Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.

Background: Medical degree programs use scholarly activities to support development of basic research skills, critical evaluation of medical information and promotion of medical research. The University of Sydney Doctor of Medicine Program includes a compulsory research project. Medical student projects are supervised by academic staff and affiliates, including biomedical science researchers and clinician-academics. This study investigated research supervisors’ observations of the barriers to and enablers of successful medical student research projects. Methods: Research supervisors (n = 130) completed an anonymous, online survey after the completion of the research project. Survey questions targeted the research supervisors’ perceptions of barriers to successful completion of projects and sources of support for their supervision of the student project. Data were analysed by descriptive statistics and using manifest content analysis. Further quantitative investigation was made by cross-tabulation according to prior research supervision experience. Results: Research supervisors reported that students needed both generic skills (75%) and research-based skills (71%) to successfully complete the project. The major barrier to successful research projects was the lack of protected time for research activities (61%). The assessment schedule with compulsory progress milestones enabled project completion (75%), and improved scientific presentation (90%) and writing (93%) skills. Supervisors requested further support for their students for statistics (75%), scientific writing (51%), and funding for projects (52%). Prior research supervision experience influenced the responses. Compared to novice supervisors, highly experienced supervisors were significantly more likely to want students to be allocated dedicated time for the project (P < 0.01) and reported higher rates of access to expert assistance in scientific writing, preparing ethics applications and research methodology. Novice supervisors reported higher rates of unexpected project delays and data acquisition problems (P < 0.05). Co-supervision was favoured by experienced supervisors but rejected by novice supervisors. Conclusions: Both generic and research-related skills were important for medical student research project success. Overall, protected research time, financial and other academic support were identified as factors that would improve the research project program. Prior research supervision experience influences perceptions of program barriers and enablers. These findings will inform future support needs for projects and research supervisor training for the research supervision role.

Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression. Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome. Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation. Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.

Background: Thoracic aortic aneurysm (TAA) is an indolent, potentially fatal disease, which progresses at variable rates that are influenced by pathogenesis and patient characteristics. We conducted a systematic review and meta‐analysis to synthesize the current evidence on growth rate (GR) and predictive factors among patients with syndromic and nonsyndromic heritable thoracic aortic disease, bicuspid aortic valve, and sporadic TAA. Methods and Results: Online databases were searched for studies that reported aortic growth on adult patients with asymptomatic TAA. Pooled GRs were calculated for 3 different TAA groups: syndromic heritable thoracic aortic disease, bicuspid aortic valve, and sporadic TAA. The search yielded 6297 studies, of which 85 were included in the systematic review, and 55 in the meta‐analysis of growth rate (10 syndromic heritable thoracic aortic disease, 31 bicuspid aortic valve, and 34 sporadic subgroups). Mean observed TAA GR was 0.25 mm/y (95% CI, −0.18 to 0.68) in Turner syndrome, 0.45 mm/y (95% CI, 0.00–0.90) in Marfan syndrome, and 0.81 mm/y (95% CI, −0.46 to 2.08) in Loeys–Dietz syndrome. The mean observed GR in patients with bicuspid aortic valve before aortic valve surgery was 0.37 mm/y (95% CI, 0.29–0.46), compared with 0.18 mm/y (95% CI, 0.14–0.33) in postsurgical studies. Mean observed GR in sporadic ascending TAA was 0.33 mm/y (95% CI, 0.13–0.52) and 2.71 mm/y (95% CI, 0.53–4.88) in descending TAA. Conclusions: Considering all pathogeneses, ascending TAAs typically grow at 0.25 to 1 mm/y, and thus annual surveillance is likely too frequent to detect growth in most patients. Studies vary widely in populations, methodology, and outcomes, with few high‐quality longitudinal studies and no predictors of aortic GR.