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

Rationale: Acute cellular rejection (ACR) after lung transplant 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. Objectives: 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 time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-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. Conclusions: 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.

Single center utilization and post-transplant outcomes of thoracoabdominal normothermic regional perfusion deceased cardiac donor organs.

INTRODUCTION: Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS: We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS: All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION: Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.

Multimodal opioid-sparing pain management after lung transplantation and the impact of liposomal bupivacaine intercostal nerve block.

Opioid analgesics are commonly used post-lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid-sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient-reported pain scores early post-lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre-transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228 mg vs. 517 mg, P= .032). A multimodal opioid-sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge.

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.

Rapidly Growing Mycobacterium tuberculosis in the Form of Empyema Necessitans: A Case Report.

We present a case of rapidly growing disseminated Mycobacterium tuberculosis (MTB) that presented as an empyema necessitans (EN) in a 65-year-old woman with a single right lung transplant admitted for progressive dyspnea. While hospitalized, she had daily fevers and was found to have a right-sided chest wall abscess and pleural effusion. Acid-fast bacilli cultures from the abscess and pleural fluid grew MTB within 4 and 6 days, respectively. Blood cultures later grew MTB as well. Upon initiation of rifampin, isoniazid, pyrazinamide, and ethambutol, she developed hemorrhagic pancreatitis and distributive shock secondary to antituberculosis medications and disseminated MTB. Noteworthy features of this case include the rapid rate of MTB culture growth in less than a week, the development of a likely donor-derived MTB EN, and the clinical challenges of MTB screening and MTB infection management in a solid organ transplant recipient.

Percutaneous Dilational Tracheostomy for Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation.

OBJECTIVES: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING: Critical care units at two large metropolitan hospitals in New York City. PATIENTS: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.

Hemoadsorption for management of patients on veno-venous ECMO support for severe COVID-19 acute respiratory distress syndrome.

BACKGROUND AND AIM: Patients with severe coronavirus disease 2019 (COVID-19) develop a profound cytokine-mediated pro-inflammatory response. This study reports outcomes in 10 patients with COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO) who were selected for the emergency use of a hemoadsorption column integrated in the ECMO circuit. MATERIALS AND METHODS: Pre and posttreatment, clinical data, and inflammatory markers were assessed to determine the safety and feasibility of using this system and to evaluate the clinical effect. RESULTS: During hemoadsorption, median levels of interleukin (IL)-2R, IL-6, and IL-10 decreased by 54%, 86%, and 64%, respectively. Reductions in other markers were observed for lactate dehydrogenase (-49%), ferritin (-46%), d-dimer (-7%), C-reactive protein (-55%), procalcitonin (-76%), and lactate (-44%). Vasoactive-inotrope scores decreased significantly over the treatment interval (-80%). The median hospital length of stay was 53 days (36-85) and at 90-days post cannulation, survival was 90% which was similar to a group of patients without the use of hemoadsorption. CONCLUSIONS: Addition of hemoadsorption to VV-ECMO in patients with severe COVID-19 is feasible and reduces measured cytokine levels. However, in this small series, the precise impact on the overall clinical course and survival benefit still remains unknown.

Management of Diaphragm Paralysis and Eventration.

An elevated diaphragm may be due to eventration or paralysis. Diaphragm elevation is often asymptomatic and found incidentally on imaging. Fluoroscopic testing can be used to differentiate eventration (no paradoxic motion) from paralysis (paradoxic motion). Regardless of etiology, a diaphragm plication is indicated in all symptomatic patients with an elevated diaphragm. Plication can be approached either from a thoracic or abdominal approach, though most thoracic surgeons perform minimally invasive thoracoscopic plication. The goal of plication is to improve lung volumes and decrease paradoxic elevation of the hemidiaphragm. Diaphragm plication is safe, has excellent outcomes, and is associated with symptom improvement.

History of Lung Transplantation.

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.

Assessing donor organ quality according to recipient characteristics in lung transplantation.

OBJECTIVE: There is a shortage of donor lungs relative to need, but overall donor organ utilization remains low. The most common reason for refusal is organ quality, but the standards applied to selection vary. In this study we sought to characterize differences in lung utilization according to quality across several clinically distinct recipient pools. METHODS: Data on donor lungs recovered (April 2006 to September 2019) were extracted from the Scientific Registry of Transplant Recipients database. Organs were classified as ideal, standard, or extended quality according to their poorest metric among selected parameters. Subanalyses were performed on the basis of procedure type, age, lung allocation score, era, and alternative definitions of extended quality. Recipient traits and survival according to organ quality were assessed. RESULTS: Of 156,022 lungs analyzed during the study period, 25,777 (16.5%) were transplanted. There was no difference in quality distribution for single and bilateral transplants. Young candidates were more likely to receive ideal (14.7% vs 12.3%) or standard (9.5% vs 8.2%) lungs, but not extended lungs (75.9% vs 79.5%; all P < .01). Absolute differences in distribution according to lung allocation score quartile were small (<2%). Extended quality donor utilization increased over time. Survival according to donor category was similar at 1 and 3 years post transplant in unadjusted and Cox regression analyses. CONCLUSIONS: Extended quality lungs comprise an increasing share of transplants in a national sample. Organ selection varies according to recipient age and lung allocation score. However, absolute differences in quality distribution are small, and adverse effects on outcomes are limited to organs with multiple extended qualifying characteristics.

Double-Barrel Vascularized Free Fibula Flap for Reconstruction of Sternal Nonunion with Bone Defect: A Case Report.

CASE: Given the rare incidence of sternal nonunion after traumatic injury, literature describing the management of posttraumatic sternal reconstruction is limited. We present a case of a 54-year-old man with a history of traumatic chest wall injury with multiple unsuccessful attempts at sternal repair who presented with chronic sternal nonunion and persistent bone defect. Sternal reconstruction using a vascularized double-barrel free fibula flap with rigid fixation in multiple planes was performed, with confirmed bony union at 6 months. CONCLUSION: This novel approach to sternal nonunion management allowed effective bridging of posttraumatic sternal bone defects while facilitating osseous integration and long-term stabilization.

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.

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.

Digital spatial profiling to predict recurrence in grade 3 stage I lung adenocarcinoma.

OBJECTIVE: Early-stage lung adenocarcinoma is treated with local therapy alone, although patients with grade 3 stage I lung adenocarcinoma have a 50% 5-year recurrence rate. Our objective is to determine if analysis of the tumor microenvironment can create a predictive model for recurrence. METHODS: Thirty-four patients with grade 3 stage I lung adenocarcinoma underwent surgical resection. Digital spatial profiling was used to perform genomic (n = 31) and proteomic (n = 34) analyses of pancytokeratin positive and negative tumor cells. K-means clustering was performed on the top 50 differential genes and top 20 differential proteins, with Kaplan-Meier recurrence curves based on patient clustering. External validation of high-expression genes was performed with Kaplan-Meier plotter. RESULTS: There were no significant clinicopathologic differences between patients who did (n = 14) and did not (n = 20) have recurrence. Median time to recurrence was 806 days; median follow-up with no recurrence was 2897 days. K-means clustering of pancytokeratin positive genes resulted in a model with a Kaplan-Meier curve with concordance index of 0.75. K-means clustering for pancytokeratin negative genes was less successful at differentiating recurrence (concordance index 0.6). Genes upregulated or downregulated for recurrence were externally validated using available public databases. Proteomic data did not reach statistical significance but did internally validate the genomic data described. CONCLUSIONS: Genomic difference in lung adenocarcinoma may be able to predict risk of recurrence. After further validation, stratifying patients by this risk may help guide who will benefit from adjuvant therapy.

Discharging Patients by Postoperative Day One After Robotic Anatomic Pulmonary Resection.

BACKGROUND: Our objective is to assess the feasibility and safety of discharging patients by postoperative day one (POD1) after robotic segmentectomy and lobectomy, and to describe outcomes for patients. METHODS: A retrospective analysis was made of a prospectively collected database of a quality improvement initiative by a single surgeon. Factors associated with discharge by POD1 were evaluated using a multivariate logistic regression model. RESULTS: From January 2018 to July 2020, of 253 patients who underwent robotic anatomic pulmonary resection, 134 (53%) were discharged by POD1, 67% after segmentectomy and 41% after lobectomy. Discharge by POD1 improved with experience and was achieved in 97% of patients after segmentectomy and 68% after lobectomy in the final quartile. Thirty-one patients (12%) were discharged home with a chest tube, including 7 (2.8%) on POD1. On multivariate analysis, never smokers and segmentectomy were associated with discharge by POD1. Conversely, decreased baseline performance status and perioperative complications were associated with discharge after POD1. There were 10 minor morbidities (4%), 6 major morbidities (2.4%), and no 30- or 90-day mortality. There were 4 readmissions (1.6%), of which 1 (0.4%) was after POD1 discharge. Patient satisfaction remained high throughout the study period. CONCLUSIONS: With experience and communication, select patients can be discharged home on POD1 after robotic segmentectomy and lobectomy with excellent outcomes and high satisfaction. Discharge by POD1 was associated with never smokers and segmentectomy, and inversely associated with decreased baseline performance status and perioperative complications.

One-Year Outcomes With Venovenous Extracorporeal Membrane Oxygenation Support for Severe COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can cause acute respiratory failure requiring mechanical ventilation. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used in patients in whom conventional mechanical ventilatory support has failed. To date, published data have focused on survival from ECMO and survival to discharge. In addition to survival to discharge, this study reports 1-year follow-up data for patients who were successfully discharged from the hospital. METHODS: A single-institution, retrospective review of all patients with severe COVID-19 who were cannulated for VV-ECMO between March 10, 2020 and May 1, 2020 was performed. A multidisciplinary ECMO team evaluated, selected, and managed patients with ECMO support. The primary outcome of this study was survival to discharge. Available 1-year follow-up data are also reported. RESULTS: A total of 30 patients were supported with VV-ECMO, and 27 patients (90%) survived to discharge. All patients were discharged home or to acute rehabilitation on room air, except for 1 patient (3.7%), who required supplemental oxygen therapy. At a median follow-up of 10.8 months (interquartile range [IQR], 8.9-14.4 months) since ECMO cannulation, survival was 86.7%, including 1 patient who underwent lung transplantation. Of the patients discharged from the hospital, 44.4% (12/27) had pulmonary function testing, with a median percent predicted forced expiratory volume of 100% (IQR, 91%-110%). For survivors, a 6-minute walk test was performed in 59.3% (16/27), with a median value of 350 m (IQR, 286-379 m). CONCLUSIONS: A well-defined patient selection and management strategy of VV-ECMO support in patients with severe COVID-19 resulted in exceptional survival to discharge that was sustained at 1-year after ECMO cannulation.

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

Objectives: Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO). Methods: A single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results: In total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged. Conclusions: Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

Managing Scarcity: Innovation and Resilience During the COVID-19 Pandemic.

The Coronavirus Disease 2019 (COVID-19) pandemic remains a disruptive force upon the health care system, with particular import for thoracic surgery given the pulmonary pathophysiology and disease implications of the virus. The rapid and severe onset of disease required expedient innovation and change in patient management and novel approaches to care delivery and nimbleness of workforce. In this review, we detail our approaches to patients with COVID-19, including those that required surgical intervention, our expedited and novel approach to bronchoscopy and tracheostomy, and our expansion of telehealth. The pandemic has created a unique opportunity to reflect on our delivery of care in thoracic surgery and apply lessons learned during this time to "rethink" how to optimize resources and deliver excellent and cutting-edge patient care.

Postoperative Air Leaks After Lung Surgery: Predictors, Intraoperative Techniques, and Postoperative Management.

Postoperative air leak is one of the most common complications after pulmonary resection and contributes to postoperative pain, complications, and increased hospital length of stay. Several risk factors, including both patient and surgical characteristics, increase the frequency of air leaks. Appropriate intraoperative tissue handling is the most important surgical technique to reduce air leaks. Digital drainage systems have improved the management of postoperative air leak via objective data, portability, and ease of use in the outpatient setting. Several treatment strategies have been used to address prolonged air leak, including pleurodesis, blood patch, placement of endobronchial valves, and reoperative surgery.