Brandon Alan Guenthart

All Publications

• JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle. Life science alliance Shrager, J. B., Randle, R., Lee, M., Ahmed, S. S., Trope, W., Lui, N., Poultsides, G., Liou, D., Visser, B., Norton, J. A., Nesbit, S. M., He, H., Kapula, N., Wallen, B., Fatodu, E., Sadeghi, C. A., Konsker, H. B., Elliott, I., Guenthart, B., Backhus, L., Cooke, R., Berry, M., Tang, H. 2024; 7 (11)

  Abstract

  Reduction in muscle contractile force associated with many clinical conditions incurs serious morbidity and increased mortality. Here, we report the first evidence that JAK inhibition impacts contractile force in normal human muscle. Muscle biopsies were taken from patients who were randomized to receive tofacitinib (n = 16) or placebo (n = 17) for 48 h. Single-fiber contractile force and molecular studies were carried out. The contractile force of individual diaphragm myofibers pooled from the tofacitinib group (n = 248 fibers) was significantly higher than those from the placebo group (n = 238 fibers), with a 15.7% greater mean maximum specific force (P = 0.0016). Tofacitinib treatment similarly increased fiber force in the serratus anterior muscle. The increased force was associated with reduced muscle protein oxidation and FoxO-ubiquitination-proteasome signaling, and increased levels of smooth muscle MYLK. Inhibition of MYLK attenuated the tofacitinib-dependent increase in fiber force. These data demonstrate that tofacitinib increases the contractile force of skeletal muscle and offers several underlying mechanisms. Inhibition of the JAK-STAT pathway is thus a potential new therapy for the muscle dysfunction that occurs in many clinical conditions.

  View details for DOI 10.26508/lsa.202402885

  View details for PubMedID 39122555

  View details for PubMedCentralID PMC11316201

• Enhancing Cytoplasmic Expression of Exogenous mRNA Through Dynamic Mechanical Stimulation. Advanced healthcare materials Chen, J., Patel, A., Mir, M., Hudock, M. R., Pinezich, M. R., Guenthart, B., Bacchetta, M., Vunjak-Novakovic, G., Kim, J. 2024: e2401918

  Abstract

  Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.

  View details for DOI 10.1002/adhm.202401918

  View details for PubMedID 39440644

• The Role of Primary Care Providers in Lung Cancer Screening: A Cross-Sectional Survey. Clinical lung cancer Wong, L. Y., Kapula, N., Kang, A., Phadke, A. J., Schechtman, A. D., Elliott, I. A., Guenthart, B. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024

  Abstract

  Multidisciplinary lung cancer screening (LCS) programs that perform shared decision-making visits (SDMV) and follow up annual low dose computed tomography (LDCT) have been emerging. We hypothesize that primary care providers (PCPs) prefer to refer patients to LCS programs instead of facilitating the screening process themselves.This is a mixed-methods, cross-sectional study in which an online survey was administered to PCPs between April 2023 and June 2023.58 PCPs in the same hospital network participated in the study with a median age of 43 (34-51), predominance of women (77.6%), and clinicians of white and Asian race (44.8% and 48.3%). Respondents estimated that 26.1% (SD 32.4%) of their eligible patients participate in LCS screening. PCPs thought that an LCS program was equally convenient to performing screening themselves for identifying eligible patients and ordering LDCT. However, 63.8% of participants preferred an LCS program for performing SDMVs, 62.1% for ensuring annual follow-up on negative LDCTs, 70.7% for deciding next steps on positive LDCTs, and 60.4% for performing smoking cessation counseling. PCPs agreed that an LCS program saves time (69%), allows patients to receive specialty care (65.6%), addresses patient concerns (70.7%), ensures annual follow-up (77.6%), and manages abnormal findings (79.3%). However, they also expressed concerns about an additional visit for the patient (48.2%) and patient cost (46.5%).Most PCPs believe that formal LCS programs have many benefits including providing specialized care and follow up, although there were concerns about patient time and cost.

  View details for DOI 10.1016/j.cllc.2024.10.002

  View details for PubMedID 39472235

• Extracorporeal membrane oxygenation as a bridge to thoracic multiorgan transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Heng, E. E., Krishnan, A., Elde, S., Garrison, A., Fawad, M., Ruaengsri, C., Shudo, Y., Guenthart, B. A., Joseph Woo, Y., MacArthur, J. W. 2024

  Abstract

  Extracorporeal membrane oxygenation (ECMO) has emerged as a crucial tool in the care of patients with multiorgan failure, and is increasingly utilized as a bridge to transplantation. While data on ECMO as a bridge to isolated heart and lung transplantation have been described, our emerging experience with ECMO as a bridge to thoracic multiorgan transplantation is not yet well understood. This study aims to investigate temporal trends, utilization, and outcomes in ECMO as a bridge to thoracic multiorgan transplantation.The United Network for Organ Sharing database was used to identify adult patients undergoing thoracic multiorgan transplantation between 1987 and 2022. Exclusion criteria were recipient age <18 and bridging with other mechanical circulatory support including ventricular assist device (VAD) and intra-aortic balloon pump (IABP). Survival analysis was performed to compare outcomes between patients bridged to transplantation with ECMO and those who were not bridged.Of 3,927 patients undergoing thoracic multiorgan transplantation, a total of 203 (5.2%) patients received ECMO as a bridge to transplantation. Among ECMO recipients, patients were most commonly bridged to heart-lung (45.8%), followed by heart-kidney (34.5%), and lung-kidney transplantation (11.8%). At a median follow-up of 35.5 months, unadjusted survival among patients bridged with ECMO was decreased versus multiorgan transplant recipients who were not bridged (p<0.001). With adjusted multivariable Cox regression, ECMO was independently associated with an elevated risk of mortality following multiorgan transplantation (HR 1.56 [1.21-2.02], p<0.01). Among patients surviving past 30 days following transplantation, conditional long-term survival was similar between those bridged with ECMO and those not bridged (p = 0.82).ECMO is increasingly utilized as a bridge to thoracic multiorgan transplantation, and is associated with increased 30 day mortality and decreased long-term survival. In select patients surviving to 30 days following transplantation, similar long-term survival is seen between patients bridged with ECMO and those not bridged.

  View details for DOI 10.1016/j.healun.2024.09.015

  View details for PubMedID 39343333

• Trends in Heart Transplant Outcomes for Patients Over the Age of 70 Years in the United States: an Analysis of the Scientific Registry of Transplant Recipients Database. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Henricksen, E. J., Wayda, B., Teuteberg, J. J., Luikart, H., Njoroge, J., Guenthart, B. A., Khush, K. K. 2024

  Abstract

  Patients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies.This was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant.Recipients ≥70 had a one-year survival of 87.5%, compared to 91.1% for <60, and 88.4% for 60-69 years (p<0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at five years for <60 years (80.6%), compared to 60-69 years (78.2%) and ≥70 years (77.1%). When comparing 60-69 years to ≥70 years by this same metric, there was significant difference (p=0.12). One year survival for those ≥70 years has improved from 2000-2009 (80.7%) to 88.5% since October 2018 (p<0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (p<0.001).Overall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.

  View details for DOI 10.1016/j.healun.2024.08.001

  View details for PubMedID 39122221

• Survival, Function, and Immune Profiling after Beating Heart Transplantation. The Journal of thoracic and cardiovascular surgery Krishnan, A., Elde, S., Ruaengsri, C., Guenthart, B. A., Zhu, Y., Fawad, M., Lee, A., Currie, M., Ma, M. R., Hiesinger, W., Shudo, Y., MacArthur, J. W., Woo, Y. J. 2024

  Abstract

  Ex-vivo normothermic perfusion of cardiac allografts has expanded the donor pool. Utilizing a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia reperfusion injury typically associated with ex-vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation.This was a single-institution retrospective study of adult patients who underwent heart transplantation utilizing ex-vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A sub-analysis of our institutional series of non-beating DCD heart transplantation was also performed.Twenty-four patients underwent isolated heart transplantation with the use of ex-vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) patients received hearts from DBD donors. Median follow-up was 192 days (interquartile range of 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow up. No patients required initiation of mechanical circulatory support. The majority of patients had pathological grade 0 rejection at the time of biopsy (n=16, 66.7%), and the median cell-free DNA percent was 0.04% (interquartile range 0.04-0.09). The rate of mechanical circulatory support initiation in the 22-patient non-beating DCD heart transplant cohort was significantly higher at 36.4% (p<0.005).A beating heart implantation technique can be used on DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

  View details for DOI 10.1016/j.jtcvs.2024.07.058

  View details for PubMedID 39111693

• Greater ipsilateral rectus muscle atrophy after robotic thoracic surgery compared with open and video-assisted thoracoscopic surgery approaches. JTCVS open Wang, Y., Randle, R. J., Bhandari, P., He, H., Trope, W. L., Guenthart, B. A., Guo, H. H., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024; 20: 202-209

  Abstract

  Robotic thoracic surgery provides another minimally invasive approach in addition to video-assisted thoracoscopic surgery (VATS) that yields less pain and faster recovery compared with open surgery. However, robotic incisions are generally placed more inferiorly, which may increase the risk of intercostal nerve injury that affects the abdominal wall. We hypothesized that a robotic approach causes greater ipsilateral rectus muscle atrophy compared with open and VATS approaches.The cross-sectional area and density of bilateral rectus abdominis muscles were measured on computed tomography scans in patients who underwent lobectomy in 2018. The differences between the contralateral and ipsilateral muscles were compared between preoperative and 6-month surveillance scans. Changes were compared among the open, VATS, and robotic approaches through a mixed effects model after adjustments of correlation and covariates.Of 99 lobectomies, 25 (25.3%) were open, 56 (56.6%) VATS, and 18 (18.1%) robotic. The difference between the contralateral and ipsilateral rectus muscle cross-sectional area was significantly larger at 6 months after robotic surgery compared with open (31.4% vs 9.5%, P = .049) and VATS (31.4% vs 14.1%, P = .021). There were no significant differences in the cross-sectional area between the open and VATS approach.In this retrospective analysis, there was greater ipsilateral rectus muscle atrophy associated with robotic thoracic surgery compared with open or VATS approaches. These findings should be correlated with clinical symptoms and followed to assess for resolution or persistence.

  View details for DOI 10.1016/j.xjon.2024.05.011

  View details for PubMedID 39296450

  View details for PubMedCentralID PMC11405974

• A Minimally Invasive Robotic Tissue Palpation Device IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Mir, M., Chen, J., Patel, A., Pinezich, M. R., Guenthart, B. A., Vunjak-Novakovic, G., Kim, J. 2024; 71 (6): 1958-1968

  Abstract

  Robot-assisted minimally invasive surgery remains limited by the absence of haptic feedback, which surgeons routinely rely on to assess tissue stiffness. This limitation hinders surgeons' ability to identify and treat abnormal tissues, such as tumors, during robotic surgery.To address this challenge, we developed a robotic tissue palpation device capable of rapidly and non-invasively quantifying the stiffness of soft tissues, allowing surgeons to make objective and data-driven decisions during minimally invasive procedures. We evaluated the effectiveness of our device by measuring the stiffness of phantoms as well as lung, heart, liver, and skin tissues obtained from both rats and swine.Results demonstrated that our device can accurately determine tissue stiffness and identify tumor mimics. Specifically, in swine lung, we determined elastic modulus (E) values of 9.1 ± 2.3, 16.8 ± 1.8, and 26.0 ± 3.6 kPa under different internal pressure of the lungs (PIP) of 2, 25, and 45 cmH2O, respectively. Using our device, we successfully located a 2-cm tumor mimic embedded at a depth of 5 mm in the lung subpleural region. Additionally, we measured E values of 33.0 ± 5.4, 19.2 ± 2.2, 33.5 ± 8.2, and 22.6 ± 6.0 kPa for swine heart, liver, abdominal skin, and muscle, respectively, which closely matched existing literature data.Results suggest that our robotic palpation device can be utilized during surgery, either as a stand-alone or additional tool integrated into existing robotic surgical systems, to enhance treatment outcomes by enabling accurate intraoperative identification of abnormal tissue.

  View details for DOI 10.1109/TBME.2024.3357293

  View details for Web of Science ID 001230139500012

  View details for PubMedID 38261510

• What is an Adequate Margin During Sublobar Resection of ≤3cm N0 Subsolid Lung Adenocarcinomas? The Annals of thoracic surgery Kamtam, D. N., Berry, M. F., Lui, N. S., Satoyoshi, M., Elliott, I. A., Liou, D. Z., Guenthart, B., Backhus, L. M., Shrager, J. B. 2024

  Abstract

  Sublobar resection offers non-inferior survival vs. lobectomy for ≤2cm NSCLC and is commonly employed for subsolid tumors. While data exists for solid tumors, the minimum adequate margin of resection for subsolid adenocarcinomas remains unclear.Retrospective review of 1101 adenocarcinoma resections at our institution, 2006-2022.tumors≤3cm with ≥10% radiographic ground glass, excised by sublobar resection.positive nodes, positive or unreported margin. The primary outcome was rate of local recurrence(LR) at multiple thresholds of margin distance. Relationship between margin distance and solid-component size was also explored.194 patients met inclusion criteria. Median(IQR) tumor diameter and margin distance were 12(9-17)mm and 10(5-17)mm, respectively. Median follow-up was 42.5 months. There was a progressive increase in LR with diminishing margin (0.1cm decrements) from 1.5cm to 0.5cm. The difference in the rate of LR between "over"(n=143) and "under"(n=51) was most significant at 0.5cm [8/51(15.7%) vs. 6/143(4.2%),p=0.01] but did not reach α adjusted for multiple comparisons. On Cox regression for LR-free survival (LRFS), margin ≤0.5cm(p=0.19) and %solid component (p=0.14) trended to significance. Combining these using margin-distance-to-solid-component-size ratio, a ratio≤1 did show a significantly higher rate of local recurrence [7(14.3%) vs. 2(2.0%),p=0.009]. Treatment of local recurrences provided at least intermediate-term survival in 87% of recurrences (median post-recurrence follow-up 44 months).During sublobar resection of subsolid lung adenocarcinomas, margin-to-solid-component-size ratio>1.0 appears to be a more reliable factor than margin distance alone to minimize local recurrence. Local recurrence, however, may not impact survival in patients with subsolid adenocarcinomas if timely treatment is administered.

  View details for DOI 10.1016/j.athoracsur.2024.04.018

  View details for PubMedID 38734402

• Barriers to Completing Low Dose Computed Tomography Scan for Lung Cancer Screening. Clinical lung cancer Wong, L. Y., Choudhary, S., Kapula, N., Lin, M., Elliott, I. A., Guenthart, B. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2024

  Abstract

  Annual low-dose computed tomography (LDCT) screening has been shown to reduce lung cancer mortality in high-risk individuals by detecting the disease at an earlier stage. This study aims to assess the barriers to completing LDCT in a cohort of patients who were determined eligible for lung cancer screening (LCS).We performed a single institution, mixed methods, cross-sectional study of patients who had a LDCT ordered from July to December 2022. We then completed phone surveys with patients who did not complete LDCT to assess knowledge, attitude, and perceptions toward LCS.We identified 380 patients who met inclusion criteria, including 331 (87%) who completed LDCT and 49 (13%) who did not. Patients who completed a LDCT and those who did not were similar regarding age, sex, race, primary language, household income, body mass index, median pack years, and quit time. Positive predictors of LDCT completion were: meeting USPSTF guidelines (97.9% vs 81.6%), being married (58.3% vs 44.9%), former versus current smokers (55% vs 41.7%), personal history of emphysema (60.4% vs 42.9%), and family history of lung cancer (13.9% vs 4.1%) (all P < .05). Of the patients who participated in the phone survey, only 7% of respondents thought they were high risk for developing lung cancer despite attending a shared decision-making visit and only 10% wanted to re-schedule their LDCT.There exist barriers to completing LDCT even after patients are identified as eligible and complete a shared decision-making visit secondary to knowledge barriers, misperceptions, and patient disinterest.

  View details for DOI 10.1016/j.cllc.2024.04.014

  View details for PubMedID 38749902

• Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death. JAMA network open Krishnan, A., Ruaengsri, C., Guenthart, B. A., Shudo, Y., Wang, H., Ma, M. R., MacArthur, J. W., Hiesinger, W., Woo, Y. J. 2024; 7 (3): e241828

  Abstract

  The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation.To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively.This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023.Using a beating heart method of implantation of the donor allograft.The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes.In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation.In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.

  View details for DOI 10.1001/jamanetworkopen.2024.1828

  View details for PubMedID 38466306

• Four Decades of Progress in Heart-Lung Transplantation: 271 Cases at a Single Institution. The Journal of thoracic and cardiovascular surgery Elde, S., Baccouche, B. M., Mullis, D. M., Leipzig, M. M., Deuse, T., Krishnan, A., Fawad, M., Dale, R., Walsh, S., Padilla-Lopez, A., Wesley, B., He, H., Yajima, S., Zhu, Y., Wang, H., Guenthart, B. A., Shudo, Y., Reitz, B. A., Woo, Y. J. 2024

  Abstract

  OBJECTIVE: The objective of this study is to evaluate survival for combined heart-lung transplant (HLTx) recipients across four decades at a single institution. We aim to summarize our contemporary practice based upon more than 271 HLTx over 40 years.METHODS: Data were collected from a departmental database and the United Network for Organ Sharing (UNOS). Recipients <18y, those undergoing redo HLTx , or triple-organ system transplantation were excluded, leaving 271 patients for analysis. The Pioneering Era was defined by date of transplant between 1981-2000 (N=155), and the Modern Era between 2001-2022 (N=116). Survival analysis was performed using cardinality matching of populations based on donor and recipient age, donor and recipient sex, ischemic time, and sex-matching.RESULTS: Between 1981-2022, 271 HLTx were performed at a single institution. Recipients in the Modern Era were older (42 vs 34y, P<0.001) and had shorter waitlist times (78 vs 234d, P<0.001). Allografts from female donors were more common in the Modern Era (59% vs 39%, P=0.002). In the matched survival analysis, 30-day survival (97% vs 84%, P=0.005), 1-year survival (89% vs 77%, P=0.041), and 10-year survival (53% vs 26%, P=0.012) significantly improved in the Modern Era relative to the Pioneering Era, respectively.CONCLUSIONS: Long-term survival in HLTx is achievable with institutional experience and may continue to improve in the coming decades. Advances in mechanical circulatory support, improved maintenance immunosuppression, and early recognition and management of acute complications such as primary graft dysfunction and acute rejection have dramatically improved the prognosis for HLTx recipients in our contemporary institutional experience.

  View details for DOI 10.1016/j.jtcvs.2024.01.042

  View details for PubMedID 38320627

• Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak. Advanced healthcare materials Pinezich, M. R., Mir, M., Graney, P. L., Tavakol, D. N., Chen, J., Hudock, M., Gavaudan, O., Chen, P., Kaslow, S. R., Reimer, J. A., Van Hassel, J., Guenthart, B. A., O'Neill, J. D., Bacchetta, M., Kim, J., Vunjak-Novakovic, G. 2024: e2303026

  Abstract

  Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients, yet there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue and therefore fail to seal air leak. To address this therapeutic gap, we developed and systematically evaluated a sealant with structural and mechanical similarity to subpleural lung. Our "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant showed minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulated key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, our lung-mimetic sealant rapidly sealed air leak and restored baseline lung mechanics. Altogether, these data indicate that our lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/adhm.202303026

  View details for PubMedID 38279961

• Beating Heart Transplantation: How to Do It. Innovations (Philadelphia, Pa.) Krishnan, A., Guenthart, B. A., Ruengesri, C., Elde, S., Zhu, Y., MacArthur, J. W., Woo, Y. J. 2024: 15569845231220678

  Abstract

  Heart transplantation utilizing deceased after circulatory death (DCD) donors has expanded the donor pool through the use of ex vivo normothermic perfusion. Compared with brain death donation, the conventional method of performing DCD heart transplantation includes an additional period of warm and cold ischemia. We have developed a beating heart implantation technique that obliviates the need for a second cardioplegic arrest and the associated reperfusion injury. We hypothesize this reproducible method may improve short-term and long-term outcomes to mirror results seen in brain death donors and provide details on how to perform beating heart transplantation.

  View details for DOI 10.1177/15569845231220678

  View details for PubMedID 38258625

• Beating Heart Transplants-Overview and Implications for Anesthesiologists. Journal of cardiothoracic and vascular anesthesia Kothari, P., Kiwakyou, L. M., Guenthart, B. A., Vanneman, M. 2023

  Abstract

  As the demand for heart allografts for transplantation continues to rise, ex vivo organ perfusion strategies are playing an increasingly important role in the preservation of organs from donation after circulatory death and extended-criteria donors. One such method uses the Organ Care System (TransMedics, Andover, MA). Traditionally, this technique of preservation requires 2 periods of warm ischemia and subsequent cardioplegic arrest. In a novel surgical technique pioneered at the authors' institution, heart allograft implantation no longer requires a second cardioplegic arrest. This article discusses the surgical approach for this procedure, the advantages and disadvantages of this approach, and analogs to current clinical practice to theorize what impact this may have on cardiac transplantation volumes in the future.

  View details for DOI 10.1053/j.jvca.2023.12.031

  View details for PubMedID 38228423

• Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer. JTCVS open Wong, L., Kapula, N., He, H., Guenthart, B. A., Vitzthum, L. K., Horst, K., Liou, D. Z., Backhus, L. M., Lui, N. S., Berry, M. F., Shrager, J. B., Elliott, I. A. 2023; 16: 919-928

  Abstract

  Background: Radiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3decades to quantify this risk over time as modern oncologic treatment continues to evolve.Methods: The SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9years, 10 to 15years, and >15years after breast cancer diagnosis.Results: Of the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P=.036) after 5 to 9years of follow-up, 1.28 (P=.002) after 10 to 15years of follow-up, and 1.30 (P=.014) after >15years of follow-up. The HR of contralateral lung cancer was not increased at any time interval.Conclusions: The increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

  View details for DOI 10.1016/j.xjon.2023.10.031

  View details for PubMedID 38204675

• Comparison of failure to rescue in younger versus elderly patients following lung cancer resection. JTCVS open Wang, Y., Kapula, N., Yang, C. J., Manapat, P., Elliott, I. A., Guenthart, B. A., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Liou, D. Z. 2023; 16: 855-872

  Abstract

  Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients.Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80years) cohort.Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n=139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n=39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P<.001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P=.01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P=.028).Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

  View details for DOI 10.1016/j.xjon.2023.08.002

  View details for PubMedID 38204720

• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival. Journal of thoracic disease Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023; 15 (11): 6140-6150

  Abstract

  Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

  View details for DOI 10.21037/jtd-23-466

  View details for PubMedID 38090290

  View details for PubMedCentralID PMC10713319

• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival JOURNAL OF THORACIC DISEASE Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023

  View details for DOI 10.21037/jtd-23-466

  View details for Web of Science ID 001101361100001

• Recovery of Extracorporeal Lungs Using Cross-Circulation with Injured Recipient Swine. The Journal of thoracic and cardiovascular surgery Chen, P., Van Hassel, J., Pinezich, M. R., Diane, M., Hudock, M. R., Kaslow, S. R., Gavaudan, O. P., Fung, K., Kain, M. L., Lopez, H., Saqi, A., Guenthart, B. A., Hozain, A. E., Romanov, A., Bacchetta, M., Vunjak-Novakovic, G. 2023

  Abstract

  Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia.Swine donor lungs (n = 6) were stored at 4°C for 24 hours, while recipient swine (n = 6) underwent gastric aspiration injury prior to cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation.Recipient swine lung injury resulted in sustained, impaired oxygenation (PaO2/FiO2 ratio 205 ± 39 mmHg versus 454 ± 111 mmHg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, PaO2/FiO2 138 ± 28.2 mmHg; 24 hours, 539 ± 156 mmHg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours.We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease, who are candidates for this clinical application.

  View details for DOI 10.1016/j.jtcvs.2023.09.032

  View details for PubMedID 37741314

• Tracheal stenosis and airway complications in the Coronavirus Disease-19 era. Annals of thoracic surgery short reports Krishnan, A., Guenthart, B. A., Choi, A., Trope, W., Berry, G. J., Pinezich, M. R., Vunjak-Novakovic, G., Shaller, B., Sung, C. K., Liou, D. Z., Damrose, E. J., Lui, N. S. 2023

  Abstract

  Severe Coronavirus Disease 2019 (COVID-19) infection is associated with prolonged intubation and its complications. Tracheal stenosis is one such complication that may require specialized surgical management. We aimed to describe the surgical management of post-COVID-19 tracheal stenosis.This case series describes consecutive patients with tracheal stenosis from intubation for severe COVID-19 infection at our single, tertiary academic medical center between January 1st, 2021, and December 31st, 2021. Patients were included if they underwent surgical management with tracheal resection and reconstruction, or bronchoscopic intervention. Operative through six-month, symptom-free survival and histopathological analysis of resected trachea were reviewed.Eight patients are included in this case series. All patients are female, and most (87.5%) are obese. Five patients (62.5%) underwent tracheal resection and reconstruction (TRR), while three patients (38.5%) underwent non-resection-based management. Among patients who underwent TRR, six-month symptom free survival is 80%; one patient (20%) required tracheostomy after TRR due to recurrent symptoms. Two of the three (66.7%) of patients who underwent non-resection-based management experienced durable relief from symptoms of tracheal stenosis with tracheal balloon dilation, and the remaining patient required laser excision of tracheal tissue prior to experiencing symptomatic relief.The incidence of tracheal stenosis may increase as patients recover from severe COVID-19 infection requiring intubation. Management of tracheal stenosis with TRR is safe and effective, with comparable rates of success to TRR for non-COVID-19 tracheal stenosis. Non-resection-based management is an option to manage tracheal stenosis in patients with less severe stenosis or in poor surgical candidates.

  View details for DOI 10.1016/j.atssr.2023.05.013

  View details for PubMedID 37360840

  View details for PubMedCentralID PMC10246306

• World's first en bloc heart-lung transplantation using the paragonix lungguard donor preservation system. Journal of cardiothoracic surgery Neto, D., Guenthart, B., Shudo, Y., Currie, M. E. 2023; 18 (1): 131

  Abstract

  We present the first en bloc heart-lung donor transplant procurement using the Paragonix LUNGguard™ donor preservation system. This system offers reliable static hypothermic conditions designed to prevent major complications such as cold ischemic injury, uneven cooling and physical damage. While this represents a single case, the encouraging results warrant further investigation.

  View details for DOI 10.1186/s13019-023-02281-7

  View details for PubMedID 37041582

  View details for PubMedCentralID PMC10091844

• Sound-guided assessment and localization of pulmonary air leak. Bioengineering & translational medicine Pinezich, M. R., Mir, S. M., Reimer, J. A., Kaslow, S. R., Chen, J., Guenthart, B. A., Bacchetta, M., O'Neill, J. D., Vunjak-Novakovic, G., Kim, J. 2023; 8 (1): e10322

  Abstract

  Pulmonary air leak is the most common complication of lung surgery, with air leaks that persist longer than 5 days representing a major source of post-surgery morbidity. Clinical management of air leaks is challenging due to limited methods to precisely locate and assess leaks. Here, we present a sound-guided methodology that enables rapid quantitative assessment and precise localization of air leaks by analyzing the distinct sounds generated as the air escapes through defective lung tissue. Air leaks often present after lung surgery due to loss of tissue integrity at or near a staple line. Accordingly, we investigated air leak sounds from a focal pleural defect in a rat model and from a staple line failure in a clinically relevant swine model to demonstrate the high sensitivity and translational potential of this approach. In rat and swine models of free-flowing air leak under positive pressure ventilation with intrapleural microphone 1 cm from the lung surface, we identified that: (a) pulmonary air leaks generate sounds that contain distinct harmonic series, (b) acoustic characteristics of air leak sounds can be used to classify leak severity, and (c) precise location of the air leak can be determined with high resolution (within 1 cm) by mapping the sound loudness level across the lung surface. Our findings suggest that sound-guided assessment and localization of pulmonary air leaks could serve as a diagnostic tool to inform air leak detection and treatment strategies during video-assisted thoracoscopic surgery (VATS) or thoracotomy procedures.

  View details for DOI 10.1002/btm2.10322

  View details for PubMedID 36684064

  View details for PubMedCentralID PMC9842055

• Outcomes of Heart Transplantation Using a Temperature-controlled Hypothermic Storage System. Transplantation Zhu, Y., Shudo, Y., He, H., Kim, J. Y., Elde, S., Williams, K. M., Walsh, S. K., Koyano, T. K., Guenthart, B., Woo, Y. J. 2022

  Abstract

  The SherpaPak Cardiac Transport System is a novel technology that provides stable, optimal hypothermic control during organ transport. The objectives of this study were to describe our experience using the SherpaPak system and to compare outcomes after heart transplantation after using SherpaPak versus the conventional static cold storage method (non-SherpaPak).From 2018 to June 2021, 62 SherpaPak and 186 non-SherpaPak patients underwent primary heart transplantation at Stanford University with follow-up through May 2022. The primary end point was all-cause mortality, and secondary end points were postoperative complications. Optimal variable ratio matching, cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed.Before matching, the SherpaPak versus non-SherpaPak patients were older and received organs with significantly longer total allograft ischemic time. After matching, SherpaPak patients required fewer units of blood product for perioperative transfusion compared with non-SherpaPak patients but otherwise had similar postoperative outcomes such as hospital length of stay, primary graft dysfunction, inotrope score, mechanical circulatory support use, cerebral vascular accident, myocardial infarction, respiratory failure, new renal failure requiring dialysis, postoperative bleeding or tamponade requiring reoperation, infection, and survival.In conclusion, this is one of the first retrospective comparison studies that evaluated the outcomes of heart transplantation using organs preserved and transported via the SherpaPak system. Given the excellent outcomes, despite prolonged total allograft ischemic time, it may be reasonable to adopt the SherpaPak system to accept organs from a remote location to further expand the donor pool.

  View details for DOI 10.1097/TP.0000000000004416

  View details for PubMedID 36510359

• Resection of a synovial cell sarcoma by cardiac autotransplantation: A case report. JTCVS techniques Mullis, D. M., Zhu, Y., Guenthart, B. A., Bonham, S. A., Trope, W. L., Berry, G. J., Woo, Y. J., MacArthur, J. W. 2022; 16: 123-127

  View details for DOI 10.1016/j.xjtc.2022.09.009

  View details for PubMedID 36510550

  View details for PubMedCentralID PMC9735421

• Technique for xenogeneic cross-circulation to support human donor lungs ex vivo. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Kelly Wu, W., Guenthart, B. A., O'Neill, J. D., Hozain, A. E., Tipograf, Y., Ukita, R., Stokes, J. W., Patel, Y. J., Pinezich, M., Talackine, J. R., Cardwell, N. L., Fung, K., Vunjak-Novakovic, G., Bacchetta, M. 2022

  Abstract

  Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and recover injured human donor lungs ex vivo.Human donor lungs (n = 9) declined for transplantation were procured, cannulated, and subjected to 24 hours of xenogeneic XC with anesthetized xeno-support swine (Yorkshire/Landrace) treated with standard immunosuppression (methylprednisolone, mycophenolate mofetil, tacrolimus) and complement-depleting cobra venom factor. Standard lung-protective perfusion and ventilation strategies, including periodic lung recruitment maneuvers, were used throughout xenogeneic XC. Every 6 hours, ex vivo donor lung function (gas exchange, compliance, airway pressures, pulmonary vascular dynamics, lung weight) was evaluated. At the experimental endpoint, comprehensive assessments of the lungs were performed by bronchoscopy, histology, and electron microscopy. Student's t-test and 1-way analysis of variance with Dunnett's post-hoc test was performed, and p < 0.05 was considered significant.After 24 hours of xenogeneic XC, gas exchange (PaO2/FiO2) increased by 158% (endpoint: 364 ± 142 mm Hg; p = 0.06), and dynamic compliance increased by 127% (endpoint: 46 ± 20 ml/cmH2O; p = 0.04). Airway pressures, pulmonary vascular pressures, and lung weight remained stable (p > 0.05) and within normal ranges. Over 24 hours of xenogeneic XC, gross and microscopic lung architecture were preserved: airway bronchoscopy and parenchymal histomorphology appeared normal, with intact blood-gas barrier.Xenogeneic cross-circulation is a robust method for ex vivo support, evaluation, and improvement of injured human donor lungs declined for transplantation.

  View details for DOI 10.1016/j.healun.2022.11.002

  View details for PubMedID 36456408

• Type A Aortic Dissection With Concurrent Aortic Valve Endocarditis, Subarachnoid Hemorrhage, and Disseminated Intravascular Coagulation. JACC. Case reports Elde, S. F., Guenthart, B. A., de Biasi, A., Dalal, A. R., Casselman, K. G., Hiesinger, W., Burton, E. C. 2022; 4 (14): 839-843

  Abstract

  We describe surgical repair of a Stanford Type A aortic dissection with concurrent aortic valve Streptococcus equi endocarditis in the setting of subarachnoid hemorrhage and disseminated intravascular coagulation. Multidisciplinary collaboration among specialists from a variety of disciplines is essential when treating acutely ill cardiovascular patients with multisystem involvement. (Level of Difficulty: Beginner.).

  View details for DOI 10.1016/j.jaccas.2021.05.008

  View details for PubMedID 35912321

• Half of Anastomotic Leaks after Esophagectomy are Undetected on Initial Postoperative Esophagram. The Annals of thoracic surgery Elliott, I. A., Berry, M. F., Trope, W., Lui, N. S., Guenthart, B. A., Liou, D. Z., Whyte, R. I., Backhus, L. M., Shrager, J. B. 2022

  Abstract

  The sensitivity of fluoroscopic esophagrams with oral contrast to exclude anastomotic leak after esophagectomy is not well-documented, and the consequences of missing a leak in this setting have not been previously described.We performed a retrospective cohort study of a prospectively maintained institutional database of patients undergoing esophagectomy with esophagogastric anastomosis 2008-2020. Relevant details regarding leaks, management, and outcomes were obtained from the database and formal chart review. Statistical analysis was performed to compare patients with and without leaks, and those with false negative versus positive esophagrams.There were 384 patients who underwent esophagectomy with gastric reconstruction: the majority were Ivor-Lewis (82%), and 51% were wholly or partially minimally-invasive. Using a broad definition of leak, 55 patients (16.7%) developed an anastomotic leak. Twenty-seven of the 55 patients (49%) who ultimately were found to have a leak initially had a negative esophagram (performed on average on postoperative day 6). Those with a negative initial esophagram were more likely to have an uncontained leak (81% vs. 29%, p<0.01), require unplanned readmission (70% vs. 39%, p=0.02), and undergo reoperation (44% vs. 11%, p<0.01).Early postoperative esophagrams intended to evaluate anastomotic integrity have a low sensitivity of 51%, and leaks missed on initial esophagram have greater clinical consequences than those identified on initial esophagram. These findings suggest a high index of suspicion must be maintained even after a normal esophagram and calls into question the common practice of using this test to triage patients for diet advancement.

  View details for DOI 10.1016/j.athoracsur.2022.04.053

  View details for PubMedID 35618049

• Pathological remodeling of distal lung matrix in end-stage cystic fibrosis patients. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society Pinezich, M. R., Tamargo, M. A., Fleischer, S., Reimer, J. A., Hudock, M. R., Hozain, A. E., Kaslow, S. R., Tipograf, Y., Soni, R. K., Gavaudan, O. P., Guenthart, B. A., Marboe, C. C., Bacchetta, M., O'Neill, J. D., Dorrello, N. V., Vunjak-Novakovic, G. 2022

  Abstract

  Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung 'matrisome' (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies.We performed liquid chromatography-mass spectrometry, gene ontology analysis, and multi-modal imaging, including histology, immunofluorescence, and electron microscopy for a comprehensive evaluation of distal human lung extracellular matrix (matrix) structure and composition in end-stage cystic fibrosis.Quantitative proteomic profiling identified sixty-eight (68) matrix constituents with significantly altered expression in end-stage cystic fibrosis. Over 90% of significantly different matrix peptides detected, including structural and basement membrane proteins, were expressed at lower levels in cystic fibrosis. However, the total abundance of matrix in cystic fibrosis lungs was not significantly different from control lungs, suggesting that cystic fibrosis leads to loss of diversity among lung matrix proteins rather than an absolute loss of matrix. Visualization of distal lung matrix via immunofluorescence and electron microscopy revealed pathological remodeling of distal lung tissue architecture and loss of alveolar basement membrane, consistent with significantly altered pathways identified by gene ontology analysis.Dysregulation of matrix organization and aberrant wound healing pathways are associated with loss of matrix protein diversity and obliteration of distal lung tissue structure in end-stage cystic fibrosis. While many therapeutics aim to functionally restore defective cystic fibrosis transmembrane conductance regulator (CFTR), drugs that target dysregulated matrix pathways may serve as adjunct interventions to support lung recovery.

  View details for DOI 10.1016/j.jcf.2022.04.016

  View details for PubMedID 35525782

• Sound-guided assessment and localization of pulmonary air leak BIOENGINEERING & TRANSLATIONAL MEDICINE Pinezich, M. R., Mir, S., Reimer, J. A., Kaslow, S. R., Chen, J., Guenthart, B. A., Bacchetta, M., O'Neill, J. D., Vunjak-Novakovic, G., Kim, J. 2022

  View details for DOI 10.1002/btm2.10322

  View details for Web of Science ID 000790166300001

• Imaging-Guided Bioreactor for Generating Bioengineered Airway Tissue. Journal of visualized experiments : JoVE Mir, S. M., Chen, J., Pinezich, M. R., O'Neill, J. D., Guenthart, B. A., Vunjak-Novakovic, G., Kim, J. 2022

  Abstract

  Repeated injury to airway tissue can impair lung function and cause chronic lung disease, such as chronic obstructive pulmonary disease. Advances in regenerative medicine and bioreactor technologies offer opportunities to produce lab-grown functional tissue and organ constructs that can be used to screen drugs, model disease, and engineer tissue replacements. Here, a miniaturized bioreactor coupled with an imaging modality that allows in situ visualization of the inner lumen of explanted rat trachea during in vitro tissue manipulation andculture is described. Using this bioreactor, the protocol demonstrates imaging-guided selective removal of endogenous cellular components while preserving the intrinsic biochemical features and ultrastructure of the airway tissue matrix. Furthermore, the delivery, uniform distribution, and subsequent prolonged culture of exogenous cells on the decellularized airway lumen with optical monitoring in situ are shown. The results highlight that the imaging-guided bioreactor can potentially be used to facilitate the generation of functional in vitro airway tissues.

  View details for DOI 10.3791/63544

  View details for PubMedID 35467661

• Exvivo aortic valve replacement before orthotopic heart transplantation. JTCVS techniques Elde, S. F., Guenthart, B. A., Shudo, Y., Woo, Y. J. 2022; 12: 118-120

  View details for DOI 10.1016/j.xjtc.2022.01.008

  View details for PubMedID 35403016

• Cannulation Strategies in Ex Vivo Lung Perfusion. ASAIO journal (American Society for Artificial Internal Organs : 1992) Guenthart, B. A., O'Neill, J. D., Bacchetta, M. 2021

  View details for DOI 10.1097/MAT.0000000000001621

  View details for PubMedID 34882646

• Homogeneous Distribution of Exogenous Cells onto De-epithelialized Rat Trachea via Instillation of Cell-Loaded Hydrogel. ACS biomaterials science & engineering Chen, J., Mir, S. M., Pinezich, M. R., O'Neill, J. D., Guenthart, B. A., Bacchetta, M., Vunjak-Novakovic, G., Huang, S. X., Kim, J. 2021

  Abstract

  Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can facilitate in vitro investigation of human lung diseases and accelerate the development of effective therapeutics. Here, we report robust tissue manipulation modalities that allow: (i) selective removal of the endogenous epithelium of in vitro cultured airway tissues and (ii) spatially uniform distribution and prolonged cultivation of exogenous cells that are implanted topically onto the denuded airway lumen. Results obtained highlight that our approach to airway tissue manipulation can facilitate controlled removal of the airway epithelium and subsequent homogeneous distribution of newly implanted cells. This study can contribute to the creation of innovative tissue engineering methodologies that can facilitate the treatment of lung diseases, such as cystic fibrosis, primary ciliary dyskinesia, and chronic obstructive pulmonary disease.

  View details for DOI 10.1021/acsbiomaterials.1c01031

  View details for PubMedID 34874712

• Extended Static Hypothermic Preservation In Cardiac Transplantation: A Case Report. Transplantation proceedings Guenthart, B. A., Krishnan, A., Koyano, T., La Francessca, S., Chan, J., Alassar, A., Macarthur, J. W., Shudo, Y., Hiesinger, W., Woo, Y. J. 2021

  Abstract

  BACKGROUND: The donor shortage poses a major limitation to use of heart transplantation. Novel strategies such as use of expanded-criteria donors with prolonged ischemia times are being employed to address this need. Recent developments in static hypothermia have allowed for the safe use of cardiac allografts with prolonged ischemic times.CASE REPORT: We present the case of a 68-year-old woman with valvular cardiomyopathy refractory to medical therapy who underwent orthotopic heart transplantation with a cardiac allograft exposed to elevated ischemic times. This was achieved through use of the federally approved SherpaPak Cardiac Transport System for transportation of the allograft. This method of static hypothermic organ preservation allowed for a 330-minute total ischemic time, including 283 minutes of storage within the preservation system. The patient tolerated the procedure well and was discharged on postoperative day 10, with excellent graft function and no evidence of rejection 3 months postoperatively.CONCLUSIONS: Though traditionally ischemic times of 240 minutes or less are recommended for cardiac allografts, we demonstrate, to our knowledge, the longest reported ischemic time of 330 minutes via use of a novel method of static hypothermia for organ preservation. The recipient had an excellent outcome postoperatively, demonstrating the potential for this new organ preservation system to expand the donor pool and improve access and use of heart transplantation.

  View details for DOI 10.1016/j.transproceed.2021.08.021

  View details for PubMedID 34521542

• Xenogeneic support for the recovery of human donor organs. The Journal of thoracic and cardiovascular surgery O'Neill, J. D., Guenthart, B. A., Hozain, A. E., Bacchetta, M. 2021

  Abstract

  VIDEO ABSTRACT.

  View details for DOI 10.1016/j.jtcvs.2021.07.055

  View details for PubMedID 34607726

• Resection of a Giant Epithelioid Hemangioendothelioma Arising from the Superior Vena Cava. The Annals of thoracic surgery Elliott, I. A., Kasinpila, P., Guenthart, B. A., MacArthur, J. W., Berry, M. F. 2021

  Abstract

  Epithelioid hemangioendothelioma is a rare malignant vascular sarcoma. Here we present a patient with a very large tumor arising from the superior vena cava (SVC), in whom a resection with negative margins was accomplished using veno-venous bypass and bovine pericardial patch reconstruction of the SVC.

  View details for DOI 10.1016/j.athoracsur.2021.01.034

  View details for PubMedID 33529605

• First lung and kidney multi-organ transplant following COVID-19 Infection. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Guenthart, B. A., Krishnan, A., Alassar, A., Madhok, J., Kakol, M., Miller, S., Cole, S. P., Rao, V. K., Acero, N. M., Hill, C. C., Cheung, C., Jackson, E. C., Feinstein, I., Tsai, A. H., Mooney, J. J., Pham, T., Elliott, I. A., Liou, D. Z., La Francesca, S., Shudo, Y., Hiesinger, W., MacArthur, J. W., Brar, N., Berry, G. J., McCarra, M. B., Desai, T. J., Dhillon, G. S., Woo, Y. J. 2021

  Abstract

  As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

  View details for DOI 10.1016/j.healun.2021.02.015

  View details for PubMedID 34059432

• Non-destructive vacuum-assisted measurement of lung elastic modulus. Acta biomaterialia Chen, J., Mir, S. M., Pinezich, M. R., O'Neill, J. D., Guenthart, B. A., Bacchetta, M., Vunjak-Novakovic, G., Huang, S. X., Kim, J. 2021

  Abstract

  In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. STATEMENT OF SIGNIFICANCE: Accurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.

  View details for DOI 10.1016/j.actbio.2021.06.037

  View details for PubMedID 34192570

• Surgical technique for atrial-esophageal fistula repair after catheter ablation: An underrecognized complication JTCVS TECHNIQUES Guenthart, B. A., Sun, B., De Biasi, A., Fischbein, M. P., Liou, D. Z. 2020; 4: 169-172

  View details for DOI 10.1016/j.xjtc.2020.07.022

  View details for Web of Science ID 000655724800059

• Surgical technique for atrial-esophageal fistula repair after catheter ablation: An underrecognized complication. JTCVS techniques Guenthart, B. A., Sun, B., De Biasi, A., Fischbein, M. P., Liou, D. Z. 2020; 4: 169-172

  View details for DOI 10.1016/j.xjtc.2020.07.022

  View details for PubMedID 34318000

  View details for PubMedCentralID PMC8303005

• Gut bioengineering strategies for regenerative medicine. American journal of physiology. Gastrointestinal and liver physiology O'Neill, J. D., Pinezich, M. R., Guenthart, B. A., Vunjak-Novakovic, G. 2020

  Abstract

  Gastrointestinal disease burden continues to rise in the United States and worldwide. The development of bioengineering strategies to model gut injury or disease and to re-establish functional gut tissue could expand therapeutic options and improve clinical outcomes. Current approaches leverage a rapidly evolving gut bioengineering toolkit aimed at: (i) de-novo generation of gut-like tissues at multiple scales for microtissue models or implantable grafts, and (ii) regeneration of functional gut in vivo. Although significant progress has been made in intestinal organoid cultures and engineered tissues, development of predictive in-vitro models and effective regenerative therapies remains challenging. In this review, we survey emerging bioengineering tools and recent methodological advances to identify future opportunities and challenges in gut bioengineering for disease modeling and regenerative medicine.

  View details for DOI 10.1152/ajpgi.00206.2020

  View details for PubMedID 33174453

• Intracardiac paragangliomas: surgical approach and perioperative management. General thoracic and cardiovascular surgery Guenthart, B. A., Trope, W., Keeyapaj, W., Weiel, J. J., Edmonson, A., MacArthur, J. W., Annes, J. P., Woo, Y. J., Lui, N. S. 2020

  Abstract

  Intracardiac paragangliomas most commonly arise from the left atrium and are often infiltrative and densely adherent to surrounding structures. Given their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established. We describe a case of a 60-year-old woman with a mildly functioning intracardiac paraganglioma in which division of the superior vena cava improved exposure and enabled a complex limited resection. Further, we provide an overview of the diagnostic workup, perioperative medical management, surgical approach, and surveillance strategy in patients with these challenging tumors.

  View details for DOI 10.1007/s11748-020-01503-2

  View details for PubMedID 33074472

• Greater Ipsilateral Rectus Muscle Atrophy after Robotic Thoracic Surgery Compared to Open and VATS Approaches Wang, Y., Bhandari, P., Trope, W., Guenthart, B. A., Guo, H., Liou, D., Backhus, L. M., Berry, M., Ben Shrager, J., Lui, N. ELSEVIER SCIENCE INC. 2020: S289

  View details for Web of Science ID 000582792300536

• Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs. Nature medicine Hozain, A. E., O'Neill, J. D., Pinezich, M. R., Tipograf, Y., Donocoff, R., Cunningham, K. M., Tumen, A., Fung, K., Ukita, R., Simpson, M. T., Reimer, J. A., Ruiz, E. C., Queen, D., Stokes, J. W., Cardwell, N. L., Talackine, J., Kim, J., Snoeck, H., Chen, Y., Romanov, A., Marboe, C. C., Griesemer, A. D., Guenthart, B. A., Bacchetta, M., Vunjak-Novakovic, G. 2020; 26 (7): 1102–13

  Abstract

  Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.

  View details for DOI 10.1038/s41591-020-0971-8

  View details for PubMedID 32661401

• Resident education in robotic thoracic surgery VIDEO-ASSISTED THORACIC SURGERY Guenthart, B. A., Lui, N. S. 2020; 5

  View details for DOI 10.21037/vats.2020.01.01

  View details for Web of Science ID 000534549000008

• Commentary: Lung cancer outcomes reporting within the VA system: room for improvement. Seminars in thoracic and cardiovascular surgery Guenthart, B. A., Backhus, L. M., Lui, N. S. 2020

  View details for DOI 10.1053/j.semtcvs.2020.06.008

  View details for PubMedID 32569647