Recent Submissions

  • Eight pruning deep learning models for low storage and high-speed COVID-19 computed tomography lung segmentation and heatmap-based lesion localization: A multicenter study using COVLIAS 2.0

    Agarwal M; Agarwal S; Saba L; Chabert GL; Gupta S; Carriero A; Pasche A; Danna P; Mehmedovic A; Faa G; et al. (Elsevier, 2022-06-25)
    Background:�COVLIAS 1.0: an automated lung segmentation was designed for COVID-19 diagnosis. It has issues related to storage space and speed. This study shows that COVLIAS 2.0 uses pruned AI (PAI) networks for improving both storage and speed, wiliest high performance on lung segmentation and lesion localization. Method:�ology: The proposed study uses multicenter ?9,000 CT slices from two different nations, namely, CroMed from Croatia (80 patients, experimental data), and NovMed from Italy (72 patients, validation data). We hypothesize that by using pruning and evolutionary optimization algorithms, the size of the AI models can be reduced significantly, ensuring optimal performance. Eight different pruning techniques (i) differential evolution (DE), (ii) genetic algorithm (GA), (iii) particle swarm optimization algorithm (PSO), and (iv) whale optimization algorithm (WO) in two deep learning frameworks (i) Fully connected network (FCN) and (ii) SegNet were designed. COVLIAS 2.0 was validated using "Unseen NovMed" and benchmarked against MedSeg. Statistical tests for stability and reliability were also conducted. Results:�Pruning algorithms (i) FCN-DE, (ii) FCN-GA, (iii) FCN-PSO, and (iv) FCN-WO showed improvement in storage by 92.4%, 95.3%, 98.7%, and 99.8% respectively when compared against solo FCN, and (v) SegNet-DE, (vi) SegNet-GA, (vii) SegNet-PSO, and (viii) SegNet-WO showed improvement by 97.1%, 97.9%, 98.8%, and 99.2% respectively when compared against solo SegNet. AUC > 0.94 (p < 0.0001) on CroMed and > 0.86 (p < 0.0001) on NovMed data set for all eight EA model. PAI <0.25 s per image. DenseNet-121-based Grad-CAM heatmaps showed validation on glass ground opacity lesions. Conclusions:�Eight PAI networks that were successfully validated are five times faster, storage efficient, and could be used in clinical settings.
  • Autonomous motivation to reduce sedentary behaviour is associated with less sedentary time and improved health outcomes in rheumatoid arthritis: a longitudinal study

    O'Brien CM; Duda JL; Kitas GD; Veldhuijzen van Zanten JJCS; Metsios GS; Fenton SAM. (BMC, 2022-10-09)
    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?�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?-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.
  • Reducing the environmental footprint of gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement

    Rodr�guez de Santiago E; Dinis-Ribeiro M; Pohl H; Agrawal D; Arvanitakis M; Baddeley R; Bak E; Bhandari P; Bretthauer M; Burga P; et al. (Thieme Gruppe, 2022-07-08)
    Climate change and the destruction of ecosystems by human activities are among the greatest challenges of the 21st century and require urgent action. Health care activities significantly contribute to the emission of greenhouse gases and waste production, with gastrointestinal (GI) endoscopy being one of the largest contributors. This Position Statement aims to raise awareness of the ecological footprint of GI endoscopy and provides guidance to reduce its environmental impact. The European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) outline suggestions and recommendations for health care providers, patients, governments, and industry. MAIN STATEMENTS 1: GI endoscopy is a resource-intensive activity with a significant yet poorly assessed environmental impact. 2: ESGE-ESGENA recommend adopting immediate actions to reduce the environmental impact of GI endoscopy. 3: ESGE-ESGENA recommend adherence to guidelines and implementation of audit strategies on the appropriateness of GI endoscopy to avoid the environmental impact of unnecessary procedures. 4: ESGE-ESGENA recommend the embedding of reduce, reuse, and recycle programs in the GI endoscopy unit. 5: ESGE-ESGENA suggest that there is an urgent need to reassess and reduce the environmental and economic impact of single-use GI endoscopic devices. 6: ESGE-ESGENA suggest against routine use of single-use GI endoscopes. However, their use could be considered in highly selected patients on a case-by-case basis. 7: ESGE-ESGENA recommend inclusion of sustainability in the training curricula of GI endoscopy and as a quality domain. 8: ESGE-ESGENA recommend conducting high quality research to quantify and minimize the environmental impact of GI endoscopy. 9: ESGE-ESGENA recommend that GI endoscopy companies assess, disclose, and audit the environmental impact of their value chain. 10: ESGE-ESGENA recommend that GI endoscopy should become a net-zero greenhouse gas emissions practice by 2050.
  • Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration

    Ng GA; Mistry A; Newton M; Schlindwein FS; Barr C; Bates MG; Caldwell J; Das M; Farooq M; Herring N; et al. (BMJ Publishing Group, 2022-01-04)
    Introduction:�The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication. Methods and analysis:�Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia�>200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained. Ethics and dissemination:�Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries.
  • Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study

    Rostami K; Ensari A; Marsh MN; Srivastava A; Villanacci V; Carroccio A; Asadzadeh Aghdaei H; Bai JC; Bassotti G; Becheanu G; et al. (MDPI, 2022-06-24)
    Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in ?m), crypt depth (CrD, in ?m), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400?705) than controls (900, IQR: 667?1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 �m (IQR: 390?620) vs. 427 �m (IQR: 348?569, p = 0�176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
  • Reducing risks for infant mortality in the Midlands, UK: a qualitative study identifying areas for improvement in the delivery of key public health messages in the perinatal period

    Pillay T; Feeney J; Walters C; Nelson H; Thomas L; Lewis D; Anderson K; Petkar A. (BMC, 2022-10-17)
    Background: The Midlands has amongst the highest rates of neonatal and infant mortality in the UK. A public health parent education and empowerment programme, aimed at reducing key risks associated with this mortality was established and evaluated in the region. This was undertaken in an attempt to identify areas for optimal delivery of the public health messages around reducing risks for neonatal and infant mortality. Method: Qualitatively assessment, using the software package Dedoose, was undertaken. This involved analysis of reflections by the programme trainers, after the delivery of their training sessions to parents, families and carers, between 01 January and 31 December 2021. These were intended to capture insights from the trainers on parent, family, carer and staff perspectives, perceptions/misperceptions around reducing risks for infant mortality. Potential areas for improvement in delivery of the programme were identified from this analysis. Results: A total of 323 programmes, comprising 524 parents, family members and carers were offered the programme. Analysis of 167 reflections around these interactions and those of staff (n = 29) are reported. The programme was positively received across parents, families, carers and staff. Four overall themes were identified: (a) reach and inclusion, (b) knowledge, (c) practical and emotional support and (d) challenges for delivery of the programme. Recommendations for improved delivery of the programme were identified, based on qualitative analysis. Conclusion: This novel approach to empowerment and education around neonatal public health messaging is a valuable tool for parents, families, carers and staff in the Midlands. Key practical recommendations for enhancing delivery of these critical public health messages were identified
  • Exercise intervention on cardiorespiratory fitness in rheumatoid arthritis patients with high cardiovascular disease risk: a single-arm pilot study

    Sobejana M; van den Hoek J; Metsios GS; Kitas GD; van der Leeden M; Verberne S; Jorstad HT; Pijnappels M; Lems WF; Nurmohamed MT; et al. (Springer, 2022-08-25)
    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).
  • Knowledge and Perceptions of Reactive Arthritis Diagnosis and Management Among Healthcare Workers During the COVID-19 Pandemic: Online Survey

    Bekaryssova D; Joshi M; Gupta L; Yessirkepov M; Gupta P; Zimba O; Gasparyan AY; Ahmed S; Kitas GD; Agarwal V. (Korean Academy of Medical Sciences, 2022-12-27)
    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.
  • COVLIAS 1.0(Lesion) vs. MedSeg: An Artificial Intelligence Framework for Automated Lesion Segmentation in COVID-19 Lung Computed Tomography Scans

    Suri JS; Agarwal S; Chabert GL; Carriero A; Pasch� A; Danna PSC; Saba L; Mehmedovi? A; Faa G; Singh IM; et al. (MDPI, 2022-05-28)
    Background: COVID-19 is a disease with multiple variants, and is quickly spreading throughout the world. It is crucial to identify patients who are suspected of having COVID-19 early, because the vaccine is not readily available in certain parts of the world. Methodology: Lung computed tomography (CT) imaging can be used to diagnose COVID-19 as an alternative to the RT-PCR test in some cases. The occurrence of ground-glass opacities in the lung region is a characteristic of COVID-19 in chest CT scans, and these are daunting to locate and segment manually. The proposed study consists of a combination of solo deep learning (DL) and hybrid DL (HDL) models to tackle the lesion location and segmentation more quickly. One DL and four HDL models�namely, PSPNet, VGG-SegNet, ResNet-SegNet, VGG-UNet, and ResNet-UNet�were trained by an expert radiologist. The training scheme adopted a fivefold cross-validation strategy on a cohort of 3000 images selected from a set of 40 COVID-19-positive individuals. Results: The proposed variability study uses tracings from two trained radiologists as part of the validation. Five artificial intelligence (AI) models were benchmarked against MedSeg. The best AI model, ResNet-UNet, was superior to MedSeg by 9% and 15% for Dice and Jaccard, respectively, when compared against MD 1, and by 4% and 8%, respectively, when compared against MD 2. Statistical tests�namely, the Mann?Whitney test, paired t-test, and Wilcoxon test�demonstrated its stability and reliability, with p < 0.0001. The online system for each slice was <1 s. Conclusions: The AI models reliably located and segmented COVID-19 lesions in CT scans. The COVLIAS 1.0Lesion lesion locator passed the intervariability test.
  • An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries

    Rollefstad S; Ikdahl E; Wibetoe G; Sexton J; Crowson CS; van Riel P; Kitas GD; Graham I; Dahlqvist SR; Karpouzas G; et al. (Oxford University Press, 2021-07-07)
    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.
  • Corrigendum to 'An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs' [J Hepatol 2021;75(3):572-581]

    Cordell HJ; Fryett JJ; Ueno K; Darlay R; Aiba Y; Hitomi Y; Kawashima M; Nishida N; Khor SS; Gervais O; et al. (Elsevier, 2021-12-13)
  • The cost-effectiveness of antenatal and postnatal education and support interventions for women aimed at promoting breastfeeding in the UK

    Mavranezouli I; Varley-Campbell J; Stockton S; Francis J; Macdonald C; Sharma S; Fleming P; Punter E; Barry C; Kallioinen M; et al. (BMC, 2022-01-22)
    Background:�Breastfeeding is associated with health benefits to mothers and babies and cost-savings to the health service. Breastfeeding rates in the UK are low for various reasons including cultural barriers, inadequate support to initiate and sustain breastfeeding, lack of information, or choice not to breastfeed. Education and support interventions have been developed aiming at promoting breastfeeding rates. The objective of this study was to assess the cost-effectiveness of such interventions for women, initiated antenatally or in the first 8 weeks postnatally, aiming at improving breastfeeding rates, in the UK. Methods:�A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of a breastfeeding intervention from the perspective of health and personal social services in England. Data on intervention effectiveness and the benefits of breastfeeding were derived from systematic reviews. Other model input parameters were obtained from published sources, supplemented by expert opinion. Results:�The incremental cost-effectiveness ratio (ICER) of the modelled intervention added on standard care versus standard care was �51,946/QALY, suggesting that the intervention is not cost-effective under National Institute for Health and Care Excellence (NICE) criteria in England. Sensitivity analysis suggested that the cost-effectiveness of the intervention improved as its effectiveness increased and intervention cost decreased. At the base-case effect (increase in breastfeeding rates 16-26 weeks after birth by 19%), the intervention was cost-effective (<�20,000/QALY) if its cost per woman receiving the intervention became ?�40-�45. At the base-case cost (�84), the intervention was cost-effective if it increased breastfeeding rates by at least 35-40%. Conclusions:�Available breastfeeding interventions do not appear to be cost-effective under NICE criteria in England. Future breastfeeding interventions need to have higher effectiveness or lower cost compared with currently available interventions in order to become cost-effective. Public health and other societal interventions that protect, promote and support breastfeeding may be key in improving breastfeeding rates in the UK.
  • COVLIAS 2.0-cXAI: Cloud-Based Explainable Deep Learning System for COVID-19 Lesion Localization in Computed Tomography Scans

    Suri JS; Agarwal S; Chabert GL; Carriero A; Pasch� A; Danna PSC; Saba L; Mehmedovi? A; Faa G; Singh IM; et al. (MDPI, 2022-06-24)
    Background: The previous COVID-19 lung diagnosis system lacks both scientific validation and the role of explainable artificial intelligence (AI) for understanding lesion localization. This study presents a cloud-based explainable AI, the �COVLIAS 2.0-cXAI� system using four kinds of class activation maps (CAM) models. Methodology: Our cohort consisted of ~6000 CT slices from two sources (Croatia, 80 COVID-19 patients and Italy, 15 control patients). COVLIAS 2.0-cXAI design consisted of three stages: (i) automated lung segmentation using hybrid deep learning ResNet-UNet model by automatic adjustment of Hounsfield units, hyperparameter optimization, and parallel and distributed training, (ii) classification using three kinds of DenseNet (DN) models (DN-121, DN-169, DN-201), and (iii) validation using four kinds of CAM visualization techniques: gradient-weighted class activation mapping (Grad-CAM), Grad-CAM++, score-weighted CAM (Score-CAM), and FasterScore-CAM. The COVLIAS 2.0-cXAI was validated by three trained senior radiologists for its stability and reliability. The Friedman test was also performed on the scores of the three radiologists. Results: The ResNet-UNet segmentation model resulted in dice similarity of 0.96, Jaccard index of 0.93, a correlation coefficient of 0.99, with a figure-of-merit of 95.99%, while the classifier accuracies for the three DN nets (DN-121, DN-169, and DN-201) were 98%, 98%, and 99% with a loss of ~0.003, ~0.0025, and ~0.002 using 50 epochs, respectively. The mean AUC for all three DN models was 0.99 (p < 0.0001). The COVLIAS 2.0-cXAI showed 80% scans for mean alignment index (MAI) between heatmaps and gold standard, a score of four out of five, establishing the system for clinical settings. Conclusions: The COVLIAS 2.0-cXAI successfully showed a cloud-based explainable AI system for lesion localization in lung CT scans.
  • The role of asymmetric dimethylarginine in endothelial dysfunction and abnormal nitric oxide metabolism in systemic sclerosis: results from a pilot study

    Pagkopoulou E; Soulaidopoulos S; Katsiki N; Malliari A; Loutradis C; Karagiannis A; Doumas M; Garyfallos A; Kitas G; Dimitroulas T. (Springer, 2022-12-19)
    Introduction/objectives:�Systemic sclerosis (SSc) is characterized by generalized vasculopathy affecting mainly small vessels while macrovascular involvement is less investigated. The aim of this study was to examine associations between asymmetric dimethylarginine (ADMA) - a biomarker of atherosclerosis - and assessments of macrovascular endothelial function in patients with SSc. Methods:�This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA measurement in serum samples was based on an enzyme immunoassay technique. Participants underwent blood pressure measurement according to 2018 ESC/ESH Guidelines, applanation tonometry for the evaluation of arterial stiffness, and carotid ultrasound for the measurement of the intima-media thickness (cIMT). Results:�Eighty-one Caucasians (82.3% female) SSc individuals with mean age 55.44 � 13.4 years were included in this analysis. The correlation analysis of ADMA levels (unadjusted and adjusted values) with functional and morphological parameters of atherosclerosis revealed no statistically significant associations. Subgroup analysis based on disease duration (? 4 years), immunologic profile (SCL-70 and ACA antibodies), disease type (limited, diffuse), and inflammatory status (erythrocyte sedimentation rate [ESR] > 25 mm/h and C-reactive protein [CRP] > 5 mg/L) showed no associations, except from a significant positive correlation between ADMA levels and c???mean�(r = 0.370, p = 0.044) in individuals with early SSc. Conclusions:�The results of the study suggest that ADMA may be related with accelerated atherosclerosis in early stages of the disease. However, the lack of association between other morphological and functional parameters of endothelial dysfunction may suggest that other regulators of nitric oxide metabolism may contribute to macrovascular injury in SSc in various phases of the disease. Key Points � ADMA is a biomarker of atherosclerosis and has been linked with microvascular complications of SSc. �ADMA was not correlated with morphological and functional parameters of atherosclerosis in the population of the study. �The demonstrated association between ADMA and cIMT in patients with early SSc may suggest a role of NO/ADMA pathway in the initiation of macrovascular injury in SSc.
  • Cardiovascular disease detection using machine learning and carotid/femoral arterial imaging frameworks in rheumatoid arthritis patients

    Konstantonis G; Singh KV; Sfikakis PP; Jamthikar AD; Kitas GD; Gupta SK; Saba L; Verrou K; Khanna NN; Ruzsa Z; et al. (Springer, 2022-01-11)
    The study proposes a novel machine learning (ML) paradigm for cardiovascular disease (CVD) detection in individuals at medium to high cardiovascular risk using data from a Greek cohort of 542 individuals with rheumatoid arthritis, or diabetes mellitus, and/or arterial hypertension, using conventional or office-based, laboratory-based blood biomarkers and carotid/femoral ultrasound image-based phenotypes. Two kinds of data (CVD risk factors and presence of CVD-defined as stroke, or myocardial infarction, or coronary artery syndrome, or peripheral artery disease, or coronary heart disease) as ground truth, were collected at two-time points: (i) at visit 1 and (ii) at visit 2 after 3 years. The CVD risk factors were divided into three clusters (conventional or office-based, laboratory-based blood biomarkers, carotid ultrasound image-based phenotypes) to study their effect on the ML classifiers. Three kinds of ML classifiers (Random Forest, Support Vector Machine, and Linear Discriminant Analysis) were applied in a two-fold cross-validation framework using the data augmented by synthetic minority over-sampling technique (SMOTE) strategy. The performance of the ML classifiers was recorded. In this cohort with overall 46 CVD risk factors (covariates) implemented in an online cardiovascular framework, that requires calculation time less than 1 s per patient, a mean accuracy and area-under-the-curve (AUC) of 98.40% and 0.98 (p < 0.0001) for CVD presence detection at visit 1, and 98.39% and 0.98 (p < 0.0001) at visit 2, respectively. The performance of the cardiovascular framework was significantly better than the classical CVD risk score. The ML paradigm proved to be powerful for CVD prediction in individuals at medium to high cardiovascular risk.
  • The Effect of Gluten-Free Diet Duration on Body Mass Index of Iranian Patients with Celiac Disease

    Asri N; Taraghikhah N; Baniasadi R; Ishaq S; Rezaei-Tavirani M; Sadeghi A; Ehsani-Ardakani MJ; Jahani-Sherafat S; Asadzadeh Aghdaei H; Rostami-Nejad M. (2023-01-09)
    Background: A gluten-free diet (GFD) is the only effective treatment of celiac disease (CD) that is associated with body mass index (BMI) changes. This study aimed to determine how GFD duration affects the BMI of Iranian patients with CD.�Methods: In this prospective study, 215 patients with CD, who were on a GFD, were categorized into three groups according to the duration of compliance to GFD: 1. patients with less than 6 months of diet, 2. Patients who had a diet for 6 months to 2 years, and 3. patients with more than 2 years of diet. The BMI changes were assessed before and after adherence to the GFD.�Results: Most patients' weight remains in the same BMI category during different courses of GFD adherence. Patients who were underweight showed significant changes in their BMI following the diet in less than 6 months (P=0.033) and more than 2 years (P<0.001), and the number of weight gain cases increased over time.�Conclusion: There is a need for careful, updated, and personalized nutrition management of patients with CD in different periods of the diet. Conducting similar studies with larger sample sizes in different regions can lead to providing expert dietary counseling for patients with CD.
  • Oral anticoagulant treatment in rheumatoid arthritis patients with atrial fibrillation results of an international audit

    Semb AG; Rollefstad S; Sexton J; Ikdahl E; Crowson CS; van Riel P; Kitas G; Graham I; Kerola AM; SURF-RA. (Elsevier, 2022-09-19)
    Objective:�To describe the prevalence of atrial fibrillation (AF) in patients with rheumatoid arthritis (RA), and to evaluate the proportion of patients with AF receiving guideline-recommended anticoagulation for prevention of stroke, based on data from a large international audit. Methods:�The cohort was derived from the international audit�SUrvey of cardiovascular disease�Risk�Factors in patients with�Rheumatoid�Arthritis (SURF-RA) which collected data from 17 countries during 2014-2019. We evaluated the prevalence of AF across world regions and explored factors associated with the presence of AF with multivariable logistic regression models. The proportion of AF patients at high risk of stroke (CHA2DS2-VASc ? 2 in males and ? 3 in females) receiving anticoagulation was examined. Results:�Of the total SURF-RA cohort (n = 14,503), we included RA cases with data on whether the diagnosis of AF was present or not (n = 7,665, 75.1% women, mean (SD) age 58.7 (14.1) years). A total of 288 (3.8%) patients had a history of AF (4.4% in North America, 3.4% in Western Europe, 2.8% in Central and Eastern Europe and 1.5% in Asia). Factors associated with the presence of AF were older age, male sex, atherosclerotic cardiovascular disease, heart failure and hypertension. Two-hundred and fifty-five (88.5%) RA patients had a CHA2DS2-VASc score indicating recommendation for oral anticoagulant treatment, and of them, 164 (64.3%) were anticoagulated. Conclusion:�Guideline-recommended anticoagulant therapy for prevention of stroke due to AF may not be optimally implemented among RA patients, and requires special attention.
  • A Clinical Audit of Cardiovascular Risk Factors and Disease in Patients with Rheumatoid Arthritis - SURF-RA

    Semb AG; Ikdahl E; Kerola AM; Wibetoe G; Sexton J; Crowson CS; van Riel P; Kitas G; Graham I; Rollefstad S; et al. (Greek Rheumatology Society and Professional Association of Rheumatologists, 2022-09-21)
    Background and aims:�Rheumatoid arthritis (RA) patients are at a high risk of atherosclerotic cardiovascular disease (ASCVD). This implies a need for meticulous CVD risk factor recording and control. Objectives:�The aim was to evaluate the international prevalence of ASCVD in RA patients and to audit the prevalence and control of CVD risk factors. Methods:�A�SUrvey of cardiovascular disease�Risk�Factors in patients with�Rheumatoid�Arthritis (SURF-RA) was performed at 53 centres in 19 countries in three continents between 2014 and 2019. CVD risk factors, medication, and physical and laboratory measurements were recorded. CVD risk was estimated using the ESC's SCORE system. Results:�Among 14503 RA patients in Western (n=8493) and Central and Eastern (n=923) Europe, Mexico (n=407), North America (n=4030) and Asia (n=650) (mean age 59.9 years, 74.5% female), ASCVD was present in 15%, varying from 2.5% in Mexico to 21% in Central and Eastern Europe. Sixty-two percent reported hypertension and 63% had a LDL-c of > 2.5 mmol/L. Mean BMI was 27.4 kg/m2�in the total cohort, highest in North America (29.7 kg/m2), and lowest in Asia (23.8 kg/m2). A sixth of patients were current smokers, and 13% had diabetes mellitus. Approximately 45% had an estimated high or very high risk of fatal CVD according to SCORE algorithm, and � of patients had only ?4/6 CVD risk factors at recommended target. Conclusion:�Among RA patients across three continents, established CVD and CVD risk factors are common, although geographical variation exists. Furthermore, CVD risk factors often remain inadequately controlled.
  • Highly cited papers in Takayasu arteritis on Web of Science and Scopus: cross-sectional analysis

    Misra DP; Agarwal V; Gasparyan AY; Zimba O; Sharma A. (Springer, 2021-09-04)
    Background:�Takayasu arteritis (TAK) is a large vessel vasculitis affecting relatively younger population. Since literature on bibliometric analysis of TAK is scarce, we analyzed top-cited articles in TAK to address this knowledge gap. Methods:�We analyzed the top hundred cited articles in TAK on Web of Science and Scopus for time of publication, article type, country of origin, source journal, and authors. Furthermore, we conducted univariable- and multivariable-adjusted linear regression analyses to explore associations of rank of cited articles, mean number of annual citations, and total citations with traditional (journal impact factor, CiteScore) and alternative (PlumX) metrics. Results:�Concordance between databases was 76%. Most top-cited articles were from the USA, Japan, or the UK, and published in Annals of the Rheumatic Diseases, Arthritis and Rheumatism, and Circulation and Rheumatology (Oxford). Original articles comprised a majority of these top-cited articles. Articles describing criteria or disease management recommendations received the highest mean number of citations. Performing multivariable-adjusted linear regression analyses, years of publication associated with mean annual citations on Web of Science as well as total citations across databases (p < 0.01). The 2-year JIF significantly associated with mean annual citations on Web of Science (p = 0.047). On Scopus, the number of captures denoted under PlumX metrics consistently associated with citations (p < 0.001). Conclusion:�Both traditional and alternative metrics associate with higher citations in TAK. Development of disease assessment and clinical practice guidelines and conduct and reporting of randomized controlled trials to guide TAK management are important research areas. The key points themselves are all right. Key Points � A majority of top-cited papers in TAK are original articles. � Both traditional and alternative metrics associate with number of citations for these papers. � Recommendations for disease assessment or clinical practice and clinical trials are important research
  • An Unusual Presentation of Subacute Thyroiditis As Pyrexia of Unknown Origin With Normal Thyroid Functions

    Waqar M; Okaneme C; Rasthapuram S; Aadil M; Saeed T. (Springer, 2022-10-13)
    Subacute thyroiditis is a rare condition believed as immune-mediated inflammation of the thyroid gland that frequently manifests after a viral upper respiratory tract infection. A 52-year-old South-Asian female patient presented to Same Day Emergency Care (SDEC) with feeling unwell and sore throat. Moreover, she reported low-grade fever, fatigue, headache, and breathlessness on exertion for the past five weeks. She had a past medical history of gastroesophageal reflux disease. She had no associated cough, rigors, chills, urinary symptoms, night sweats, or weight loss. There was no history of recent travel abroad. On examination, she was tachycardic; however, there was no lymphadenopathy, palpable thyroid gland, skin rash, or signs of infective endocarditis. Routine blood analysis showed elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and normal white blood cell count. Her thyroid stimulating hormone (TSH) was normal. Chest X-ray and echocardiogram were unremarkable. She was prescribed clarithromycin with no effect. After inconclusive results of the routine investigation and no response to antibiotics, a computed tomography (CT) scan of the thorax, abdomen, and pelvis (TAP) was performed, which revealed a thickened thyroid isthmus. Positron Emission Tomography (PET) scan revealed bulky appearances of the thyroid gland with diffuse increased uptake suggestive of thyroiditis. Prednisolone 30mg daily was prescribed, which was later reduced by 5mg weekly for six weeks. The patient showed improvement in symptoms, and normal ESR and CRP were achieved.

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