Search

In gout research, serum urate has been widely accepted as the primary endpoint in clinical trials of urate-lowering therapies by both the FDA and EMA for many years. However, for serum urate to be a meaningful outcome measure, it should reflect at least one important patient-centered clinical outcome, such as gout flares. The relationship between achieving a pre-specified "target" serum urate and a corresponding improvement in patient-centered outcomes has been difficult to show due to variation in reporting of both serum urate and gout flares in clinical trials; a paradoxical rise in gout flares after starting urate-lowering therapy and a delay after achieving the pre-specified target serum urate before gout flares settle coupled with the relatively short duration of the trials. However, recent evidence from individual-level patient data from two, two-year randomized controlled trials clearly shows that achieving target urate is associated with a subsequent reduction and cessation of gout flares. In this review, we examine the evidence supporting serum urate as a surrogate outcome for gout flares, the methods, and the challenges of showing the validity of surrogacy. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study is to investigate the relationship between joint inflammation and damage of the wrists and hands, measured by semiquantitative ultrasound and magnetic resonance imaging scoring systems, with functional disability and handgrip strength (HGs)., Materials and Methods: Consecutive adult RA patients with active disease, as defined by a Disease Activity Score 28 joints C-reactive protein (DAS28-CRP) > 3.2, underwent a cross-sectional evaluation comprehensive of a clinimetric assessment, an HGs evaluation, an ultrasound assessment aimed at calculating the UltraSound-CLinical ARthritis Activity (US-CLARA), and a magnetic resonance imaging scored according to the modified Simplified Rheumatoid Arthritis Magnetic Resonance Imaging Score (mod SAMIS). The Spearman's rho correlation coefficient was used to test the correlations., Results: Sixty-six patients with RA were investigated (age 55.6 ± 12.2 years). The mod SAMIS total score and the US-CLARA had a weak but significant correlation (rho = 0.377, p = 0.0018). Among the mod SAMIS sub-scores, there was a significant relationship between mod SAMIS bone edema (SAMIS-BME) and US-CLARA (rho = 0.799, p < 0.001) and mod SAMIS synovitis (SAMIS synovitis) and US-CLARA (rho = 0.539, p < 0.001). There were also significant negative relationships between the HGs score and the mod SAMIS total score and US-CLARA (rho = - 0.309, p = 0.011 and rho = - 0.775, p < 0.0001, respectively)., Conclusions: BME and synovitis have an influence on the function of the upper extremities. The US-CLARA and the mod SAMIS total score are intriguing options for semiquantitative assessment of joint inflammation and damage in RA., (© 2022. The Author(s).)

Rheumatoid arthritis (RA) is a potentially devastating disorder associated with increased risk of fractures, but current studies do not completely evaluate the RA fracture risk profile. This study estimates fracture incidence by site of fracture and makes comparisons between RA and controls using the key variables gender, age, and comorbidities., Background: Rheumatoid arthritis RA is a potentially devastating osteoimmunological disorder, predisposing to osteoporosis (OP), fragility fracture (FF), and major osteoporotic fractures (MOF). As few studies incorporate statistical matching, comorbidity and non-MOF sites, we compared the incidence of first FF, MOF, and non-MOF in RA patients with a matched control cohort adjusting for comorbidities., Methods: This longitudinal cohort study uses routinely collected administrative data from the West Australian Rheumatic Disease Epidemiological Registry (WARDER) between 1980 and 2015. RA patients, as defined using International Classification of Disease (ICD) codes, were compared to hospitalised patients free of rheumatic disease. Case-control matching adjusted for age, gender, and comorbidities (Charlson Comorbidity Index). Incidence rates (IR) per 1000 person years (PY) with 95% confidence intervals (CI) were compared by incidence rate ratios (IRR)., Findings: In RA patients from 2000 to 2010, the first fracture IR was 18.3 (15.7-21.2) for an IRR of 1.32 (1.10-1.60). Upper limb, lower limb, and axial IR were 5.56 (95% CI 4.18-7.26), 10.60 (95% CI 8.66-12.87), and 2.47 (95% CI 2.58-3.68) with IRR of 1.18 (95% CI 0.84-1.65), 1.44 (95% CI 1.19-1.86), and 1.01 (95% CI 0.61-1.63) respectively. The first fracture IR increased 6 years before first RA hospital record (RR 1.58, CI 1.05-2.39)., Conclusions: After age, gender, and comorbidity adjustment, RA is associated with a 32% higher incidence of first fracture, increased MOF, and a fracture incidence that is already increased before a first recorded RA diagnosis. This suggests a need for early attention to prevention of all fractures in RA patients., Competing Interests: Declarations Consent to participate For this type of study, formal consent is not required. Conflicts of interest None., (© 2024. Crown.)

Objectives: To evaluate the risk of liver fibrosis and associated factors with the non-invasive fibrosis score-4 (FIB-4) index in patients with inflammatory arthritis using methotrexate (MTX)., Methods: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who were followed up in the rheumatology outpatient clinic, who were on methotrexate only and for whom FIB-4 index was could be calculated at methotrexate initiation and follow-up were included. The FIB-4 index was calculated according to the following formula: age (years) × AST(IU/L)/(platelet count(10 (9)/L) × √ALT(IU/L)). The patients' demographics, comorbidities, other treatments, cumulative MTX dose, and reasons for MTX cessation were assessed. For the multivariate analysis, possible factors associated with intermediate-high risk FIB-4 index at last visit were determined., Results: A total of 107 patients were enrolled in the study, of whom 82 (76.6%) had RA and 25 (23.4%) had PsA. At the initiation of MTX, 24 (22.4%) patients had intermediate-high risk FIB-4 index. Comorbidities and the rate of ≥3-4 Charlson comorbidity index were more common in patients with intermediate-high risk FIB-4 index. A total of 37 (34.5%) patients had intermediate-high risk FIB-4 index at the last visit after median 3.6 (0.3-22.06) years follow-up. The median cumulative MTX dose was 2550 mg (1050-13.991). Cumulative MTX dose [OR 1.18 (1.01-1.33), p = .03] and diabetes mellitus [OR 4.60 (1.74-12.50), p = .002] were associated factors with intermediate-high risk FIB-4 index. The concomitant use of hydroxychloroquine (HCQ) was found to be a low-risk factor for FIB-4 index [OR 0.28 (0.10-0.78) p = .015]., Conclusion: The FIB-4 index is a non-invasive method that can be used in daily rheumatology practice for the evaluation and follow-up of patients who will use methotrexate. Comorbidities and cumulative MTX dose seem to be related with the risk of liver fibrosis. Concomitant use of HCQ with MTX may reduce the risk of liver fibrosis., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect. This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves cytokines in its pathogenesis. This study is aimed at investigating if gene polymorphisms in cytokines like IL-17, IL-4, IL-6, and IL-12 affect RA susceptibility and severity in the Bangladeshi population. This was a cross-sectional comparative study that included 40 diagnosed RA patients according to the American College of Rheumatology (ACR) criteria 2010, who were free from other rheumatological diseases, and 40 healthy subjects for comparison. The study used PCR-RFLP to determine the IL-17, IL-4, IL-6, and IL-12 cytokine gene polymorphisms. Patients had a mean age of 37.22 ± 6.70 years. Among the patients, 31 were female and 9 were male. The mean disease duration was 18.11 ± 7.39 months. The study found that rheumatoid arthritis patients with the IL-17F (7488 A/G) polymorphism with GG genotype (P = 0.006 , OR = 8.56 , 95% CI = 1.77 − 41.33) and IL-12B (1188 A/C) polymorphism with AC (P = 0.012 , OR = 3.69 , 95% CI = 1.43 − 9.53) and CC (P = 0.013 , OR = 7.58 , 95% CI = 1.56 − 36.88) genotypes were significantly associated with disease risk. Furthermore, patients with the IL-17F (7488) GG genotype and IL-12B (1188) AC and CC genotypes had higher rheumatoid arthritis disease severity and activity parameters. The study found no significant association between polymorphisms involving IL-4 (590 C/T) and IL-6 (174 G/C) genes and rheumatoid arthritis disease risk in the Bangladeshi population. Gene polymorphisms in cytokines IL-17F (7488 A/G) and IL-12B (1188 A/C) can predict disease susceptibility and severity in Bangladeshi rheumatoid arthritis patients. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis (OA) is a chronic secondary musculoskeletal pain condition resulting in disability, reduced quality of life, and high societal costs. Pain associated with knee OA is linked to increased sensitivity in sensory, cognitive, and emotional areas of the brain. Self-regulation training targeting brain functioning related to pain experience could reduce pain and its associated disability. Self-regulatory treatments such as mindfulness meditation (MM) and electroencephalography neurofeedback (EEG-NF) training improve clinical outcomes in people with knee OA. A feasibility clinical trial can address factors that could inform the design of the full trial investigating the effectiveness of self-regulation training programmes in people with knee OA. This clinical trial will evaluate the feasibility, safety, acceptability, experience and perceptions of the self-regulatory training programmes. Methods: The proposed feasibility trial is based on a double-blind (outcome assessor and investigators), three-arm (MM usual care, EEG-NF + usual care and usual care control group) randomised controlled parallel clinical trial. Participants with knee OA will be recruited from the community and healthcare practices. A research assistant (RA) will administer both interventions (20-min sessions, four sessions each week, and 12 sessions over three successive weeks). Feasibility measures (participant recruitment rate, adherence to interventions, retention rate), safety, and acceptability of interventions will be recorded. An RA blinded to the group allocation will record secondary outcomes at baseline, immediately post-intervention (4th week), and 3 months post-intervention. The quantitative outcome measures will be descriptively summarised. The qualitative interviews will evaluate the participants' experiences and perceptions regarding various aspects of the trial, which includes identifying the barriers and facilitators in participating in the trial, evaluating their opinions on the research procedures, such as their preferences for the study site, and determining the level of acceptability of the interventions as potential clinical treatments for managing knee OA. Māori participant perceptions of how assessment and training practices could be acceptable to a Māori worldview will be explored. The interviews will be audio-recorded and analysed thematically. Discussion: This trial will provide evidence on the feasibility, safety, and acceptability of the MM and EEG-NF training in people with knee OA, thus informing the design of a full randomised clinical control trial. [ABSTRACT FROM AUTHOR]

Background: Worldwide, > 1.3 million adults are diagnosed with a gynecologic cancer each year, affecting their wellbeing and quality of life. This manuscript describes the protocol for a study that sought to assess the feasibility, acceptability, and fidelity of a community-based co-created yoga program and proposed evaluative methods, and estimate program effects on self-reported outcomes. Methods: Using a multiple baseline single-subject research design with a follow-up phase (ABA), quantitative and qualitative data were collected from program participants and the instructor. Participants were randomly assigned to varying baseline lengths and completed weekly surveys for 3–5 weeks pre-program. Then, participants engaged in a bi-modal 12-week hatha yoga program consisting of 2 60-min group classes a week, with optional supplemental features (January–April, 2023). Participants completed surveys after classes 1, 12, and 24. All yoga classes were audio- and video-recorded. Post-program, participants completed surveys 1, 4, and 8 weeks after the last class and took part in a semi-structured interview 1 week after to discuss program acceptability, suitability, relevance, and potential benefits. Feasibility outcomes (i.e., recruitment, retention, and program adherence rates, engagement with optional program features) were tracked by the instructor assistant and study team during the study. The yoga instructor was interviewed about their experience delivering the program 2 weeks after the last class. Planned analysis: Feasibility outcomes will be analyzed using descriptive statistics. Interview transcripts will be coded using reflexive thematic analysis. Class recordings will be coded using duration and frequency coding. Survey responses for self-reported outcomes will be analyzed visually and using multilevel modeling. Expected outcomes: Data will help determine refinements, if any, required to the program and instructor guidebook, implementation approach, and proposed evaluation methods before scale-up projects and definitive trials are started. Trial registration: ClinicalTrials.gov NCT05610982. November 3, 2022. [ABSTRACT FROM AUTHOR]

The present work used the electrical resistivity approach to conduct a three-dimensional modeling and initial volume estimation of the limestone layer in the Mintom region located in southern Cameroon. In order to achieve the objectives of the study, a total of 21 electrical soundings spaced 250 m were first collected in the field using the Schlumberger array. These soundings were conducted along three profiles oriented in an east-west direction, spaced 500 m. Additionally, a geological survey was conducted to identify and emphasize the presence of limestone formations within the designated study region. The interpretation of the sounding data was conducted based on the analysis of the sounding curves. The interpretation outcomes, specifically resistivity and thickness, were compared with the geological field data, resulting in the development of lithostratigraphic logs for each sounding. The geological sections were constructed using the logs of the designated profile. The lithological logs were utilized to establish a lithological interface model and calculate the volume of the limestone layer at 260 ± 13 × 106 m3, utilizing the inverse distance method built into RockWorks software. A resistivity value is assigned to each geological layer in a sounding curve, allowing for the development of a resistivity variation model specific to the limestone layer. The proposed model facilitates the categorization of limestone layers based on their resistivity variations, thus serving as a fundamental reference for prospective exploratory activities within the designated study region. Our integrated approach provides a replicable model for a better understanding of the limestone reserve and effective management of this valuable resource. [ABSTRACT FROM AUTHOR]

Objective: Developing and evaluating new treatment guidelines for rheumatoid arthritis (RA) based on observational data requires a quantitative understanding of patterns in current treatment practice with biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs). Methods: We used data from the CorEvitas RA registry to study patients starting their first b/tsDMARD therapy, defined as the first line of therapy, between 2012 and the end of 2021. We identified treatment patterns as unique sequences of therapy changes following and including the first‐line therapy. Therapy cycling was defined as switching back to a treatment from a previously used therapeutic class. Results: A total of 6015 b/tsDMARD‐naïve patients (77% female) were included in the analysis. Their median age was 58 years, and their median disease duration was 3 years. In 2012–2014, 80% of the patients started a tumor necrosis factor inhibitor (TNFi) as their first b/tsDMARD. However, the use of TNFi decreased in favor of Janus kinase inhibitors since 2015. Although the number of treatment patterns was large, therapy cycling was relatively common. For example, 601 patterns were observed among 1133 patients who changed therapy at least four times, of whom 85.3% experienced therapy cycling. Furthermore, the duration of each of the first three lines of therapy decreased over the past decade. For example, the median duration of the first‐line therapy was 153 days in 2018–2021 compared to 208 days in 2015–2017 (P < 0.001). Conclusion: First‐line therapy was almost always TNFi, but diversity in treatment choice was high after that. This practice variation allows for proposing and evaluating new guidelines for sequential treatment of RA. It also presents statistical challenges to compare patients with different treatment sequences. [ABSTRACT FROM AUTHOR]

The treatment of a patient with juvenile idiopathic arthritis (JIA) is best monitored with standardized and validated tools to measure joint changes over time. Treatment approaches are best indicated if the clinicians are aware of the structural status of the joint at a given time, especially in anatomically deep joints for which clinical assessment is limited. Magnetic resonance imaging (MRI) is of utmost importance for assessment of deep joints and extra-articular soft tissue of the entire body for which ultrasound may be suboptimal. Because the distinction between pathologic and physiologic joint changes on MRI is key for proper diagnosis and treatment of patients with arthropathies, a comprehensive standardized approach is needed to effectively measure outcomes of growing joints of children with JIA. Such an approach is essential for both clinical assessment and to conduct clinical trials in patients with JIA treated in different centers around the world. To meet this need, several international imaging collaborative research groups have been developing MRI scales over the past years, including the MRI in JIA (JAMRI) special interest group within the Outcome Measures in Rheumatology (OMERACT) research network. This manuscript reviews the efforts of the OMERACT JAMRI working group to generate and validate pediatric MRI scoring systems for different joints in children with JIA that can have ubiquitous utilization anywhere in the world. In particular, it describes the different steps of development and validation of an MRI scale using the TMJ as a model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Knee pain is the main symptom of knee osteoarthritis. Walking is effective against knee pain, and some studies have shown that gait modification can also relieve this condition. However, the quality of evidence for the clinically significant effects of gait modification on knee pain has not been examined. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the level of evidence for the clinically significant effects of gait modification on knee pain and determine if the effects are greater than the minimal clinically important difference (MCID). METHODS: We comprehensively searched electronic databases such as MEDLINE, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, and Cumulative Index to Nursing and Allied Health Literature. Intervention studies with experimental groups who received gait modification and control groups who did not were evaluated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the level of evidence. RESULTS: Nine studies met the inclusion criteria. All were included in the systematic review and two in the meta-analysis. Results showed that gait modification have significant effects (p = 0.02), and the quality of evidence was very low. However, several studies have revealed that the effects of gait modification, when used as a foot-focused intervention, were greater than the MCID. CONCLUSIONS: We concluded that there is a lack of high-quality evidence that supports the general efficacy of gait modification. Although based on low-quality evidence, when applied to the foot, it may have clinically significant effects. [ABSTRACT FROM AUTHOR]

Cardiometabolic risk factors have been shown to decrease biologic efficacy in patients treated for inflammatory conditions. The purpose of this systematic review is to provide a qualitative evaluation of studies investigating biologic response among psoriasis patients with cardiometabolic comorbidities. Methods: A comprehensive review was conducted according to the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analysis guidelines to screen for studies including patients with cardiometabolic risk factors receiving biologic therapy for psoriasis. Studies not including a Psoriasis Area and Severity Index (PASI) score to evaluate treatment outcomes were not included. All studies underwent quality/bias analysis using the Methodological Index for Non-Randomized Studies (MINORS) scale. Results: Obesity and Body Mass Index (BMI) were the most studied cardiometabolic risk factors. The majority of the studies reported a lower frequency of achieving PASI75 and PASI90 response with increasing BMI/obesity rates. Diabetes and hypertension showed similar findings but were not studied as frequently. Hyperlipidemia and other lipid disorders were less frequently studied. Conclusion: Relationships between cardiometabolic risk factors and lower frequencies of achieving PASI75/90 exist in current literature. This qualitative systematic review reports evidence of lower PASI75 and PASI90 response rates in the presence of cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

The article discusses how digitization in libraries, museums, and archives (LAM) can become more democratic. Digitization within LAM scholarship has been seen historically as a democratic act because it provides universal access to cultural heritage content, breaks down authoritative narratives, and enables participation from users. The article critiques the misconception that online collections democratize artifact information for public consumption and explores the ways in which LAM institutions fall short of living up to their democratic ideals when it comes to digital collections projects. Inspired by others with similar critiques, the authors discuss how LAM institutions can better fulfill the ideal of accessible and equitable access to their collections. The article emphasizes the importance of five areas of digital collections projects: system design, metadata practices, digitization selection and prioritization, labor, and user participation and engagement. The widespread misconception that digitization and digital collections are democratizing is a result of institutional biases that have masked undemocratic processes and systems which the authors strive to expose. [ABSTRACT FROM AUTHOR]

Introduction: Ankylosing spondylitis (AS) is a chronic condition that requires lifelong treatment and results in a serious disease burden. Health state utility values (HSUVs) are a valuable tool for quantifying this burden and conducting cost-utility analysis., Objective: We conducted a systematic review and meta-analysis to obtain estimates of HSUVs in patients with AS, explored potential sources of heterogeneity, and compared pooled patient HSUVs with population norms., Method: We searched PubMed, Embase, Web of science, Cochrane database and Scopus until July, 2023 to obtain eligible studies. The methodological quality of the included studies was assessed using the ROBINS-I checklist., Results: Forty-two publications involving 11,354 participants were included in this systematic review. The most commonly used instrument is the EQ-5D (38 studies). The estimated HSUVs for patients with AS from all available studies was pooled as 0.62 (95% CI 0.59 to 0.65). The pooled mean utility estimates from the random effects meta-analysis for SF-6D, EQ-5D-3L, EQ-5D-5L, and HUI3 were 0.65 (95% CI 0.62,0.68), 0.63 (95% CI 0.59,0.66), 0.60 (95% CI 0.42,0.79), and 0.48 (95% CI 0.43,0.53), respectively. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression based on key subgroups. The pooled estimates of EQ-5D-3L were lower for patients published before 2010, with high disease activity, long duration of disease, and in developed countries., Conclusion: Pooled estimates of HSUVs for people with AS were substantially lower than population norms. These estimates provide robust evidence that can inform the economic evaluation of new therapies for individuals with AS., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Theory and research indicate that coping plays a central role in the experience of psychological distress in people with rheumatoid arthritis (RA). This study meta-analysed the associations of adaptive and maladaptive coping strategies with psychological distress in people with RA to quantify and better understand the proposed differential relationships, as well as the factors that might influence these links., Methods: Searches of four databases identified eligible studies according to a pre-registered protocol. Two random effects meta-analyses examined the direction and magnitude of the links between adaptive coping (problem-focused and emotional approach coping) and maladaptive coping (emotional avoidance and pre-occupation coping) and psychological distress (stress, anxiety, and depression). Study quality was evaluated using a bespoke tool. Moderator analyses for sample characteristics and distress type were conducted., Results: Searches identified 16 eligible studies with 46 effects. Meta-analysis of maladaptive coping and distress yielded a significant, medium sized association, k = 12, r = .347, 95% CIs [.23, .46]. Moderator analyses were significant only for type of distress, with effects for depression being larger than that for combined distress. Effects did not vary as a function of age, participant sex, or disease duration. Meta-analysis for adaptive coping was not significant, k = 10, r = -.155, 95% CIs [-.31, .01]., Conclusions: Findings from this first meta-analysis of coping and distress in RA indicate that maladaptive but not adaptive coping is associated with greater distress. Further research is needed to grow the evidence base to verify the current findings especially with respect to adaptive coping., (© 2024 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune etiology. Increased scientific evidence suggests that immune-mediated inflammatory dis-eases are associated with autonomic nervous system (ANS) dysfunction. Studies proved that autonomic imbalance is correlated with RA evolution and may explain augmented cardiovascular pathology and mortality not attributable to classical risk factors. (2) Methods: 75 patients (25 males, 50 females) with RA were submitted to standard ECG recording and 24 h Holter monitoring. Twenty-five healthy patients were used as controls. Both time (SDNN, SDANN, SDANN Index, RRmed, rMSSD, and pNN50) and frequency domain (TP, VLF, HF, LF and LF/HF) heart rate variability (HRV) parameters were obtained. Parameters were compared to controls, and correlations with the QTc-interval and inflammatory status expressed through the C-reactive protein (CRP) were evaluated. (3) Results: In patients with a CRP > 5 mg/L, HRV parameters were lower compared to controls and to patients with a CRP ≤ 5 mg/L. All HRV parameters generated by Holter monitoring are negatively correlated with CRP levels and QTc values. The number of premature ventricular contractions (PVC) recorded is correlated with SDNN, SDANN, and LF/HF values. (4) Conclusions: Our study supports recent data suggesting that in RA there is an autonomic system dysfunction strongly connected with the inflammatory status of the patient. The autonomic dysfunction can contribute to the increased risk of cardiovascular death observed in patients with RA. [ABSTRACT FROM AUTHOR]

The present work is a comparative study of sand mortars from various geological origins to highlight their influence on mortar qualities. Five different sands and the cement CEM II/B–P 42.5R were used to produce mortars with similar water/cement ratios (W/C). These are the "Sanaga" sand from the Sanaga River, the "Wouri" sand from the Wouri River, the Nyambaka basalt sand, the Meiganga granite sand, and the Leboudi gneiss sand. The physical, chemical, and mineralogical features of these sands were used to characterize and classify them. They were then used to formulate mortars, which were analyzed and compared. According to the results of the mortar setting time tests, the initial setting time ranges from 195 minutes for Sanaga sand mortar (MS04) to 210 minutes for gneiss sand mortar (MGN03), passing Wouri sand mortar (MW05) with 200 minutes, basalt sand mortar (MB01) with 198 minutes, and granite sand mortar (MGR02) with 196 minutes. The final setting time ranged from 496 minutes (MGR02) to 510 minutes (MGN03), with an average of 300 minutes added to the initial setting time. The flexural strength tests of the mortars reveal that crushed sands outperform alluvial sands. They range from 1.64 to 2.18 MPa after 2 days, 3 to 3.90 MPa after 7 days, and 7 to 14.84 MPa after 28 days. The results of the compressive strength tests show that quarry sand mortars have greater average compressive strengths than alluvial sand mortars, with basalt sand providing the greatest performance. These strengths range from 6.35 to 10.83 MPa after 2 days, 7.55 to 18.96 MPa after 7 days, and 22.81 to 34.58 MPa after 28 days, with the MB01 being the best sand. These findings reveal that the geological origin of sands, which specifies certain of their physicochemical and mineralogical attributes, has an impact on the properties of mortars. This impact is also influenced by granulometry and organic matter concentration. [ABSTRACT FROM AUTHOR]

Background. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic, progressive inflammatory diseases that can be accompanied by other diseases. In recent years, with the increase in the lifespan of individuals, the concept of polypharmacy has become more prominent. We aimed to show the prevalence of polypharmacy and the effects of polypharmacy on disease activity in RA and PsA. Methods. This study included PsA patients who had peripheral joint involvement and, RA patients. Since PsA has a heterogeneous clinical picture, only patients with peripheral joint involvement were included in the study and patients with inflammatory low back pain or radiological sacroiliitis or spondylitis, dactylitis or enthesitis were not included in the study due to homogeneity concerns. The numbers of medications used by the patients at the onset of their treatment and at sixth months into their treatment were recorded. Polypharmacy was accepted as the simultaneous use of at least five medications by the person. The Disease Activity Score 28 joints C-Reactive Protein (DAS-28 CRP) was used to assess disease activity for both disease. The modified Charlson Comorbidity Index (CCI) scores of the patients were calculated based on their chronic diseases. Results. The sample of the study included 232 RA and 73 PsA patients. Polypharmacy was present at the treatment onset in 115 (49.6%) of the RA patients and 28 (38.4%) of the PsA patients. At the sixth month of treatment, polypharmacy was present in the sixth month of the treatment in 217 (93.5%) RA and 61 (83.6%) PsA patients. The mean ages of the RA and PsA patients who were receiving polypharmacy treatment at the beginning were significantly older than the mean ages of those who were not receiving polypharmacy treatment. In both the RA and PSA groups, the patients with polypharmacy at the beginning had statistically significantly higher DAS-28 CRP scores at six months of treatment than those without polypharmacy at the beginning (p<0:001). Conclusion. Polypharmacy was present both at the time of diagnosis and in the treatment process in the RA and PsA patients, and the presence of polypharmacy at the beginning of the treatment was among the factors that affected the treatment of these patients by significantly affecting their 6th-month DAS-28 CRP values. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA. Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review. Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRING-MODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors. Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data? SUMMARY ANSWER Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways. WHAT IS KNOWN ALREADY Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data. STUDY DESIGN, SIZE, DURATION Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17 786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause. MAIN RESULTS AND THE ROLE OF CHANCE In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P  < 0.001), 1.62 times for antral follicular count <5 (P  < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P  < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13–1.49, P  < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways. LIMITATIONS, REASONS FOR CAUTION The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population. WIDER IMPLICATIONS OF THE FINDINGS Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25–28 June 2023 (Poster number: P-477). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Observational studies have found an increased risk of stroke in patients with spondyloarthritis, but the results are susceptible to reverse causality and confounders. Therefore, the study aimed to further explore the association between spondyloarthritis and different subtypes of stroke by using a two sample Mendelian randomization (MR) analysis. Methods: Genetic instrumental variables for spondyloarthritis were identified using summary level data from a genome-wide association study involving 201,581 people. Summary statistics fromtheMultiancestry Genome-wide Association Study of Stroke Consortium were used to obtain genetic data on stroke. There was no sample overlap between the exposure and outcome datasets. Inverse-variance weighted was considered the primary MR method for causal analysis. Heterogeneity, pleiotropy and sensitivity analyses were performed to ensure robustness, and single nucleotide polymorphism (SNP) with potential confounders was further screened in the PhenoScanner database to better evaluate the stability of our study. Results: One SNP (rs1065045) was excluded due to schizophrenia. After excluding SNP (rs1065045), results of the second MR analysis were slightly different from the first, which were considered as the final result: a significant positive causality between spondyloarthritis and cardioembolic stroke (OR=1.296, 95% CI:1.094-1.534, p=0.003); a possible positive causality between spondyloarthritis and any stroke (OR=1.082, 95% CI:1.016-1.152, p=0.013)/any ischemic stroke (OR=1.086, 95% CI:1.013-1.163, p=0.020); no significant/possible causality between spondyloarthritis and small vessel stroke (OR=1.168, 95% CI:0.993-1.375, p=0.061). Insufficient power may be one possible reason why a causality was not observed between spondyloarthritis in our study. Conclusions: This study suggests that the possible causative effects of spondyloarthritis predicted by genetics on stroke may be limited to any stroke, any ischemic stroke, and cardioembolic stroke, especially the last. [ABSTRACT FROM AUTHOR]

Hyperuricemia with consequent monosodium urate crystal deposition leads to gout, characterized by painful, incapacitating inflammatory arthritis flares that are also associated with increased cardiovascular event and related mortality risk. This narrative review focuses on emerging pharmacologic urate-lowering treatment (ULT) and management strategies in gout. Undertreated, gout can progress to palpable tophi and joint damage. In oral ULT clinical trials, target serum urate of < 6.0 mg/dL can be achieved in ~ 80–90% of subjects, with flare burden reduction by 1–2 years. However, real-world ULT results are far less successful, due to both singular patient nonadherence and prescriber undertreatment, particularly in primary care, where most patients are managed. Multiple dose titrations commonly needed to optimize first-line allopurinol ULT monotherapy, and substantial potential toxicities and other limitations of approved, marketed oral monotherapy ULT drugs, promote hyperuricemia undertreatment. Common gout comorbidities with associated increased mortality (e.g., moderate–severe chronic kidney disease [CKD], type 2 diabetes, hypertension, atherosclerosis, heart failure) heighten ULT treatment complexity and emphasize unmet needs for better and more rapid clinically significant outcomes, including attenuated gout flare burden. The gout drug armamentarium will be expanded by integrating sodium-glucose cotransporter-2 (SGLT2) inhibitors with uricosuric and anti-inflammatory properties as well as clinically indicated antidiabetic, nephroprotective, and/or cardioprotective effects. The broad ULT developmental pipeline is loaded with multiple uricosurics that selectively target uric acid transporter 1 (URAT1). Evolving ULT approaches include administering selected gut anaerobic purine degrading bacteria (PDB), modulating intestinal urate transport, and employing liver-targeted xanthine oxidoreductase mRNA knockdown. Last, emerging measures to decrease the immunogenicity of systemically administered recombinant uricases should simplify treatment regimens and further improve outcomes in managing the most severe gout phenotypes. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). Methods: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. Results: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. Conclusions: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX. [ABSTRACT FROM AUTHOR]

Diagnosis of hip osteoarthritis (OA) is based on clinical arguments, and medical imaging is obtained to confirm the diagnosis and rule out other possible sources of pain. Conventional radiographs are recommended as the first line imaging modality to investigate chronic hip pain. They should be obtained in a rigorous technique that includes an antero-posterior (AP) radiograph of the pelvis. The choice of the appropriate lateral view depends on the clinical indication, Lequesne's false profile being valuable in the assessment of OA. Magnetic resonance imaging (MRI) is more sensitive to detect joint effusion/synovitis, cartilage, labral, and bone marrow lesions. However, structural joint changes are frequent in asymptomatic population and neither radiographs nor MRI have shown a good correlation with pain and functional impairment. MRI seems to be more suitable than radiographs as a biomarker for clinical trials addressing early OA. The absence of a validated MR biomarker of early OA, together with issues related to machine availability and MRI protocol repeatability, prevent the widespread use of MRI in clinical trials. [ABSTRACT FROM AUTHOR]

Key recommendations: In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature.Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C]Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C]Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C]Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D]Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP]Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B]Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C]Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C]Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2, smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D]For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B]There are currently insufficient data to support the routine use of PGT‐A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C]Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C]Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A]Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B]Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C] [ABSTRACT FROM AUTHOR]

Objective: Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination. Although ultrasonography (US) allows for discrimination of the 2 entities, only definitions and scoring of synovitis in children have been established. This study was undertaken to produce consensus‐based US definitions of tenosynovitis in JIA. Methods: A systematic literature search was performed. Selection criteria included studies focused on US definition and scoring systems for tenosynovitis in children, as well as US metric properties. Through a 2‐step Delphi process, a panel of international US experts developed definitions for tenosynovitis components (step 1) and validated them by testing their applicability on US images of tenosynovitis in several age groups (step 2). A 5‐point Likert scale was used to rate the level of agreement. Results: A total of 14 studies were identified. Most used the US definitions developed for adults to define tenosynovitis in children. Construct validity was reported in 86% of articles using physical examination as a comparator. Few studies reported US reliability and responsiveness in JIA. In step 1, experts reached a strong group agreement (>86%) by applying adult definitions in children after one round. After 4 rounds of step 2, the final definitions were validated on all tendons and at all locations, except for biceps tenosynovitis in children <4 years old. Conclusion: The study shows that the definition of tenosynovitis used in adults is applicable to children with minimal modifications agreed upon through a Delphi process. Further studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background: The present study revealed the grafting of extracted oleo gum resin of Boswellia serrata with polyacrylamide by conventional method with a principle of radical polymerization by using potassium per sulfate/ascorbic acid as redox initiator. A series of copolymer were synthesized using varying concentration of acrylamide at varying temperature. The optimum ratio for grafting was selected (1:2.5), on the basis of percent grafting and grafting efficiency. The grafted gum was further used as a nanocarrier to encapsulate cefuroxime axetil for their sustained release. Then, the nanoparticles were further analyzed by FT-IR, scanning electron microscopy, and DLS. The encapsulation efficiency (%), loading capacity (%) and drug content (%) was also calculated. Result: The optimized nanoparticles have shown spherical morphology with dimension of 209.4 ± 20.46 nm along with entrapment efficiency (62.47 ± 4.23%), loading capacity (33.57 ± 3.01%) and drug content (89.35 ± 6.47%). The prepared nanoparticles had found to be more stable at 4 °C. The experiential results rationalize the effectiveness of cefuroxime axetil-loaded boswellic acid nanoparticles owing to higher cellular uptake, nonstop intercellular drug withholding and improved antiproliferative effect by initiating apoptosis. Conclusion: The significant anti-arthritic effect of developed nanoparticles may be endorsed due to its dimension, encapsulation efficiency, and long-lasting drug release profile. Thus, the developed nanoparticles may assume to be a hopeful formulation for rheumatoid arthritis, which requires further investigation and may recommend a novel track to arthritis patients. [ABSTRACT FROM AUTHOR]

Background: Despite remarkable medical advances in the treatment of rheumatoid arthritis (RA), a subset of patients fails to achieve complete clinical remission, as the Patient Global Assessment (PGA) of disease activity remains above 1, even after the inflammatory process is brought under control. This so-called state of 'PGA-near-remission' negatively impacts individuals' functioning and potentiates inadequate care. Fatigue is a distressing and disabling symptom frequently reported by patients in PGA-near-remission, and its management remains challenging. While classic cognitive-behavioural interventions show some benefits in managing fatigue, there is potential for improvement. Recently, contextual-cognitive behavioural therapies (CCBT), like mindfulness, acceptance, and compassion-based interventions, have shown promising results in fatigue-associated disorders and their determinants. This study primarily aims to examine the efficacy of the Compassion and Mindfulness Intervention for RA (MITIG.RA), a novel intervention combining different components of CCBT, compared to treatment-as-usual (TAU) in the management of RA-associated fatigue. Secondary aims involve exploring whether MITIG.RA produces changes in the perceived impact of disease, satisfaction with disease status, levels of depression, and emotion-regulation skills. Methods: This is a single center, two-arm parallel randomized controlled trial. Patients will be screened for eligibility and willingness to participate and will be assessed and randomized to the experimental (MITIG.RA + TAU) or control condition (TAU) using computer randomization. MITIG.RA will be delivered by a certified psychologist and comprises eight sessions of 2 h, followed by two booster sessions. Outcomes will be assessed through validated self-report measures, including fatigue (primary outcome), perceived impact of disease, depressive symptoms, mindfulness, self-compassion, safety, and satisfaction (secondary outcomes). Assessment will take place at baseline, post-intervention, before the first and second booster sessions (weeks 12 and 20, respectively), and at 32 and 44 weeks after the interventions' beginning. Discussion: We expect MITIG.RA to be effective in reducing levels of RA-associated fatigue. Secondarily, we hypothesize that the experimental group will show improvements in the overall perceived impact of disease, emotional distress, and emotion regulation skills. Our findings will contribute to determine the benefits of combining CCBT approaches for managing fatigue and associated distress in RA. Trial registration: ClinicalTrials.gov NCT05389189. Registered on May 25, 2022. [ABSTRACT FROM AUTHOR]

Advanced head and neck squamous cell carcinoma (HNSCC) patients have been treated with cisplatin (CDDP) chemoradiation, and the variability of treatment effects has been attributed to single nucleotide variants (SNVs) in genes of metabolic pathways. This study investigated the roles of GSTM1, GSTT1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.93G>A, MSH2 c.211+9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-182-247G>T, FAS c.-1378G>A and c.-671A>G and FASL c.-844C>T SNVs in outcome of 109 patients treated with CDDP chemoradiation. Genotypes were identified in genomic DNA by PCR-based methods. Conventional criteria and tests analyzed response and survival. Patients with XPC c.2815AC or CC had 3.43 times more chances of presenting partial response or stable disease. Patients with FAS c.-671GG, GSTM1 present plus XPC c.2815AA, or plus XPD c.934GG, or plus XPD c.2251AA, or plus TP53 c.215GC or CC, and XPD c.2251AA plus XPF c.2505TT had up to 2.70 and 2.37 times more chances of presenting tumor progression and evolving to death, respectively. Our data indicate, for the first time, preliminary evidence that combined SNVs of CDDP metabolism act as independent prognostic factors and can be used to select patients for distinct treatments. [ABSTRACT FROM AUTHOR]

Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an inflammatory disease with a high prevalence of cardiovascular (CV) events due to traditional cardiovascular risk factors and increased systemic inflammation. In this review, our objectives were to (i) evaluate the cardiovascular events and risk factors and (ii) investigate the relationship between autonomic dysfunction and CV diseases in PsA. A systematic review of the literature was done on the Medline/PubMed, Scopus, and the Directory of Open Access Journals databases between January 2017 and July 2022. After screening and exclusions, 73 studies were included for the final review. Patients with PsA have a greater risk of CV diseases and increased traditional CV risk factors, including hypertension, diabetes mellitus, obesity, metabolic syndrome, and dyslipidemia. Although autonomic dysfunction is more common in PsA than in the general population, its relationship with increased CV diseases in these patients is still unclear. Limitations in explaining CV risk in these patient groups complicate patient assessment as cardiovascular risk factors are linked to the morbidity and mortality of PsA, and it is essential to improve an optimal screening and management strategy for CV disease. All CV risk scoring systems cannot fully assess the CV risk in these patients, so in addition to scoring systems, carotid ultrasound evaluation may be a part of the CV evaluation. Key Points • Psoriatic arthritis is associated with an increased risk of cardiovascular disease due to traditional cardiovascular risk factors, increased systemic inflammation, and autonomic system dysfunction, although not fully demonstrated. • The autonomic nervous system is crucial in regulating cardiovascular disease through its effect on the heart, blood vessels, and kidneys. Although the relationship between autonomic dysfunction and cardiovascular diseases has been shown, this relationship is still unclear in PsA. [ABSTRACT FROM AUTHOR]

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters. [ABSTRACT FROM AUTHOR]

Uncontrolled artisanal and semi-mechanized mining activities generate growing pressure on water resources. This work investigated the water quality status and the metal contamination of the Lom River water in the vicinity of gold mining area of Bekao, Adamawa region of Cameroon using water quality index (WQI) and five pollutions indices, supported by multivariate statistical analyses (MSA) that include factor analysis (FA), hierarchical cluster analysis (HCA), and Pearson's correlation analysis. For this purpose, a total of thirty-two (32) water samples were systematically collected in four campaigns during the rainy and dry seasons in order to determine physicochemical parameters, major ions, and trace elements and heavy metals (Cu, Cr, Cd, Pb, Ni, As, Fe, and Hg). The results obtained were compared with (2017) WHO standards. The results indicated that the water samples were acidic to neutral (4.54–7.12), very turbid (583.00–130.99 NTU), and weakly mineralized (27.40–36.12 μS/cm) with high levels of suspended solids (42.21–532.68 mg/L). The predominant water facies was CaMg-HCO3, with no dominant cation and high proportions of bicarbonate. The elements concentration decreased in the following order: Fe ˃ As ˃ Pb ˃ Cu ˃ Cr ˃ Ni ˃ Hg ˃ Cd whereas the mean concentration of Pb, Ni, As, Fe, and Hg exceeded the maximum allowable limits defined by the World Health Organization (WHO) guidelines. The WQI values demonstrated that about 56.25% of samples were unfitted for domestic purposes. The heavy pollution index (HPI), the heavy metal evaluation index (HMEI), and the contamination index (CI) suggested a high level of heavy metal pollution, resulting mainly from gold mining washing and panning processes. Strong correlations (R ≥ 0.70) were observed between PO43−-Cu (R = 0.70), PO43−-Cd (R = 0.73), Ca2+-PO43− (R = 0.72), Ca2+-Cu (R = 0.76), Mg2+-Cu (R = 0.73), Mg2+-Ca2+ (R = 0.78), Cu-Pb (R = 0.73), and Cu-As (R = 0.73). The MSA also allowed to identify anthropogenic activities as the major source of the Lom River water pollution: (i) most of major ions were originated from crops activities and domestic sewage of temporal dwellings of artisans and also from agricultural, and (ii) heavy metals were released mainly from gold mining exploitation activities, especially from washing, panning, and refining steps. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) affects 24.5 million people worldwide and has been associated with increased cancer risks. However, the extent to which the observed risks are related to the pathophysiology of rheumatoid arthritis or its treatments is unknown. Leveraging nationwide health insurance claims data with 85.97 million enrollees across 8 years, we identified 92 864 patients without cancers at the time of rheumatoid arthritis diagnoses. We matched 68 415 of these patients with participants without rheumatoid arthritis by sex, race, age and inferred health and economic status and compared their risks of developing all cancer types. By 12 months after the diagnosis of rheumatoid arthritis, rheumatoid arthritis patients were 1.21 (95% confidence interval [CI] [1.14, 1.29]) times more likely to develop any cancer compared with matched enrollees without rheumatoid arthritis. In particular, the risk of developing lymphoma is 2.08 (95% CI [1.67, 2.58]) times higher in the rheumatoid arthritis group, and the risk of developing lung cancer is 1.69 (95% CI [1.32, 2.13]) times higher. We further identified the five most commonly used drugs in treating rheumatoid arthritis, and the log‐rank test showed none of them is implicated with a significantly increased cancer risk compared with rheumatoid arthritis patients without that specific drug. Our study suggested that the pathophysiology of rheumatoid arthritis, rather than its treatments, is implicated in the development of subsequent cancers. Our method is extensible to investigating the connections among drugs, diseases and comorbidities at scale. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory illness that mostly affects the joints of the hands and feet and can reduce life expectancy by an average of 3 to 10 years. Although tremendous progress has been achieved in the treatment of RA, a large minority of patients continue to respond poorly to existing medications, owing in part to a lack of appropriate therapeutic targets. Methods: To find therapeutic targets for RA, a Mendelian randomization (MR) was performed. Cis-expression quantitative trait loci (cis-eQTL, exposure) data were obtained from the eQTLGen Consortium (sample size 31,684). Summary statistics for RA (outcome) were obtained from two largest independent cohorts: sample sizes of 97,173 (22,350 cases and 74,823 controls) and 269,377 (8279 cases and 261,098), respectively. Colocalisation analysis was used to test whether RA risk and gene expression were driven by common SNPs. Drug prediction and molecular docking was further used to validate the medicinal value of drug targets. Results: Seven drug targets were significant in both cohorts in MR analysis and supported by localization. PheWAS at the gene level showed only ATP2A1 associated with other traits. These genes are strongly associated with immune function in terms of biological significance. Molecular docking showed excellent binding for drugs and proteins with available structural data. Conclusion: This study identifies seven potential drug targets for RA. Drugs designed to target these genes have a higher chance of success in clinical trials and is expected to help prioritise RA drug development and save on drug development costs. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease, causing joint-swelling and pain. International literature highlights that patients with RA are more likely to report high levels of alexithymia, adverse childhood events (ACEs) and stress, but studies investigating the association between these dimensions are lacking. The general aim of the present study is to investigate the association between alexithymia, ACEs, and stress in RA patients and to highlight possible predictors of greater perceived stress. One hundred and thirty-seven female patients with RA (mean age = 50.74; SD = 10.01) participated in an online survey between April and May 2021. Participants completed a questionnaire for the collection of sociodemographic and clinical information, the 20-item Toronto Alexithymia Scale, the Adverse Childhood Events questionnaire and the 10-item Perceived Stress Scale. The correlational analysis highlighted several significant associations between the dimensions evaluated. Regression analyses showed that alexithymia, ACEs and the perceived health status have a predictive effect on the perceived stress of RA patients. More specifically, the role of difficulty in identifying feelings, and the physical and emotional neglect, has been highlighted. ACEs and high levels of alexithymia are common in RA clinical populations and seem to affect the wellbeing of these patients. The use of a biopsychosocial approach to RA treatment appears essential in achieving a better quality of life and illness control in this specific clinical population. [ABSTRACT FROM AUTHOR]

Objective: Pain in rheumatoid arthritis (RA) is considered to be associated with non‐inflammatory factors, including physical disabilities, psychiatric disorders, and pain catastrophizing (PC). PC is reportedly a key driver in the development of pain in patients with RA without clinical signs of inflammation; however, previous studies enroled patients with RA who were potentially in an inflammatory state. Hence, our aim was to investigate the role of PC as the possible link between pain, physical disabilities, and psychiatric disorders in patients with RA without clinical signs of inflammation. Materials and Methods: In this cross‐sectional study, 81 patients with RA without clinical signs of inflammation were included; all patients had serum C‐reactive protein levels <0.5 mg/dL, without any inflammatory joints. We examined the demographic and clinical data and administered the pain visual analogue scale (VAS), pain catastrophizing scale (PCS), Health Assessment Questionnaire Disability Index (HAQ‐DI), and patient version of the Brief Scale for Psychiatric Problems in Orthopaedic Patients (pBS‐POP). A series of multivariate‐adjusted multiple regression analyses were performed to examine the associations between PC and pain intensity, physical disabilities, and psychiatric disorders. Results: We found associations between all the above‐mentioned variables in separate models with HAQ‐DI, pBS‐POP, and PCS scores. However, in the model associated with pain VAS, the PCS score (β = 0.34, p = 0.0073) emerged as the only variable showing a statistically significant association. Conclusions: PC is associated with pain in patients with RA without clinical signs of inflammation, and this association may be mediated through pathways involving physical disabilities and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the relationship between physical therapy response and the presence of central sensitization (CS) in patients with painful knee osteoarthritis (OA). Patients and methods: Between May 2019 and March 2020, a total of 84 patients with knee OA (12 males, 72 females; mean age: 60.7±7.7 years; range 50 to 74 years) and 30 age and sex-matched controls (6 males, 24 females; mean age: 59.2±8.9 years; range 50 to 75 years) were included in this study. Knee pain and functional status were evaluated by Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Structural damage was assessed by knee radiography. The Central Sensitization Inventory (CSI), Beck Depression Inventory (BDI), Insomnia Severity Index (ISI), Pain Catastrophizing Scale (PCS), and PainDETECT Questionnaire (PDQ) were applied at baseline. Pain pressure thresholds (PPTs) of the patients were measured and compared with the control group. All patients underwent a total of 15 sessions of physical therapy program for five sessions/weekly. After treatment, the patients were divided into two groups as responders and non-responders according to the Osteoarthritis Research Society International (OARSI) criteria. Results: The CSI score of the patients in non-responder group was significantly higher compared to the responder group (p=0.004). Using a cut-off value of =40, the proportion of patients with CSI scores of =40 was significantly lower in the responder group compared to non-responder group (p=0.021). The PPT measurement values were significantly lower in the non-responder group compared to the responder and control groups (p<0.01). There was a significant difference in the frequency of hyperalgesia between the groups (p=0.021). Central sensitization and depression were the most significant predictors of non-response to physical therapy (p=0.045 and p=0.024, respectively). Conclusion: Our study results suggest the presence of CS and depression may result in an inadequate response to physical therapy in patients with knee OA. Clinicians should consider the findings of CS and depression in treatment planning. [ABSTRACT FROM AUTHOR]

Virtual Private LAN Services (VPLS) is an ethernet-based Virtual Private Network (VPN) service that provides multipoint-to-multipoint Layer 2 VPN service, where each site is geographically dispersed across a Wide Area Network (WAN). The adaptability and scalability of VPLS are limited despite the fact that they provide a flexible solution for connecting geographically dispersed sites. Furthermore, the construction of tunnels connecting customer locations that are separated by great distances adds a substantial amount of latency to the user traffic transportation. To address these issues, a novel Hierarchical VPLS (H-VPLS) architecture has been developed using 802.1Q tunneling (also known as Q-in-Q) on high-speed and commodity routers to satisfy the additional requirements of new VPLS applications. The Vector Packet Processing (VPP) performs as the router's data plane, and FRRouting (FRR), an open-source network routing software suite, acts as the router's control plane. The router is designed to seamlessly forward VPLS packets using the Request For Comments (RFCs) 4762, 4446, 4447, 4448, and 4385 from The Internet Engineering Task Force (IETF) integrated with VPP. In addition, the Label Distribution Protocol (LDP) is used for Multi-Protocol Label Switching (MPLS) Pseudo-Wire (PW) signaling in FRR. The proposed mechanism has been implemented on a software-based router in the Linux environment and tested for its functionality, signaling, and control plane processes. The router is also implemented on commodity hardware for testing the functionality of VPLS in the real world. Finally, the analysis of the results verifies the efficiency of the proposed mechanism in terms of throughput, latency, and packet loss ratio. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study was planned to investigate the anti-arthritic property of flowers of E. crassipes in a Sprague–Dawley rat model by administering Freund's Complete Adjuvant (FCA). Materials and Methods: Arthritis was induced at day 0 in all rats except negative controls, while arthritic progress and paw edema were analyzed on specific days (8th, 13th, 18th, and 23rd) via the macroscopic arthritic scale and a digital Vernier caliper, respectively. Histopathological parameters were examined using a Hematoxylin and Eosin (H&E) staining method. Blood samples were withdrawn from rats to investigate the effects of the E. crassipes flower on the mRNA expression values of inflammatory markers, via a reverse transcription PCR technique. Serum samples were used to determine prostaglandin E2 (PGE2) levels using enzyme-linked immunosorbent assay (ELISA). Values of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine, and urea, besides hematological parameters, i.e., the hemoglobin (Hb) content and complete blood count (CBC), were investigated. Results: The data showed that E. crassipes inhibited the arthritic progress and ameliorated the paw edema. The amelioration of parameters assessed via the histopathological analysis of ankle joints, as well as via hematological analysis, confirmed the diminution of rheumatoid arthritis (RA) in the plant-treated groups. Treatment with E. crassipes inhibited the expression levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6), nuclear factor KappaB (NF-κB), matrix metalloproteinase (MMP-2 and MMP-3), and vascular endothelial growth factor (VEGF). Serum PGE2 levels were also found to be reduced in treatment groups. A biochemical investigation revealed the improvements in hepatic markers in plant-treated groups. The data indicated that the plant has no hepatotoxic or nephrotoxic effects at the studied dose. GC-MS (Gas Chromatography-Mass Spectrometry) analysis displayed the presence of phytochemicals having known anti-inflammatory and antioxidant properties. Conclusions: Therefore, it may be concluded that E. crassipes possesses anti-arthritic characteristics that could be attributed to the modulation of pro-inflammatory cytokines, MMPs, and PGE2 levels. [ABSTRACT FROM AUTHOR]

Introduction: There is much literature about the role of 2-[ 18 F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject., Purpose: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA)., Methods: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[ 18 F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria., Results: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[ 18 F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[ 18 F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[ 18 F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[ 18 F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising., Conclusion: 2-[ 18 F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios., (© 2024. The Author(s).)

Immune-mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)-α-mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case-control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random-effects meta-analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non-biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta-analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58-0.95, p = 0.025; IRR = 0.77, 95% CI 0.67-0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi-treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64-0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

The objective is to determine the global population prevalence of rheumatoid arthritis (RA) based on population-based studies and assess factors that influence RA prevalence estimates. Four electronic databases were searched (ProQuest Central, MEDLINE, Web of Science, and EMBASE) for peer-reviewed English publications that report prevalence estimates of RA from 1980 and 2019. We included case-control studies, cross-sectional studies, and prospective or retrospective cohort studies in our search strategy. A random-effect meta-analysis model was used to produce the pooled prevalence estimates. The potential between-study heterogeneity was identified using sensitivity analysis, sub-group and meta-regression analyses. A total of 67 studies were included in the meta-analysis, containing 742,246 RA patients and 211,592,925 healthy controls in the study period. The global RA prevalence estimate was 0.46% (95% confidence interval [CI] 0.39-0.54; I 2  = 99.9%) with a 95% prediction interval (0.06-1.27). The RA point-prevalence was 0.45% (95% CI 0.38-0.53%) between 1986 and 2014, while the pooled period-prevalence was 0.46% (95% CI 0.36% and 0.57%) from 1955 to 2015. The highest RA pooled prevalence (0.69%; 95% CI 0.47-0.95) was derived from linked data source studies. Based on meta-regression, the factors that explain the studies' heterogeneity of RA prevalence, including geographical location, the risk bias assessment of studies and sample size. The global prevalence of RA between 1980 and 2019 was 460 per 100,000 population, with variations due to geographical location and study methodology. Linked data are the preferred method to estimate RA population prevalence as they provide the best case ascertainment.

Objective: Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods: The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results: In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER-BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER-BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95% CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions: This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER-BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC. [ABSTRACT FROM AUTHOR]