Rowebjerregaard9469

Introduction Ankylosing spondylitis (AS) patients seems to be at risk of osteoporosis but bone screening is not often performed. The objective was to evaluate the effect of vertebral ankylosis on scanographic bone attenuation coefficient (SBAC) on lumbar vertebrae in AS patients. Methods This study included AS patients fulfilling New York criteria who underwent both thoraco-abdomino-pelvic computed tomography and X-rays during routine follow-up. The modified stoke ankylosing spondylitis spinal score (mSASSS) was scored on X-rays, and the presence of at least one syndesmophyte (mSASSS≥2) defined mSASSS+ patients. Ankylosis of a lumbar vertebra was defined by the presence of bone bridges to its two adjacent vertebrae. The SBAC was measured from L1 to L5, and the fracture threshold was set at SBAC≤145 HU. Vitamin A acid Results A total of 73 AS patients were included (mean age 60.3 (±10.7) years, 65 men (89%)). Sixty patients (82.2%) were mSASSS+; 13 patients (17.8%) presented ankylosis of at least one lumbar vertebra. The SBAC of each lumbar vertebra was not significantly different between mSASSS- and mSASSS+ patients. The SBAC was lower for patients with at least one bone bridge than for patients without (p less then 0.05). Patients with lumbar vertebral ankylosis had a higher risk of presenting an SBAC≤145 HU (OR 4.95 (95% CI 1.1-17.4)). Conclusion The presence of a bone bridge and complete ankylosis of lumbar vertebra were associated with a higher risk of SBAC under the fracture threshold, suggesting structural deterioration of trabecular bone in ankylosed vertebrae in AS patients.Objective To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Methods Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI]≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models. Results Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6-81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR] 18.00, 95% CI 2.80-115.56) and extended dosing interval of tocilizumab (OR 12.00, 95% CI 1.72-83.80) were independent predictors of disease flare. Conclusion Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. Trial registration number jRCTs041180071, UMIN000021247.Introduction The aim of our study was to assess the association between the Alternate Dietary Inflammatory Index (ADII) and the risk of fracture in a French cohort of women and men older than 50 years. Methods A total of 15,096 participants were included from the French NutriNet-Santé cohort. link2 The ADII score was calculated at inclusion. Incident low trauma fractures were retrospectively self-reported by participants on a specific additional questionnaire.Multivariate hazard ratio obtained from Cox proportional hazard regression models were used to characterize an association between ADII (in quartiles) and incident low trauma fractures. Results 12,046 participants (7607 (63.2%) women and 4,439 (36.8%) men) were included in our study. For fractures, 806 (10.6%) and 191 (4.3%) low trauma fractures were recorded respectively in women and in men. Mean ADII was -1.23 (+/-3.13) for women and - 0.87 (+/- 3.64) for men. No association was detected between the ADII score and the risk of vertebral fracture (p = 0.21), major osteoporotic fracture (p = 0.93) and any low trauma fracture (p = 0.72) in women nor in men (p = 0.06 for major fracture and p = 0.10 for low trauma fracture) after adjustment for sociodemographic, lifestyle variables and for bone treatments. Conclusion This study in postmenopausal women and men older than 50 years from the general population did not show any association between inflammatory dietary pattern measured using the ADII and the risk of incident low trauma fracture.Cobalt-containing hip prosthesis may cause systemic toxicity due to the release of cobalt from metal-on-metal (MoM) joint arthroplasty into the bloodstream. High cobalt blood levels can lead to a variety of clinical manifestations, mimicking other disorders, especially autoimmune, hematologic, and infectious diseases. Our purpose is to describe a clinical case of cobalt hip prosthesis intoxication mimicking an autoimmune disease, with systemic inflammation signs, arthro-myalgias unrelated to overt synovitis, and multiple autoantibody positivity. A 69-years-old woman presented with a 1-year history of right coxalgia, recurrent fever, arthro-myalgias, mediastinal and right iliac reactive lymphadenopathy. She underwent hip replacement surgery seven years earlier. The physical examination was unremarkable except for right hip pain. Laboratory tests showed markedly increased inflammatory indices and microbiological tests were all negative. Ultrasound-guided arthrocentesis of right hip yielded limpid fluid with negative cultures. Increased cobalt levels in plasma and urine showed metal intoxication. Magnetic resonance imaging with metal artifact reduction sequence (MARS) confirmed a periprosthetic mass as usually seen in reaction to metal debris. Prosthesis substitution was performed with a resolution of the clinical picture and normalization of cobalt levels.Background Functional restoration programs (FRPs) are integrative programs to improve function in chronic low back pain (cLBP). They are costly and time-consuming. The aim was to assess the effectiveness of a condensed FRP (CFRP) for patients with cLBP in professional activity. Methods Longitudinal 3 months study of patients with cLBP in one tertiary care hospital, participating in a CFRP over 4 separate days. The primary outcome was the Oswestry Disability Index (ODI). Secondary outcomes included pain, quality of life (EQ5D), patient acceptable symptom state, presenteeism, absenteeism and psychological distress. Outcomes were compared using paired sample Student's t-test or Chi2 between baseline and last follow-up. Logistic regression was used to identify factors associated with better response (improvement of ODI higher than 12.8). Results In all, 193 patients were analysed, mean age 44.6 (standard deviation (SD) 10.4) years, mean cLBP duration 9.0 (SD 8.8) years. A small improvement was observed for ODI (mean difference -5.9, 95% confidence interval -7.6, -4.1), as well as most other outcomes. Multivariate analysis showed an association between ODI improvement and higher duration of low back pain (odds ratio for 5 years 1.41 (1.06,1.88)) and lower baseline back strength (Sorensen, odds ratio for 1 minute 0.54 (0.29,0.99)). Conclusion this CFRP showed small effect to improve function, pain and other quality of life, in cLBP. Four-day programs may be an interesting option in cLBP patients still in professional activity for whom a long 1-month FRP is difficultly manageable. Further studies with randomized controlled designs are needed to confirm the benefits.Leishmaniasis is one of the major global endemic diseases. Among all the different forms of the disease, cutaneous Leishmaniasis has the highest prevalence worldwide. Treatment with current drugs has not had a significant effect on the improvement of the disease. An attempt to replace an appropriate vaccine that can stimulate host cellular immunity and induce the response of Major histocompatibility complex I (MHCI) and Major histocompatibility complex II (MHCII) against Leishmania is essential. Vaccine production remains a challenge despite the use of different antigens for vaccination against Leishmania major. Hence, we were used the immunoinformatics approach to design a new multi-epitope vaccine against L. major using immunogenic outer membrane proteins. Helper T-lymphocyte (HTL) and Cytotoxic T lymphocyte (CTL) epitopes were predicted and for final confirmation of the selected epitopes, docking analysis, and molecular dynamics simulation was performed. link3 Then, GDGDG linker and profilin adjuvant were added to enhance the immunity of vaccines. The designed vaccine was evaluated in terms of molecular weight, PI, immunogenicity, and allergenicity. Moreover, the secondary and three-dimensional structure of the final construct was identified. In silico cloning approach was carried out to improve expression of the vaccine construct. Finally, molecular docking, followed by molecular dynamic was performed to determine the interaction between multi-epitope vaccine and TLR11. We hope that the designed vaccine can be a good candidate for the development of cutaneous leishmaniasis vaccine. but its effectiveness should be assessed in vivo.SUVN-G3031 is a potent and selective inverse agonist of Histmine-3 (H3) receptor that is being investigated for the treatment of narcolepsy. SUVN-G3031 has high passive permeability, not a substrate for P-glycoprotein, has high plasma unbound fractions and was equally distributed between blood and plasma. Major routes of metabolism in vitro were cyclization (Metabolite A) in microsomes and dealkylation (Metabolite D) in hepatocytes. Intrinsic clearance in liver microsomes and hepatocytes was low as monitored by metabolite formation approach. CYP3A4 and MAO-A were the major enzymes involved in the formation of metabolite A and metabolite D respectively. The human hepatic clearance estimated by well-stirred model from hepatocytes was low (2.7 L.h-1) illustrating the importance of metabolite formation kinetics for prediction of human clearance for SUVN-G3031. Renal clearance in humans (9.7 L.h-1) was predicted from dog renal clearance and accounts for ∼78% of the total clearance. SUVN-G3031 was neither an inhibitor nor inducer of the P450 enzymes at clinically relevant concentrations. SUVN-G3031 did not inhibit the major uptake transporters and was not a substrate for the uptake transporters. The potential of SUVN-G3031 as a victim and perpetrator of drug-drug interactions is remote. The predicted human pharmacokinetic parameters were consistent with those observed in the first-in-human study.The coumarins are heterocyclic compounds belonging to the class of benzopyrone enriched in various plants like tonka beans. Coumarins and their derivatives exert a vast array of bioactive properties such as anticoagulant, antibacterial, anti-inflammatory, antioxidant, antitumor, antiviral, and enzyme inhibition. Higher doses of coumarin are found to be hepatotoxic however they exhibit beneficial effects by reducing the risk of cancer and other neuronal and cardiovascular ailments. Most of these effects can be attributed to their free radical scavenging effects. Coumarins such as umbelliferone, esculetin and quercetin show antioxidant properties and protect the cellular DNA from oxidative damage. The dicumarol shows anticoagulant properties by inhibiting the action of vitamin K, whereas angelmarin has been reported to be cytotoxic in pancreatic cancer. Coumarins also reduce edema and inflammation by inhibiting the prostaglandins biosynthesis. Hydroxyl aromatic substituted derivatives such as 5-hydroxycoumarin or vicinal dihydroxy coumarins have also been found to be potent anti-inflammatory agents.