All Publications


  • Seeing is Believing. The Annals of thoracic surgery Williams, K. M., Backhus, L. M. 2021

    View details for DOI 10.1016/j.athoracsur.2020.12.065

    View details for PubMedID 33581155

  • National Institutes of Health R01 Grant Funding Is Associated with Enhanced Research Productivity and Career Advancement Among Academic Cardiothoracic Surgeons. Seminars in thoracic and cardiovascular surgery Bajaj, S. S., Wang, H., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020

    Abstract

    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. 78 (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). 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.

    View details for DOI 10.1053/j.semtcvs.2020.12.002

    View details for PubMedID 33359763

  • Early Engagement in Cardiothoracic Surgery Research Enhances Future Academic Productivity. The Annals of thoracic surgery Wang, H., Bajaj, S. S., Williams, K. M., Heiler, J. C., Pickering, J. M., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020

    Abstract

    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 prior to 2004 and who published at least one manuscript prior to 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: In total, 370 surgeons (78.4%) co-authored a CT surgery manuscript before fellowship training, while 102 (21.6%) published only on subjects unrelated to CT surgery. Regardless of whether surgeons pursued dedicated research training or not, those who co-authored a CT surgery manuscript prior to fellowship training published more papers per year as an attending (p<0.01), resulting in more total publications (p<0.01) and a higher H-index (p<0.01) over comparably long careers. Among CT surgeons who did not publish CT surgery research prior to fellowship training, those who co-authored a CT surgery manuscript during fellowship also exhibited enhanced future academic productivity.CONCLUSIONS: Academic CT surgeons who published CT surgery research prior to fellowship training ultimately exhibit more prolific and impactful research profiles compared to 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.

    View details for DOI 10.1016/j.athoracsur.2020.10.013

    View details for PubMedID 33159869

  • New Attending Surgeons Hired by Their Training Institution Exhibit Greater Research Productivity. The Annals of thoracic surgery Bajaj, S. S., Wang, H., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020

    Abstract

    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 (CSF) 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 U.S. cardiothoracic surgery training programs and who trained via the general surgery residency and CSF pathway in 2018 were included (n=904). Surgeon-specific data regarding professional history, publications, and grant funding were obtained from publicly available sources.RESULTS: 294/904 (32.5%) surgeons were hired as first-time faculty at their CSF institution while 610/904 (67.5%) surgeons were hired at a different institution (start year 2005 vs 2006, p=0.3424). Both groups exhibited similar research productivity upon starting their first job (total papers: 7.0 vs 7.0, p=0.5913). Following them to the present, surgeons hired at their CSF institution produced more total papers (64.5 vs 39.0, p<0.0001) and exhibited a higher H-index (20.0 vs 14.0, p<0.0001). Surgeons in both groups required a similar amount of time to achieve associate (p=0.2079) and full professor (p=0.5925) ranks.CONCLUSIONS: Surgeons hired as first-time faculty at their CSF 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.

    View details for DOI 10.1016/j.athoracsur.2020.09.026

    View details for PubMedID 33152331

  • Impact of advanced clinical fellowship training on future research productivity and career advancement in adult cardiac surgery. Surgery Wang, H., Bajaj, S. S., Williams, K. M., Pickering, J. M., Heiler, J. C., Manjunatha, K., O'Donnell, C. T., Sanchez, M., Boyd, J. H. 2020

    Abstract

    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.

    View details for DOI 10.1016/j.surg.2020.06.016

    View details for PubMedID 32747139

  • Safety of photosynthetic Synechococcus elongatus for in vivo cyanobacteria-mammalian symbiotic therapeutics. Microbial biotechnology Williams, K. M., Wang, H., Paulsen, M. J., Thakore, A. D., Rieck, M., Lucian, H. J., Grady, F., Hironaka, C. E., Chien, A. J., Farry, J. M., Shin, H. S., Jaatinen, K. J., Eskandari, A., Stapleton, L. M., Steele, A. N., Cohen, J. E., Woo, Y. J. 2020

    Abstract

    The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n=12), sterile saline (n=12) or E. coli lipopolysaccharide (LPS, n=4), and a subset (8 SE, 8 saline) received a repeat injection 4weeks later. At baseline, 4h, 24h, 48h, 8days and 4weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria-mammalian symbiotic therapeutics using this organism.

    View details for DOI 10.1111/1751-7915.13596

    View details for PubMedID 32476224

  • Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model. Cytokine Steele, A. N., Paulsen, M. J., Wang, H., Stapleton, L. M., Lucian, H. J., Eskandari, A., Hironaka, C. E., Farry, J. M., Baker, S. W., Thakore, A. D., Jaatinen, K. J., Tada, Y., Hollander, M. J., Williams, K. M., Seymour, A. J., Totherow, K. P., Yu, A. C., Cochran, J. R., Appel, E. A., Woo, Y. J. 2020; 127: 154974

    Abstract

    Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

    View details for DOI 10.1016/j.cyto.2019.154974

    View details for PubMedID 31978642

  • Type A Aortic Dissection-Experience Over 5 Decades: JACC Historical Breakthroughs in Perspective. Journal of the American College of Cardiology Zhu, Y., Lingala, B., Baiocchi, M., Tao, J. J., Toro Arana, V., Khoo, J. W., Williams, K. M., Traboulsi, A. A., Hammond, H. C., Lee, A. M., Hiesinger, W., Boyd, J., Oyer, P. E., Stinson, E. B., Reitz, B. A., Mitchell, R. S., Miller, D. C., Fischbein, M. P., Woo, Y. J. 2020; 76 (14): 1703–13

    Abstract

    The Stanford classification of aortic dissection was described in 1970. The classification proposed that type A aortic dissection should be surgically repaired immediately, whereas type B aortic dissection can be treated medically. Since then, diagnostic tools and management of acute type A aortic dissection (ATAAD) have undergone substantial evolution. This paper evaluated historical changes of ATAAD repair at Stanford University since the establishment of the aortic dissection classification 50 years ago. The surgical approaches to the proximal and distal extent of the aorta, cerebral perfusion methods, and cannulation strategies were reviewed. Additional analyses using patients who underwent ATAAD repair at Stanford University from 1967 through December 2019 were performed to further illustrate the Stanford experience in the management of ATAAD. While technical complexity increased over time, post-operative survival continued to improve. Further investigation is warranted to delineate factors associated with the improved outcomes observed in this study.

    View details for DOI 10.1016/j.jacc.2020.07.061

    View details for PubMedID 33004136

  • Women in Thoracic Surgery Scholarship: Impact on Career Path and Interest in Cardiothoracic Surgery. The Annals of thoracic surgery Williams, K. M., Hironaka, C. E., Wang, H., Bajaj, S. S., O'Donnell, C. T., Sanchez, M., Boyd, J., Kane, L., Backhus, L. 2020

    Abstract

    Women remain underrepresented in Cardiothoracic Surgery (CTS). In 2005, Women in Thoracic Surgery (WTS) began offering scholarships to promote engagement of women in CTS careers. This study explores the effect of WTS scholarships on CTS career milestones.We assessed career development using the number of awardees matching into CTS residency/fellowship, American Board of Thoracic Surgery (ABTS) certification, and academic CTS appointment. Scholarship awardee data were obtained from our WTS database. Comparison data were gathered from the National Residency Match Program and ABTS. Details of the current roles of ABTS certified women were determined from public resources. Qualitative results were gathered from post-scholarship surveys.106 WTS scholarships have been awarded to 38 medical students (MS, 36%), 41 General Surgery residents (GR, 39%), and 27 CTS residents/fellows (CR, 25%). Among MS, 26% of awardees entered integrated CTS residency (vs. <0.1% for medical students, p<0.0001), while 37% entered general surgery residency (vs. 4.8% for medical students, p<0.0001). Of GR awardees, 59% entered CTS fellowships (vs. 7.7% for general surgery residents, p<0.0001), and of CR awardees, 100% earned ABTS certification (vs. 73% ABTS pass rate, p=.01). Of ABTS certified awardees, 44% are practicing CT surgeons at U.S. academic training institutions (vs. 33% of non-awardee ABTS certified women, p=0.419). All awardees reported that their scholarship was valuable in their development.Receipt of a WTS scholarship is associated with successful pursuit of CTS career milestones at significantly higher rates than contemporaries. These scholarships foster a supportive community for women trainees in CTS.

    View details for DOI 10.1016/j.athoracsur.2020.07.020

    View details for PubMedID 32961134

  • Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction. Journal of the mechanical behavior of biomedical materials Wang, H., Wisneski, A., Paulsen, M. J., Imbrie-Moore, A., Wang, Z., Xuan, Y., Hernandez, H. L., Lucian, H. J., Eskandari, A., Thakore, A. D., Farry, J. M., Hironaka, C. E., von Bornstaedt, D., Steele, A. N., Stapleton, L. M., Williams, K. M., Wu, M. A., MacArthur, J. W., Woo, Y. J. 2019; 96: 165–71

    Abstract

    Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

    View details for PubMedID 31035067

  • Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature biomedical engineering Stapleton, L. M., Steele, A. N., Wang, H., Lopez Hernandez, H., Yu, A. C., Paulsen, M. J., Smith, A. A., Roth, G. A., Thakore, A. D., Lucian, H. J., Totherow, K. P., Baker, S. W., Tada, Y., Farry, J. M., Eskandari, A., Hironaka, C. E., Jaatinen, K. J., Williams, K. M., Bergamasco, H., Marschel, C., Chadwick, B., Grady, F., Ma, M., Appel, E. A., Woo, Y. J. 2019; 3 (8): 611–20

    Abstract

    Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

    View details for DOI 10.1038/s41551-019-0442-z

    View details for PubMedID 31391596

  • Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst NATURE COMMUNICATIONS Saiz, N., Williams, K. M., Seshan, V. E., Hadjantonakis, A. 2016; 7

    Abstract

    Intercellular communication is essential to coordinate the behaviour of individual cells during organismal development. The preimplantation mammalian embryo is a paradigm of tissue self-organization and regulative development; however, the cellular basis of these regulative abilities has not been established. Here we use a quantitative image analysis pipeline to undertake a high-resolution, single-cell level analysis of lineage specification in the inner cell mass (ICM) of the mouse blastocyst. We show that a consistent ratio of epiblast and primitive endoderm lineages is achieved through incremental allocation of cells from a common progenitor pool, and that the lineage composition of the ICM is conserved regardless of its size. Furthermore, timed modulation of the FGF-MAPK pathway shows that individual progenitors commit to either fate asynchronously during blastocyst development. These data indicate that such incremental lineage allocation provides the basis for a tissue size control mechanism that ensures the generation of lineages of appropriate size.

    View details for DOI 10.1038/ncomms13463

    View details for Web of Science ID 000387993300001

    View details for PubMedID 27857135

    View details for PubMedCentralID PMC5120222