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

Rationale: Acute cellular rejection (ACR) after lung transplantation is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objective: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple timepoints. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired one month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) compared to those with current or future (beyond one month) ACR. However, a subgroup analysis of those who developed ACR beyond one month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared to baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in alpha diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusion: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Sensorineural hearing loss after cardiac surgery: a systematic review.

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: 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: 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.

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

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.

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

BACKGROUND: The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) 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 August 2005 and March 2020 was performed. Primary outcome was the 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 total pulmonary vascular resistance 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 are important. Further investigations into possible mechanisms to explain the differences are warranted.

Potentially avoidable mortality after endoscopic retrograde cholangiopancreatography in Australia: an 8-year qualitative analysis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly performed procedure worldwide. The aim of this study was to examine cases of mortality after ERCP to identify clinical incidents that are potentially preventable, to improve patient safety. METHODS: The Australian and New Zealand Audit of Surgical Mortality provides an independent and externally peer-reviewed audit of surgical mortality pertaining to potentially avoidable issues. A retrospective review of prospectively collected data within this database was performed for the 8-year audit period from 1 January 2009 to 31 December 2016. Clinical incidents were identified by assessors through first- or second-line review, and thematically coded into periprocedural stages. These themes were then qualitatively analysed. RESULTS: There were 58 potentially avoidable deaths following ERCP, with 85 clinical incidents. Preprocedural incidents were most common (n = 37), followed by postprocedural (n = 32) and then intraprocedural (n = 8). Communication issues occurred across the periprocedural period (n = 8). Preprocedural incidents included delay to procedure, inadequate resuscitative management, decision to perform procedure and inadequate assessment. Intraprocedural incidents comprised technical factors and inadequate support. Postprocedural incidents involved inappropriate treatment, delay in definitive surgical treatment or in recognizing complications, inappropriate second-line intervention and inadequate assessment. Communication incidents comprised inadequate documentation, failure to escalate care and poor inter-clinician communication. CONCLUSION: Causes of mortality following ERCP are wide-ranging, and reviewing clinical incidents associated with potentially avoidable mortality can serve to inform and educate practitioners. In collating a subset of cases in which procedure-related mortality was deemed avoidable, a series of cautionary tales about ERCP is presented that may provide cues to practitioners on improving patient safety and inform future surgical practice.

Surgical interhospital transfer mortality: national analysis.

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.

Future of Lung Transplantation: Xenotransplantation and Bioengineering Lungs.

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.

Trends in the Extracorporeal Membrane Oxygenation Literature: A Bibliometric Analysis in the COVID-19 Era.

Extracorporeal Membrane Oxygenation (ECMO) was first used in the 1970s. Its use is increasingly common in critical care and perioperative settings and has gained newfound prominence during COVID-19. To guide future research, we conducted a bibliometric analysis of ECMO literature. Thomson Reuters Web of Science was searched to March 7, 2021. Articles were ranked by total number of citations. Data was extracted from the 100 most cited papers relevant to ECMO for study design, topic, author, year, and institution. Journal impact factor for 2019 and Eigenfactor scores were also recorded. Our search retrieved a total of 18,802 articles. Median number of citations for the top 100 articles was 220 (range 157-1,819). These were published in 34 journals, with first authors originating from 15 countries. The Annals of Thoracic Surgery had the highest number of articles (n = 9) while Lancet publications had the most citations (n = 3,191). Use of ECMO was most commonly observed in cardiogenic shock or acute respiratory distress syndrome. United States had the greatest article output (n = 49). With 10 publications, 2013 was the most prolific year. Using linear regression, when controlled for time since publication, there was no statistically significant relationship between 2019 journal impact factor and number of article citations (p = .09). Top articles in the ECMO literature are of considerable impact and quality. As the United States produced the bulk of the prominent evidence base, and most data were regarding respiratory issues, outsized advances in ECMO may be possible within the United States during the COVID-19 era.

Endovascular thrombectomy for large vessel occlusion acute ischemic stroke after cardiac surgery.

INTRODUCTION: Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life-saving intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery. METHODS: We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed. RESULTS: Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0-9 days). Median NIHSS was 26 (range 10-32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97-263). Two patients received Intra-arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3-month mRS was 3 (range 0-6). CONCLUSION: We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.

Geographical distribution of authorship for leading cardiothoracic surgery journals.

BACKGROUND: Evolution of surgical practice is influenced by publications in the leading journals of that field. If the authorship of a publication lacks geographical diversity, this could create bias and limit generalizability of the evidence. Accordingly, we conducted a geographical analysis of the leading Cardiothoracic Surgery journals worldwide. METHODS: Using 2020 Impact Factor, we searched the leading Cardiothoracic Surgery journals over the past decade. Only original articles were included. Data regarding first, second and last authors were extracted from every article. From this, we analysed country of affiliation, highest academic degree obtained and author location by metropolitan or rural setting. RESULTS: A total of 12,706 original articles were published in the top 5 ranked Cardiothoracic journals between 2011 and 2020. Authors originated from 69 countries, with the majority being from North America and Western Europe. The United States was the most common country of affiliation (42.8%) in all five journals, with New York City the most prominent city. A total of  63.7% of the authorship originated from large metropolitan areas (estimated as population greater than 500,000 residents), and the most common degrees obtained by authors were MD and PhD. CONCLUSION: The prominent Cardiothoracic authorship is predominantly located in Western countries, most commonly large metropolitan centers in the United States. This raises questions as to whether the literature adequately reflects populations in other geographical areas such as the continents of South America and Africa and rural settings. Leading journals should consider policies which encourage publication by authors from geographical locations that are underrepresented globally.

One-year immunologic outcomes of lung transplantation utilizing hepatitis C-viremic donors.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.

Cardiac surgery on patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: The COVID-19 pandemic has had a significant impact on global surgery. In particular, deleterious effects of SARS-CoV-2 infection on the heart and cardiovascular system have been described. To inform surgical patients, we performed a systematic review and meta-analysis aiming to characterize outcomes of COVID-19 positive patients undergoing cardiac surgery. METHODS: The study protocol was registered with PROSPERO (CRD42021228533) and conformed with PRISMA 2020 and MOOSE guidelines. PubMed, Ovid MEDLINE and Web of Science were searched between 1 January 2019 to 24 February 2022 for studies reporting outcomes on COVID-19 positive patients undergoing cardiac surgery. Study screening, data extraction and risk of bias assessment were conducted in duplicate. Meta-analysis was conducted using a random-effects model where at least two studies had sufficient data for that variable. RESULTS: Searches identified 4223 articles of which 18 studies were included with a total 44 patients undergoing cardiac surgery. Within these studies, 12 (66.7%) reported populations undergoing coronary artery bypass graft (CABG) surgery, three (16.7%) aortic valve replacements (AVR) and three (16.7%) aortic dissection repairs. Overall mean postoperative length of ICU stay was 3.39 (95% confidence interval (CI): 0.38, 6.39) and mean postoperative length of hospital stay was 17.88 (95% CI: 14.57, 21.19). CONCLUSION: This systematic review and meta-analysis investigated studies of limited quality which characterized cardiac surgery in COVID-19 positive patients and demonstrates that these patients have poor outcomes. Further issues to be explored are effects of COVID-19 on decision-making in cardiac surgery, and effects of COVID-19 on the cardiovascular system at a cellular level.

Maintaining technical proficiency in senior surgical fellows during the COVID-19 pandemic through virtual teaching.

BACKGROUND: The novel coronavirus (COVID-19) pandemic has resulted in a severe reduction in operative opportunities for trainees. We hypothesized that augmenting independent practice with a bench model of vascular anastomoses using regular videoconferences and individual feedback would provide a meaningful benefit in the maintenance of technical skills in senior lung transplant surgical fellows. METHODS: A lung transplantation virtual technical skills course was developed, and surgical fellows were provided with a bench model and surgical instruments. Using a virtual communication platform, teaching sessions were held twice weekly, and fellows performed an anastomosis on camera. Video recordings were reviewed and critiqued by attending staff. At the end of the 3-month course, participants were surveyed about their experience. Warm ischemic time was compared between the fellows' 5 most recent cases before and after the pandemic. RESULTS: Seven senior surgical fellows participated and provided feedback. The fellows had graduated medical school an average of 14 years before fellowship, and spent an average of 5 hours (range, 1.3-15 hours) of home practice. Five of the 7 participants (71%) reported improvement in their technical skills and increased confidence in performing lung transplantation. No significant difference in average warm ischemic time in procedures performed by fellows was identified (70.3 minutes prepandemic vs 68.3 minutes postpandemic; P = .68). CONCLUSIONS: A program of virtual technical skills teaching, individual video coaching, and independent practice has provided a benefit in maintaining technical skills in lung transplant surgical fellows during the COVID-19 pandemic, when equivalent operative experience was unavailable. Lessons learned from this exceptional time can be used to create simulation curricula for senior trainees.

How to do whole lung lavage for treatment of pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis is a rare condition characterized by progressive accumulation of surfactant lipoproteins in the alveolar space, leading to poor gas exchange. We describe our technique of whole lung lavage for management of pulmonary alveolar proteinosis.

Mortality in Australian Cardiothoracic Surgery: Findings From a National Audit.

BACKGROUND: Independent peer review of mortality cases has potential to identify issues in cardiothoracic surgical patients. The Australian and New Zealand Audit of Surgical Mortality aims to improve surgical care through peer-reviewed assessment of all surgical mortality. The aim of this study was to describe common clinical management issues that contribute to patient mortality in a cohort of Australian cardiothoracic surgical patients. This approach may subsequently provide a basis for quality improvement. METHODS: Cardiothoracic mortality reports to the Australian and New Zealand Audit of Surgical Mortality from February 2009 through December 2015 were reviewed. The surgeon report and assessor comments were coded to identify clinical management issues. These were divided into perioperative stages (preoperative, intraoperative, and postoperative), and at each stage a thematic analysis was performed. RESULTS: Of the 908 cases analyzed, 1371 clinical management issues were identified. Postoperative issues were the most common (n = 552), followed by preoperative (n = 378) and intraoperative issues (n = 370). Communication issues were present at all 3 stages (n = 71). Overall the most common theme was intraoperative technical issues (n = 287). Many of these issues revolved around unintentional injury to anatomic structures during surgery and inadequate myocardial protection. Communication issues commonly related to surgical handover to the intensive care unit and lack of shared decision-making. Also common were consultant surgeons being unaware of patient deterioration or significant changes in management. CONCLUSIONS: The Australian and New Zealand Audit of Surgical Mortality provides valuable insights into issues affecting mortality in cardiothoracic patients. Potentially avoidable management issues play a large role in determining the outcome of these patients. Quality improvement initiatives targeting these areas may be valuable.

"Nobody told me": Communication Issues Affecting Australian Cardiothoracic Surgery Patients.

BACKGROUND: Failure of communication can have potentially severe results in cardiothoracic surgery. Previous literature regarding patient safety highlighted communication as a common area for improvement. This study utilized a qualitative approach to analyze a national mortality audit data set to identify and describe communication issues that could potentially contribute to patient mortality following cardiothoracic surgery. METHODS: We utilized a peer-reviewed audit of surgical deaths after cardiothoracic surgery in Australian hospitals from 2009 to 2015 via the Australian and New Zealand Audit of Surgical Mortality. Cases were identified with clinical management issues then individual analysis of cases highlighting communication issues was undertaken. A total of 91 reports from surgeons and assessors were analysed using a thematic analytic approach. RESULTS: A total of 908 cases of potentially avoidable mortality were identified as being associated with clinical management issues, and communication issues were identified in 91 (10%) of these cases, which served as the basis for this analysis. The study found that failure to achieve shared decision making was the most common theme (n = 38, 41.8%), followed by failure to notify patient deterioration (n = 22, 24.1%), misreporting of patient condition (n = 10, 11.0%) and issues related to informed consent (n = 9, 10.0%). The most frequent communication issues occurred between surgeons and the intensive care unit. CONCLUSIONS: Poor communication was identified in patients who died after cardiothoracic surgery. Communication is an important modifiable factor in patient mortality. Efforts to address teamwork and communication have the potential to improve safety and quality of care for patients undergoing cardiothoracic surgery.

Novel Sternal Reconstruction With Custom Three-Dimensional-Printed Titanium PoreStar Prosthesis.

Resection of sternal tumors can leave large defects, which exposes major mediastinal structures, and can affect respiratory mechanics. If feasible, resection is potentially a complex reconstructive challenge to restore normal and functional anatomy using conventional techniques. We report the first Australian use of a three-dimensional-printed titanium and PoreStar prosthesis in a 39-year-old woman for reconstruction after major surgical resection of the sternum for metastatic breast cancer. The patient successfully underwent excision of the sternum and costal cartilages as well as implantation of the prosthesis. We conclude that three-dimensional-printed prostheses are technically feasible to deliver excellent cosmetic result.