Metatranscriptomic RNA-Seq Data Analysis of Virus-Infected Host Cells.

RNA sequencing (RNA-seq) analysis of virus-infected host cells enables researchers to study a wide range of phenomena involving host-virus interactions. This includes genomic analysis of the viral population itself, as well as analysis of the transcriptional dynamics of the virus and host during infection. In this chapter, we provide a guide for researchers interested in performing RNA-seq data analysis of virus-infected host cells or cell lines. We outline several bioinformatic protocols for quantifying viral abundance, assembling viral genomes from mixed samples, and performing differential expression analysis, among other common workflows. These workflows can be used as starting points for researchers aiming to analyze RNA-seq datasets of mixed samples containing both host and viral RNA, such as virus-infected cell lines or clinical samples.

COVID-19 severity gradient differentially dysregulates clinically relevant drug processing genes in nasopharyngeal swab samples.

AIM: Understanding how COVID-19 impacts the expression of clinically relevant drug metabolizing enzymes and membrane transporters (DMETs) is vital for addressing potential safety and efficacy concerns related to systemic and peripheral drug concentrations. This study investigates the impact of COVID-19 severity on DMETs expression and the underlying mechanisms to inform the design of precise clinical dosing regimens for affected patients. METHODS: Transcriptomics analysis of 102 DMETs, 10 inflammatory markers, and 12 xenosensing regulatory genes was conducted on nasopharyngeal swabs from 50 SARS-CoV-2 positive (17 outpatients, 16 non-ICU, and 17 ICU) and 13 SARS-CoV-2 negative individuals, clinically tested through qPCR, in the Greater Toronto area from October 2020 to October 2021. RESULTS: We observed a significant differential gene expression for 42 DMETs, 6 inflammatory markers, and 9 xenosensing regulatory genes. COVID-19 severity was associated with the upregulation of AKR1C1, MGST1, and SULT1E1, and downregulation of ABCC10, CYP3A43, and SLC29A4 expressions. Altogether, SARS-CoV-2-positive patients showed an upregulation in CYP2C9, CYP2C19, AKR1C1, SULT1B1, SULT2B1, and SLCO4A1 and downregulation in FMO5, MGST3, ABCC5, and SLCO4C1 compared with SARS-CoV-2 negative individuals. These dysregulations were associated with significant changes in the expression of inflammatory and xenosensing regulatory genes driven by the disease. GSTM3, PPARA, and AKR1C1 are potential biomarkers of the observed DMETs dysregulation pattern in nasopharyngeal swabs of outpatients, non-ICU, and ICU patients, respectively. CONCLUSION: The severity of COVID-19 is associated with the dysregulation of DMETs involved in processing commonly prescribed drugs, suggesting potential disease-drug interactions, especially for narrow therapeutic index drugs.

Canadian Cardiovascular Society 2023 Guidelines on the Fitness to Drive.

Cardiovascular conditions are among the most frequent causes of impairment to drive, because they might induce unpredictable mental state alterations via diverse mechanisms like myocardial ischemia, cardiac arrhythmias, and vascular dysfunction. Accordingly, health professionals are often asked to assess patients' fitness to drive (FTD). The Canadian Cardiovascular Society previously published FTD guidelines in 2003-2004; herein, we present updated FTD guidelines. Because there are no randomized trials on FTD, observational studies were used to estimate the risk of driving impairment in each situation, and recommendations made on the basis of Canadian Cardiovascular Society Risk of Harm formula. More restrictive recommendations were made for commercial drivers, who spend longer average times behind the wheel, use larger vehicles, and might transport a larger number of passengers. We provide guidance for individuals with: (1) active coronary artery disease; (2) various forms of valvular heart disease; (3) heart failure, heart transplant, and left ventricular assist device situations; (4) arrhythmia syndromes; (5) implantable devices; (6) syncope history; and (7) congenital heart disease. We suggest appropriate waiting times after cardiac interventions or acute illnesses before driving resumption. When short-term driving cessation is recommended, recommendations are on the basis of expert consensus rather than the Risk of Harm formula because risk elevation is expected to be transient. These recommendations, although not a substitute for clinical judgement or governmental regulations, provide specialists, primary care providers, and allied health professionals with a comprehensive list of a wide range of cardiac conditions, with guidance provided on the basis of the level of risk of impairment, along with recommendations about ability to drive and the suggested duration of restrictions.

Assessment of the well-being of significant others of cardiothoracic surgeons.

OBJECTIVES: We aimed to evaluate how the current working climate of cardiothoracic surgery and burnout experienced by cardiothoracic surgeons influences their spouses and significant others (SOs). METHODS: A 33-question well-being survey was developed by the American Association for Thoracic Surgery Wellness Committee and distributed by e-mail to the SOs of cardiothoracic surgeons and to all surgeon registrants of the 2020 and 2021 American Association for Thoracic Surgery Annual Meetings with a request to share it with their SO. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by χ2 or independent samples t tests, as appropriate. RESULTS: Responses from 238 SOs were analyzed. Sixty-six percent reported that the stress on their cardiothoracic surgeon partner had a moderate to severe influence on their family, and 63% reported that their partner's work demands didn't leave enough time for family. Fifty-one percent reported that their partner rarely had time for intimacy, 27% reported poor work-life balance, and 23% reported that interactions at home were usually or always not good-natured. SOs were most affected when their partner was <5 years out from training, worked in private vs academic practice, and worked longer hours. Having children, particularly younger than age 19 years, and a lack of workplace support resources further diminished well-being. CONCLUSIONS: The current work culture of cardiothoracic surgeons adversely affects their SOs, and the risk for families is concerning. These data present a major area for exploration as we strive to understand and mitigate the factors that lead to burnout among cardiothoracic surgeons.

2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Academic Rank and Productivity Among United States Cardiothoracic Surgeons.

BACKGROUND: Despite a significant growth of women trainees in cardiothoracic surgery recently, women remain a minority of cardiothoracic surgeons and hold a minority of leadership positions. This study evaluates differences in cardiothoracic surgeon subspecialty choices, academic rank, and academic productivity between men and women. METHODS: The Accreditation Council for Graduate Medical Education database was used to identify 78 cardiothoracic surgery academic programs in the United States, including integrated, 4+3, and traditional fellowships, as of June 2020. A total of 1179 faculty members were identified within these programs, 585 adult cardiac surgeons (50%), 386 thoracic surgeons (33%), and 168 congenital surgeons (14%), and other, 40 (3%). Data were collected using institutional websites, ctsnet.org, doximity.com, linkedin.com, and Scopus. RESULTS: Of the 1179 surgeons, only 9.6% were women. Overall, women composed 6.7% of adult cardiac, 15% of thoracic, and 7.7% of congenital surgeons. Among subspecialties, women represent 4.5% (17 of 376) of full professors and 5% (11 of 195) of division chiefs in cardiothoracic surgery in the United States, have shorter career durations, and lower h-indices compared with men. However, women had similar m-indices, which factors in career length, compared with men in adult cardiac (0.63 vs 0.73), thoracic (0.77 vs 0.90), and congenital (0.67 vs 0.78) surgeons. CONCLUSIONS: Career duration, including cumulative research productivity, appears to be the most important factors predicting full professor rank, potentially contributing to persistent sex-based disparities in academic cardiothoracic surgery.

Gender Bias in the Evaluation of Surgical Performance: Results of a Prospective Randomized Trial.

OBJECTIVE: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance. SUMMARY OF BACKGROUND DATA: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias. METHODS: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores by respondent demographic was evaluated using regression analyses. Inter-rater reliability was assessed using the Cronbach's alpha. RESULTS: 103 cardiothoracic surgeons completed the Checklist (trainee gender: male n=50, female n=53) and 112 completed the GRS (trainee gender: male n=56, female n=56). For the Checklist, male cardiothoracic surgeons who were in practice <10 years ( P = 0.036) and involved in training residents ( P = 0.049) were more likely to score male trainees higher than female trainees. The GRS demonstrated high inter-rater reliability across male and female trainees by years and scope of practice for the respondent (alpha >0.900) when compared to the Checklist assessment tool. CONCLUSIONS: Early career male surgeons may exhibit gender bias against women when evaluating trainee performance of coronary anastomoses. The GRS demonstrates higher interrater reliability and robustness against gender bias in the assessment of technical performance than the Checklist, and such scales should be emphasized in educational evaluations.

Vascular Surgery Research in the Coronavirus Disease 2019 Pandemic: A Sex-Based Bibliometric Analysis.

INTRODUCTION: The COVID-19 pandemic has disrupted vascular surgery services globally and its impact on researchers has illustrated disproportionate barriers for female researchers. We assessed the pandemic's consequences on bibliometric trends in vascular surgery and vascular medicine throughout the pandemic. METHODS: A scoping review was performed using the PubMed/MEDLINE, Scopus, and EMBASE databases from January to December 2020 to identify articles related to COVID-19 and vascular surgery or vascular medicine. Articles only describing cardiac or neurovascular care were excluded. The scoping review was performed according to the PRISMA-ScR guidelines. Bibliometric data were extracted and analyzed. RESULTS: Four hundred and fourteen articles were identified, including 125 (30.2%) original articles, 42 (10.1%) review papers, 105 (25.4%) case reports, 27 (6.5%) editorials and commentaries, 94 (22.7%) letters and correspondences, and 21 (5.1%) conference abstracts. The 5 most common countries of study or discussion were all high-income countries. English was the predominant (n = 393, 94.9%) language. Funding was reported for 5.1% (n = 21) of articles. In the first 6 months, 17.6% (n = 30) of first authors and 10.6% (n = 18) of last authors were female, while the last 6 months saw an increase in representation to 30.6% (n = 74) and 15.6% (n = 38) for first and last author, respectively. CONCLUSION: The pandemic caused a rapid surge in vascular publications related to COVID-19. Female authors remain underrepresented in vascular research and the share in female authorship has dropped early in the pandemic, but rose after the end of the first wave. High-income countries remain overrepresented in research productivity, alluding to important disparities in COVID-19-related literature.

Authorship Trends and Disparities in Cardiothoracic Surgery.

BACKGROUND: Previous investigations have revealed significant gender disparities in the academic arenas of cardiothoracic surgery. However, the status of gender representation in cardiothoracic publications has not been well described. This study aimed to evaluate authorship trends by gender in two high-impact cardiothoracic surgical journals. METHODS: In this bibliometric analysis, PubMed was searched for articles published in The Annals of Thoracic Surgery and the Journal of Thoracic and Cardiovascular Surgery from 2010 to 2021. The web-based application Genderize.io was used to classify names of first and last authors as men vs women. The Cochran-Armitage trend test and multivariable logistic regression were used to evaluate authorship per year and the association of first and last author gender, respectively. RESULTS: Among 14,443 articles, 16.7% had women first authors and 8.1% had women last authors. The proportion of articles written by women authors increased, rising from 12.6% to 21.1% (P < .0001) for first and 5.4% to 11.5% (P < .0001) for last authors. Papers written with women as first author were associated with 2.0 higher odds of having a woman as last author (95% CI, 1.7-2.3; P < .0001). The mean number of last author publications was higher for men than for women (2.4 vs 1.7, P < .0001). CONCLUSIONS: Over the past decade, despite a welcomed increase in women authorship in high-impact journals in cardiothoracic surgery, women represent a small proportion of published authors. Women first authors are more likely to publish with women last authors, demonstrating the impact of same-gender collaborations while emphasizing a need for cross-gender mentorship.

Optimal Extent of Repair for Acute Type I Aortic Dissection-Frozen Elephant Trunk? How Long and Why?

Acute Type A dissection is a life-threatening condition requiring urgent surgical treatment. The operative technique involves repairs of a variety of distal extents of the transverse aortic arch and the downstream aorta. We review the evidence surrounding the extent of repair for acute Type A aortic dissection and describe our approach to this disease.

Opening the "Black Box" for Canadian Cardiac Surgery Residency Applicants∗.

Background: This study reports on the main criteria used by Canadian cardiac surgery residency program committees (RPCs) to select applicants and the perceptions of Canadian medical students interested in cardiac surgery. Methods: A 50-question online survey was sent to all 12 Canadian cardiac surgery RPCs. A similar 52-question online survey targeted at Canadian medical students interested in applying to cardiac surgery residency programs was distributed. Data from both surveys were analyzed using descriptive statistics. Results: A total of 62% of all cardiac surgery RPC members (66 of 106) participated, including committee members from all 12 programs (range: 1-12 members per program; 9%-100% response rate per program) and 67% of program directors (8 of 12). Forty-one Canadian medical students (22 pre-clerks [54%], 2 MD/PhD students [5%], and 17 clinical clerks [41%]) participated. Committee members considered the following criteria to be most important when selecting candidates: on-service clinical performance, the interview, quality of reference letters from cardiac surgeons, and completing a rotation at the target program's institution. In contrast, the following criteria relating to the candidate were considered to be less important: wanting to practice in the city or province of training, having a connection to the program location, and personally knowing committee members. Medical students' perceptions were concordant regarding what factors are the most important but they overestimated the influence of non-clinical factors and research productivity in increasing their competitiveness. Conclusion: Canadian cardiac surgery residency programs seek applicants who demonstrate clinical excellence, as assessed by surgical rotations and reference letters from colleagues, and strong interview performance.

Contexte: Cette étude fait état des principaux critères utilisés par les comités des programmes de résidence (CPR) canadiens en chirurgie cardiaque pour sélectionner les candidats, ainsi que des perceptions des étudiants en médecine canadiens qui s'intéressent à la chirurgie cardiaque. Méthodologie: Un sondage en ligne comptant 50 questions a été envoyé aux 12 CPR canadiens en chirurgie cardiaque. Un sondage en ligne semblable (comptant 52 questions) a été distribué aux étudiants en médecine qui souhaitaient soumettre leur candidature à un programme de résidence en chirurgie cardiaque au Canada. Les données des deux sondages ont été analysées à l'aide de statistiques descriptives. Résultats: Au total, 62 % des membres de CPR en chirurgie cardiaque (66 sur 106) ont répondu au sondage, y compris des membres des comités des 12 programmes (plage : 1 à 12 membres par programme; taux de réponse de 9 à 100 % par programme) et 67 % des directeurs de programme (8 sur 12). Au total, 41 étudiants en médecine canadiens (22 en préexternat [54 %], 2 étudiants au M.D./Ph. D. [5 %] et 17 stagiaires en formation clinique [41 %]) ont répondu au sondage. Les membres du comité ont considéré les critères suivants comme étant les plus importants dans le choix de candidats : le rendement clinique en service, l'entrevue, la qualité des lettres de recommandation de chirurgiens cardiaques et la réalisation d'un stage dans l'établissement associé au programme. En revanche, les critères suivants étaient considérés comme moins importants : le désir de pratiquer dans la ville ou la province de formation, un lien avec le lieu du programme, et la connaissance personnelle de membres du co-mité. Les perceptions des étudiants en médecine concordaient quant aux facteurs les plus importants, mais les étudiants surestimaient l'influence de facteurs non cliniques et de la productivité en recherche dans l'aspect concurrentiel de leur candidature. Conclusion: Les programmes de résidence canadiens en chirurgie cardiaque recherchent des candidats forts d'une excellence clinique, évaluée par les stages en chirurgie et les lettres de recommandation de collègues, et offrant une bonne performance en entrevue.

Well-being of Cardiothoracic Surgeons in the Time of COVID-19: A Survey by the Wellness Committee of the American Association for Thoracic Surgery.

The prevalence of burnout among physicians has been increasing over the last decade, but data on burnout in the specialty of cardiothoracic surgery are lacking. We aimed to study this topic through a well-being survey. A 54-question well-being survey was developed by the Wellness Committee of the American Association for Thoracic Surgery (AATS) and sent by email from January through March of 2021 to AATS members and participants of the 2021 annual meeting. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by Chi-square tests or independent samples t-tests, as appropriate. The results from 871 respondents (17% women) were analyzed. Many respondents reported at least moderately experiencing: 1) a sense of dread coming to work (50%), 2) physical exhaustion at work (58%), 3) a lack of enthusiasm at work (46%), and 4) emotional exhaustion at work (50%). Most respondents (70%) felt that burnout affected their personal relationships at least "some of the time," and many (43%) experienced a great deal of work-related stress. Importantly, most respondents (62%) reported little to no access to workplace resources for emotional support, but those who reported access reported less burnout. Most respondents (57%) felt that the COVID-19 pandemic has negatively affected their well-being. On a positive note, 80% felt their career was fulfilling and enjoyed their day-to-day job at least "most of the time." Cardiothoracic surgeons experience high levels of burnout, similar to that of other medical professionals. Interventions aimed at mitigating burnout in this profession are discussed.

Early effect of the COVID-19 pandemic on the North American cardiothoracic surgery job market.

Background: The present study aims to report the early effect of the coronavirus disease 2019 (COVID-19) pandemic on the cardiothoracic surgery job market in North America. Methods: The Cardiothoracic Surgery Network (CTSNet) job market database was queried, and patterns from January to May for 2019 versus January to May 2020 were compared for trends in job postings and job seekers. Results: Our study is comprised of 395 cardiothoracic surgery job postings, of which 98% were positions located in North America and 63% were academic. The negative impact of the pandemic on the cardiothoracic surgery job market was greatest in the cardiothoracic/cardiovascular combined subspecialty, followed by congenital and adult cardiac surgery, whereas general thoracic surgery experienced an increase in proportion of jobs available. Despite an increase in views per job posted in 2020 vs. 2019 (532 vs. 290), employer views of job seeker curriculum vitae declined over the same time period in 2020 (January, 380 views/month to May, 3 views/month) compared to 2019 (January, 100 views/month to May, 54 views/month). Conclusions: An analysis of job postings from CTSNet suggests a decline in job availability in the North American cardiothoracic surgical job market following declaration of the pandemic with acknowledgement that there is month to month variability and a supply-demand mismatch. The COVID-19 pandemic has had an unprecedented impact on our field, and the ultimate consequences remain unknown.

The utilization of educational resources published by the Thoracic Surgery Residents Association.

Objective: The Thoracic Surgery Residents Association (TSRA) is a trainee-led cardiothoracic surgery organization in North America that has published a multitude of educational resources. However, the utilization of these resources remains unknown. Methods: Surveys were constructed, pilot-tested, and emailed to 527 current cardiothoracic trainees (12 questions) and 780 former trainees who graduated between 2012 and 2019 (16 questions). The surveys assessed the utilization of TSRA educational resources in preparing for clinical practice as well as in-training and American Board of Thoracic Surgery (ABTS) certification examinations. Results: A total of 143 (27%) current trainees and 180 (23%) recent graduates responded. A higher proportion of recent graduates compared with current trainees identified as male (84% vs 66%; P = .001) and graduated from 2- or 3-year traditional training programs (81% vs 41%; P < .001), compared with integrated 6-year (8% vs 49%; P < .001) or 4 + 3 (11% vs 10%; P = .82) pathways. Current trainees most commonly used TSRA resources to prepare for the in-training exam (75%) and operations (73%). Recent graduates most commonly used them to prepare for Oral and/or Written Board Exams (92%) and the in-training exam (89%). Among recent graduates who passed the ABTS Oral Board Exam on the first attempt, 82% (97/118) used TSRA resources to prepare, versus only 48% (25/52) of recent graduates who passed after multiple attempts, failed, have not taken the exam, or preferred not to answer (P < .001). Conclusions: Current cardiothoracic trainees and recent graduates have utilized TSRA educational resources extensively, including to prepare for in-training and ABTS Board examinations.