Search

Panagiota Anyfanti,1 Athanasia Dara,2 Elena Angeloudi,1 Eleni Bekiari,1 Theodoros Dimitroulas,2 George D Kitas3,4 1Second Medical Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS Foundation Trust, Dudley, UK; 4School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UKCorrespondence: Panagiota AnyfantiHippokration General Hospital, 49, Konstantinoupoleos str, 54642, Thessaloniki, GreeceTel +30 2310 892 244Fax +30 2310 512 378Email panyfan@hotmail.comGeorge D KitasDudley Group NHS Foundation Trust, Russells Hall Hospital, Clinical Research Unit, Dudley, DY1 2HQ, UKEmail george.kitas@nhs.netAbstract: Cardiovascular disease (CVD) is common in immune-mediated inflammatory diseases (IMIDs) and it is predominately attributed to the interplay between chronic inflammation and traditional CVD risk factors. CVD has significant impact on the survival of patients with IMIDs as it is associated with increased morbidity and mortality. Despite recommendations for monitoring and managing CVD in patients with IMIDs, the individual CVD risk assessment remains problematic as CVD risk calculators for the general population consistently underestimate the risk in patients with IMIDs. Application of new technologies utilizing artificial intelligence techniques have shown promising potential for tailoring predictive medicine to the individual patient, but further validation of their role in clinical decision-making is warranted. In the meantime, individuals with IMIDs should be encouraged to adopt behavioral interventions targeting at modifiable lifestyle CVD risk factors, whereas rheumatologists need to be well aware of the unfavorable effects of antirheumatic medication on various CVD risk factors and outcomes. In the current paper, we aim to provide an overview of current and emerging strategies for mitigating CVD risk in patients with IMIDs, based on a practical approach.Keywords: chronic inflammatory diseases, cardiovascular risk assessment, lifestyle modifications, pharmacological management

George E Fragoulis,1,* Stergios Soulaidopoulos,2,* Petros P Sfikakis,1 Theodoros Dimitroulas,3 George D Kitas4,5 1Rheumatology Unit, Joint Rheumatology Program, Medical School, First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, “Laiko” General Hospital, Athens, 115 27, Greece; 2First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, 115 27, Greece; 3Fourth Department of Internal Medicine, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 546 41, Greece; 4Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, DY1 2HQ, UK; 5Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, M13 9PT, UK*These authors contributed equally to this workCorrespondence: Stergios SoulaidopoulosFirst Department of Cardiology, National and Kapodistrian University of Athens, 114 Vasilissis Sofias av., Athens, 11527, GreeceTel +306932528561Fax +302132088676Email soulaidopoulos@hotmail.comAbstract: It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.Keywords: atherosclerosis, cardiovascular disease, biologic agents, interleukins, inflammatory disorders

Aamer Sandoo,1,2 George D Kitas,2 Amtul R Carmichael2 1School of Sport, Health and Exercise Sciences, Bangor University, Bangor, Wales, 2Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, UK Abstract: Breast cancer is the most common cancer in the UK. Advances in the methods of early diagnosis as well as newer and more effective treatments have led to improvements of disease-free and overall survival over the last decade. Almost one-third of breast cancers present with an aggressive form characterized by increased expression of human epidermal growth receptor 2 (HER2) proteins. A targeted treatment using monoclonal antibodies against HER2 expression such as trastuzumab has been shown to improve survival. Unfortunately, there is a degree of cardiotoxicity associated with these agents, as inhibition of HER2 pathways can also impair cardioprotective pathways. In the present review, we discuss the mechanisms by which trastuzumab might affect vascular homeostasis leading to endothelial dysfunction. We also provide suggestions for future research examining the effects of trastuzumab on the vasculature in breast cancer. Keywords: endothelial dysfunction, microvasculature, macrovasculature, congestive heart failure

Objectives: The aim of our study was to determine whether asymmetric dimethylarginine (ADMA) levels are associated with homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene variants in patients with rheumatoid arthritis (RA).Method: Serum ADMA and Hcy levels were measured in 201 RA individuals [155 (77.1%) females, median age 67 years (interquartile range 59-73)]. The MTHFR C677T polymorphism was assessed by using the LightCyclerTM System. Initially, ADMA was compared across the categories of MTHFR using a one-way analysis of variance (ANOVA), followed by a multivariate model, which accounted for Hcy, age, erythrocyte sedimentation rate (ESR), and homeostatic model assessment (HOMA).Results: In univariable analysis, ADMA differed significantly across the categories of MTHFR (p = 0.037). Patients with the MTHFR 677TT genotype had the highest ADMA levels, with a mean of 0.62 (SE = 0.03), significantly higher than either those patients carrying the MTHFR 677CT (0.55, SE = 0.01) or the MTHFR 677CC (0.55, SE = 0.01) genotype (p = 0.042) in both cases. In the multivariable model, Hcy (p = 0.022) and ESR (p < 0.001) were found to have significant positive associations with ADMA but the relationship between MTHFR gene variants and ADMA was found to be non-significant (p = 0.102).Conclusions: Hcy and ADMA are significantly associated in RA. It is plausible that abnormal Hcy metabolism plays an important role in premature atherosclerosis in RA by promoting ADMA accumulation and leading to the derangement of vascular haemostasis. [ABSTRACT FROM AUTHOR]

In the context of holistic therapeutic practices, the cardiovascular risk of patients with rheumatoid arthritis (RA) needs to be addressed as a major factor of compromised disease prognosis and increased mortality. The elevated prevalence of cardiovascular disease (CVD) by more than twofold in RA has been attributed, inter alia, to chronic inflammation exacerbating arterial stiffness, increased onset of hypertension, dyslipidaemia and diabetes mellitus, sedentary lifestyle, and antirheumatic drug complications. CVD risk in RA can be currently assessed by practitioners through accessible adapted calculators, but it remains problematic as their diagnostic accuracy is not superior to calculators designed for the general population. Implementation of guideline-oriented personalised interventions remains the cornerstone for cardiovascular risk management in RA. Remarkably, there is lack of a consortium that brings together different health care providers engaged in the care of patients with RA (e.g., rheumatologists, cardiologists, general practitioners, etc), to guide cardiovascular risk assessment and management. This narrative review aims at providing an overview of current CVD risk assessment and management options, highlighting their pivotal role in the comprehensive treatment of RA patients., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Background: The cardiovascular disease (CVD) risk is elevated by 1.5 times among South Asians with rheumatological conditions like rheumatoid arthritis (RA) in the UK. However, there is a dearth of culturally sensitive educational interventions tailored to this population. We have culturally adapted an existing cognitive behavioural patient education intervention, originally designed for predominantly White populations, to address this gap., Methods: The adaptation process followed the Ecological Validity Model, comprising four phases: stage-setting and expert consultations, preliminary content adaptation, iterative content adaptation with patient partners, and finalisation with patient partners and feedback. The Theoretical Domains Framework (TDF) was employed to evaluate the relevance, acceptability, and cultural adaptation of the existing intervention. Seven South Asian Patient Experts with RA were interviewed, and their input aided in developing new content for the culturally sensitive intervention., Results: The intervention was successfully adapted to suit South Asians. Cultural adaptation involved reviewing elements of the existing intervention, including language tone, content, and metaphors. Moreover, by incorporating behaviour change techniques, the content was designed to enhance understanding of RA, CVD risk associated with RA, and promote a healthy lifestyle. The newly developed educational intervention addressed topics such as community resistance, perspectives on health and culture, societal pressure, and opportunities for change. Key messages were visually illustrated through pictorial diagrams in a twenty-five-minute online resource., Conclusion: The first culturally adapted CVD intervention targeting South Asian individuals with RA, particularly those who are non-English-speaking, is now accessible free of charge at www.nras.org.uk/apnijung nationally and internationally., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients., Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima-media thickness was assessed with ultrasound., Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities., Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA., Competing Interests: The authors declare no conflicts of interest.

Background: Individuals with rheumatoid arthritis (RA) are at a high risk of cardiovascular diseases (CVD). A reduced chronotropic response (CR), which produces exercise intolerance, is known to be a contributing factor to CVD and mortality. Studies have shown that patients with RA have a reduced CR. However, knowledge of CR-related factors in patients with RA is limited. This study aimed to explore CR-related factors, including CVD risk factors, inflammatory markers, and cardiorespiratory fitness (VO 2PEAK )., Methods: A total of 106 RA patients underwent a treadmill test, heart rate monitoring, and various assessments, including serological CVD risk factors, inflammatory markers, and VO 2PEAK ., Results: A total of 34% of participants demonstrated a reduced CR (≤80%). Body mass index, HOMA, hsCRP, and fibrinogen were inversely related to CR, while HDL, QUICKi, VO 2PEAK , and RER exhibited a positive association. HDL and VO 2PEAK emerged as independent CR-related factors in regression analysis., Conclusions: The current findings suggest that reduced CR in RA is associated with several CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Future studies should investigate the effects of controlling these associated variables on CR in patients with RA.

Vascular injury eventually resulting in the establishment of cardiovascular disease is a serious complication in rheumatoid arthritis (RA). Nailfold videocapillaroscopy (NVC) is a non-invasive imaging modality that enables the quantitative and qualitative assessment of the peripheral microvasculature. Nevertheless, capillaroscopic patterns remain inadequately defined in RA, especially regarding their clinical significance as potential markers of systemic vascular impairment. Consecutive RA patients underwent NVC using a standardized protocol, to assess the following parameters: capillary density, avascular areas, capillary dimensions, microhemorrhages, subpapillary venous plexus, and presence of ramified, bushy, crossed and tortuous capillaries. Carotid-femoral pulse wave velocity (PWV) and pulse pressure were measured as well-acknowledged markers of large artery stiffening. The vast majority of our cohort (n = 44) presented a combination of non-specific and abnormal capillaroscopic parameters. Capillary ramification was associated with both PWV and pulse pressure, even after adjustment for cardiovascular risk factors and systemic inflammation. Our study highlights the high prevalence of a wide range of capillaroscopic deviations from the normal patterns in RA. Furthermore, it provides for the first time evidence of an association between structural disorders of the microcirculation and markers of macrovascular dysfunction, suggesting that NVC might have a role as an index of generalised vascular impairment in RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP 3 ) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP 3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with systemic autoimmunity due to autoimmune rheumatic diseases (ARDs) or sarcoidosis frequently present with systemic manifestations including cardiac involvement. Cardiac rhythm disturbances and specifically ventricular arrhythmias (VAs) may affect the prognosis of these patients. Cardiovascular magnetic resonance imaging (CMR) is a non-invasive imaging modality that can provide valuable diagnostic and prognostic information in patients with ARDs or systemic autoimmunity in general. In this narrative review, we briefly present the underlying pathophysiologic mechanisms contributing to arrhythmogenicity in patients with systemic autoimmunity. Furthermore, we discuss recent advances underlying the role and value of CMR for use in the detection and risk stratification of arrhythmogenic substrates in patients with systemic autoimmunity and VAs., Competing Interests: The authors declare no conflict of interest. Sophie I. Mavrogeni is serving as Guest Editor and Editorial Board of this journal. We declare that Sophie I. Mavrogeni had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Zhonghua Sun., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Introduction: Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions., Objectives: We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability., Methods: The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups., Results: High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP., Conclusion: PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation., Competing Interests: D.F.M. has grant support from Eli Lilly and Pfizer for projects outside of this study. D.A.W. has grant support from Eli Lilly, UCB and Pfizer for projects outside of this study. Consultancies for Pfizer, AbbVie, GSK. No other potential conflicts were declared by other authors.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

The global health crisis caused by the COVID-19 pandemic overwhelmed the capacity of healthcare systems to cope with the rapidly spreading infection and its associated complications. Among these complications, autoimmune phenomena such as systemic vasculitis emerged as a significant challenge. Both the SARS-CoV-2 virus and the vaccines developed to combat it appeared to induce clinical manifestations resembling various types of systemic vasculitis, affecting large, medium, and small vessels. These virus- or vaccine-induced vasculitides exhibited a distinct natural history and course from de novo vasculitis, as they were more responsive to steroid therapy and some mild cases even resolved spontaneously. Notably, there have been no confirmed cases of SARS-CoV-2 infection or vaccination triggering variable vessel vasculitis like Behcet's disease or Kawasaki disease. IgA vasculitis, which is predominantly a pediatric condition, was more prevalent in adults after COVID-19 infection and they had a favorable outcome with glucocorticoid treatment. The impact of immunosuppression, especially B-cell-depleting agents, on the immunogenicity of the vaccine was evident, but there was no significant increase in the incidence of SARS-CoV-2 infection in these patients compared to the general population. Considering their relatively benign course, these post-COVID or post-vaccine vasculitides seem to be amenable to 0.8 to 1 mg/kg prednisolone or equivalent, which could be gradually tapered. The need for immunosuppression and the duration of steroid therapy should be determined on an individual basis. While the world still reels from the perils of a deadly pandemic, the aftermath continues to haunt. Our narrative review aims to explore the effects of COVID and the vaccine on systemic vasculitis, as well as the effect of disease and immunosuppression on the immunogenicity of the COVID vaccine., (© 2023. International League of Associations for Rheumatology (ILAR).)

Background: Lifestyle physical activity (PA) is defined as any type of PA undertaken as part of daily life. It can include engagement in activities of daily living (i.e., household chores, gardening, walking to work), incidental PA, walking and/or reducing sedentary or sitting behaviours (SB). Regular PA is recommended for people with Rheumatoid Arthritis (RA) to reduce disease activity and systemic inflammation, as well as to improve patient- and clinician-important health outcomes. However, there is no summarised evidence of the effectiveness of interventions specifically targeting lifestyle PA and SB in this population. The aims of this systematic review with meta-analysis were to evaluate interventions targeting lifestyle PA and/or SB on 1) disease activity; 2) PA, SB and 3) patient- and clinician-important outcomes in people with RA., Methods: Eight databases [Medline, Cochrane Library CENTRAL, Web of Science, PsychINFO, Cumulative Index to Nursing & Allied Health Literature, Scopus, Excerpta Medica database and Physiotherapy Evidence Database] were searched from inception-August 2022. Inclusion criteria required interventions to target lifestyle PA and/or SB, conducted in adults with RA, assessing patient- and/or clinician-important outcomes., Results: Of 880 relevant articles, 16 interventions met the inclusion criteria. Meta-analyses showed statistically significant effects of interventions on disease activity (standardised mean difference = -0.12 (95% confidence interval = -0.23 to -0.01, I 2  = 6%, z = 2.19, p = .03), moderate-to-vigorous PA, light/leisure PA, steps, functional ability, and fatigue. Whereas, no intervention effects were visualised for total PA, pain, anxiety or quality of life., Conclusions: Lifestyle PA interventions led to increased PA, reductions in SB and improvements in disease activity and other patient- and/or clinician-important health outcomes in people with RA. Future interventions should be less heterogenous in content, structure, focus and outcome measures used to aid understanding of the most effective intervention components for improving health. More SB interventions are needed to determine their effectiveness at producing clinical benefits., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study aimed to determine the minimum number of days required to reliably estimate free-living sedentary time, light-intensity physical activity (LPA) and moderate-intensity physical activity (MPA) using accelerometer data in people with Rheumatoid Arthritis (RA), according to Disease Activity Score-28-C-reactive protein (DAS-28-CRP). Secondary analysis of two existing RA cohorts with controlled (cohort 1) and active (cohort 2) disease was undertaken. People with RA were classified as being in remission (DAS-28-CRP < 2.4, n = 9), or with low (DAS-28-CRP ≥ 2.4-≤ 3.2, n = 15), moderate (DAS-28-CRP > 3.2-≤ 5.1, n = 41) or high (DAS-28-CRP > 5.1, n = 16) disease activity. Participants wore an ActiGraph accelerometer on their right hip for 7 days during waking hours. Validated RA-specific cut-points were applied to accelerometer data to estimate free-living sedentary time, LPA and MPA (%/day). Single-day intraclass correlation coefficients (ICC) were calculated and used in the Spearman Brown prophecy formula to determine the number of monitoring days required to achieve measurement reliability (ICC ≥ 0.80) for each group. The remission group required ≥ 4 monitoring days to achieve an ICC ≥ 0.80 for sedentary time and LPA, with low, moderate and high disease activity groups requiring ≥ 3 monitoring days to reliably estimate these behaviours. The monitoring days required for MPA were more variable across disease activity groups (remission =  ≥ 3 days; low =  ≥ 2 days; moderate =  ≥ 3 days; high =  ≥ 5 days). We conclude at least 4 monitoring days will reliably estimate sedentary time and LPA in RA, across the whole spectrum of disease activity. However, to reliably estimate behaviours across the movement continuum (sedentary time, LPA, MPA), at least 5 monitoring days are required., (© 2023. Crown.)

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank - based on their perceived importance - known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors. Key Points • Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement. • RMD symptoms are the factors that people with RMDs want to improve when engaging in PA. • The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The global mortality rate is known to be the highest due to cardiovascular disease (CVD). Thus, preventive, and early CVD risk identification in a non-invasive manner is vital as healthcare cost is increasing day by day. Conventional methods for risk prediction of CVD lack robustness due to the non-linear relationship between risk factors and cardiovascular events in multi-ethnic cohorts. Few recently proposed machine learning-based risk stratification reviews without deep learning (DL) integration. The proposed study focuses on CVD risk stratification by the use of techniques mainly solo deep learning (SDL) and hybrid deep learning (HDL). Using a PRISMA model, 286 DL-based CVD studies were selected and analyzed. The databases included were Science Direct, IEEE Xplore, PubMed, and Google Scholar. This review is focused on different SDL and HDL architectures, their characteristics, applications, scientific and clinical validation, along with plaque tissue characterization for CVD/stroke risk stratification. Since signal processing methods are also crucial, the study further briefly presented Electrocardiogram (ECG)-based solutions. Finally, the study presented the risk due to bias in AI systems. The risk of bias tools used were (I) ranking method (RBS), (II) region-based map (RBM), (III) radial bias area (RBA), (IV) prediction model risk of bias assessment tool (PROBAST), and (V) risk of bias in non-randomized studies-of interventions (ROBINS-I). The surrogate carotid ultrasound image was mostly used in the UNet-based DL framework for arterial wall segmentation. Ground truth (GT) selection is vital for reducing the risk of bias (RoB) for CVD risk stratification. It was observed that the convolutional neural network (CNN) algorithms were widely used since the feature extraction process was automated. The ensemble-based DL techniques for risk stratification in CVD are likely to supersede the SDL and HDL paradigms. Due to the reliability, high accuracy, and faster execution on dedicated hardware, these DL methods for CVD risk assessment are powerful and promising. The risk of bias in DL methods can be best reduced by considering multicentre data collection and clinical evaluation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-438/coif). IMS is on the clinical advisory board of AtheroPoint™, Roseville, CA, USA. LS serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from September 2021 to August 2023. JSS is with AtheroPointTM, Roseville, CA, USA, focusing in the area of Stroke and Cardiovascular Imaging. The other authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background and Motivation: Lung computed tomography (CT) techniques are high-resolution and are well adopted in the intensive care unit (ICU) for COVID-19 disease control classification. Most artificial intelligence (AI) systems do not undergo generalization and are typically overfitted. Such trained AI systems are not practical for clinical settings and therefore do not give accurate results when executed on unseen data sets. We hypothesize that ensemble deep learning (EDL) is superior to deep transfer learning (TL) in both non-augmented and augmented frameworks., Methodology: The system consists of a cascade of quality control, ResNet-UNet-based hybrid deep learning for lung segmentation, and seven models using TL-based classification followed by five types of EDL's. To prove our hypothesis, five different kinds of data combinations (DC) were designed using a combination of two multicenter cohorts-Croatia (80 COVID) and Italy (72 COVID and 30 controls)-leading to 12,000 CT slices. As part of generalization, the system was tested on unseen data and statistically tested for reliability/stability., Results: Using the K5 (80:20) cross-validation protocol on the balanced and augmented dataset, the five DC datasets improved TL mean accuracy by 3.32%, 6.56%, 12.96%, 47.1%, and 2.78%, respectively. The five EDL systems showed improvements in accuracy of 2.12%, 5.78%, 6.72%, 32.05%, and 2.40%, thus validating our hypothesis. All statistical tests proved positive for reliability and stability., Conclusion: EDL showed superior performance to TL systems for both (a) unbalanced and unaugmented and (b) balanced and augmented datasets for both (i) seen and (ii) unseen paradigms, validating both our hypotheses.

Research evidence suggests that, individually, diet and physical activity are effective interventions for reducing levels of inflammation in inflammatory joint diseases (IJD), however little is known about their combined use. This systematic review and meta-analysis aimed to examine the effects and/or associations of combined diet and physical activity interventions in IJD, specifically rheumatoid arthritis (RA) and the spondyloarthropathies (SpA) (PROSPERO registration number: CRD42022370993). Ten out of 11 eligible studies examined RA patients. We found that a combination of diet/nutrition and physical activity/exercise improved Health Assessment Questionnaire score (standardized mean difference = -1.36, confidence interval (CI) = (-2.43)-(-0.30), I 2 = 90%, Z = 2.5, p = 0.01), while surprisingly they increased erythrocyte sedimentation rate (mean difference = 0.20, CI = 0.09-0.31, I 2 = 0%, Z = 3.45, p < 0.01). No effects were found on C-reactive protein or weight ( p > 0.05) of RA patients. We did not find studies in other IJDs that provided sufficient data for a meta-analysis. The narrative data synthesis provided limited evidence to address our research question. No firm conclusions can be made as to whether the combination of diet/nutrition and physical activity/exercise affects inflammatory load in IJDs. The results of this study can only be used as a means of highlighting the low-quality evidence in this field of investigation and the need for further and better-quality research.

The present review summarizes the burden, risk factors, biomarkers of and therapeutic consideration for cardiovascular disease in systemic vasculitis. Ischemic heart disease (IHD) and stroke are intrinsic features of Kawasaki disease, Takayasu arteritis, Giant Cell Arteritis (GCA), and Behcet's disease. The risk of IHD and stroke is increased in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and cryoglobulinemic vasculitis. Behcet's disease could present with venous thromboembolism. The risk of venous thromboembolism is increased in AAV, polyarteritis nodosa, and GCA. The risk of cardiovascular events is greatest at or immediately after the diagnosis of AAV or GCA, therefore, controlling vasculitis disease activity is of utmost importance. Traditional as well as disease-related risk factors drive the heightened cardiovascular risk in vasculitis. Aspirin or statins reduce the risk of IHD or stroke in GCA or the risk of IHD in Kawasaki Disease. Venous thromboembolism in Behcet's disease should be treated with immunosuppressive therapy rather than with anticoagulation., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Cardiac involvement is common in systemic sclerosis occurring in up to 80% of patients. Primary myocardial dysfunction results from impairment of coronary microvascular circulation, myocardial inflammation and fibrosis with the prevalence of atherosclerosis remaining contradictory., Areas Covered: This review presents the various aspects of cardiac involvement in SSc from a pathophysiological, clinical, diagnostic and therapeutic standpoint. Imaging modalities with emerging role in the understanding of mechanisms and prompt diagnosis of myocardial fibrosis namely cardiac magnetic resonance are also discussed., Expert Opinion: Cardiac involvement in SSc - and particularly primary myocardial disease - remains a challenge as clinical symptoms manifest in advanced stages of heart failure and convey poor prognosis. Over the last years the introduction of sophisticated imaging methods of myocardial function has resulted in a better understanding of the underlying pathophysiological processes of myocardial damage such as microvasculopathy, inflammation, diffuse or focal fibrosis. Such developments could contribute to the identification of patients at higher risk for subclinical heart involvement for whom diligent surveillance and prompt initiation of therapy with cardioprotective and/or immunosuppressive drugs coupled with invasive interventions namely radiofrequency ablation, implantable cardioverter-defibrillator when indicated, may improve long-term outcomes.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by necrotizing inflammation of small and medium-size vessels that often manifest with devastating multi-organ effects. They present with a myriad of systemic features and require potent immunosuppression. Since they are uncommonly encountered in clinical practice, it is necessary to understand physicians' knowledge and perceptions about this group of diseases. An online questionnaire was designed featuring 28 questions based on relevant global practice guidelines, recommendations, and previous online surveys on AAV. The questionnaire was validated by a core group of specialists with an interest in AAV. It was shared via social networking sites and entries were restricted to physicians. Only completed entries were analyzed with descriptive statistics. A total of 113 respondents from 21 different countries responded of whom the commonest were rheumatologists, internists, and general practitioners. Forty-five (40%) ran clinics dedicated to AAV patients as a part of their practice. They commented on organs involved in AAV; vasculitis secondary to infections, drugs or other rheumatic diseases; various tests useful for AAV diagnosis; and drug choices for induction and maintenance. They mentioned their experience regarding COVID-19 in AAV patients as well as vasculitic manifestations of COVID-19. Various methods to mitigate cardiovascular risks in AAV were mentioned. Finally, the respondents indicated how medical education needed to be strengthened to increase awareness and knowledge regarding AAV. This survey helped to inform about various perceptions regarding AAV across countries, including current practices and recent evolution of management. It also provided information on treatment of the COVID-19 in AAV patients. This survey showed that there is still a lack in understanding the prevalent definitions and there is gap between guidelines and current practice. Key Points • Perception about ANCA-associated vasculitis differ across countries. • The number of cases encountered across 21 different countries are limited implying a need for multi-national cooperation to study this disease further. • The COVID-19 pandemic has changed the approach towards ANCA-associated vasculitis by the various clinicians., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Cardiovascular disease (CVD) constitutes a real pandemic of the 21st century. According to data from the Centers for Disease Control and Prevention, one person dies every 34 min due to some form of CVD in the United States. Apart from the extremely high morbidity and mortality accompanying CVD, the economic burden seems to be unbearable even for developed countries in the Western World. The role of inflammation in the development and progression of CVD appears to be crucial, while, various inflammatory pathways, such as the Nod-like receptor protein 3 (NLRP3) inflammasome-interleukin (IL)-1/IL-6 pathway of the innate immunity, have attracted scientific interest during the last decade, as a potential treatment target in primary and/or secondary prevention of CVD. Whereas there is a significant amount of evidence, stemming mainly from observational studies, concerning the cardiovascular safety of IL-1 and IL-6 antagonists in patients with rheumatic diseases, evidence from relevant randomized controlled trials (RCTs) is rather scarce and conflicting, especially for patients without underlying rheumatic disease. In this review, we summarize and critically present the currently available evidence, both from RCTs and observational studies, concerning the place that IL-1 and IL-6 antagonists may hold in the treatment of CVD., Competing Interests: The authors declare no conflict of interest.

Systemic sclerosis (SSc) presents high morbidity/mortality, due to internal organ fibrosis, including the heart. Cardiac magnetic resonance (CMR) can perform myocardial function and tissue characterization in the same examination. The Lake Louise criteria (LLC) can identify recent myocardial inflammation using CMR. Abnormal values include: (a) myocardial over skeletal muscle ratio in STIRT2-W images >2, (b) early gadolinium enhancement values >4, (c) epicardial/intramyocardial late gadolinium enhancement (LGE). The diagnosis of myocarditis using LLC is considered if 2/3 criteria are positive. Parametric imaging including T2, native T1 mapping and extracellular volume fraction (ECV) has been recently used to diagnose inflammatory cardiomyopathy. According to expert recommendations, myocarditis should be considered if at least 2 indices, one T2 and one T1 parameter are positive, whereas native T1 mapping and ECV assess diffuse fibrosis or oedema, even in the absence of LGE. Moreover, transmural/subendocardial fibrosis following the distribution of coronary arteries and diffuse subendocardial fibrosis not related with epicardial coronary arteries are indicative of epicardial and micro-vascular coronary artery disease, respectively. To conclude, CMR can identify acute/active myocardial inflammation and myocardial infarction using classic and parametric indices in parallel with ventricular function evaluation., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022. Published by Elsevier Inc.)

Cardiovascular disease (CVD) risk is increased in most inflammatory rheumatic diseases (IRDs), reiterating the role of inflammation in the initiation and progression of atherosclerosis. An inverse association of CVD risk with body weight and lipid levels has been described in IRDs. Coronary artery calcium scores, plaque burden and characteristics, and carotid plaques on ultrasound optimize CVD risk estimate in IRDs. Biomarkers of cardiac injury, autoantibodies, lipid biomarkers, and cytokines also improve risk assessment in IRDs. Machine learning and deep learning algorithms for phenotype and image analysis hold promise to improve CVD risk stratification in IRDs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the last decade, studies into sedentary behaviour in inflammatory arthritis have raised important questions regarding its role in this condition. Specifically, evidence is needed on whether sedentary behaviour might exacerbate adverse inflammatory arthritis outcomes, and whether reducing sedentary behaviour might offer an effective avenue for self-management in this population. Research exploring these important research questions is still very much in its infancy and lacks the direction and scientific rigour required to inform effective intervention design, delivery and evaluation. Behavioural epidemiology refers to research that aims explicitly to understand and influence health behaviour patterns to prevent disease and improve health. To this end, the Behavioural Epidemiology Framework specifies a focused approach to health behaviour research, which leads to the development of evidence-based interventions directed at specific populations. In this review, we introduce the Behavioural Epidemiology Framework in the context of research into sedentary behaviour in inflammatory arthritis and ask: where are we, and where do we need to go?, (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort., Materials and Methods: Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later., Results: One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up., Discussion: Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thomas, Lazarini, Kaltsonoudis, Voulgari, Drosos, Repa, Sali, Sidiropoulos, Tsatsani, Gazi, Fragkiadaki, Tektonidou, Sfikakis, Katsimbri, Boumpas, Argyriou, Boki, Karagianni, Katsiari, Evangelatos, Iliopoulos, Grika, Vlachoyiannopoulos, Dimitroulas, Garyfallos, Melissaropoulos, Georgiou, Georganas, Vounotrypidis, Ntelis, Areti, Kitas and Vassilopoulos.)

Background: Systemic sclerosis (SSc) is a connective tissue disease characterized primarily by micro-angiopathy and endothelial dysfunction which stimulate a fibrotic process. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor and represents a novel biomarker for vascular dysfunction. Nailfold video capillaroscopy (NVC) represents a non-invasive and reliable technique for the evaluation of microvasculopathy in SSc., Objectives: The aim of this study was to examine the possible association between ADMA and microvascular involvement in patients with SSc., Methods: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA was measured in serum samples using a commercial enzyme immunoassay. Participants underwent NVC with qualitative and semi-quantitative assessment and all NVC parameters were measured in the distal row of each finger. The findings were classified in one of the three qualitative NVC patterns: early, active, and late., Results: Eighty-one (92,6 % women) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. Within-groups comparisons revealed a trend between higher ADMA levels and progressive micro-vasculopathy (1,29 [2,1] vs 1,57 [1,95] vs 2,41 [3,87]; for early, active and late patterns respectively, p = 0.039). Furthermore, ADMA concentration was significantly associated with the number of capillaries/mm (r = -0.235; p = 0.035)., Conclusions: Serum ADMA levels were significantly associated with advancing stages of microcirculatory abnormalities suggesting that ADMA may have a role in promoting microvascular endothelial dysfunction in SSc individuals., Competing Interests: Declaration of competing interest All authors disclose that they don't have any financial or other relationships, which might lead to a conflict of interest regarding this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Reactive arthritis (ReA) is an often neglected disease that received some attention during the coronavirus disease 2019 (COVID-19) pandemic. There is some evidence that infection with severe acute respiratory syndrome coronavirus 2 can lead to "reactive" arthritis. However, this does not follow the classical definition of ReA that limits the organisms leading to this condition. Also, there is no recommendation by any international society on the management of ReA during the current pandemic. Thus, a survey was conducted to gather information about how modern clinicians across the world approach ReA., Methods: An e-survey was carried out based on convenient sampling via social media platforms. Twenty questions were validated on the pathogenesis, clinical presentation, and management of ReA. These also included information on post-COVID-19 arthritis. Duplicate entries were prevented and standard guidelines were followed for reporting internet-based surveys., Results: There were 193 respondents from 24 countries. Around one-fifth knew the classical definition of ReA. Nearly half considered the triad of conjunctivitis, urethritis and asymmetric oligoarthritis a "must" for diagnosis of ReA. Other common manifestations reported include enthesitis, dermatitis, dactylitis, uveitis, and oral or genital ulcers. Three-fourths opined that no test was specific for ReA. Drugs for ReA were non-steroidal anti-inflammatory drugs, intra-articular injections, and conventional disease-modifying agents with less than 10% supporting biological use., Conclusion: The survey brought out the gap in existing concepts of ReA. The current definition needs to be updated. There is an unmet need for consensus recommendations for the management of ReA, including the use of biologicals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Motivation : The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.

Outcomes of COrona VIrus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) reported in various studies are heterogenous owing to the influence of age and comorbidities which have a significant bearing on the infection risk, severity, morbidity, and mortality. Diabetes mellitus (DM) and RDs are closely linked with underlying pathobiology and treatment of RDs affecting the risk for DM as well as the glycemic control. Hence, we undertook this narrative review to study the influence of DM on outcomes of COVID-19 in patients with RDs. Additionally, aspects of patient attitudes and immune response to COVID-19 vaccination were also studied. The databases of MEDLINE/PubMed, Scopus, and Directory of Open Access Journals (DOAJ) were searched for relevant articles. Studies from mixed cohorts revealed insufficient data to comment on the influence of DM on the risk of infection, while most studies showed twice the odds for hospitalization and mortality with DM. Specific cohorts of rheumatoid arthritis and systemic lupus erythematosus revealed a similar association. Poor health was noted in patients with spondyloarthritis and DM during the pandemic. The presence of DM did not affect patient attitudes towards vaccination and did not predispose to additional vaccine-related adverse effects. Immune response to inactivated vaccines was reduced but mRNA vaccines were maintained in patients with DM. Detailed assessment of DM with its duration, end-organ damage, and glycemic control along with a focused association of DM with various aspects of COVID-19 like risk, hospitalization, severity, mortality, post-COVID sequelae, immune response to infection, and vaccination are needed in the future. Key Points • Diabetes mellitus is associated with the severity of infection, COVID-19-related hospitalization, and mortality in rheumatic diseases across most studies but studies analyzing its specific role are lacking. • Poor outcomes of COVID-19 in RA and poor health in spondyloarthritis are strongly associated with diabetes mellitus. • Diabetes mellitus may negatively influence the humoral response to inactivated vaccines but does not seem to affect the immune responses to mRNA vaccines. • Diabetes mellitus does not influence the attitude towards vaccination or deviation from the prescribed medications during the pandemic., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises., Methods: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors., Results: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg -1  min -1 , p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors., Conclusion: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases. Key Points 1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention. 2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk. 3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg-1min-1 compared to the 20.9 ml.kg-1min-1 baseline mean of the RA patients without CVD risk)., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients.

Background: This longitudinal study investigated whether changes in autonomous and controlled motivation to reduce sedentary behaviour were associated with variability in sedentary, standing and stepping time and, in turn, disease activity, systemic inflammation, pain and fatigue in rheumatoid arthritis (RA)., Methods: People with RA undertook assessments at baseline (T1, n = 104) and 6 months follow-up (T2, n = 54) to determine autonomous and controlled motivation to reduce sedentary behaviour (Behavioural Regulation in Exercise Questionnaire-2), free-living sedentary, standing and stepping time (7 days activPAL3 μ wear), Disease Activity Score-28 (DAS-28), systemic inflammation (c-reactive protein [CRP]), pain (McGill Pain Questionnaire) and fatigue (Multidimensional Assessment of Fatigue Scale). N = 52 participants provided complete data at T1 and T2., Statistical Analyses: In a series of models (A and B), path analyses examined sequential associations between autonomous and controlled motivation to reduce sedentary behaviour with activPAL3 μ -assessed behaviours and, in turn, RA outcomes., Results: Models demonstrated good fit to the data. Model A (sedentary and stepping time): autonomous motivation was significantly negatively associated with sedentary time and significantly positively related to stepping time. In turn, sedentary time was significantly positively associated with CRP and pain. Stepping time was not significantly associated with any health outcomes. Model B (standing time): autonomous motivation was significantly positively associated with standing time. In turn, standing time was significantly negatively related to CRP, pain and fatigue., Conclusions: Autonomous motivation to reduce sedentary behaviour is associated with sedentary and standing time in RA which may, in turn, hold implications for health outcomes., (© 2022. The Author(s).)

Aims: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP)., Methods and Results: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was &lt;140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination., Conclusion: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the "treat-to-target" approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with systemic lupus erythematosus (SLE) form a vulnerable group in terms of the impact of the COVID-19 pandemic on disease management. We conducted this overview by searches through Medline/PubMed, Scopus, and the Directory of Open Access Journals (DOAJ). The prevalence and severity of COVID-19, efficacy of COVID-19 vaccination, impact on the management of SLE, and the attitudes of SLE patients to COVID-19 and vaccination were explored. After screening and due exclusions, 198 studies were included for the final review. Patients with SLE have a greater risk of acquiring COVID-19 (0.6-22%) and related hospitalization (30%), severe disease (13.5%), and death (6.5%) than the general population. Older age, male gender, comorbidities, moderate or high disease activity, and glucocorticoid, rituximab, and cyclophosphamide use are associated with unfavorable outcomes, whereas methotrexate and belimumab use showed no association with outcomes. COVID-19 vaccines are safe in SLE with minimal risk of severe flares (< 2%). Vaccine efficacy is negatively associated with glucocorticoids. The overall attitude of patients towards vaccination is positive (54-90%). The pandemic has negatively affected access to medical care, hospitalizations, procurement of drugs, employment, and the mental health of patients which need to be addressed as part of holistic care in SLE. Key Points • Lupus patients are at a greater risk of acquiring COVID-19, related hospitalization,  severe  disease, and death than the general population. • COVID-19 vaccines are relatively safe for lupus patients with minimal risk of severe flares. • Lupus patients' attitude towards COVID-19 vaccination is predominantly positive., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)