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Summary: Pseudoxanthoma elasticum (PXE) is a rare disorder characterized by fragmentation and progressive calcification of elastic fibres in connective tissues. Overlap has been reported between the inherited PXE phenotype associated with ENPP1,ABCC6 or NT5E mutations and acquired PXE clinical manifestations associated with haemoglobinopathies induced by HBB mutations. No treatment is currently available for PXE. A young boy presented with severe early‐onset systemic calcifications occurring in the skin as elastosis perforans serpiginosa (EPS) and in the arteries, causing mesenteric and limb ischaemia. Analyses revealed deleterious ABCC6,ENPP1 and HBB mutations. The diagnosis of severe PXE was retained and we have coined the term 'PXE+ syndrome' to describe the cumulative effects of the various mutations in this uncommon phenotype. Given the severity, rapid progression and a potentially fatal prognosis, intravenous sodium thiosulfate (STS) was initiated at 25 g three times weekly for 6 months. Numerous side‐effects prompted dosage adjustment to 10 g intravenously daily. Treatment efficacy was evaluated at 6 months. Asthaenia, anorexia and pre‐/postprandial pain had subsided, entailing weight gain. Abdominal EPS had diminished. Calcific stenosis of the coeliac and mesenteric arteries was no longer detectable on arterial ultrasonography. Follow‐up revealed only transient efficacy of STS. Discontinuation of treatment to evaluate the persistence of effects resulted in relapse of the initial symptomatology after 4 months. STS efficacy is conceivably due to strong antioxidant properties and chelation of calcium to form soluble calcium thiosulfate complexes. This case is suggestive of PXE+ syndrome for which STS may represent potential treatment in severe cases. What's already known about this topic? Generalized arterial calcification of infancy may occur in association with ABCC6 mutations and pseudoxanthoma elasticum (PXE) can be linked to ENPP1 mutations.A PXE‐like phenotype has also been reported in a subset of patients with inherited haemoglobinopathies, namely sickle cell disease or β‐thalassaemia, related to HBB mutations.To date, there is still no cure for PXE. What does this study add? We report a severe case of PXE resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB. We suggest the term 'PXE+ syndrome' to describe such patients.Sodium thiosulfate therapy could represent a potential option in severe cases of PXE+ syndrome. [ABSTRACT FROM AUTHOR]

Background: The sensitivity and specificity of exercise testing have never been studied simultaneously against an objective quantification of arterial stenosis. Aims were to define the sensitivity and specificity of several exercise tests to detect peripheral artery disease (PAD), and to assess whether or not defined criteria defined in patients suspected of having a PAD show a difference dependent on the resting ABI. Methods: In this prospective study, consecutive patients with exertional limb pain referred to our vascular center were included. All patients had an ABI, a treadmill exercise-oximetry test, a second treadmill test (both 10% slope; 3.2km/h speed) with post-exercise pressures, and a computed-tomography-angiography (CTA). The receiver-operating-characteristic curve was used to define a cut-off point corresponding to the best area under the curve (AUC; [CI95%]) to detect arterial stenosis ≥50% as determined by the CTA. Results: Sixty-three patients (61+/-11 years-old) were included. Similar AUCs from 0.72[0.63–0.79] to 0.83[0.75–0.89] were found for the different tests in the overall population. To detect arterial stenosis ≥50%, cut-off values of ABI, post-exercise ABI, post-exercise ABI decrease, post-exercise ankle pressure decrease, and distal delta from rest oxygen pressure (DROP) index were ≤0.91, ≤0.52, ≥43%, ≥20mmHg and ≤-15mmHg, respectively (p<0.01). In the subset of patients with an ABI >0.91, cut-off values of post-exercise ABI decrease (AUC = 0.67[0.53–0.78]), and DROP (AUC = 0.67[0.53–0.78]) were ≥18.5%, and ≤-15mmHg respectively (p<0.05). Conclusion: Resting ABI is as accurate as exercise testing in patients with exertional limb pain. Specific exercise testing cut-off values should be used in patients with normal ABI to diagnose PAD. [ABSTRACT FROM AUTHOR]

Introduction L’IL–26 possède grâce à ses propriétés pharmaco-chimiques et à sa conformation en multimère, une activité bactéricide en formant des pores à la surface des cellules bactériennes. L’IL–26 peut se lier à l’ADN bactérien et former un complexe permettant de protéger l’ADN lié à des DNases présentes dans le milieu extracellulaire et lui confère une immunogénicité après contact avec les cellules dendritiques. Chez l’homme, la formation de complexe ADN humain avec l’IL–26 a également été confirmée après mise en contact in-vitro de cellules apoptotiques et d’IL–26, qui en présence de cellules dendritiques aboutit à la production de cytokines pro-inflammatoires. L’IL-26 apparaît comme une cytokine pouvant être impliquée dans la physiopathogénèse du LES, du fait de son mode d’action, notamment, sa liaison à l’ADN et de sa possible co-responsabilité dans la genèse des anticorps anti-DNA ; de son appartenance à la famille des IL–10, dont la concentration sérique semble augmentée et corrélée à l’activité du lupus ; de sa sécrétion principalement par les lymphocytes Th17. Ainsi, nous avons réalisé une étude multicentrique afin d’évaluer si le taux d’IL26 est surexprimé chez les patients avec un LES par rapport aux témoins. Les objectifs secondaires consistaient, dans la recherche, des corrélations entre le taux de IL26 et des différents paramètres clinico-biologiques des patients lupiques. Patients et méthodes Dans le cadre de l’étude, nous avons recueilli des sérums provenant de l’étude Plaquénil Lupus systémique (PLUS). Nous avons étudié 110 sérums, dont 55 des patients SAPL + et 55 patients SAPL. Quatre-vingt-huit sérums ont été recueillis auprès de l’EFS du CHU d’Angers sur des témoins sains appariés sur l’âge et sexe. L’âge, le sexe, l’année du diagnostic du lupus, les critères de SAPL, les critères ACR du lupus, la créatininémie, la protéinurie, la présence d’anticorps anti-nucléaires, le titre d’anticorps anti-nucléaires et le score d’activité SLEDAI à la visite, ont été recueillis pour les 110 patients de l’étude PLUS. Les patients inclus dans l’étude bénéficiaient du dosage de la concentration sérique en IL–26. La concentration d’IL-26 sérique a été mesurée au laboratoire d’immunologie du CHU d’Angers par méthode ELISA comme décrit précédemment. L’analyse statistique a été réalisée avec l’aide des logiciels Excel ® version 2010 de Microsoft ® et du logiciel IBM ® SPSS ® statistics version 23. Pour l’analyse comparative des groupes, le test t de Student a été utilisé pour les variables quantitatives après avoir préalablement vérifié l’égalité des variances pour les paramètres étudiés et le test du Chi 2 pour les variables qualitatives nominales. La recherche de corrélation utilisait le calcul du coefficient rho de Spearman du fait de l’effectif faible de patients, du caractère non paramétrique et de la distribution non normale des données. Il était admis un risque d’erreur alpha de 5 % avec une significativité pour p < 0,05. Résultats La concentration sérique en IL–26 était significativement plus élevée chez les patients lupiques versus les témoins sains. La concentration sérique d’IL–26 était corrélée de façon significative au SLEDAI avec un coefficient de corrélation rho de Spearman à 0,697 ; p < 0,0001. La concentration sérique d’IL–26 était statistiquement corrélée au taux d’anticorps anti-nucléaires évalués en immunofluorescence indirecte avec un coefficient de corrélation rho de Spearman à 0,219 avec p < 0,05. La concentration sérique en IL–26 était aussi corrélée à la durée d’évolution de la maladie avec un coefficient rho de Spearman à 0,198 avec p < 0,05. En dernier la concentration sérique en IL–26 était statistiquement corrélée à la protéinurie sur échantillon avec un coefficient de corrélation rho de Spearman à 0,371 avec p < 0,0001. De même la concentration d’IL–26 était corrélée au ratio protéinurie/créatinurie avec un coefficient rho de Spearman à 0,328 ; p = 0,01. Il n’y avait pas de différence significative en ce qui concernes les concentrations de l’IL–26 dans les deux sous-groupes de patients lupiques, avec ou sans un syndrome des anti-phospholipides associé. Conclusion Nous avons pu observer dans notre étude que les patients lupiques ont une concentration sérique en IL-26 plus importante que les témoins sains. IL26 était coorélé avec des paramètres d’activité du LES dont en principalleSLEDAI, le titre d’anticorps ANA, la protéinurie. L’étude met en évidence un possible nouveau biomarqueur dans le lupus et de nouvelles perspectives de recherche dans l’étude de la physiopathologie du lupus. [ABSTRACT FROM AUTHOR]

Introduction La fatigue ne fait pas partie des critères diagnostiques du syndrome de Sjögren mais elle constitue une des principales plaintes des patients souffrant du syndrome de Sjögren. Les explorations menées ont parfois incriminé la dépression et la fibromyalgie sans toutefois apparaître unicistes. Plus récemment, un lien entre cytokines pro-inflammatoires et fatigue a été mis en évidence. Nous avons donc décidé d’évaluer la sévérité et les différentes composantes de la fatigue dans notre population de syndromes de Sjögren, exprimant une fatigue. Patients et méthodes Nous avons inclus de façon prospective les patients souffrants d’un syndrome de Sjögren répondant aux critères diagnostiques américano-européens et exprimant une fatigue ( n = 32). Nous avons évalué les échelles visuelles analogiques (sur 100 mm) des symptômes suivants : sécheresses oculaire et buccale, arthralgies et fatigue. La sévérité de la fatigue a été appréciée à l’aide du score Fatigue Severity Scale (FSS) dont un score supérieur à 4 sur 7 témoigne d’une fatigue sévère, validée chez des patients lupiques. L’auto-questionnaire WHOQOL-Bref (World Health Organization Quality Of Life) a permis de comparer l’impact de la fatigue sur les dimensions physique, psychologique, sociale et environnemental du bien-être, chacune sur 100 (100 équivaut à une qualité de vie optimale). La dépression a été évaluée par l’auto-questionnaire Hospital Anxiety and Depression Scale-Depression (HADS-D) avec un seuil diagnostique à 11. Le diagnostic de fibromyalgie a été apprécié par le score Fibromyalgia ACR 2010 (FA2010) avec un seuil diagnostique des 2 items associés à 12. Les données quantitatives sont exprimées en moyenne ± écart à la moyenne (SEM). Résultats L’EVA fatigue (58,3 mm) n’est pas différente de l’EVA sécheresse buccale (57,6 mm) mais supérieure aux EVA sécheresse oculaire (46 mm, p = 0,038) et arthralgies (40,7 mm, p = 0,01). Le score FSS moyen est de 4,82 ± 0,24 avec 24 patients (75 %) présentant un score supérieur à 4. La dimension physique du WHOQOL (47,9 ± 2,9) est inférieure aux dimensions psychologiques (59 ± 2,8, p = 0,008), sociale (65,8 ± 3,1, p < 0,0001) et environnementale (69,7±2,6, p < 0,0001). Le score moyen HADS-D est de 6,3 ± 0,6 avec 2 patients (6,8 %) supérieur au seuil diagnostique. Le score moyen FA2010 est de 9,7 ± 0,9 avec 11 patients (34,3 %) supérieur au seuil diagnostique. Discussion Dans notre population de syndromes de Sjögren, la fatigue est un symptôme de premier plan et elle apparaît sévère chez 75 % d’entre eux. Le domaine physique est plus altéré que les autres dimensions de la qualité de vie. Chez ces patients, la dépression et la fibromyalgie seules ne peuvent expliquer la fatigue. Nous pensons que la fatigue dans le syndrome de Sjögren est physique, probablement liée à l’activité de la maladie comme l’efficacité des biothérapies anti-CD20 peut le laisser sous-entendre. Conclusion Cette étude démontre l’intérêt de poursuivre les investigations afin de comprendre l’origine de la fatigue dans le syndrome de Sjögren. [ABSTRACT FROM AUTHOR]

Background: Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose Lower Extremity Artery Disease (LEAD) and allows the quantification of limb ischemia during exercise on treadmill. Exercise-TcPO2 test-retest reliability in patients with LEAD and severe walking impairment is unknown. The aim of this study was to evaluate the test-retest reliability, standard error of measurement (SEM), and Minimal Detectable Change (MDC) of exercise-TcPO2 in patients with claudication., Methods: Data were collected from patients that performed 2 treadmill tests within a 1-month interval. Delta from Rest of Oxygen Pressure (DROP) values were measured at both buttocks (proximal) and both calves (distal). Test-retest reproducibility was assessed by recording transcutaneous oximetry measurements twice and expressed as SEM and intra-class correlation coefficients. MDC was calculated using the formula MDC = SEM x 1.96 x √ 2., Results: Twenty eight LEAD patients (61 ± 9 years old) were included. Intra-class correlation coefficients were 0.66 [0.50, 0.79] and 0.65 [0.49, 0.79] for the proximal and distal levels, respectively. The SEM of DROP at the proximal and distal levels were 7 [6, 9] mm Hg and 9 [8, 11] mm Hg, respectively. The SEM for all (proximal and distal) DROP values was 8 [7, 10] mm Hg and the MDC of DROP was 23 mm Hg., Conclusions: Exercise-TcPO2 with measurement of DROP values has a moderate test-retest reliability in LEAD patients with a maximal walking distance ≤ 300m. For an individual, an improvement or deterioration in DROP of ≥ 23 mm Hg after an intervention would be required to be 95% confident that the change is significant. It should be considered in evaluating the impact of treatment in patients with claudication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Ankle-brachial index (ABI) is commonly used for screening lower extremity peripheral artery disease (PAD) according to the international guidelines. Arterial Doppler waveform recordings is a tool to diagnose and assess PAD severity. We hypothesized that ABI measurement could be simplified by measuring only the pressure where the best arterial flow is recorded. The aim of this study was to evaluate the concordance between ABI performed according to the American Heart Association guidelines (AHA-ABI) and ABI measured according to best arterial waveform (FLOW-ABI)., Design: This was a monocentric cross-sectional study., Methods: We included patients with exertional limb symptoms suspected of PAD. Arterial Doppler waveforms and ABI were acquired on both lower extremities at the pedis and tibial posterior arteries. Each arterial waveform was classified using the Saint-Bonnet classification. Concordances were analyzed with the kappa coefficient (confidence interval 95%). Exercise PAD study was registered n° NCT03186391., Results: In total, one hundred and eighty-eight patients (62+/-12 years and 26.8+/-4.5 kg/m 2 ) with exertional limb symptoms were included from May 2016 to June 2019. On each extremity, FLOW-ABI had excellent concordance for the diagnosis of PAD with the AHA-ABI with a kappa of 0.95 (95% CI: 0.90, 0.99) in the right extremity and 0.91 (95% CI: 0.86, 0.97) in the left extremity., Conclusion: There is almost perfect concordance between AHA-ABI and FLOW-ABI. Thus, ABI can be simplified into five pressure measurements instead of seven in patient suspected of PAD with exertional limb symptoms. The question remains in patients with chronic limb ischemia., 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 © 2022 Métairie, Tollenaere, Lanéelle, Le Faucheur, Le Pabic, Omarjee and Mahé.)

Objective: Digital ulcers related to digital occlusive arterial disease (DOAD) are frequent in patients with SSc. Finger systolic blood pressure (FSBP) and digital-brachial pressure index (DBI) using laser Doppler flowmetry constitute a non-invasive means of detecting DOAD in SSc, although thresholds have yet to be established for defining DOAD. The purpose of this study was to ascertain FSBP and DBI thresholds to detect DOAD in SSc patients. The intra/interday reproducibility of curve reading by four vascular physicians in relation to finger pressure measurement was also investigated., Methods: SSc patients were followed in this single-centre study (Rennes University Hospital, France) between November 2017 and October 2019.These patients underwent tests before and after heating at two visits spaced 10 days apart. DOAD was diagnosed on the basis of post-warming skin blood flow of ≤206 arbitrary units measured by laser Doppler flowmetry, contingent on previous results validated by arteriography as a gold standard. An interday kappa coefficient with a 95% confidence interval was used to assess reproducibility., Results: Sixteen [10 females; mean age: 63 (9) years] SSc patients were included. Mean time interval between visits was 9 (5) days. The best FSBP threshold for DOAD diagnosis was 76 mmHg and DBI was 0.74 after warming. FSBP and DBI sensitivity/specificity were 59.1% (95% CI: 49.6, 68.5%)/92.5% (95% CI: 85.3, 99.6%) and 73.3% (95% CI: 64.9, 81.8%)/83.0% (95% CI: 72.9, 93.1%), respectively. Intra/interday reproducibility ranged from fair to good., Conclusion: The conclusions drawn from this study suggest that FSBP ≤ 76 mmHg and DBI ≤ 0.74 thresholds are potentially reliable indicators of DOAD and demonstrate fair to good intra- and interday reproducibility., Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03264820., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Nothing is known about the interest of the combination of exercise tests to diagnose Lower-extremity Peripheral Artery Disease (LEPAD). The aim of this study was to assess if combining exercise testing criteria [post-exercise Ankle-Brachial Index (ABI) + exercise-oximetry (exercise-TcPO2)] improves the detection of lower limbs arterial stenoses as compared with post-exercise ABI using American Heart Association (AHA) criteria, or exercise-TcPO2 alone. Material and Methods: In a prospective monocentric study, consecutive patients with exertional-limb pain and normal resting-ABI referred to our vascular center (Rennes, France) were assessed from May 2016 to February 2018. All included patients had a computed tomography angiography (CTA), a resting-ABI, a post-exercise ABI and an exercise-TcPO2. AHA post-exercise criteria, new validated post-exercise criteria (post-exercise ABI decrease ≥18.5%, post-exercise ABI decrease <0.90), and Delta from Rest of Oxygen Pressure (Total-DROP) ≤-15mmHg (criterion for exercise-TcPO2) were used to diagnose arterial stenoses ≥50%. For the different combinations of exercise testing criteria, sensitivity or specificity or accuracies were compared with McNemar's test. Results: Fifty-six patients (mean age 62 ± 11 years old and 84% men) were included. The sensitivity of the combination of exercise testing criteria (post-exercise ABI decrease ≥18.5%, or post-exercise ABI decrease <0.90 or a Total-DROP ≤-15mmHg) was significantly higher (sensitivity = 81% [95% CI, 71-92]) than using only one exercise test (post-exercise AHA criteria (sensitivity = 57% [43-70]) or exercise-TcPO2 alone (sensitivity = 59% [45-72]). Conclusions: Combination of post-exercise ABI with Exercise-TcPO2 criteria shows better sensitivity to diagnose arterial stenoses compared with the AHA post-exercise criteria alone or Exercise-TcPO2 criteria used alone. A trend of a better accuracy of this combined strategy was observed but an external validation should be performed to confirm this diagnostic strategy., 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 © 2021 Stivalet, Paisant, Belabbas, Le Faucheur, Landreau, Le Pabic, Omarjee and Mahé.)

Background: Anticoagulants are the recommended treatment for venous thromboembolic disease (VTE). The mode of anticoagulant administration may influence compliance, and therefore the effectiveness of the treatment. Unlike in atrial fibrillation or cancer-associated thrombosis, there is only limited data on patient preferences regarding the choice of anticoagulation in VTE. This study aims to evaluate patient preferences regarding anticoagulants in terms of administration: types (oral or injectable treatment) and number of doses or injections per day. Patients and Methods: This is a national survey through a questionnaire sent by e-mail to 1936 French vascular physicians between February and April 2019. They recorded the responses for each patient admitted for VTE. Results: Three hundred and eleven (response rate of 16%) of the 1936 contacted physicians responded for 364 patients. Among these, there were 167 fully completed questionnaires. Most patients (63%) express concerns about VTE and prefer oral treatment (81.5%), justified by the ease of administration (74%) and a fear of the injections (22%). When patients were taking more than three oral treatments they statistically chose injectable treatment more often (54%) than oral treatment (25%, p = 0.002). Patients who chose injectable treatment were also older (70 ± 16 vs. 58 ± 17 years old, p = 0.001). There was no statistically difference in anticoagulation preference according to gender or to the expected duration of treatment (6 weeks, 3 months, 6 months or unlimited). When oral treatment was preferred (81%), most chose oral treatment without dose adjustment and biomonitoring (74.3%). Among them, very few (5.8%) preferred a twice-daily intake. Conclusion: Patient preference in terms of anticoagulant treatment in VTE disease is in favor of oral treatment without adjustment or biomonitoring and with once-daily intake. When an injectable treatment is chosen, a prolonged duration of treatment does not seem to be a constraint for the patient. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03889457]., Competing Interests: GM has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, GSK, and Bayer. DL has received fees as speaker from Bristol-Myers-Squibb, Leo Pharma, and Bayer. The remaining 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 © 2021 Lanéelle, Le Brun, Mauger, Guillaumat, Le Pabic, Omarjee, Mahé and SFMV VTE Study Group.)

Background: Arterial Doppler Ultrasound waveform (DW) analysis allows the detection and evaluation of lower extremity peripheral artery disease. The high heterogeneity of the reported description of DW is reduced by the use of classification. However, the reliability of these classifications is either unknown or low to moderate and practices of vascular caregivers regarding the use of these classifications remain unknown. Aims: This study aims to assess the inter-observer reliability of the Saint-Bonnet classification, a 13-category DW classification. The secondary objective was to determine the utilization rate of the most common classifications and the ability of these classifications to describe DW. Methods: A national survey was conducted among all vascular physicians of French society of vascular medicine. They were invited by email to describe on a website 20 DW without and with the display of the Saint-Bonnet classification. The reliability of this classification was estimated by Fleiss' Kappa expressed with [95% confidence interval]. A semantic analysis allowed us to classify the physicians' responses according to the terms used. Finally we have evaluated for each classification the rate of misuse, i.e., the addition of a complementary term to the defined categories. Results: One hundred and ten physicians participated and only 5% of these were familiar with Saint-Bonnet classification. Fifty-four percent of vascular physicians used no classification at all. Vascular physicians used the Spronk (four-category), Descotes (five-category) and Saint-Bonnet (13-category) classifications for respectively, 31, 10, and 5%. Kappa coefficient of Fleiss (κ) was 0.546 [0.544-0.547] ( p < 0.001). Reliability by category ranges from κ of 0.075 to 0.864. In multivariate analysis, the use of a classification was associated with fewer years of experience and was dependent on geographic location. Misuse rate by classification was 88, 82, and 5% using Spronk, Descotes and Saint-Bonnet classifications respectively. Conclusion: The reliability of Saint-Bonnet classification is weak to moderate by vascular physicians who are not familiar with its use. However, unlike the other classifications, it seems to be sufficiently precise so that the user does not need to complete its description. There is a significant heterogeneity in the use of arterial Doppler classifications in France., 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 © 2021 Lanéelle, Guillaumat, Trihan, Pottier, Omarjee, Mahé and SFMV PAD Study Group.)

Background: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare the efficacy of the categorisation rate of Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications., Methods: This is a multicentre prospective study where 130 patients attending a vascular arterial ultrasound were enrolled and Doppler waveform acquisition was performed at the common femoral, the popliteal, and the distal arteries at both sides. Experienced vascular specialists categorized these waveforms according to the three classifications., Results: of 1033 Doppler waveforms, 793 (76.8%), 943 (91.3%) and 1014 (98.2%) waveforms could be categorized using Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications, respectively. Differences in categorisation between classifications were significant (Chi squared test, p < 0.0001). Of 19 waveforms uncategorized using the simplified Saint-Bonnet classification, 58% and 84% were not categorized using the Spronk et al. and Descotes and Cathignol classifications, respectively., Conclusions: The results of the present study suggest that the simplified Saint-Bonnet classification provides a superior categorisation rate when compared with Spronk et al. and Descotes and Cathignol classifications.

Inflammaging constitutes the common factor for comorbidities predisposing to severe COVID-19. Inflammaging leads to T-cell senescence, and immunosenescence is linked to autoimmune manifestations in COVID-19. As in SLE, metabolic dysregulation occurs in T-cells. Targeting this T-cell dysfunction opens the field for new therapeutic strategies to prevent severe COVID-19. Immunometabolism-mediated approaches such as rapamycin, metformin and dimethyl fumarate, may optimize COVID-19 treatment of the elderly and patients at risk for severe disease.

Background: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and ectopic calcification. There is growing evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. Since PXE has never been considered as an inflammatory condition, no incidence of chronic inflammation leading to calcification in PXE has been reported and should be investigated. In atherosclerosis and aortic stenosis, positron emission tomography combined with computed tomographic (PET-CT) imaging has demonstrated a correlation between inflammation and calcification. The purpose of this study was to assess skin/artery inflammation and calcification in PXE patients . Methods: 18F-FluroDeoxyGlucose (18F-FDG) and 18F-Sodium Fluoride (18F-NaF) PET-CT, CT-imaging and Pulse wave velocity (PWV) were used to determine skin/vascular inflammation, tissue calcification, arterial calcium score (CS) and stiffness, respectively. In addition, inorganic pyrophosphate, high-sensitive C-reactive protein and cytokines plasma levels were monitored., Results: In 23 PXE patients, assessment of inflammation revealed significant 18F-FDG uptake in diseased skin areas contrary to normal regions, and exclusively in the proximal aorta contrary to the popliteal arteries. There was no correlation between 18F-FDG uptake and PWV in the aortic wall. Assessment of calcification demonstrated significant 18F-NaF uptake in diseased skin regions and in the proximal aorta and femoral arteries. 18F-NaF wall uptake correlated with CS in the femoral arteries, and aortic wall PWV. Multivariate analysis indicated that aortic wall 18F-NaF uptake is associated with diastolic blood pressure. There was no significant correlation between 18F-FDG and 18F-NaF uptake in any of the artery walls., Conclusion: In the present cross-sectional study, inflammation and calcification were not correlated. PXE would appear to more closely resemble a chronic disease model of ectopic calcification than an inflammatory condition. To assess early ectopic calcification in PXE patients, 18F-NaF-PET-CT may be more relevant than CT imaging. It potentially constitutes a biomarker for disease-modifying anti-calcifying drug assessment in PXE., Competing Interests: The authors declare no conflict of interest.

Lower extremity peripheral artery disease (PAD) induces an ischemic pain in the lower limbs and leads to walking impairment. Electrical stimulation has been used in patients with PAD, but no systematic review has been proposed to address the efficacy of the technique as a treatment for walking impairment in PAD. A systematic search was performed to identify trials focused on electrical stimulation for the treatment of walking impairment in patients with PAD in the Cochrane Central Register, PubMed, Embase, and the Web of Science. Studies were included where the primary outcomes were pain-free walking distance and/or maximal walking distance. When appropriate, eligible studies were independently assessed for quality using the Cochrane Collaboration's tool for assessing risk of bias. Five studies eligible for inclusion were identified, of which only two were randomized controlled studies. Trial heterogeneity prevented the use of the GRADE system and the implementation of a meta-analysis. Three types of electrical stimulation have been used: neuromuscular electrical stimulation (NMES, n = 3), transcutaneous electrical stimulation ( n = 1), and functional electrical stimulation ( n = 1). The two available randomized controlled studies reported a significant improvement in maximal walking distance (+40 m/+34% and +39 m/+35%, respectively) following a program of NMES. Owing to the low number of eligible studies, small sample size, and the risk of bias, no clear clinical indication can be drawn regarding the efficacy of electrical stimulation for the management of impaired walking function in patients with PAD. Future high-quality studies are required to define objectively the effect of electrical stimulation on walking capacity.

Pseudoxanthoma Elasticum (PXE) is a rare disorder characterized by fragmentation and progressive calcification of elastic fibres in connective tissues. Although arterial hypertension (AHT) has been reported in PXE patients, its impact on pathological manifestations has as yet been unexplored. We investigated the consequences of experimental AHT on Abcc6-/- PXE mouse models. Experimental AHT was induced by deoxycorticosterone acetate (DOCA-salt) in uni-nephrectomised mice. Blood pressure (BP) and vascular reactivity were monitored using tail-cuff plethysmography and myography respectively. Calcium content and fibrosis were assessed using colorimetry, Von Kossa and Sirius red staining respectively. The gene expression implicated in vascular biology was measured using quantitative polymerase chain reaction. DOCA-salt induced a matching rise in BP in Abcc6-/- and WT mice. Aortic ring contraction and relaxation in vitro were comparable. Calcium accumulated in the hearts of hypertensive Abcc6-/- mice along with significant fibrosis in the myocardium and aorta by contrast with the WT mice. In hypertensive Abcc6-/- mouse aortas, these results were corroborated by gene expression patterns favouring calcification, fibrosis and extracellular matrix remodelling. Abcc6 loss-of-function is associated with greater cardiovascular calcification and fibrosis in mice subjected to DOCA-Salt hypertension. These results suggest likely cardiovascular deterioration in PXE patients with AHT, necessitating diligent BP monitoring.

Background: Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication., Methods: The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied., Results: Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p < 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women., Conclusions: The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication., Clinical Trial Registration: This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The resting ankle-brachial index (ABI) is a clinical test to diagnose peripheral artery disease. The Wyatt's score has been proposed to assess the students' performance on ABI measurement on a healthy volunteer (HV). No study has shown that this score is sensitive to different teaching methods. In this randomized controlled trial, we wanted to determine whether didactic learning alone or didactic learning combined with experiential learning improves proficiency in the ABI procedure assessed by the Wyatt's score., Methods: Medical students (n = 30) received a didactic learning, including (1) a presentation of the ABI guidelines and (2) a video demonstration. Each student was then randomized into 2 groups ("the no experiential learning group" and "the experiential learning group"). An initial evaluation was performed after the didactic learning and then the final evaluation at the end of the intervention. A student was considered to be proficient when he performed a correct ABI procedure on an HV. The correct procedure corresponds to the following: (1) correctly answered Wyatt's score and (2) a difference in the ABI measurement between a professor in vascular medicine and a student was ≤0.15., Results: No student was proficient at the initial evaluation. At the final evaluation, there was a significant difference between the number of proficient students for the Wyatt's score depending on their learning group [didactic alone (1/10) or didactic + experiential training (15/20)] and also for the ABI procedure [didactic alone (0/10) or didactic + experiential training (16/20)]. At 6 months, among the 12 students who passed the final evaluation, 4 students passed both the Wyatt's score and the ABI measurement., Conclusions: Our study demonstrates that the Wyatt's score was sensitive to an educational intervention and no improvement was found in the case of "no experiential learning." The Wyatt's score could be used to evaluate the student on ABI measurement after an educational intervention., Trial Registration: A randomized controlled trial was conducted in the Vascular Medicine Department of Rennes University Hospital (France). This was approved by the ethics review board of our institution (no. 16.150)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS., (Copyright © 2018. Published by Elsevier B.V.)

Background: The analysis of Doppler ultrasound waveforms (DW) provides a method for detecting and evaluating arterial stenosis in the lower limb arteries but no recommendation exists on how to describe the DWs. Aims of this study were to assess the heterogeneity of the description of DWs among vascular residents and the impact of the use of a 4-item classification., Methods: Thirty different DWs were presented to residents using Microsoft PowerPoint ® slides. They were invited to describe the 30 DWs before and after the presentation of a 4-item classification (triphasic, biphasic, monophasic, and others). The heterogeneity was assessed by the number of different answers used by the residents. Nineteen residents with six to eighteen months of vascular medicine training and ultrasound experience were included., Results: The average of different answers was 9 ± 4 for the whole analysis of the 30 DWs without the use of a specific classification, whereas the average was 2 ± 1 using the 4-item classification (p < 0.005). There was a significant difference in correct answers, i. e. in combined continuous waveforms and pulsed waveforms between experienced residents and younger residents (p < 0.05)., Conclusions: Using a 4-item classification for DWs reduced the heterogeneity of the DW description. There is an urgent need to standardize the DW description in order to improve the patients care with peripheral artery disease.

Background: Atherosclerosis is the leading cause of death worldwide. Ischaemic stroke, coronary heart disease (CHD), and peripheral artery disease (PAD) are different forms of atherosclerotic disease. Knowledge among general practitioners (GPs) about the three main locations of atherosclerosis has never been conjointly explored in a single study. The aim of this survey was to compare GP awareness on the subject of these three different clinical presentations., Materials and Methods: Between February 2017 and May 2017, a self-administered survey was emailed to 18,500 French GPs. The questionnaire comprised three clinical cases involving cases of transient ischaemic attack (TIA), stable angina (SA), and intermittent claudication (IC). Each case was explored with seven similar questions. The primary endpoint was the number of physicians who correctly answered five questions for each clinical case., Results: The survey was completed by 1,724 GPs. TIA knowledge (48.2 %) was significantly higher than the SA knowledge (3.0 %) and IC knowledge (0.4 %). We also found a significant difference between SA knowledge and IC knowledge. The percentages of GPs who correctly diagnosed TIA, SA or IC were 96.7, 89.7, and 96.5 %, respectively (p < 0.0001). Poor knowledge ratings for all three locations were observed for inadequate prescription of supplementary investigations and treatments., Conclusions: Our study demonstrates that GPs' knowledge about atherosclerosis disease varies significantly depending on disease location. GPs diagnose correctly but need to be backed up for their management of patients with atherosclerosis.

Rationale: Buerger disease (BD) is a nonatherosclerotic, inflammatory, segmental vascular occlusive disease, which affects small and medium-sized arteries and veins and is triggered by substantial tobacco exposure. Angiographic findings consistent with BD are required for diagnosis. Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) could represent potential noninvasive alternative techniques to angiography., Patient Concerns: We report the case of a 49-year-old smoker who developed an ischemic ulcer in the distal segment of the second finger of the left hand. He had no medical history., Diagnoses: In our vascular center, LDF and LSCI are conducted routinely for digital artery disease diagnosis. LDF was indicative of digital obstructive artery disease (DOAD). Postocclusive reactive hyperemia, assessed by LCSI, demonstrated no skin blood flow (SBF) perfusion in the distal phalanx of the thumb, index, middle, and auricular fingers. Angiography confirmed BD, showing distally located multisegmental vessel occlusion and corkscrew collaterals in this patient's hands., Interventions: Ilomedine treatment was initiated and smoking cessation was definitive., Outcomes: Recently, the patient had an improvement in clinical condition despite the persistence of a small zone of necrosis of the left index finger 28 days post-treatment., Lessons: Our observation suggests that where suspicion of BD is based on clinical criteria, combining LDF and LSCI could represent a noninvasive, safe means of reaching BD diagnosis. Further clinical trials are necessary to confirm this novel observation.

Primary antiphospholipid syndrome (PAPS) and antiphospholipid syndrome associated to lupus (SAPS) have several overlapping characteristics. As systemic manifestations are also reported in patients with PAPS, and as a subgroup of PAPS patients could evaluate to a SAPS, the differentiation between the two types of APS could be performed based on the clinical experience of the medical teams and is related to a variety of clinical, biological, histological and genetic features. Several data are available in the literature with respect to the identification of distinctive features between these two entities. However, there are some limitation in the interpretation of results issued from studies performed prior to updated Sydney criteria. Based on recent data, a certain number of features more frequent in one type of APS as compared to the other could be distinguished. The major differentiation between these two entities is genetical. New genetic data allowing the identification of specific subgroups of APS are ongoing., (Copyright © 2018. Published by Elsevier B.V.)

Background: Ankle-brachial index (ABI) at rest, postexercise ABI, and toe-brachial index (TBI) are essential diagnostic tools recommended for peripheral artery disease (PAD) diagnosis. Our study investigates the level of knowledge on these 3 tests among vascular medicine residents from 4 French medical schools in France., Methods: We included 19 vascular medicine residents in a cross-sectional study. During an annual obligatory seminar, all residents accepted to fill 3 questionnaires concerning knowledge about these 3 tests., Results: All residents accepted to fill 3 questionnaires. None of the residents correctly knows how to perform all pressure measurements (ABI, postexercise ABI, and TBI). Two residents had the knowledge to perform the whole ABI at rest procedure, whereas no resident had the knowledge to perform neither the postexercise ABI (P = 0.48) nor the TBI (P = 0.48). Twelve residents correctly completed the question regarding the interpretation of ABI at rest, whereas 2 correctly completed the postexercise ABI question (P = 0.001) and 4 the TBI question (P = 0.02). The number of residents who have performed more than 20 measurements is higher regarding ABI at rest than postexercise ABI and TBI (84%, 5%, and 37% respectively; P < 0.001 and P = 0.006 respectively) and significantly less often in postexercise ABI than TBI (5% vs. 37%; P = 0.04)., Conclusions: This study shows for the first time that residents' knowledge of pressure measurements (resting-ABI, postexercise ABI, and TBI) of 4 French medical school are insufficient although the importance of pressure measurement has been strongly highlighted by the newly released PAD guidelines (2016) for PAD diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)