Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5' untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.

A systematic review and meta-analysis of the incidence of post-thrombotic syndrome, recurrent thromboembolism, and bleeding after upper extremity vein thrombosis.

BACKGROUND: Data on complications after upper extremity vein thrombosis (UEVT) are limited and heterogeneous. METHODS: The aim of the present study was to evaluate the pooled proportions of venous thromboembolism (VTE) recurrence, bleeding, and post-thrombotic syndrome (PTS) in patients with UEVT. A systematic literature review was conducted of PubMed, Embase, and the Cochrane Library databases from January 2000 to April 2023 in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies included patients with UEVT and were published in English. Meta-analyses of VTE recurrence, bleeding, and of PTS after UEVT were performed to compute pooled estimates and associated 95% confidence intervals (CIs). Subgroup analyses of cancer-associated UEVT and catheter-associated venous thrombosis were conducted. Patients with Paget-Schroetter syndrome or effort thrombosis were excluded. RESULTS: A total of 55 studies with 15,694 patients were included. The pooled proportions for VTE recurrence, major bleeding, and PTS were 4.8% (95% CI, 3.8%-6.2%), 3.0% (95% CI, 2.2%-4.0%), and 23.8% (95% CI, 17.0%-32.3%), respectively. The pooled proportion of VTE recurrence was 2.7% (95% CI, 1.6%-4.6%) for patients treated with direct oral anticoagulants (DOACs), 1.7% (95% CI, 0.8%-3.7%) for patients treated with low-molecular-weight heparin (LMWH), and 4.4% (95% CI, 1.5%-11.8%) for vitamin K antagonists (VKAs; P = .36). The pooled proportion was 6.3% (95% CI, 4.3%-9.1%) for cancer patients compared with 3.1% (95% CI, 2.1%-4.6%) for patients without cancer (P = .01). The pooled proportion of major bleeding for patients treated with DOACs, LMWH, and VKAs, was 2.1% (95% CI, 0.9%-5.1%), 3.2% (95% CI, 1.4%-7.2%), and 3.4% (95% CI, 1.4%-8.4%), respectively (P = .72). The pooled proportion of PTS for patients treated with DOACs, LMWH, and VKAs was 11.8% (95% CI, 6.5%-20.6%), 27.9% (95% CI, 20.9%-36.2%), and 24.5% (95% CI, 17.6%-33.1%), respectively (P = .02). CONCLUSIONS: The results from this study suggest that UEVT is associated with significant rates of PTS and VTE recurrence. Treatment with DOACs might be associated with lower PTS rates than treatment with other anticoagulants.

Upper extremity venous thrombosis in hospitalized patients: A prospective epidemiological study.

BACKGROUND: The frequency of upper extremities vein thrombosis (UEVT) is rising with the increasing use of endovenous devices. These thromboses are particularly common among hospitalized patients. The epidemiology and risk factors for UEVT are poorly understood in a hospitalized population. OBJECTIVE: To assess the prevalence of UEVT in hospitalized patients and study thrombosis risk factors according to their location. METHODS: Prospective evaluation of patients hospitalized in a university hospital with clinical and Doppler ultrasound (DUS) assessment of the upper extremities. RESULTS: Of the 400 patients included, 91(22.8 %) had UEVT including 8 (8.8 %) proximal thrombosis, 32 (35.2 %) arm venous thrombosis and 51 (56.0 %) forearm venous thrombosis; 7 (7.7 %) patients with UEVT had a concomitant symptomatic pulmonary embolism. In this population of hospitalized patients, 40 (10 %) had proximal or arm thrombosis and 51 (12.8 %) forearm thrombosis. All patients with UEVT had a venous catheter and 63 (69.2 %) of UEVT patients had therapeutic or prophylactic anticoagulation at the time of DUS evaluation. In multivariate analysis, peripheral intravenous catheter (PIVC) OR 3.71 [1.90; 7.91] (p < 0.001); MID line OR 3.58 [1.46; 8.91] (p = 0.005) and infection disease OR 2.21 [1.26; 4386] (p = 0.005) were associated with UEVT. Central venous catheter OR 66.24 [12.64; 587.03] was associated with proximal UEVT and MID line OR 12.61 [4.64; 35.77] (p < 0.001) with arm UEVT. Forearm UEVT were associated with PIVCOR 10.71[3.14; 67.37] (p = 0.001); infectious disease OR 2.87 [1.48; 5.60] (p = 0.002), iron infusion OR 3.11 [1.23; 7.47] and hospitalization for postpartum OR 4.37 [0.97; 18.06] (p = 0.04). CONCLUSION: One in 5 hospitalized patients suffers from UEVT. Proximal venous thrombosis is uncommon. The presence of a catheter and hospitalization for infection are the factors most frequently associated with UEVT.

Observational and prospective study: evaluation of beliefs and representations of chronic treatments of polymedicated patients hospitalised in a vascular medicine and surgery department.

OBJECTIVES: Today, the involvement of patients in their care is essential. As the population ages increases, the number of patients with chronic diseases is increasing. In the vascular medicine and surgery departments, patients are polymedicated and mostly suffer from several chronic diseases. Approximately 50% of patients with a chronic disease are not adherent. Among the factors that can influence therapeutic adherence are the beliefs and representations of patients.To evaluate the beliefs and representations of chronic treatments in patients with multiple medications and hospitalised in a vascular medicine and surgery department, and to evaluate the medication adherence, the knowledge and the importance patients attach to their treatments. DESIGN: Observational, prospective and a single-centre study. SETTING: The study was conducted in a French tertiary hospital centre of around 3000 beds in 9 institutions. PARTICIPANTS: Adult polymedicated (ie, minimum of five chronic treatments) patients hospitalised in a vascular medicine and surgery department were included after application of the exclusion criteria. METHODS: Patient interviews were carried out in the department and were based on three interviewer-administered questionnaires (a global questionnaire, the Belief Medical Questionnaire and the GIRERD questionnaire). RESULTS: Our study showed that patients perceived their treatments as beneficial rather than worrying. A correlation between medication adherence and beliefs was observed. 'Non-adherent'patients had a more negative overall view of medication than 'adherent' patients. The level of compliance and knowledge of our patients was low. Only 11% of the patients were 'good adherent', 16% of the patients could perfectly name their treatment and 36% knew all the indications. CONCLUSION: Knowledge of treatment representation and beliefs are central to understanding patient behaviour. Considering patients' representations will allow the identification of levers, and the development of actions and educational tools adapted to improve their adherence, their knowledge and therefore their drug management.

Long-Term Outcome and Prognosis of Noninfectious Thoracic Aortitis.

BACKGROUND: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known. OBJECTIVES: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis. METHODS: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis. RESULTS: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died. CONCLUSIONS: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures.

Semi-Quantitative [18F]FDG-PET/CT ROC-Analysis-Based Cut-Offs for Aortitis Definition in Giant Cell Arteritis.

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p < 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging.

Emergence of Lyme Disease on the French Riviera, a Retrospective Survey.

Background: The French Riviera has been declared free of Lyme Borreliosis (LB) for years. Many patients are referred for presumed LB, sometimes with atypical clinical signs and/or doubtful serology, calling the diagnosis into question. Methods: Patients were assessed for LB diagnosis, depending on clinical presentation, laboratory findings, and further examination by other medical professionals. Results: Among 255 patients, 45 (18%) were classified as confirmed LB cases [including 28 ongoing LB (10%) and 17 past LB (8%)], and for 210 (82%) a Lyme borreliosis diagnosis was ruled out. Among ongoing LB, 56% had been exposed to or bitten by ticks, exclusively in rural locations of the Alpes-Maritimes. As a result of the diagnostic procedure, 132 (52%) patients had been treated. An alternative diagnosis was established for 134 (52%) patients, covering a wide range of conditions, including mainly psychological (28%) and neurological conditions (25%) or inflammatory and systemic diseases (22%). Conclusions: Our results strongly suggest the endemicity of LB in the Alpes-Maritimes region. Confirmed LB accounted for 18% of patients while 52% were diagnosed with other conditions.

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.