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Sherene Shalhub – One of the best experts on this subject based on the ideXlab platform.

  • A multi-institutional experience in the aortic and Arterial Pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome.
    Journal of vascular surgery, 2019
    Co-Authors: Sherene Shalhub, Peter H. Byers, Kelli L. Hicks, Kristofer M. Charlton-ouw, Devin S. Zarkowsky, Dawn M. Coleman, Frank M. Davis, Ellen S. Regalado, Giovanni De Caridi, K. Nicole Weaver

    Abstract:

    Abstract Objective Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and Arterial Pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. Methods This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and Arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without Arterial events were compared. Results Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/Arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/Arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were Arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic Pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/Arterial Pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). Conclusions Most of the vEDS Arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

  • molecular diagnosis in vascular ehlers danlos syndrome predicts pattern of Arterial involvement and outcomes
    Journal of Vascular Surgery, 2014
    Co-Authors: Sherene Shalhub, James H Black, Alana C Cecchi, Ben F Griswold, Hazim J Safi, Dianna M Milewicz, Nazli B Mcdonnell

    Abstract:

    Objective The management of Arterial Pathology in individuals with vascular Ehlers-Danlos syndrome (vEDS) remains a challenge. Here we describe the correlation between COL3A1 gene mutation type and the clinical phenotype in individuals with vEDS. Methods Individuals with confirmed molecular diagnoses of vEDS were enrolled in a multi-institutional natural history study. Data collected included demographics, clinical and family histories, Arterial Pathology (aneurysm, dissection, and rupture), operative details, and autopsy reports. Individuals were classified into two cohorts by the type of COL3A1 mutations and their effect on the amount of normal collagen produced: those with mutations that lead to minimal (MIN) production (10%-15%) of normal type III collagen and those with haploinsufficiency (HI) mutations that lead to production of 50% of the normal type III collagen. Results A cohort of 68 individuals (72%) from 56 families had Arterial Pathology (44% male) with 13% HI. The HI group was older at the time of their first vascular event (mean, 42 [range, 26-58] years vs 33 [range, 8-62] years; P  = .016) and had a higher incidence of aortic Pathology than the MIN group (56% vs 21%; P  = .025). Visceral Arterial Pathology was seen in 43 arteries in 23 individuals in the MIN group vs only one artery in five individuals in the HI group. Emergency surgical procedures were more likely to be undertaken when vEDS diagnosis was not known (81% vs 41%; P  = .005), and 81% of these procedures were open surgical repair compared with 19% endovascular repairs ( P  = .019). Open and endovascular repairs were equally used in the elective setting. Postoperative complications were highest when the diagnosis of vEDS was not known (62% vs 14%; P P P  = .132). Conclusions Arterial Pathology in vEDS individuals is related to the underlying COL3A1 mutation type. The Arterial Pathology in individuals with HI mutations occurs at later ages with a higher incidence of aortic disease compared with other COL3A1 mutation types. Molecular diagnosis is recommended because diagnosis confirmation, appropriate surveillance, and prophylactic interventions in an elective setting improve surgical outcomes.

Dianna M Milewicz – One of the best experts on this subject based on the ideXlab platform.

  • consideration of sex differences in design and reporting of experimental Arterial Pathology studies statement from atvb council
    Arteriosclerosis Thrombosis and Vascular Biology, 2018
    Co-Authors: Peggy Robinet, Hong Lu, Dianna M Milewicz, Lisa A Cassis, Nicholas J Leeper, Jonathan D Smith

    Abstract:

    There are many differences in Arterial diseases between men and women, including prevalence, clinical manifestations, treatments, and prognosis. The new policy of the National Institutes of Health, which requires the inclusion of sex as a biological variable for preclinical studies, aims to foster new mechanistic insights and to enhance our understanding of sex differences in human diseases. The purpose of this statement is to suggest guidelines for designing and reporting sex as a biological variable in animal models of atherosclerosis, thoracic and abdominal aortic aneurysms, and peripheral Arterial disease. We briefly review sex differences of these human diseases and their animal models, followed by suggestions on experimental design and reporting of animal studies for these vascular pathologies.

  • Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies—Statement From ATVB Council
    Arteriosclerosis thrombosis and vascular biology, 2018
    Co-Authors: Peggy Robinet, Dianna M Milewicz, Lisa A Cassis, Nicholas J Leeper, Jonathan D Smith

    Abstract:

    There are many differences in Arterial diseases between men and women, including prevalence, clinical manifestations, treatments, and prognosis. The new policy of the National Institutes of Health, which requires the inclusion of sex as a biological variable for preclinical studies, aims to foster new mechanistic insights and to enhance our understanding of sex differences in human diseases. The purpose of this statement is to suggest guidelines for designing and reporting sex as a biological variable in animal models of atherosclerosis, thoracic and abdominal aortic aneurysms, and peripheral Arterial disease. We briefly review sex differences of these human diseases and their animal models, followed by suggestions on experimental design and reporting of animal studies for these vascular pathologies.

  • molecular diagnosis in vascular ehlers danlos syndrome predicts pattern of Arterial involvement and outcomes
    Journal of Vascular Surgery, 2014
    Co-Authors: Sherene Shalhub, James H Black, Alana C Cecchi, Ben F Griswold, Hazim J Safi, Dianna M Milewicz, Nazli B Mcdonnell

    Abstract:

    Objective The management of Arterial Pathology in individuals with vascular Ehlers-Danlos syndrome (vEDS) remains a challenge. Here we describe the correlation between COL3A1 gene mutation type and the clinical phenotype in individuals with vEDS. Methods Individuals with confirmed molecular diagnoses of vEDS were enrolled in a multi-institutional natural history study. Data collected included demographics, clinical and family histories, Arterial Pathology (aneurysm, dissection, and rupture), operative details, and autopsy reports. Individuals were classified into two cohorts by the type of COL3A1 mutations and their effect on the amount of normal collagen produced: those with mutations that lead to minimal (MIN) production (10%-15%) of normal type III collagen and those with haploinsufficiency (HI) mutations that lead to production of 50% of the normal type III collagen. Results A cohort of 68 individuals (72%) from 56 families had Arterial Pathology (44% male) with 13% HI. The HI group was older at the time of their first vascular event (mean, 42 [range, 26-58] years vs 33 [range, 8-62] years; P  = .016) and had a higher incidence of aortic Pathology than the MIN group (56% vs 21%; P  = .025). Visceral Arterial Pathology was seen in 43 arteries in 23 individuals in the MIN group vs only one artery in five individuals in the HI group. Emergency surgical procedures were more likely to be undertaken when vEDS diagnosis was not known (81% vs 41%; P  = .005), and 81% of these procedures were open surgical repair compared with 19% endovascular repairs ( P  = .019). Open and endovascular repairs were equally used in the elective setting. Postoperative complications were highest when the diagnosis of vEDS was not known (62% vs 14%; P P P  = .132). Conclusions Arterial Pathology in vEDS individuals is related to the underlying COL3A1 mutation type. The Arterial Pathology in individuals with HI mutations occurs at later ages with a higher incidence of aortic disease compared with other COL3A1 mutation types. Molecular diagnosis is recommended because diagnosis confirmation, appropriate surveillance, and prophylactic interventions in an elective setting improve surgical outcomes.

Benjamin Hibbert – One of the best experts on this subject based on the ideXlab platform.

  • Letter by Ramirez and Hibbert Regarding Article, “Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the Arteriosclerosis, Thrombosis, and Vascular Biology Council”.
    Arteriosclerosis thrombosis and vascular biology, 2018
    Co-Authors: F. Daniel Ramirez, Benjamin Hibbert

    Abstract:

    We read with interest the recent article titled “Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the Arteriosclerosis, Thrombosis, and Vascular Biology Council” in which Robinet et al1 review sex differences in Arterial diseases in both humans and animal models. The authors provide suggestions for examining the influence of sex when designing and reporting preclinical Arterial Pathology experiments. They propose that both sexes should be included in experiments unless scientifically justified, the sex of the animals should be clearly reported, the studies should be adequately powered to observe sex differences, and the data should be analyzed and reported separately by sex. We commend the authors for their initiative and expect that their article will inform preclinical research in the field.

    However, linked to the authors’ recommendations is the perception that preclinical Arterial disease researchers do not consider or report on sex as a biological variable—at least not sufficiently. Yet, data to support this are notably limited in their report. It has been suggested that cardiovascular researchers may already be more attuned to the …