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Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation

Natalini, Jake G; Wong, Kendrew K; Nelson, Nathaniel C; Wu, Benjamin G; Rudym, Darya; Lesko, Melissa B; Qayum, Seema; Lewis, Tyler C; Wong, Adrian; Chang, Stephanie H; Chan, Justin C Y; Geraci, Travis C; Li, Yonghua; Wang, Chan; Li, Huilin; Pamar, Prerna; Schnier, Joseph; Mahoney, Ian J; Malik, Tahir; Darawshy, Fares; Sulaiman, Imran; Kugler, Matthias C; Singh, Rajbir; Collazo, Destiny E; Chang, Miao; Patel, Shrey; Kyeremateng, Yaa; McCormick, Colin; Barnett, Clea R; Tsay, Jun-Chieh J; Brosnahan, Shari B; Singh, Shivani; Pass, Harvey I; Angel, Luis F; Segal, Leopoldo N
PMID: 38358857
ISSN: 1535-4970
CID: 5633542

Anatomical considerations and surgical technique of porcine cardiac xenotransplantation [Editorial]

Hussain, Syed T; Kumar, Akshay; Chan, Justin; James, Les; Smith, Deane; Moazami, Nader
PMCID:11184667
PMID: 38899090
ISSN: 2666-2507
CID: 5672192

Sensorineural hearing loss after cardiac surgery: a systematic review

Daniel, Jonathan; Glynatsis, John M; Kovoor, Joshua G; Stretton, Brandon; Bacchi, Stephen; Ovenden, Christopher D; To, Minh-Son; Goh, Rudy; Hewitt, Joseph N; Sahota, Raguwinder S; Chan, Justin C Y; Ramponi, Fabio; Krishnan, Giri; Gupta, Aashray K
BACKGROUND:Sensorineural hearing loss (SNHL) may occur following cardiac surgery. Although preventing post-operative complications is vitally important in cardiac surgery, there are few guidelines regarding this issue. This review aimed to characterize SNHL after cardiac surgery. METHOD/METHODS:This systematic review was registered on PROSPERO and conducted in accordance with PRISMA guidelines. A systematic search of the PubMed, Embase and Cochrane Library were conducted from inception. Eligibility determination, data extraction and methodological quality analysis were conducted in duplicate. RESULTS:There were 23 studies included in the review. In the adult population, there were six cohort studies, which included 36 cases of hearing loss in a total of 7135 patients (5.05 cases per 1000 operations). In seven cohort studies including paediatric patients, there were 88 cases of hearing loss in a total of 1342 operations. The majority of cases of hearing loss were mild in the adult population (56.6%). In the paediatric population 59.2% of hearing loss cases had moderate or worse hearing loss. The hearing loss most often affected the higher frequencies, over 6000 Hz. There have been studies indicating an association between hearing loss and extracorporeal circulation, but cases have also occurred without this intervention. CONCLUSION/CONCLUSIONS:SNHL is a rare but potentially serious complication after cardiac surgery. This hearing loss affects both paediatric and adult populations and may have significant long-term impacts. Further research is required, particularly with respect to the consideration of screening for SNHL in children after cardiac surgery.
PMID: 37872745
ISSN: 1445-2197
CID: 5726352

Concurrent tracheobronchoplasty and bilateral lung transplant for obstructive lung disease [Case Report]

Geraci, Travis C; Chan, Justin; Angel, Luis; Chang, Stephanie H
PMCID:10859567
PMID: 38351993
ISSN: 2666-2507
CID: 5635722

Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

Chan, Justin C Y; Man, H S Jeffrey; Asghar, Usman M; McRae, Karen; Zhao, Yidan; Donahoe, Laura L; Wu, Licun; Granton, John; de Perrot, Marc
BACKGROUND:The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. METHODS:Retrospective study of 401 consecutive patients undergoing PEA at our institution between 08/2005 and 03/2020 was performed. Primary outcome was need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. RESULTS:Females (n=203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final TPR after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p<0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p=0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs. 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04). CONCLUSIONS:Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients is important. Further investigations into possible mechanisms to explain the differences is warranted.
PMID: 37422146
ISSN: 1557-3117
CID: 5539602

Pig-to-human heart xenotransplantation in two recently deceased human recipients

Moazami, Nader; Stern, Jeffrey M; Khalil, Karen; Kim, Jacqueline I; Narula, Navneet; Mangiola, Massimo; Weldon, Elaina P; Kagermazova, Larisa; James, Les; Lawson, Nikki; Piper, Greta L; Sommer, Philip M; Reyentovich, Alex; Bamira, Daniel; Saraon, Tajinderpal; Kadosh, Bernard S; DiVita, Michael; Goldberg, Randal I; Hussain, Syed T; Chan, Justin; Ngai, Jennie; Jan, Thomas; Ali, Nicole M; Tatapudi, Vasishta S; Segev, Dorry L; Bisen, Shivani; Jaffe, Ian S; Piegari, Benjamin; Kowalski, Haley; Kokkinaki, Maria; Monahan, Jeffrey; Sorrells, Lori; Burdorf, Lars; Boeke, Jef D; Pass, Harvey; Goparaju, Chandra; Keating, Brendan; Ayares, David; Lorber, Marc; Griesemer, Adam; Mehta, Sapna A; Smith, Deane E; Montgomery, Robert A
Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.
PMID: 37488288
ISSN: 1546-170x
CID: 5595152

Prolonged Ischemia Increases Complications Among High- and Low-Volume Centers in Lung Transplantation

Wadowski, Benjamin J; Wang, Simeng; Angel, Luis F; Geraci, Travis C; Chan, Justin C Y; Chang, Stephanie H
BACKGROUND:The effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample. METHODS:Data on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation. RESULTS:Among 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score-matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P = .031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P < .01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation. CONCLUSIONS:PIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers.
PMID: 37489398
ISSN: 1552-6259
CID: 5592042

Surgical interhospital transfer mortality: national analysis

Murshed, Ishraq; Gupta, Aashray K; Camilos, Angelique N; Sabab, Ahad; Bacchi, Stephen; Kovoor, Joshua G; Chan, Justin C Y; Maddern, Guy J
BACKGROUND:Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality. METHODS:Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons' reports and assessors' evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes. RESULTS:Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable. CONCLUSION:This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.
PMID: 36857150
ISSN: 1365-2168
CID: 5462292

History of Lung Transplantation

Chang, Stephanie H; Chan, Justin; Patterson, G Alexander
Lung transplantation remains the only available therapy for many patients with end-stage lung disease. The number of lung transplants performed has increased significantly, but development of the field was slow compared with other solid-organ transplants. This delayed growth was secondary to the increased complexity of transplanting lungs; the continuous needs for surgical, anesthetics, and critical care improvements; changes in immunosuppression and infection prophylaxis; and donor management and patient selection. The future of lung transplant remains promising: expansion of donor after cardiac death donors, improved outcomes, new immunosuppressants targeted to cellular and antibody-mediated rejection, and use of xenotransplantation or artificial lungs.
PMID: 36774157
ISSN: 1557-8216
CID: 5421102

Future of Lung Transplantation: Xenotransplantation and Bioengineering Lungs

Chan, Justin C Y; Chaban, Ryan; Chang, Stephanie H; Angel, Luis F; Montgomery, Robert A; Pierson, Richard N
Xenotransplantation promises to alleviate the issue of donor organ shortages and to decrease waiting times for transplantation. Recent advances in genetic engineering have allowed for the creation of pigs with up to 16 genetic modifications. Several combinations of genetic modifications have been associated with extended graft survival and life-supporting function in experimental heart and kidney xenotransplants. Lung xenotransplantation carries specific challenges related to the large surface area of the lung vascular bed, its innate immune system's intrinsic hyperreactivity to perceived 'danger', and its anatomic vulnerability to airway flooding after even localized loss of alveolocapillary barrier function. This article discusses the current status of lung xenotransplantation, and challenges related to immunology, physiology, anatomy, and infection. Tissue engineering as a feasible alternative to develop a viable lung replacement solution is discussed.
PMID: 36774165
ISSN: 1557-8216
CID: 5468652