which has the potential to bring innovation in diagnostic imaging.
32366487 A major genetic determinant of autoimmune diseases is associated with the presence of auto 2020 Aug BACKGROUND: Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies. METHODS: 170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20. RESULTS: 60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs(+)), and 110 hypersensitivity pneumonitis patients did not (HPAbs(-)). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs(+) group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83-237.1; p=1.65×10(-4) after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37-155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05-33.05; p=0.043). CONCLUSIONS: A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.
31233285 Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case-Cont 2020 Sep OBJECTIVE: To test whether cumulative estrogen exposure, as determined by age at menarche, age at menopause, female hormone use, hysterectomy, and parity, have an effect on the development of primary Sjögren's syndrome (SS). METHODS: We performed a case-control study of 2,680 women from the Sjögren's International Collaborative Clinical Alliance registry, including 1,320 registrants with primary SS and 1,360 with sicca symptoms but no key features of primary SS (sicca controls). The composite estrogen score (CES) was calculated by point assignment for early menarche (age ≤10 years), high parity (>3 pregnancies), hysterectomy, female hormone use, and late menopause (age ≥53 years). Cumulative menstrual cycling (CMC) was calculated as years menstruating minus time pregnant. RESULTS: Using a regression model that adjusted for age, recruitment site, ethnicity, education, employment status, and smoking, we observed a progressive inverse trend between primary SS and CES. The odds ratio (OR) and 95% confidence interval (95% CI) were as follows for the sicca control group: CES 1, OR 0.81 (95% CI 0.67-0.99); CES 2, OR 0.74 (95% CI 0.57-0.97); CES 3, OR 0.50 (95% CI 0.30-0.86). This trend was corroborated by analysis of CMC. At the highest level of CMC within the postmenopausal group there was a 24% reduction in cumulative sex hormone exposure among primary SS participants relative to controls. CONCLUSION: Women with primary SS have lower estrogen exposure and CMC compared to sicca controls. Increasing estrogen exposure was negatively associated with development of primary SS. Further longitudinal studies of sex hormone exposure in primary SS are needed to confirm these findings.
32165035 Safety and effectiveness of abatacept in systemic sclerosis: The EUSTAR experience. 2020 Dec OBJECTIVE: To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). METHODS: Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. RESULTS: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. CONCLUSIONS: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.
31930936 Antibodies against carbamylated vimentin exist in systemic lupus erythematosus and correla 2020 Mar OBJECTIVES: Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguous. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE. METHODS: Serum levels of antibodies against carbamylated-vimentin (anti-Carp) were measured by enzyme immunosorbent assay in 100 patients with SLE, 76 with RA, 17 with primary Sjögren syndrome (pSS), and 68 healthy controls. Data analyses between anti-Carp antibodies and other laboratory measures were performed using SPSS 24 software for Windows. RESULTS: The levels of serum anti-CarP antibodies in patients with SLE were significantly higher than those in healthy controls. In addition, anti-CarP antibodies were present in SLE patients lacking the disease-specific antibodies, including anti-Smith-negative patients (24.4%, 21/86), anti-dsDNA-negative patients (29.3%, 12/41), anti-nucleosome-negative patients (21.4%, 9/42), and antiribosomal P protein antibody-negative patients (23.7%, 18/76). There were significant differences between the anti-CarP-positive and anti-CarP-negative SLE patients in clinical and laboratory features, such as age, erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, third-generation cyclic citrullinated peptide (CCP3), anticardiolipin, D-dipolymer, complement 3, immunoglobulin G (IgG), red blood cell count (RBC) and hemoglobin. After adjusting for age and disease duration, the high levels of anti-CarP antibodies were still correlated with low RBC, hemoglobin and high ESR, IgG and CCP3. Active SLE patients demonstrated higher anti-CarP IgG than inactive patients. Moreover, the levels of anti-CarP were significantly higher in SLE patients with arthralgia and/or arthritis than in those without joint involvement. CONCLUSIONS: Anti-CarP antibodies were present in SLE patients and associated with the disease severity. These might provide a potential supplement to other specific autoantibodies for diagnosis of SLE and serve as a promising marker for measuring joint damage in the disease.
33183349 IgG subclasses in cryoglobulins: link to composition and clinical manifestations. 2020 Nov 12 BACKGROUND: Cryoglobulins (CG) are immunoglobulins which precipitate at low temperature. The analysis of IgG subclass composition of CG is poorly reported. The aim of this study was to determine the subclasses of IgG-containing type I and mixed type II and III CG in relation to clinical manifestations. METHODS: Out of a previous series of 1675 patients, inclusion criteria were a cryoprecipitate > 1 mL and a total IgG > 300 mg/L. IgG subclasses were quantified by immunoturbidimetry, rheumatoid factor (RF), and C4 by immunonephelometry. Clinical parameters were collected from hospital charts. RESULTS: CG samples from 86 patients were included, 10 type I CG and 76 mixed CG. Type I CG subclasses were IgG1 (6/10) and IgG2/IgG3 (4/10), never IgG4. IgG subclass in type II vs. III CG were 73.3 ± 15.2% vs. 52.5 ± 20.7% for IgG1 (p < 0.0001), 15.4 ± 8.2% vs. 25.9 ± 14% for IgG2 (p < 0.0001), 8.4 ± 12.4 vs. 21.2 ± 14% for IgG3 (p < 0.0001), and 3 ± 5.2% vs. 0.5 ± 1.2 for IgG4 (p < 0.0001). In mixed CG, the higher proportion of IgG4 was associated with RF positive CG (p = 0.01) and low C4 (p = 0.01). In type I CG, IgG1 were associated with severe vasculitis manifestations, IgG2/IgG3 with cutaneous or renal manifestations. In mixed CG, IgG2 was the only subclass associated with CG manifestations, with a higher concentration in asymptomatic (162.6 ± 29.5 mg/L) vs. symptomatic patients with cutaneous (103 ± 17.8 mg/L, p = 0.04) and neurological (108 ± 24 mg/L, p = 0.04) manifestations. CONCLUSION: In type I IgG CG, IgG1 was the main CG subclass associated with CG vasculitis. In mixed CG, low IgG2 concentration was linked to CG cutaneous and neurological manifestations.
33263831 Satisfactory mid-term outcomes of condylar-constrained knee implants in primary total knee 2020 Dec 2 BACKGROUND: The purpose of this study was to evaluate (1) the reoperation rates and survivorship for septic and aseptic causes, (2) radiographic outcomes, and (3) clinical outcomes of condylar-constrained knee (CCK) implants used in primary total knee arthroplasty (TKA) with severe coronal deformity and/or intraoperative instability. MATERIALS AND METHODS: A consecutive series of CCK implants in primary TKA was retrospectively evaluated in patients with severe coronal deformities. Forty-nine patients (54 knees) were included with a mean follow-up of 9 years (range 6-12). All patients were treated with a single-design, second-generation CCK implant. The primary diagnosis was osteoarthritis in 36 knees, post-traumatic arthritis in 7 knees, and rheumatoid arthritis in 4 knees. Preoperatively, standing femorotibial alignment was varus in 22 knees and valgus in 20 knees. RESULTS: At a mean follow-up of 9 years, overall survivorship was 93.6%. Two knees (4.3%) required revision for periprosthetic joint infection. One knee (2.1%) required subsequent arthroscopy due to patellar clunk syndrome. At final follow-up, no evidence of loosening or migration of any implant was reported, and the mean Knee Society knee scores improved from 43 to 86 points (p < 0.001). The mean Knee Society function scores improved to 59 points (p < 0.001). The average flexion contracture improved from 7° preoperatively to 2° postoperatively and the average flexion from 98° to 110°. No knees reported varus-valgus instability in flexion or extension. CONCLUSION: CCK implants in primary TKA with major coronal deformities and/or intraoperative instability provide good midterm survivorship, comparable with less constrained implants. In specific cases, CCK implants can be considered a viable option with good clinical and radiographic outcomes. However, a higher degree of constraint should be used cautiously, leaving the first choice to less constrained implants. Level of evidence Therapeutic study, level IV.
32497929 Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicent 2020 Aug PURPOSE: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). DESIGN: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. SUBJECTS: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behçet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. METHODS: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. MAIN OUTCOME MEASURES: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. RESULTS: The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. CONCLUSIONS: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.
33392201 CD11b Signaling Prevents Chondrocyte Mineralization and Attenuates the Severity of Osteoar 2020 Osteoarthritis (OA) is a progressive joint disease that is strongly associated with calcium-containing crystal formation (mineralization) by chondrocytes leading ultimately to cartilage calcification. However, this calcification process is poorly understood and treatments targeting the underlying disease mechanisms are lacking. The CD11b/CD18 integrin (Mac-1 or αMβ2), a member of the beta 2 integrin family of adhesion receptors, is critically involved in the development of several inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. We found that in a collagen-induced arthritis, CD11b-deficient mice exhibited increased cartilage degradation compared to WT control animals. However, the functional significance of CD11b integrin signaling in the pathophysiology of chondrocytes remains unknown. CD11b expression was found in the extracellular matrix and in chondrocytes in both healthy and damaged human and murine articular cartilage. Primary murine CD11b KO chondrocytes showed increased mineralization when induced in vitro by secondary calciprotein particles (CPP) and quantified by Alizarin Red staining. This increased propensity to mineralize was associated with an increased alkaline phosphatase (Alp) expression (measured by qRT-PCR and activity assay) and an enhanced secretion of the pro-mineralizing IL-6 cytokine compared to control wild-type cells (measured by ELISA). Accordingly, addition of an anti-IL-6 receptor antibody to CD11b KO chondrocytes reduced significantly the calcification and identified IL-6 as a pro-mineralizing factor in these cells. In the same conditions, the ratio of qRT-PCR expression of collagen X over collagen II, and that of Runx2 over Sox9 (both ratio being indexes of chondrocyte hypertrophy) were increased in CD11b-deficient cells. Conversely, the CD11b activator LA1 reduced chondrocyte mineralization, Alp expression, IL-6 production and collagen X expression. In the meniscectomy (MNX) model of murine knee osteoarthritis, deficiency of CD11b led to more severe OA (OARSI scoring of medial cartilage damage in CD11b: 5.6 ± 1.8, in WT: 1.2 ± 0.5, p < 0.05, inflammation in CD11b: 2.8 ± 0.2, in WT: 1.4 ± 0.5). In conclusion, these data demonstrate that CD11b signaling prevents chondrocyte hypertrophy and chondrocyte mineralization in vitro and has a protective role in models of OA in vivo.
32967654 Mycobacterium haemophilum scleritis: two case reports and review of literature. 2020 Sep 23 BACKGROUND: Mycobacterium haemophilum is a rare and emerging nontuberculous mycobacteria (NTM). It normally causes localized or disseminated systemic diseases, particularly skin infections and arthritis in severely immunocompromised patients. There have been 5 cases of M. haemophilum ocular infections reported in the literature. Only 1 case presented with scleritis with keratitis. Here, we reported 2 cases of M. haemophilum scleritis. One of them was immunocompetent host and had keratitis with radial keratoneuritis as a presenting sign. CASE PRESENTATION: Case 1: A 52-year-old Thai female with rheumatoid arthritis presented with scleritis. Conjunctival scraping was carried out and the culture result was positive for M. haemophilum. Despite receiving systemic and topical antibiotics, her clinical symptoms and signs worsened. Surgical debridement was performed. After surgery, the lesion was significantly improved and finally turned to conjunctival scarring. Case 2: A 32-year old healthy Thai male without underlying disease presented with nodular scleritis and keratouveitis with multiple radial keratoneuritis. Surgical debridement of the scleral nodule was performed. Initial microbiological investigations were negative. Herpes ocular infections was suspected. Topical antibiotics, oral acyclovir, low-dose topical steroids and systemic steroids were started. The scleral inflammation subsided but later the keratitis relapsed, requiring corneal biopsy. Histopathology of the specimen revealed acid-fast bacteria and M. haemophilum was identified by polymerase chain reaction (PCR) and sequencing. The diagnosis of Mycobacterial keratitis was made. Although using the combination of systemic and topical antibiotics, his clinical status progressively deteriorated. Multiple therapeutic penetrating keratoplasties were required to eradicate the infection. No recurrence was found during the 1-year follow-up in both cases. CONCLUSIONS: M. haemophilum can cause scleritis and keratitis, even in immunocompenent host. Radial keraoneuritis is first described in M. haemophilum keratitis. NTM keratitis should be considered in the differential diagnosis of patients with radial keratoneuritis. Increased awareness and early diagnosis using appropriate culture conditions and molecular techniques are important for the proper treatment of this infection. Prompt surgical intervention appears to be vital for successful management of M. haemophilum scleritis and keratitis.
33457183 Could Vitamin D influence risk for Periodontal Disease - to "D" or not to "D"? 2020 Mar PURPOSE OF REVIEW: The purpose of this review is to discuss the literature on associations between vitamin D and periodontal disease, including its strengths and weaknesses. Future direction for continued work in this area is provided. RECENT FINDINGS: Research in cross-sectional cohorts, surveys, and case-control studies provide support for a role of vitamin D in periodontal disease, especially using clinical indicators such as bleeding on probing and clinical attachment loss. However, these studies have a number of limitations. They cannot establish temporality of these associations. Most case-control studies have been limited in sample size and have inconsistent findings. A number of cross-sectional studies are restricted to select populations (e.g., persons with HIV, diabetes, rheumatoid arthritis) limiting extrapolation of findings to the general aging population.Fewer prospective studies have been conducted, and only three have examined associations using a biomarker for vitamin D that reflects exposure from all its sources (sunlight, diet and supplements). One study is limited by using self-reported measures of disease outcomes, and only two used measures of alveolar crestal height. However, of the prospective studies published, there is a suggestion that vitamin D might prevent against tooth loss. Only two randomized controlled trials have examined these associations, and they support the effects of vitamin D supplementation on prevention of tooth loss and gingival bleeding. SUMMARY: We strongly suggest that new research should focus on prospective study designs with followup of participants longer than a decade and long-term clinical trials. Such studies should incorporate measures of alveolar bone loss and tooth loss with indication for reason for tooth loss. Such clinical trials should be designed to examine both the influence of vitamin D supplementation alone as well as with other nutrients (e.g., calcium) or therapeutic medications (e.g., bisphosphonates). Currently, there is no strong evidence to suggest that vitamin D protects against development of periodontal disease.
32258830 Serum zinc levels and multiple health outcomes: Implications for zinc-based biomaterials. 2020 Jun BACKGROUND: Zinc-based biomaterials, including biodegradable metal, nanoparticles, and coatings used in medical implants release zinc ions that may increase the whole-body and serum zinc concentrations. The impact of serum zinc concentrations on major health outcomes can provide insights for device design and clinical transformation of zinc-based biomaterials. METHODS: This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) including 3607 participants. Using unadjusted and multivariate-adjusted logistic regression analyses, two-piecewise linear regression model with a smoothing function and threshold level analysis, we evaluated the associations between elevated serum zinc levels and major health outcomes. RESULTS: Elevated serum zinc levels were significantly associated with an increase in total spine and total femur bone mineral density (BMD). Every 10 μg/dL increase was associated with a 1.12-fold increase in diabetes mellitus (DM) and 1.23-fold and 1.29-fold increase in cardiovascular diseases (CVD) and coronary heart disease (CHD), in participants with serum zinc levels ≥ 100 μg/dL. It had no significant linear or nonlinear associations with risk of fractures, congestive heart failure, heart attack, thyroid disease, arthritis, osteoarthritis, rheumatoid arthritis, dyslipidemia and cancer. CONCLUSION: Serum zinc levels are significantly associated with increased BMD in the total spine and total femur, and risk of DM, and CVD/CHD among participants with serum zinc levels ≥100 μg/dL.
33282713 Epidemiology of musculoskeletal complaints and diseases in Qatar: A cross-sectional study. 2020 BACKGROUND: Musculoskeletal (MSK) conditions are considered a significant public health problem on account of their high prevalence in communities worldwide and their pervasive impact. Knowledge of the epidemiology of MSK symptoms and diseases is lacking in Qatar. Obtaining this information will guide local health policymakers in the future strategic planning of the health budget. OBJECTIVE: To estimate the prevalence rate of MSK disorders in the Qatari population above 15 years of age using the Community Oriented Program for the Control of Rheumatic Disease (COPCORD) survey. METHODS: This cross-sectional study targeted 1000 Qatari participants, including 500 males and 500 females. A door-to-door survey was conducted using the Arabic version of the COPCORD questionnaire with the help of research assistants. Participants with positive surveys were asked to visit Hamad General Hospital Rheumatology outpatient clinics for clinical evaluation by a rheumatologist. When necessary, laboratory testing and X-rays were conducted to confirm any MSK diagnosis. RESULTS: A total of 1239 (males, 50.8%) Qatari individuals randomly selected from the different municipalities of Qatar completed the COPCORD survey. Among the participants, 563 (45.4%) screened positive for MSK pain. Knee pain (24.5%) and back pain (23.3%) were the most common sites of pain, and both conditions showed no gender predominance (p = 0.073 and 0.108, respectively). Shoulder, wrist, hand, hip, and neck pain were significantly predominant in females (p < 0.001 for all). A total of 237 MSK disorders were diagnosed in 196 (15.8%) participants, including 181 degenerative joint diseases, 52 soft-tissue rheumatism conditions, and 4 autoimmune inflammatory disorders. Among degenerative joint diseases, knee osteoarthritis (6.4%) was the most common. Among soft-tissue rheumatic conditions, muscular lower back pain (1.9%), myofascial neck pain (0.64%), generalized body pain (0.32%), and shoulder tendinitis (0.7%) were the most common diseases. The autoimmune inflammatory disorders identified included rheumatoid arthritis (n = 2), connective tissue disease (n = 1), and inflammatory bowel disease-associated arthritis (n = 1). CONCLUSION: The overall prevalence rate of MSK disorders in this small cross-sectional cohort of Qatari individuals was 15.8%. Knee pain (24.5%) and knee osteoarthritis (6.4%) were the most common MSK complaints and diagnosis in the studied Qatari population. This study guides future efforts directed toward the prevention and management of MSK diseases. Further studies with a larger sample size are needed to verify the findings.
33031693 The Effect of Total Hip Arthroplasty on the Sciatic Nerve: an Electrodiagnostic Evidence S 2020 Sep OBJECTIVE: Objectively evaluate the incidence of sciatic nerve injury after a total hip arthroplasty (THA) performed through a posterolateral approach. METHODS: Patients scheduled to undergo THA were evaluated preoperatively and postoperatively with electrophysiologic studies, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) questionnaire and other methods described in the study. Patients older than 21 years with any of the following preoperative diagnoses: primary or secondary osteoarthritis, aseptic avascular necrosis, rheumatoid arthritis, and posttraumatic arthritis were included. Variables used for analysis were sex, age, and body mass index (BMI). The Mann-Whitney U and Wilcoxon tests and, Pearson and Spearman correlation statistics were used for analysis of categorical and continuous data respectively. RESULTS: Electrodiagnostic data showed alterations in 17 patients (70.8%). No signs of sciatic nerve injury. The mean preoperative and postoperative WOMAC scores were 40 and 74, respectively (p = 0.0001). Statistical differences were noted in sural sensory amplitude (SSA) and distal amplitude of the tibialis motor nerve in the female group (p=0.007; p=0.036, respectively). The SSA also demonstrated differences in the obese group (p=0.008). In terms of age, both the SSA (Pearson p=0.010 and Spearman p=0.024) and the proximal latency of the peroneal motor nerve (Pearson p=0.026 and Spearman p=0.046) demonstrated a decrease in amplitude and an increase in latency that was inversely related with age. CONCLUSION: According to our subclinical electrophysiological findings, surgeons that use the posterolateral approach in THA procedures must be conscious of the sciatic nerve's vulnerability to reduce possible clinical complications.
32937011 Positive Psychological Factors and Impairment in Rheumatic and Musculoskeletal Disease: Do 2021 Jan OBJECTIVE: Little is known about potential mechanisms of action linking protective positive psychological variables and functional disability in patients with rheumatic and musculoskeletal disease. The present study was undertaken to examine symptoms of psychopathology, including stress, depression, anxiety, and sleep quality, as serial mediators of the association between gratitude, self-compassion, self-forgiveness, and functional impairment. METHODS: We assessed risk and protective factors for functional disability in patients with fibromyalgia (FM), osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) who were recruited from an Austrian health care facility. Respondents completed online surveys, including the Gratitude Questionnaire 6-item form, the Self-Compassion Scale short form, the Self-Forgiveness and Forgiveness of Others Index, the Perceived Stress Scale 4, the Patient Health Questionnaire 2, the 2-item Generalized Anxiety Disorder Scale, the Sleep Condition Indicator, and the Health Assessment Questionnaire. Bivariate and serial mediation analyses were conducted. RESULTS: For our sample of 1,218 patients (52% female, n = 632; AS [37%], OA [34%], RA [14%], and FM [24%]), stress, depression, and anxiety, in parallel as first-order mediators, and sleep quality as a second-order mediator, explained the association between positive psychological variables and functional disability. CONCLUSION: Positive psychological factors exert a beneficial downstream effect on mental well-being, sleep health, and health-related functional impairment. Therapeutic promotion of gratitude, self-compassion, and self-forgiveness may improve mental and physical health in patients with rheumatic and musculoskeletal disease.
32673673 Macrolactin A protects against LPS-induced bone loss by regulation of bone remodeling. 2020 Sep 15 An imbalance between bone resorption and bone formation leads to several kinds of bone diseases such as rheumatoid arthritis, osteoporosis and Paget's disease. The imbalance between bone formations relative to bone resorption is responsible in bone remodeling. Several studies have suggested that macrolactin A (MA) has potent anti-inflammatory, anti-cancer and anti-angiogenic effects in various cell types. We investigate whether macrolactin A (MA) could inhibit bone loss and enhance bone formation. We used bone marrow monocytes/macrophages (BMMs) cells to study osteoclast activity and MC3T3-E1 cells to study osteoblast activity. MA suppressed tartrate resistant acid phosphatase (TRAP) positive multinucleated cells in a concentration-dependent manner, as well as at a specific time point. MA markedly reduced bone resorption activity and F-actin ring formation. Moreover, MA markedly suppressed receptor activator of nuclear factor k-B ligand (RANKL)-induced osteoclastogenic marker genes and transcription factors in-vitro. MA repressed osteoclast differentiation via activation of the phosphoinositide kinase-3/Akt, extracellular signal-regulated kinase 1/2 (ERK 1/2), c-Jun N-terminal kinase (JNK), nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and c-Fos signaling pathways. MA enhanced pre-osteoblast cell differentiation on mineralization activity, alkaline phosphatase (ALP) activity, and the expression of osteoblastogenic markers including osterix, RUNX-2, SMAD4, BMP-2, and ALP. Importantly, MA repressed lipopolysaccharide (LPS)-induced inflammatory bone loss in mice as shown by TRAP staining of femurs and μCT analysis. Therefore, MA could be a promising candidate for the inhibition and management of osteoporosis, arthritis, and bone lytic diseases.
32016482 Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentia 2020 Mar Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and joint destruction. Monocyte chemoattractant protein 1 (MCP‑1) is highly expressed in the joints of patients suffering from RA. The present study aimed to evaluate the effects of MCP‑1 on the phenotype of fibroblast‑like synoviocytes (FLSs) and their differentiation potential towards vascular endothelial cells. The expression of MCP‑1 in collagen‑induced arthritis (CIA) rats was investigated by PCR, ELISA and immunohistology. Cell proliferation induced by MCP‑1 was measured using a Cell Counting Kit‑8 (CCK‑8) and 5‑Bromo‑2‑deoxyuridine ELISA assay. In addition, the effects of MCP‑1 on the migration of FLSs was examined using a Transwell assay. Activation of PI3K and P38 were investigated by western blotting following MCP‑1 treatment. The vascular endothelial cell markers, tumor necrosis factor alpha (TNF‑α) and interleukin‑1 beta (IL‑β), were also examined by western blotting. LY294002 [PI3K inhibitor, (LY)] and SB203580 [P38 inhibitor, (SB)] were used to examine the proliferative and pro‑differentiation effect of PI3K and P38. The present findings showed that the expression level of MCP‑1 in the synovium of CIA rats was significantly higher compared with controls. The present in vitro study suggested that MCP‑1 increased the FLSs cell numbers with a maximal effect at 200 ng/ml, and induced the maximal phosphorylation of PI3K at 15 min and P38 at 30 min. In addition, MCP‑1 stimulation significantly increased the migration of FLSs. Furthermore, MCP‑1‑induced the expression of vascular endothelial growth factor and CD31 in FLSs. Suppression of PI3K and P38 was found to reduce MCP‑1 induced FLSs proliferation and migration, and decreased the expression levels of angiogenesis markers increased following MCP‑1 treatment. MCP‑1 was also found to increase the expression levels of both TNF‑α and IL‑β. Therefore, MCP‑1 could promote the proliferation and migration of FLSs, and was found to increase the expression levels of various angiogenesis markers via PI3K/P38, suggesting a role for this pathway in synovium hyperplasia in RA.
31788947 Bioresponsive microspheres for on-demand delivery of anti-inflammatory cytokines for artic 2020 Mar Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine has shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here, we describe the utility of gelatin microspheres that are responsive to proteolytic enzymes typically expressed in arthritic flares, resulting in on-demand and spatiotemporally controlled release of anti-inflammatory cytokines for cartilage preservation and repair. These microspheres were designed with a net negative charge to sequester cationic anti-inflammatory cytokines, and the magnitude of the negative charge potential increased with an increase in crosslinking density. Collagenase-mediated degradation of the microspheres was dependent on the concentration of the enzyme. Release of anti-inflammatory cytokines from the loaded microspheres directly correlated with the degradation of the gelatin matrix. Exposure of the IL-4 and IL-13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an OA joint can attenuate the stimulation of chondrocytes and the resulting secretion of catabolic factors such as proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically induced drug release. Consequently, bioresponsive microspheres can be an effective tool for cartilage preservation and arthritis treatment.
31713350 Phase 1 Dose-Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability o 2020 Jan The aim of the study was to characterize the pharmacokinetics, safety, and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis in healthy Japanese volunteers, and to compare these outcomes with those of healthy Western volunteers. Twenty-five volunteers (Japanese, n = 16; Western [white], n = 9) were randomized to receive either 3 escalating single doses of tofacitinib (1, 5, and 30 mg), single-dose tofacitinib (15 mg) followed by multiple doses (15 mg twice daily for 5 days), or placebo. No significant differences in systemic exposure to tofacitinib were detected between the 2 ethnicities. Following single tofacitinib 1, 5, and 30 mg doses, mean area under the plasma concentration-time curve from time zero to infinity ratio (Japanese/Western) values were 96.6%, 93.5%, and 95.6%, respectively. Similarly, mean maximum observed plasma concentration ratio values were 99.5%, 118%, and 119%, respectively. Mean renal clearance was also similar, ranging across doses from 134 mL/min (5 mg) to 162 mL/min (1 mg) in Japanese volunteers, and 124 mL/min (30 mg) to 160 mL/min (1 mg) in Western volunteers. In both ethnicities, most adverse events were mild. No serious adverse events or deaths were reported. The pharmacokinetics of tofacitinib were well characterized in healthy Japanese volunteers and were similar to those in Western volunteers.