Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis : A Prospective Cohort Study.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in people older than 50 years. Any delay in diagnosis impairs patients' quality of life and can lead to permanent damage, particularly vision loss. OBJECTIVE: To evaluate a diagnostic strategy for GCA using color Doppler ultrasound of the temporal artery as a first-line diagnostic test, temporal artery biopsy (TAB) as a secondary test, and physician expertise as the reference method. DESIGN: Prospective multicenter study with a 2-year follow-up. (ClinicalTrials.gov: NCT02703922). SETTING: Patients were referred by their general practitioner or ophthalmologist to a physician with extensive experience in GCA diagnosis and management in one of the participating centers: 4 general and 2 university hospitals. PATIENTS: 165 patients with high clinical suspicion of GCA, aged 79 years (IQR, 73 to 85 years). INTERVENTION: The diagnostic procedure was ultrasound, performed less than 7 days after initiation of corticosteroid therapy. Only ultrasound-negative patients underwent TAB. MEASUREMENTS: Bilateral temporal halo signs seen on ultrasound were considered positive. Ultrasound and TAB results were compared with physician-diagnosed GCA based on clinical findings and other imaging. RESULTS: Diagnosis of GCA was confirmed in 44%, 17%, and 21% of patients by ultrasound, TAB, and clinical expertise and/or other imaging tests, respectively. Their diagnosis remained unchanged at 1 month, and 2 years for those with available follow-up data. An alternative diagnosis was made in 18% of patients. The proportion of ultrasound-positive patients among patients with a clinical GCA diagnosis was 54% (95% CI, 45% to 62%). LIMITATION: Small sample size, no blinding of ultrasound and TAB results, lack of an objective gold-standard comparator, and single diagnostic strategy. CONCLUSION: By using ultrasound of the temporal arteries as a first-line diagnostic tool in patients with high clinical suspicion of GCA, further diagnostic tests for patients with positive ultrasound were avoided. PRIMARY FUNDING SOURCE: Tender "Recherche CH-CHU Poitou-Charentes 2014."

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

BACKGROUND: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. OBJECTIVES: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. METHODS: Retrospective multicenter study in French national HHT Registry patients exposed to AT. RESULTS: We included 126 patients with 180 courses of AT. Median follow-up was 24 [11-52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). CONCLUSION: Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.

Inter and intra-observer agreement of arterial wall contrast-enhanced ultrasonography in giant cell arteritis.

Objective: The aim of this study was to analyze inter- and intra-observer agreement for contrast-enhanced ultrasonography (CEUS) for monitoring disease activity in Giant Cell Arteritis (GCA) in the wall of axillary arteries, and common carotid arteries. Methods: Giant cell arteritis patients have CEUS of axillary arteries and common carotid. These images were rated by seven vascular medicine physicians from four hospitals who were experienced in duplex ultrasonography of GCA patients. Two weeks later, observers again rated the same images. GCA patients were recruited in from December 2019 to February 2021. An analysis of the contrast of the ultrasound images with a gradation in three classes (grade 0, 1, and 2) was performed. Grade 0 corresponds to no contrast, grade 1 to moderate wall contrast and grade 2 to intense contrast. A new analysis in 2 classes: positive or negative wall contrast; was then performed on new series of images. Results: Sixty arterial segments were evaluated in 30 patients. For the three-class scale, intra-rater agreement was substantial: κ 0.70; inter-rater agreement was fair: κ from 0.22 to 0.27. Thirty-four videos had a wall thickness of less than 2 mm and 26 videos had a wall thickness greater than 2 mm. For walls with a thickness lower than 2 mm: intra-rater agreement was substantial: κ 0.69; inter-rater agreement was fair: κ 0.35. For walls with a thickness of 2 mm or more: intra-rater agreement was substantial: κ 0.53; inter-rater agreement was fair: κ 0.25. For analysis of parietal contrast uptake in two classes: inter-rater agreement was fair to moderate: κ from 0.35 to 0.41; and for walls with a thickness of 2 mm or more: inter-rater agreement was fair to substantial κ from 0.22 to 0.63. Conclusion: The visual analysis of contrast uptake in the wall of the axillary and common carotid arteries showed good intra-rater agreement in GCA patients. The inter-rater agreement was low, especially when contrast was analyzed in three classes. The inter-rater agreement for the analysis in two classes was also low. The inter-rater agreement was higher in two-class analysis for walls of 2 mm thickness or more.

Use of hand hydraulic dynamometers as an overall evaluation of the upper-limb weakness in patients with thoracic outlet syndrome.

Patients with neurogenic thoracic outlet syndrome report pain and upper-limb weakness. They complain about weakness occurring on the entire upper-limb, especially at the hand and the shoulder levels. Hydraulic dynamometers can reliably assess the strength of the hand, and isokinetic shoulder testing can provide accurate and reliable evaluations of the rotators strength. Yet, isokinetic proximal assessment needs expensive tools, whereas hydraulic hand dynamometers are cheap and easy to use. We aimed to assess the correlation between the isokinetic shoulder strength and the hand grip and the key pinch strength. The grip strength was evaluated with a hydraulic hand dynamometer and the key pinch with a pinch gauge. Isokinetic rotators strength tests were performed using a Humac Norm® dynamometer at 60 and 180°/s. One-hundred and thirty patients had been included, 72% of women, mean age of 39.8 ± 9.5. Symptomatic hands presented a strength deficit of 12.2% on the grip (p < 0.0001) and 10% on the key pinch (p = 0.01). Isokinetic strength was lower on the symptomatic shoulders at 60 and 180°/s concerning medial rotators [-10.3 and -8.8%, respectively (p = 0.02)] and lateral rotators [-10.8 and -10%, respectively (p = 0.04 and p = 0.03)]. There was a moderate correlation between the grip strength of the symptomatic upper-limbs and the isokinetic rotators strength (p < 0.001). The key pinch strength was moderately correlated to the isokinetic medial and lateral rotators strength at 60°/s (p < 0.001). Hand dynamometers could prove useful during medical consultations or in outpatient management to assess upper-limb overall weakness, but isokinetic measurement remains the gold standard for a precise evaluation.

Pharmaco-mechanical catheter-directed thrombolysis versus recanalization and stenting for post thrombotic syndrome after lower limb deep vein thrombosis: a comparative study.

Background: Endovenous interventional procedures can be used in addition to therapeutic anticoagulation to treat deep vein thrombosis in selected patients with proximal vein involvement (vena cava, iliac and/or common femoral). The aim of this study was to compare venous patency and the post-thrombotic syndrome (PTS) in patients treated with pharmaco-mechanical catheter-directed thrombolysis (PMT) versus recanalization-stenting for PTS after a proximal lower limb deep vein thrombosis. Methods: Between January 2014 and December 2020, this retrospective and monocentric study included patients with very symptomatic acute iliofemoral deep vein thrombosis treated with PMT within 21 days after diagnosis (PMT group) and patients with PTS caused by chronic venous obstruction treated with recanalization and stenting (CRS group). Results: A total of 116 patients were included (26 PMT, 90 CRS). The rate of primary patency was 81.8% (18/22 patients) in the PMT group and 78.4% (69/88) in the CRS group (P>0.99). The rate of venous patency at the last follow-up was 76.9% (20/26) in the PMT group and 82.2% (74/90) in the CRS group (P=0.57). The median number of stents was 2 (range, 0-5) in the PMT group and 3 (range, 0-7) in the CRS group (P<0.001). The median stent length was 150 mm (range, 60-390 mm) and 280 mm (range, 120-820 mm), respectively (P<0.001). The median last Villalta score was 2 (range, 0-10) in the PMT group and 2 (range, 0-21) in the CRS group (P=0.55). The rate of venous claudication at the last follow-up was 19.0% (4/21) in the PMT group and 12.0% (10/83) in the CRS group (P=0.47). Conclusions: In this study, there was no difference in venous patency and in the rate and severity of PTS between the PMT and CRS groups. The number of stent and their length were significantly lower in the PMT group compared with the CRS group.

Case-Control Study on Exercise-Induced Vasculitis in Hikers.

The aim of this study was to identify clinical factors associated with exercise-induced vasculitis (EIV). This study included EIV cases and controls matched for age. Cases included were all members of a hiking club and participated in extended hiking trips. Exercise-induced vasculitis was diagnosed based on clinical signs occurring only after prolonged walks. Chronic venous disease was defined using the Clinical Etiological Anatomical Pathophysiologic classification. This study included 162 hikers: 32 EIV cases and 130 matched controls. Mean age at EIV diagnosis was 47.1 years and 24 (75.0%) of EIV cases were women. Chronic venous disease was present in 19 (57.6%) of EIV cases vs 39 (30.0%) in controls (P = .001); those with EIV had significantly more saphenous vein insufficiency and C3 venous insufficiency than controls, 85.0 vs 52.6% and 8 (25.0%) vs 13 (10.0%) (P = .02), respectively. For EIV cases, mean walking distance per hike was significantly higher than for controls (P = .002). Exercise-induced vasculitis symptoms were typical with rash and/or purpura on the leg in warm conditions. Lesions spontaneously disappear in <10 days. In this study, EIV cases had more chronic venous disease and longer mean walking distances than controls.

Prevalence of post-thrombotic syndrome in a cohort of upper extremity vein thrombosis.

OBJECTIVE: Post-thrombotic syndrome (PTS) is one of the main complications that occurs after venous thrombosis. There are few data on the proportion of patients that will develop upper extremity PTS (UE-PTS) after upper extremity venous thrombosis (UEVT). The main objective of the study was to assess the prevalence of PTS in a UEVT cohort and to identify predictive factors of UE-PTS. METHODS: This study included patients with a history of proximal or arm UEVT, diagnosed on duplex ultrasound examination, between January 1, 2015, and December 31, 2017, in a university hospital. After UEVT, each patient was evaluated by a prospective standardized recording of clinical manifestations and duplex ultrasound examination in case of upper limb symptoms. UE-PTS was defined as a modified Villalta score of 4 or higher. RESULTS: Ninety-two patients were included; 68 (73.9%) had deep vein thrombosis (DVT) and 24 (19.2%) arm superficial vein thrombosis. Thirteen patients had PTS (14.1%), 12 (17.6%) in the DVT group and 1 (4.2%) in the superficial vein thrombosis group. There was a history of DVT in 92.3% of the cases of PTS. PTS was more frequent in patients with strokes with limb movement reduction (P = .01). On multivariate Cox analysis, a history of stroke (hazard ratio, 5.4; 95% confidence interval, 1.46-20.22; P = .01) was predictive of UE-PTS. CONCLUSIONS: UE-PTS occurred in 14.1% of cases after UEVT. Stroke with a decrease in limb movement was a predictor of developing PTS. Diagnostic criteria should be established for UE-PTS and prospective studies are needed to improve the description and management of UE-PTS.

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients.

ABSTRACT: Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.

Predictive factors of venous recanalization in upper-extremity vein thrombosis.

BACKGROUND: Upper extremity venous thrombosis (UEVT) represents about 10% of venous thrombo-embolic disease. This is mainly explained by the increasing use of central venous line, for oncologic or nutritional care. The factors associated with venous recanalization are not known. OBJECTIVE: The aim of this study was to investigate prognosis factor associated with venous recanalization after UEVT. METHODS: This study included patients with UEVT diagnosed with duplex ultra-sonography (DUS) from January 2015 to December 2017 with DUS evaluations during follow-up. A multivariate Cox proportional-hazards-model analysis was performed to identify predictive factors of UEVT complete recanalization. RESULTS: This study included 494 UEVT, 304 proximal UEVT and 190 distal UEVT. The median age was 58 years, 39.5% were women. Clinical context was: hematological malignancy (40.7%), solid cancer (14.2%), infectious or inflammatory context (49.9%) and presence of venous catheters or pacemaker leads in 86.4%. The rate of recanalization without sequelae of UEVT was 38%. For all UEVT, in multivariate analysis, factors associated with complete vein recanalization were: thrombosis associated with central venous catheter (CVC) (HR:2.40, [1.45;3.95], p<0.001), UEVT limited to a venous segment (HR:1.94, [1.26;3.00], p = 0.003), occlusive thrombosis (HR:0.48 [0.34;0.67], p<0.0001), the presence of a PICC Line (HR:2.29, [1.48;3.52], p<0.001), a thrombosis of deep and distal topography (HR:1.70, [1.10;2.63], p = 0.02) or superficial thrombosis of the forearm (HR:2.79, [1.52;5.12], p<0.001). For deep and proximal UEVT, non-occlusive UEVT (HR:2.23, [1.49;3.33], p<0.0001), thrombosis associated with CVC (HR:1.58, [1.01;2.47], p = 0.04) and infectious or inflammatory context (HR:1.63, [1.10;2.41], p = 0.01) were factors associated with complete vein recanalization. CONCLUSION: In this study, factors associated with UEVT recanalization were UEVT limited to a venous segment, thrombosis associated with CVC, a thrombosis of deep and distal thrombosis topography and superficial thrombosis of the forearm. Occlusive thrombosis was associated with the absence of UEVT recanalization.

Effect of cannabis consumption on characteristics and evolution of thromboangitis obliterans.

Background: Thromboangiitis obliterans (TAO) is a distal non atherosclerotic thrombotic vasculitis affecting tobacco smokers. The role of cannabis co-exposure remains controversial. The study aims to assess how cannabis consumption influences clinical presentation and outcome of TAO in tobacco smokers. Patients and methods: TAO patients, according to Papa's criteria, were included in a retrospective bicentric study between the 1st January 2003 and the 1st march 2020. Clinical characteristics, arterial involvement at TAO diagnosis, vascular event and amputations during follow-up were analyzed according to cannabis consumption. Results: Seventy-three patients with TAO patients were included. Forty-five patients were in Tobacco group (T) and 28 in Tobacco and cannabis group (T&C). Tobacco exposure was less important in T&C group than in T group (19.4±11.3 vs 31.6±16.6 pack-years) (p=0.005) and patients in T&C group were younger at TAO diagnosis than in T group (p=0.008). Patients in T&C group presented more claudication (33.3% vs 8.9%, p=0.01) and less upper limbs resting ischemia (25.9% vs 51.1%, p=0.04) than patients in the T group. No differences were found between groups with regard to arterial distribution. Amputation rate for patients who had at least one major or minor amputation did not differ between T and T&C group (25% vs 14.8%, p=0.38). Conclusions: Cannabis consumption was associated with a younger age of TAO onset. However, it does not affect amputation-free survival, Tobacco exposure is less important in T&C patients; data of this bicentric study suggest that cannabis could be a cofactor of tobacco which accelerates TAO onset.

Subclavian Vessel Compression Assessed by Duplex Scanning in Patients with Neurogenic Thoracic Outlet Syndrome and No Vascular Signs.

Neurogenic thoracic outlet syndrome (NTOS) is the most frequent form of TOS. It may affect both sides, but specific complementary exams are lacking. We aimed to evaluate duplex scanning results in a group of patients with unilateral or bilateral NTOS and no clinical vascular signs, referred for rehabilitation. We performed a retrospective observational study in patients with unilateral or bilateral NTOS and no vascular symptoms. Subclavian vessels were assessed by duplex scanning. Compressions were considered in case of >50% of increased or decreased blood flow. A total of 101 patients met NTOS criteria; mean age was 40 +/- 10.2; 79.2% women. Seventy patients had a unilateral NTOS and 31 a bilateral form. Duplex scanning showed that 56.4% of the patients had vessels compression, 55.7% in the unilateral group and 58.1% in the bilateral (p = 0.81). In unilateral NTOS, 21 (30%) patients had bilateral vascular compression, 17 (24.3%) had ipsilateral compression and 1 (1.4%) had contralateral compression. In bilateral NTOS, 15 (48.4%) had bilateral compression and 3 (9.7%) compression on only one side. We found a significant difference of the rate of vascular compressions between symptomatic and non-symptomatic upper-limbs, 54.5% vs. 32.9%, respectively, (p = 0.002) and a significant association between symptomatic upper-limbs and vascular compression (OR = 2.45 [95%IC: 1.33-4.49]; p = 0.002). The sensitivity and the specificity of the duplex scanning were 54.5% and 67%, respectively. The ROC curve area was of 0.608 [95%IC: 0.527-0.690]. Despite a highly significant association between symptomatic upper-limbs and vascular compression, duplex scanning did not help make the diagnosis of NTOS.

Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous. The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis. In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included. A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected. Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected. Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis. D-dimers at baseline were significantly higher in patients with DVT (p < 0.001). Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE. The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE. The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively. The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer. Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients. Increased D-dimer concentrations of more than 1.0 µg/ml predict the risk of venous thromboembolism. D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

Colour Doppler ultrasound of temporal arteries for the diagnosis of giant cell arteritis: a multicentre deep learning study.

OBJECTIVES: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. In recent years, colour Doppler ultrasound of the temporal arteries (CDU) has proven to be a powerful non-invasive diagnostic tool, but its place in the diagnosis of GCA remains to be defined. A limitation of the CDU is the inter-operator reproducibility. Image analysis from a different perspective is now possible with the development of artificial intelligence algorithms. We propose to assess this technology for the detection of the halo sign on CDU images. METHODS: Three public hospitals retrospectively collected data from 137 patients suspected of having GCA between January 2017 and April 2019. CDU images (n=1,311) were labelled with the VIA software. Three sets (training, validation and test) were created and analysed with a semantic segmentation technique using a U-Net convolutional neural network. RESULTS: The area under the curve (AUC) was 0.931 and 0.835 on the validation and test set, respectively. An image positivity threshold was determined by focusing on the specificity. With this threshold, a specificity of 95% and a sensitivity of 60% were obtained for the test set. The analysis of the false interpretation showed that the acquisition modalities and the presence of thrombus caused confusion for the algorithm. CONCLUSIONS: We propose an automated image analysis tool for GCA diagnosis. The 2018 EULAR guidelines for image acquisition must be respected before generalising this algorithm. After external validation, this tool could be used as an aid for diagnosis, staff training and student education.

A STROBE cohort study of 755 deep and superficial upper-extremity vein thrombosis.

Upper extremity vein thrombosis (UE-VT) are more and more frequent pathologies and yet little studied. The aim is to describe the clinical and ultrasound features, UE-VT-related diseases, and the prevalence of pulmonary embolism (PE) and associated deaths.All UE-VT patients diagnosed by Doppler-ultrasound in Nantes University Hospital, from January 2015 to December 2017, were included retrospectively. UE-VT suspicion patterns, clinical features, UE-VT topography, and prevalence of PE and death were analyzed.Seven hundred and fifty-five UE-VT were analyzed, including 427 deep thrombosis (UE-DVT) and 328 superficial thrombosis (UE-SVT). In 86.2% (n = 651) UE-VT were related to endovascular devices. Among these thrombosis, one third is in connection with a PICC LINE and one quarter with a peripheral venous line. Forty nine percent (n = 370) of the patients had solid neoplasia or hematological malignancies. An inflammatory or systemic infectious context was found in 40.8% (n = 308) of the cases. The most frequently observed clinical sign at the UE-VT diagnosis was edema (28.6%). Among the UE-SVT it was the presence of an indurated cord (33.2%) and among the UE-DVT the indication of the Doppler-ultrasound was mainly a suspicion of infection on endovascular device (35.1%). In 10.6% (n = 80) of the cases the UE-VT were asymptomatic. The most frequently thrombosed veins were brachial basilic veins (16.7% of all thrombosed segments) followed by jugular (13%) and subclavian (12.3%) veins; 61.3% (n = 463) of UE-VT were in the right upper extremity; 63.3% (n = 478) UE-VT were occlusive. The occurrence of PE is 4% and the death rate is 10.2%, mainly related to the severe comorbidities of patients with UE-VT.UE-VT occurs in particular clinical contexts (hematological malignancies, solid cancers, systemic infections) and in the majority of endovascular devices (86.2%). The occurrence of PE is low.