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    Mild Anastomotic Stenosis in Patient-Specific CABG Model May Enhance Graft Patency: A New Hypothesis
    (Public Library of Science, 2013-09-13) Huo, Yunlong; Luo, Tong; Guccione, Julius M.; Teague, Shawn D.; Tan, Wenchang; Navia, José A.; Kassab, Ghassan S.; Surgery, School of Medicine
    It is well known that flow patterns at the anastomosis of coronary artery bypass graft (CABG) are complex and may affect the long-term patency. Various attempts at optimal designs of anastomosis have not improved long-term patency. Here, we hypothesize that mild anastomotic stenosis (area stenosis of about 40-60%) may be adaptive to enhance the hemodynamic conditions, which may contribute to slower progression of atherosclerosis. We further hypothesize that proximal/distal sites to the stenosis have converse changes that may be a risk factor for the diffuse expansion of atherosclerosis from the site of stenosis. Twelve (12) patient-specific models with various stenotic degrees were extracted from computed tomography images using a validated segmentation software package. A 3-D finite element model was used to compute flow patterns including wall shear stress (WSS) and its spatial and temporal gradients (WSS gradient, WSSG, and oscillatory shear index, OSI). The flow simulations showed that mild anastomotic stenosis significantly increased WSS (>15 dynes · cm(-2)) and decreased OSI (<0.02) to result in a more uniform distribution of hemodynamic parameters inside anastomosis albeit proximal/distal sites to the stenosis have a decrease of WSS (<4 dynes · cm(-2)). These findings have significant implications for graft adaptation and long-term patency.
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    Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model
    (Elsevier, 2014) Zhao, Yunge; Gillen, Jacob R.; Harris, David A.; Kron, Irving L.; Murphy, Michael P.; Lau, Christine L.; Surgery, School of Medicine
    Objective: Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model. Methods: A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis. Results: Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P = .015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P = .022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14. Conclusions: This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant.
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    Molecular basis for impaired collateral artery growth in the spontaneously hypertensive rat: insight from microarray analysis
    (Wiley, 2013) Unthank, Joseph L.; McClintick, Jeanette N.; Labarrere, Carlos A.; Li, Lang; DiStasi, Matthew R.; Miller, Steven J.; Surgery, School of Medicine
    Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals were similar between rat strains. Ingenuity® Pathway Analysis (IPA) identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were downregulated including JUN (-5.2×, P = 0.02), EGR1 (-4.1×, P = 0.01), and NFĸB1 (-1.95×, P = 0.04). Predicted binding sites for NFĸB and AP-1 were present in genes altered in WKY but not SHR collaterals. Immunostaining showed increased NFĸB nuclear translocation in collateral arteries of WKY and apocynin-treated SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral growth in WKY, confirming a functional role of NFkB. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin-angiotensin system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1 with losartan prevented collateral luminal expansion in WKY. Together, these results suggest that collateral growth impairment results from an abnormality in a fundamental regulatory mechanism that occurs at a level between signal transduction and gene transcription and implicate redox-dependent modulation of mechano-sensitive transcription factors such as NFĸB as a potential mechanism.
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    Human aortic allograft: an excellent conduit choice for superior vena cava reconstruction
    (Springer Nature, 2014-01-15) Spera, Kristyn; Kesler, Kenneth A.; Syed, Amjadullah; Boyd, Jack H.; Surgery, School of Medicine
    Superior vena cava (SVC) reconstruction is occasionally required in the treatment of benign and malignant conditions. We report a patient with symptomatic SVC obstruction secondary to mediastinal fibrosis successfully reconstructed with an aortic allograft.
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    Optimizing the Timing of Transplant Education: The Critical Role of Dialysis Care Professionals
    (Wolters Kluwer, 2024) McDonnell, Jenny L.; Urbanski, Megan A.; Drewry, Kelsey M.; Pastan, Stephen O.; Lea, Janice P.; Jacob Arriola, Kimberly; Escoffery, Cam; Patzer, Rachel E.; Wilk, Adam S.; Surgery, School of Medicine
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    IVUS Validation of Patient Coronary Artery Lumen Area Obtained from CT Images
    (Public Library of Science, 2014-01-29) Luo, Tong; Wischgoll, Thomas; Koo, Bon Kwon; Huo, Yunlong; Kassab, Ghassan S.; Surgery, School of Medicine
    Aims: Accurate computed tomography (CT)-based reconstruction of coronary morphometry (diameters, length, bifurcation angles) is important for construction of patient-specific models to aid diagnosis and therapy. The objective of this study is to validate the accuracy of patient coronary artery lumen area obtained from CT images based on intravascular ultrasound (IVUS). Methods and results: Morphometric data of 5 patient CT scans with 11 arteries from IVUS were reconstructed including the lumen cross sectional area (CSA), diameter and length. The volumetric data from CT images were analyzed at sub-pixel accuracy to obtain accurate vessel center lines and CSA. A new center line extraction approach was used where an initial estimated skeleton in discrete value was obtained using a traditional thinning algorithm. The CSA was determined directly without any circular shape assumptions to provide accurate reconstruction of stenosis. The root-mean-square error (RMSE) for CSA and diameter were 16.2% and 9.5% respectively. Conclusions: The image segmentation and CSA extraction algorithm for reconstruction of coronary arteries proved to be accurate for determination of vessel lumen area. This approach provides fundamental morphometric data for patient-specific models to diagnose and treat coronary artery disease.
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    Suicidal ideation, perception of personal safety, and career regret among emergency medicine residents during the COVID‐19 pandemic
    (Wiley, 2024-03-20) Akhavan, Arvin R.; Zhan, Tiannan; Lall, Michelle D.; Barton, Melissa A.; Reisdorff, Earl J.; Hu, Yue-Yung; Bilimoria, Karl Y.; Lu, Dave W.; Surgery, School of Medicine
    Objectives: The COVID-19 pandemic was disruptive for trainees and may have affected career decisions for some learners. This study examined the impact of the pandemic on emergency medicine (EM) resident perceptions of their mental health, perceptions of personal safety, and career choice regret. Methods: This was a cross-sectional survey study administered following the 2021 American Board of Emergency Medicine In-Training Examination (ITE). Survey measures included suicidal ideation (SI), COVID concerns in terms of infection prevention and control (IPC) training, COVID risk to self and/or COVID risk to family, and COVID-related career regret. COVID concerns were compared by gender and race/ethnicity using Pearson's chi-square tests. Multivariable logistic regression models were used to test the association between SI and COVID concerns, resident characteristics, and program characteristics. Results: A total of 6980 out of 8491 EM residents (82.2%) from 244 programs completed the survey. Only 1.1% of participants reported insufficient training in COVID IPC practices. Participants were concerned about COVID risk to themselves (40.3%) and to their families (63.3%) due to their job roles. These concerns were more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); senior residents (vs. PGY-1, PGY-2 residents); and residents who were married or in relationships (vs. single or divorced). A total of 6.1% of participants reported that COVID made them reconsider choosing EM as their career. Career regret in this cohort was higher than that in the proportion (3.2%) expressing career regret in the 2020 ITE (p < 0.001). Career regret was more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); and senior residents (vs. PGY-1, PGY-2 residents). The overall SI rate was 2.6%, which did not differ from that of the 2020 sample of EM residents (2.5%, p = 0.88). Conclusions: Many EM residents reported concerns about COVID risks to themselves and their families. Although the rate of SI remained unchanged, more EM residents reported career regret during the COVID pandemic.
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    Risk‐Reducing Gender‐Affirming Mastectomy: Unique Considerations in BRCA
    (Wiley, 2025-03-27) Johnson, Bailey N.; Hadad, Ivan; Hassanein, Aladdin H.; Fisher, Carla S.; Surgery, School of Medicine
    Individualized breast cancer risk assessment should be considered for transmasculine patients pursuing gender-affirming mastectomy to identify and educate high-risk patients about the option for risk-reduction gender-affirming mastectomy. This reduces oncologic risk while achieving the desired cosmetic outcome, ultimately enhancing preventative care provided to an underserved population.
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    Building an international network of young surgeons across surgical specialties - Introducing the Young Surgeons Publications Committee
    (Elsevier, 2025-02-14) Bolm, Louisa; Nebbia, Martina; Stoop, Thomas F.; Goetz, Mara R.; Conradi, Lena; Raschzok, Nathanael; Jansson, Hannes; Larsson, Patrik; Gerber, Sarah; Roldàn, Jorge; Michelakos, Theodoros; Winkel, Meike Ten; Kinny-Köster, Benedict; Rompen, Ingmar F.; Franklin, Oskar; Ziogas, Ioannis A.; Ishida, Hiroyuki; Khomiak, Andrii; Hashimoto, Daisuke; Groot, Vincent P.; Wu, Y. H. Andrew; Sugawara, Toshitaka; Oba, Atsushi; Maekawa, Aya; Oor, Jelmer E.; Morandi, Alessio; Stewart, David B.; Zyromski, Nicholas Joseph; Surgery, School of Medicine
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    Disentangling Dialysis Facility and Transplant Center Factors on Evaluation Start Following Referral for Kidney Transplantation: A Regional Study in the United States
    (Elsevier, 2025-02-07) McPherson, Laura; Plantinga, Laura C.; Howards, Penelope P.; Kramer, Michael; Patzer, Rachel E.; Surgery, School of Medicine
    Rationale & objective: Little is known about the relative importance of dialysis facilities and transplant centers on variability in starting an evaluation among patients referred for kidney transplant. The primary objective of this study was to leverage cross-classified multilevel modeling to simultaneously examine the contextual effects of dialysis facilities and transplant centers on variation in the start of the transplant evaluation process. Study design: Retrospective cohort study. Setting & participants: Dialysis patients referred for kidney transplant to transplant centers across the Southeast, Northeast, New York, or Ohio River Valley US regions from January 1, 2012, to December 31, 2020, were identified from the United States Renal Data System and the Early Steps to Transplant Access Registry and followed through June 30, 2021. A total of N=25,488 referred patients were nested with 1,720 dialysis facilities and 26 transplant centers. Outcomes: Starting an evaluation for kidney transplant at a transplant center within 6 months of referral. Analytical approach: A series of multilevel models were performed to estimate the variability in starting an evaluation for kidney transplant within 6 months of referral. The between-dialysis facility and/or transplant center variation in starting an evaluation was quantified using the median OR. Results: Among 25,488 dialysis patients referred for kidney transplantation, 51% of patients started an evaluation at a transplant center within 6 months of referral. In multilevel models, the median OR between transplant centers was higher (indicating higher unexplained variability) than the dialysis facility median OR, regardless of measured patient, dialysis facility, and transplant center characteristics. Limitations: Early transplant access data was limited to 20 of 48 transplant centers across these 4 regions. Conclusions: When taking dialysis facilities and transplant centers into account, variation in starting an evaluation for kidney transplant appeared at both the dialysis facility and transplant center-level but was more apparent among transplant centers.