Comparative finite element analysis of skull mechanical properties following parietal bone graft harvesting in adults

Introduction: Parietal bone grafts are commonly used in cranio-maxillo-facial surgery. Both the outer and the internal layer of the calvarium can be harvested. The bone defect created by this harvesting may induce significant weakening of the skull that has not been extensively evaluated. Our aim was to evaluate the consequences of parietal bone graft harvesting on mechanical properties of the skull using a finite element analysis. Methods: Finite elements models of the skull of 3 adult patients were created from CT scans. Parietal external and internal layer harvest models were created. Frontal, lateral, and parietal loading were modeled and von Mises stress distributions were compared. Results: The maximal von Mises stress was higher for models of bone harvesting, both on the whole skull and at the harvested site. Maximal von Mises stress was even higher for models with internal layer defect. Conclusions: Harvesting parietal bone modifies the skull's mechanical strength and can increase the risk of skull fracture, mainly on the harvested site. Outer layer parietal graft harvesting is indicated. Graft harvesting located in the upper part of the parietal bone, close to the sagittal suture and with smooth internal edges and corners should limit the risk of fracture

Role of the advanced nurse practitioner within the vascular team: A qualitative study of vascular physicians and nurses

ObjectiveTo assess the perception of Advanced Nurse Practitioners (ANP) by physicians and nurses in vascular medicine. As the status of ANP in France was recently enacted by law in 2018, we aimed to investigate physicians and nurses working with patients suffering from Peripheral Artery Disease (PAD) to gather their opinions and draw the cooperation outlines these practitioners could have with an ANP.MethodsA qualitative study based on in-depth interviews was conducted among healthcare practitioners taking care of patients with PAD: 10 physicians working either in a private practice settings or hospital settings or both, and eight nurses working within a hospital inpatients vascular unit. Verbatim responses were extracted and coded according to a continuous thematization method.ResultsThree main features emerged from participants’ responses. Vascular medicine has a specific organization with a significant lack of time and staff to fulfill the mission regarding patients’ severity of illness. Second, the ANP is wanted to fill part of this gap. The expected benefits include a smoother care pathway and increased capacity for cardiovascular education and prevention, especially during consultations. Lastly, some clarification is required to integrate such new practitioners within vascular teams already in place.ConclusionAdvanced nurse practitioners could be the missing link in a “Vascular team” by creating a continuum in the care of patients with PAD, ensuring clinical assessment, nursing supervision, adverse event screening, and renewing drug prescriptions with the required adaptations while ensuring essential part of therapeutic education adapted to each patient

Aortic Wall Elastic Properties in Case of Bicuspid Aortic Valve

Purpose of the ReviewBicuspid aortic valve (BAV) is associated with a significant risk of development of aneurysm and dissection of the ascending thoracic aorta. Development of what is called BAV associated aortopathy is particularly heterogeneous with an uncertain prognosis and with no prognostic biomarkers except for the aortic diameter. This situation leads to an important variability of the therapeutic strategy of this aortopathy. By reviewing the literature on aortic stiffness in the case of BAV, we aimed at evaluating its potential prognostic role in the development of aortic dilatation.Recent FindingsStudies evaluating aortic stiffness, with ultrasound or magnetic resonance imaging, converge toward the description of an increased segmental aortic stiffness in BAV patients regardless of age, diameter or aortic level, from the root to the arch. Even though there is a lack of longitudinal studies evaluating the progression of aortic dilatation, new data have recently shown the potential prognostic role of the maximal rate of systolic distension of the aortic wall with magnetic resonance imaging.SummaryAlthough the use of aortic distensibility calculation is a simple evaluation of stiffness that could be easily transposed in daily practice, its interpretation remains uncertain. New arterial stiffening indicators seem more promising but need a stronger validation

Building a successful minimally invasive mitral valve repair program before introducing the robotic approach: The Massachusetts General Hospital experience

BackgroundPatients with mitral valve prolapse (MVP) requiring surgical repair (MVr) are increasingly operated using minimally invasive strategies. Skill acquisition may be facilitated by a dedicated MVr program. We present here our institutional experience in establishing minimally invasive MVr (starting in 2014), laying the foundation to introduce robotic MVr.MethodsWe reviewed all patients that had undergone MVr for MVP via sternotomy or mini-thoracotomy between January 2013 and December 2020 at our institution. In addition, all cases of robotic MVr between January 2021 and August 2022 were analyzed. Case complexity, repair techniques, and outcomes are presented for the conventional sternotomy, right mini-thoracotomy and robotic approaches. A subgroup analysis comparing only isolated MVr cases via sternotomy vs. right mini-thoracotomy was conducted using propensity score matching.ResultsBetween 2013 and 2020, 799 patients were operated for native MVP at our institution, of which 761 (95.2%) received planned MVr (263 [34.6%] via mini-thoracotomy) and 38 (4.8%) received planned MV replacement. With increasing proportions of minimally invasive procedures (2014: 14.8%, 2020: 46.5%), we observed a continuous growth in overall institutional volume of MVP (n = 69 in 2013; n = 127 in 2020) and markedly improved institutional rates of successful MVr, with 95.4% in 2013 vs. 99.2% in 2020. Over this period, a higher complexity of cases were treated minimally-invasively and increased use of neochord implantation ± limited leaflet resection was observed. Patients operated minimally invasively had longer aortic cross-clamp times (94 vs. 88 min, p = 0.001) but shorter ventilation times (4.4 vs. 4.8 h, p = 0.002) and hospital stays (5 vs. 6 days, p < 0.001) than those operated via sternotomy, with no significant differences in other outcome variables. A total of 16 patients underwent robotically assisted MVr with successful repair in all cases.ConclusionA focused approach towards minimally invasive MVr has transformed the overall MVr strategy (incision; repair techniques) at our institution, leading to a growth in MVr volume and improved repair rates without significant complications. On this foundation, robotic MVr was first introduced at our institution in 2021 with excellent outcomes. This emphasizes the importance of building a competent team to perform these challenging operations, especially during the initial learning curve

Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve.

IMPORTANCE Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. OBJECTIVE To identify a new gene for nsBAV. DESIGN, SETTING, AND PARTICIPANTS This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. MAIN OUTCOMES AND MEASURES To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. RESULTS A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with population-based controls (2% cases vs 0.9% controls; P = .03). In replication cohort 2, MIB1 risk haplotypes significantly associated with nsBAV were identified (permutation test, 1000 repeats; P = .02). Two genetically modified mice models carrying Mib1 variants identified in our cohort showed BAV on a NOTCH1-sensitized genetic background. CONCLUSIONS AND RELEVANCE This genetic association study identified the MIB1 gene as associated with nsBAV. This underscores the crucial role of the NOTCH pathway in the pathophysiology of BAV and its potential as a target for future diagnostic and therapeutic intervention.This study was supported in part by grants PID2019-104776RB-I00 and CB16/ 11/00399 (Dr de la Pompa) from the Spanish Ministerio de Ciencia e Innovación (MCIN/ AEI/ 10.13039/501100011033/); a grant from Hadassah France Association (Drs Gilon and Tessler); a grant from the Center for Interdisciplinary Data Science Research of the Hebrew University of Jerusalem (Dr Tessler); grant R35 CA220340 from the National Institutes of Health (Dr Blacklow), and grants R21HL150373, R01HL114823 (Dr Body); BSF grants 2013269 and 2017245 (Drs. Sprinzak and Blacklow); a consolidator grant from the European Research Council (Genomia – ERC-COG-2017-771945; Dr Loeys); the European Reference Network on rare multisystemic vascular disorders (VASCERN - project ID: 769036 partly cofunded by the European Union Third Health Programme (Drs Loeys and Verstraeten); funding from the Outreach project (Dutch Heart Foundation; Dr Luyckx); funding from Heart and Stroke Foundation of Canada/Robert M Freedom Chair of Cardiovascular Science (Dr Mital); sample biobanking and sequencing from Canada were supported by grants from the Leducq Foundation Transatlantic Networks of Excellence grant, and the Ted Rogers Centre for Heart Research; ISF grant 1053/12 (Dr Durst); and grant R01HL150401 from National Heart, Lung, and Blood Institute (Dr Muehlschlegel).S

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Innovative applications of ultrasound in vascular pathology : use of ultrafast imaging in the analysis of arterial stiffness and pulsed ultrasound in therapy

Résumé confidentielConfidential abstrac

Arterial stiffness, fatness, and physical fitness:Ready for intervention in childhood and across the life course?

International audienceA rterial distensibility and its converse stiffness have come of age as physiological concepts 1 and now as a target for intervention. The central hypothesis sustained so far is that an individual's "arterial stiffness" measured as aortic pulse wave velocity (PWV) is a convenient, integrated index of vascular pathology over a person's life course, more precise and reliable than other risk factors individually. For example, blood pressure (BP), whether casual or 24 hour, is more sensitive to stimuli and, therefore, more variable. Arterial distensibility is in part dependent on BP, yet its prognostic power is because of its "independence" from BP, including pulse pressure. 2 It appears to indicate the general burden of atherosclerotic disease and subclinical damage from multiple risk factors over time: the "wear and tear" of constant distension and recoil (part of "aging"), effects of smoking, lipid metabolism, (hyper)glycemia, ethnicity, how family history expresses itself, etc. 3 European hypertension guidelines now include PWV as a recommended but optional measure. The relationship of arterial distensibility with cardiac function and structure, known as aorto-ventricular coupling, is tantalizing because, as a bioengineering feedback loop, cause and effect are still unclear. Many other key questions remain, most critically related to the natural history of arterial stiffness but also fundamental ones of basic structural biology in the vessel wall. A clue to the natural history of arterial stiffness is published in this issue of Hypertension, an Australian study of 9to 10-year-old, generally prepubescent schoolchildren. 4 The study shows a clear relationship among degree of body fat, physical fitness, and arterial stiffness, measured by carotidfemoral PWV. The link of PWV with fitness was not independent of body fat. Why should this article be of interest, being only cross-sectional, whereby association may well not imply cause? The answer is its insight into primary prevention and underlying mechanisms. The study's strengths include its community base, large number of healthy children properly sampled, gold-standard "DXA" assessment of body composition, and an accepted method for PWV measurement. Its weaknesses include PWV measured sequentially rather than simultaneously at carotid and femoral sites over only 8 cardiac cycles. Another is the use of a 20-m shuttle run to assess cardiorespiratory fitness, which can be characterized by a variety of methods that the authors understandably could not apply but do not discuss or compare. Similarly, the pedometer is insensitive for assessing physical activity, especially in children, who may remove it. Perhaps as a result, only 20% of the variance of the PWV measured was related to any of their variables. However, these weaknesses would tend to bias the results toward the null so that any association with PWV was remarkable