Biodegradable external wrapping promotes favorable adaptation in an ovine vein graft model.

Vein grafts, the most commonly used conduits in multi-vessel coronary artery bypass grafting surgery, have high intermediate- and long-term failure rates. The abrupt and marked increase in hemodynamic loads on the vein graft is a known contributor to failure. Recent computational modeling suggests that veins can more successfully adapt to an increase in mechanical load if the rate of loading is gradual. Applying an external wrap or support at the time of surgery is one way to reduce the transmural load, and this approach has improved performance relative to an unsupported vein graft in several animal studies. Yet, a clinical trial in humans has shown benefits and drawbacks, and mechanisms by which an external wrap affects vein graft adaptation remain unknown. This study aims to elucidate such mechanisms using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, hemodynamics using computational fluid dynamics, structure using histology, and transcriptional changes using bulk RNA-sequencing in an ovine carotid-jugular interposition vein graft model, without and with an external biodegradable wrap that allows loads to increase gradually. We show that a biodegradable external wrap promotes luminal uniformity, physiological wall shear stress, and a consistent vein graft phenotype, namely, it prevents over-distension, over-thickening, intimal hyperplasia, and inflammation, and it preserves mechanotransduction. These mechanobiological insights into vein graft adaptation in the presence of an external support can inform computational growth and remodeling models of external support and facilitate design and manufacturing of next-generation external wrapping devices. STATEMENT OF SIGNIFICANCE: External mechanical support is emerging as a promising technology to prevent vein graft failure following coronary bypass graft surgery. While variants of this technology are currently under investigation in clinical trials, the fundamental mechanisms of adaptation remain poorly understood. We employ an ovine carotid-jugular interposition vein graft model, with and without an external biodegradable wrap to provide mechanical support, and probe vein graft adaptation using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, fluid flow using computational fluid dynamics, vascular composition and structure using histology, and transcriptional changes using bulk RNA sequencing. We show that the wrap mitigates vein graft failure by promoting multiple adaptive mechanisms (across biological scales).

Impact of PhD Degree Versus Non-PhD Research Fellowship on Future Research Productivity Among Academic Cardiothoracic Surgeons.

BACKGROUND: A PhD degree can offer significant research experience, but previous studies yielded conflicting conclusions on the relationship between a PhD degree and future research output. We compared the impact of a PhD degree versus research fellowship (RF) training on research productivity in cardiothoracic surgeons, hypothesizing that training pathways may influence potential associations. METHODS: CT surgeons practicing at all accredited United States CT surgery training programs in 2018 who pursued dedicated time for research (n = 597), including earning a PhD degree (n = 92) or completing a non-PhD RF (n = 505), were included. To control for training pathways, we performed subanalyses of U.S. medical school graduates (n = 466) and international medical school graduates (IMGs) (n = 131). Surgeon-specific data were obtained from publicly available sources (e.g., institutional webpages, Scopus). RESULTS: PhD surgeons published greater total papers (68.5 vs. 52.0, p = 0.0179) and total papers per year as an attending (4.6 vs. 3.0, p = 0.0150). For U.S. medical school graduates, there were 40 PhD surgeons and 426 non-PhD RF surgeons; both groups published a similar number of total papers (64.5 vs. 54.0, p = 0.3738) and total papers per year (3.2 vs. 3.0, p = 0.7909). For IMGs, there were 52 PhD surgeons and 79 non-PhD RF surgeons; the PhD surgeons published greater total papers (80.5 vs. 45.0, p = 0.0101) and total papers per year (5.7 vs. 2.7, p = 0.0037). CONCLUSION: CT surgeons with dedicated research training are highly academically productive. Although a PhD degree may be associated with enhanced career-long research productivity for IMGs, this association was not observed for U.S. medical school graduates.

Analyzing the Scholarly Impact of Cardiothoracic Surgery Research Using the Relative Citation Ratio.

INTRODUCTION: The National Institutes of Health (NIH) recently developed the relative citation ratio (RCR), calculated as article citations benchmarked to NIH-funded publications in the same field. Here, we characterized the scholarly impact of academic cardiothoracic (CT) surgeons and their research using the RCR. MATERIALS AND METHODS: Using a database of 992 CT surgeons, we calculated the RCR for all articles published by each surgeon since 1980 using the NIH iCite database. All data were collected from publicly available online sources. Data are presented as median (interquartile range) or as odds ratios (ORs) for multivariable logistic regression analysis. RESULTS: Where RCR 1.00 indicates equal impact as an NIH-funded publication, the RCR among all 37,402 CT surgery articles was 0.84 (0.33-1.83) and the RCR among NIH-funded CT surgery articles was 1.07 (0.53-2.17). CT surgeons exhibited a career median RCR of 0.82 (0.54-1.13) and maximum RCR of 6.20 (3.04-13.57). Predictors of career median RCR >1.00 included female gender (OR 2.23, P = 0.001), thoracic subspecialization (OR 2.50, P < 0.001), full professor rank (OR 1.89, P = 0.001), and NIH funding (OR 1.75, P = 0.001). Predictors of career maximum RCR >50th percentile among CT surgeons included male gender (OR 1.87, P = 0.030), thoracic subspecialization (OR 2.05, P < 0.001), full professor rank (OR 4.89, P < 0.001), NIH funding (OR 3.17, P < 0.001), and career duration (OR 1.03, P = 0.002). CONCLUSIONS: We present the first assessment of the NIH-validated RCR for academic CT surgery. CT surgery research is highly impactful, although gender disparities persist with respect to the highest-impact research of our specialty.

The Academic Impact of Advanced Clinical Fellowship Training among General Thoracic Surgeons.

OBJECTIVE: Advanced clinical fellowship training has become a popular option for surgical trainees seeking to bolster their clinical training and expertise. However, the long-term academic impact of this additional training following a traditional thoracic surgery fellowship is unknown. This study aimed to delineate the impact of an advanced clinical fellowship on subsequent research productivity and advancement in academic career among general thoracic surgeons. METHODS: Using an internally constructed database of active, academic general thoracic surgeons who are current faculty at accredited cardiothoracic surgery training programs within the United States, surgeons were dichotomized according to whether an advanced clinical fellowship was completed or not. Academic career metrics measured by research productivity, scholarly impact (H-index), funding by the National Institutes of Health, and academic rank were compared. RESULTS: Among 285 general thoracic surgeons, 89 (31.2%) underwent an advanced fellowship, whereas 196 (68.8%) did not complete an advanced fellowship. The most commonly pursued advanced fellowship was minimally invasive thoracic surgery (32.0%). There were no differences between the two groups in terms of gender, international medical training, or postgraduate education. Those who completed an advanced clinical fellowship were less likely to have completed a dedicated research fellowship compared to those who had not completed any additional clinical training (58.4% vs. 74.0%, p = 0.0124). Surgeons completing an advanced clinical fellowship demonstrated similar cumulative first-author publications (p = 0.4572), last-author publications (p = 0.7855), H-index (p = 0.9651), National Institutes of Health funding (p = 0.7540), and years needed to advance to associate professor (p = 0.3410) or full rank professor (p = 0.1545) compared to surgeons who did not complete an advanced fellowship. These findings persisted in sub-analyses controlling for surgeons completing a dedicated research fellowship. CONCLUSIONS: Academic general thoracic surgeons completing an advanced clinical fellowship demonstrate similar research output and ascend the academic ladder at a similar pace as those not pursuing additional training.

Characterization of academic cardiothoracic surgeons who started as attendings in private or community practice.

BACKGROUND: Surgeons are traditionally categorized as working either in academic or private/community practice, but some transition between the two environments. Here, we profile current academic cardiothoracic surgeons who began their attending careers in private or community practice. We hypothesized that research activity may distinguish cardiothoracic surgeons who started in non-academic versus academic practice. METHODS: Publicly available data regarding professional history and research productivity were collected for 992 academic cardiothoracic surgeons on faculty at the 77 cardiothoracic surgery training programs in the United States in 2018. Data are presented as medians analyzed with the Mann-Whitney test or proportions analyzed with Fisher exact test or the χ2 test. RESULTS: A total of 80 (8.1%) academic cardiothoracic surgery faculty started their careers in non-academic practice, and 912 (91.9%) started directly in academia. Those who started in non-academic practice spent a median 7.0 y in private/community practice and were more likely to be cardiac surgeons (68.8% vs 51.6%, P = .0132). They were equally likely to pursue a protected research fellowship (56.3% vs 57.0%, P = .9067) and publish research during training (92.5% vs 91.1%, P = .8374), but they published fewer total papers by the end of cardiothoracic surgery fellowship (3.0 vs 7.0, P = .0001) and fewer papers per year as an academic attending (0.8 vs 2.9, P < .0001). Nevertheless, the majority of cardiothoracic surgery faculty who started in non-academic practice are currently active in research (68.8%), and 2 such surgeons received National Institutes of Health R01 funding. CONCLUSION: Transitioning from non-academic to academic practice is an uncommon but feasible pathway for interested cardiothoracic surgeons.

Characterization of Cardiothoracic Surgeons Actively Leading Basic Science Research.

BACKGROUND: There is increasing concern regarding the attrition of surgeon-scientists in cardiothoracic (CT) surgery. However, the characteristics of CT surgeons who are actively leading basic science research (BSR) have not been examined. We hypothesized that early exposure to BSR during training and active grant funding are important factors that facilitate the pursuit of BSR among practicing CT surgeons. MATERIALS AND METHODS: We created a database of 992 CT surgeons listed as faculty at accredited United States CT surgery teaching hospitals in 2018. Data regarding each surgeon's training/professional history, publication record, and National Institutes of Health funding were acquired from publicly available online sources. Surgeons who published at least one first- or last-author paper in 2017-2018 were considered to be active, lead researchers. RESULTS: Of the 992 CT surgeons, 73 (7.4%) were actively leading BSR, and 599 (60.4%) were actively leading only non-BSR. Only 2 women were actively leading BSR. Surgeons actively leading BSR were more likely to have earned a PhD degree (20.5% versus 9.7%, P = 0.0049), and more likely to have published a first-author BSR paper during training (76.7% versus 40.9%, P< 0.0001). Surgeons actively leading BSR were also more likely to have an active National Institutes of Health grant (34.2% versus 5.8%, P< 0.0001), especially an R01 grant (21.9% versus 2.5%, P< 0.0001). CONCLUSIONS: A small minority of CT surgeons at academic training hospitals are actively leading BSR. In order to facilitate the development of surgeon-scientists, additional support must be given to trainees and junior faculty, especially women, to enable early engagement in BSR.

Career Research Productivity Correlates With Medical School Ranking Among Cardiothoracic Surgeons.

BACKGROUND: The foundation for a successful academic surgical career begins in medical school. We examined whether attending a top-ranked medical school is correlated with enhanced research productivity and faster career advancement among academic cardiothoracic (CT) surgeons. MATERIALS AND METHODS: Research profiles and professional histories were obtained from publicly available sources for all CT surgery faculty at accredited US CT surgery teaching hospitals in 2018 (n = 992). We focused on surgeons who completed medical school in the United States during or after 1990, the first-year US News & World Report released its annual medical school research rankings (n = 451). Subanalyses focused on surgeons who completed a research fellowship (n = 299) and those who did not (n = 152). RESULTS: A total of 124 surgeons (27.5%) attended a US News & World Report top 10 medical school, whereas 327 (72.5%) did not. Surgeons who studied at a top 10 medical school published more articles per year as an attending surgeon (3.2 versus 1.9; P < 0.0001), leading to more total publications (51.5 versus 27.0; P < 0.0001) and a higher H-index (16.0 versus 11.0; P < 0.0001) over a similar career duration (11.0 versus 10.0 y; P = 0.1294). These differences in career-long research productivity were statistically significant regardless of whether the surgeons completed a research fellowship or not. The surgeons in both groups, however, required a similar number of years to reach associate professor rank (P = 0.6993) and full professor rank (P = 0.7811) after starting their first attending job. CONCLUSIONS: Attending a top-ranked medical school is associated with enhanced future research productivity but not with faster career advancement in academic CT surgery.

Impact of advanced clinical fellowship training on future research productivity and career advancement in adult cardiac surgery.

BACKGROUND: Advanced clinical fellowships are important for training surgeons with a niche expertise. Whether this additional training impacts future academic achievement, however, remains unknown. Here, we investigated the impact of advanced fellowship training on research productivity and career advancement among active, academic cardiac surgeons. We hypothesized that advanced fellowships do not significantly boost future academic achievement. METHODS: Using online sources (eg, department webpages, CTSNet, Scopus, Grantome), we studied adult cardiac surgeons who are current faculty at accredited United States cardiothoracic surgery training programs, and who have practiced only at United States academic centers since 1986 (n = 227). Publicly available data regarding career advancement, research productivity, and grant funding were collected. Data are expressed as counts or medians. RESULTS: In our study, 78 (34.4%) surgeons completed an advanced clinical fellowship, and 149 (65.6%) did not. Surgeons who pursued an advanced fellowship spent more time focused on surgical training (P < .0001), and those who did not were more likely to have completed a dedicated research fellowship (P = .0482). Both groups exhibited similar cumulative total publications (P = .6862), H-index (P = .6232), frequency of National Institutes of Health grant funding (P = .8708), and time to achieve full professor rank (P = .7099). After stratification by current academic rank, or by whether surgeons pursued a dedicated research fellowship, completion of an advanced clinical fellowship was not associated with increased research productivity or accelerated career advancement. CONCLUSION: Academic adult cardiac surgeons who pursue advanced clinical fellowships exhibit similar research productivity and similar career advancement as those who do not pursue additional clinical training.

New Attending Surgeons Hired by Their Training Institution Exhibit Greater Research Productivity.

BACKGROUND: A first attending job often sets the tone for academic surgeons' future careers, and many graduating trainees are faced with the decision to begin their career at their training institution or another institution. We hypothesized that surgeons hired as first-time faculty at their cardiothoracic surgery fellowship institution exhibit greater research productivity and career advancement than those hired as first-time faculty at a different institution. METHODS: Cardiothoracic surgeons who were listed as clinical faculty at all 77 accredited United States cardiothoracic surgery training programs in 2018 and who trained through the general surgery residency and cardiothoracic surgery fellowship pathway were included (n = 904). Surgeon-specific data regarding professional history, publications, and grant funding were obtained from publicly available sources. RESULTS: Of the 904 surgeons, 294 (32.5%) were hired as first-time faculty at their cardiothoracic surgery fellowship institution whereas 610 (67.5%) were hired at a different institution (start year 2005 vs 2006; P = .342). Both groups exhibited similar research productivity upon starting their first job (total papers: 7.0 vs 7.0, P = .591). Followed to the present, surgeons hired at their cardiothoracic surgery fellowship institution produced more total papers (64.5 vs 39.0, P < .001) and exhibited a higher H-index (20.0 vs 14.0, P < .001). Surgeons in both groups required a similar amount of time to achieve associate (P = .208) and full professor (P = .593) ranks. CONCLUSIONS: Surgeons hired as first-time faculty at their cardiothoracic surgery fellowship institution may experience benefits to research productivity but not career advancement. Trainees may find it advantageous to begin their careers in a familiar environment where they have already formed a robust specialty-specific network.

National Institutes of Health R01 Grant Funding Is Associated With Enhanced Research Productivity and Career Advancement Among Academic Cardiothoracic Surgeons.

National Institutes of Health (NIH) funding has declined among cardiothoracic surgeons. R01 grants are a well-known mechanism to support high-impact research, and we sought to clarify the association between NIH funding and academic achievement. We hypothesized that cardiothoracic surgeons who acquired R01 funding exhibit greater research output and faster career advancement. All cardiothoracic surgeons (n = 992) working at accredited United States cardiothoracic surgery training hospitals in 2018 were included. Institutional webpages, Scopus, and Grantome were utilized to collect publicly-available data regarding each surgeon's training and career history, research publications, and NIH funding. Seventy-eight (7.9%) surgeons obtained R01 funding as a principal investigator while 914 (92.1%) did not. R01-funded surgeons started their attending careers earlier (1998 vs 2005, P < 0.0001) and were more likely to have pursued dedicated research training (P < 0.0001). R01-funded surgeons authored 5.3 publications/year before their first R01 grant, 9.3 during the grant period, and 8.6 after the grant expired, all of which were greater than the publication rate of non-R01-funded surgeons at comparable career timepoints (2.0-3.0 publications/year, P < 0.0001). Among time-matched surgeons who completed medical school in 1998 or earlier (n = 73 R01-funded vs n = 602 non-funded), R01-funded surgeons have published more total publications (178.0 vs 56.5 papers, P < 0.0001) and exhibit a greater H-index (41.0 vs 19.0, P < 0.0001). These R01-funded surgeons have also advanced to higher academic ranks (P < 0.0001) and are more likely to be chiefs of their departments or divisions (42.5% vs 25.7%, P = 0.0035). Cardiothoracic surgeons who obtain R01 funding exhibit greater research productivity and faster career advancement.

Early Engagement in Cardiothoracic Surgery Research Enhances Future Academic Productivity.

BACKGROUND: Early engagement in cardiothoracic (CT) surgery research may help attract trainees to academic CT surgery, but whether this early exposure boosts career-long academic achievement remains unknown. METHODS: A database of all CT surgery faculty at accredited, academic CT surgery training programs in the United States during the year 2018 was established. Excluding international medical graduates, surgeons who started general surgery residency in the United States before 2004 and who published at least 1 manuscript before traditional CT fellowship training were included (n = 472). Each surgeon's educational background, work history, and research publications were recorded from publicly available online sources. RESULTS: Before fellowship training, 370 surgeons (78.4%) coauthored a CT surgery manuscript, and 102 (21.6%) published only on subjects unrelated to CT surgery. Regardless of whether surgeons pursued dedicated research training or not, those who coauthored a CT surgery manuscript before fellowship training published more papers per year as an attending (P < .01), resulting in more total publications (P < .01) and a higher H-index (P < .01) over comparably long careers. Among CT surgeons who did not publish CT surgery research before fellowship training, those who coauthored a CT surgery manuscript during fellowship also exhibited enhanced future academic productivity. CONCLUSIONS: Academic CT surgeons who published CT surgery research before fellowship training ultimately exhibited more prolific and impactful research profiles compared with those who published only on subjects unrelated to CT surgery during training. Efforts to increase early engagement in CT surgery research among trainees should be fully endorsed.

Genes responsive to rapamycin and serum deprivation are clustered on chromosomes and undergo reorganization within local chromatin environments.

We previously demonstrated that genome reorganization, through chromosome territory repositioning, occurs concurrently with significant changes in gene expression in normal primary human fibroblasts treated with the drug rapamycin, or stimulated into quiescence. Although these events occurred concomitantly, it is unclear how specific changes in gene expression relate to reorganization of the genome at higher resolution. We used computational analyses, genome organization assays, and microscopy, to investigate the relationship between chromosome territory positioning and gene expression. We determined that despite relocation of chromosome territories, there was no substantial bias in the proportion of genes changing expression on any one chromosome, including chromosomes 10 and 18. Computational analyses identified that clusters of serum deprivation and rapamycin-responsive genes along the linear extent of chromosomes. Chromosome conformation capture (3C) analysis demonstrated the strengthening or loss of specific long-range chromatin interactions in response to rapamycin and quiescence induction, including a cluster of genes containing Interleukin-8 and several chemokine genes on chromosome 4. We further observed that the LIF gene, which is highly induced upon rapamycin treatment, strengthened interactions with up- and down-stream intergenic regions. Our findings indicate that the repositioning of chromosome territories in response to cell stimuli, this does not reflect gene expression changes occurring within physically clustered groups of genes.

Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan.

Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth.