Faculty Bibliography

BACKGROUND:Donor to recipient size matching is an essential part of lung transplantation, with significant mismatch leading to worse patient outcomes. The current practice is based on limited data along with broadly accepted themes that have not been articulated in the form of objective and definitive guidelines. The objective of the American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) expert panel was to develop evidence- and expert-based recommendations for optimal donor to recipient lung allograft size matching based on review of the existing literature. METHODS:The AATS CPSC assembled an expert panel of 18 lung transplant surgeons from 15 centers who developed a consensus document of recommendations. The panel was divided into subgroups covering size-matching in (1) bilateral lung transplantation, (2) single lung transplantation, (3) lobar transplantation, (4) unique situations, and (5) management of complications following severe size mismatch. Following a focused literature review, each subgroup formulated recommendation statements for each subtopic, which were reviewed and further refined using a Delphi process until consensus was achieved on each final statement by the voting group. RESULTS:The expert panel achieved consensus on 20 recommendations for current best practices in donor and recipient size matching. These recommendations include utilization of a ratio of donor-to-recipient predicted total lung capacity between 0.8 to 1.2, with special considerations based on recipient pathology, single lung or lobar transplantation, and anatomic variations such as chest wall abnormalities or significant mediastinal shift. Furthermore, oversized allografts can be reduced in size via non-anatomic or anatomic resection in select cases when required. CONCLUSIONS:Consistent practice guidelines regarding donor to recipient size matching will be helpful and important to achieve optimal outcomes in lung transplantation. The recommendations described here provide guidance for professionals involved in the care of patients with end-stage lung disease considered for transplantation.

OBJECTIVE/UNASSIGNED:Mid-to-distal tracheal surgery for cancer can be safely performed minimally invasively with a one-day length of stay, avoiding a guardian chin suture, and ensuring a R0 resection in select patients. METHODS/UNASSIGNED:This is a retrospective technical review of the largest series to date of patients with mid-to-distal tracheal cancers. All were offered a right robotic approach using veno-venous extracorporeal membrane oxygenation (VV ECMO) support via percutaneous right internal jugular vein and right common femoral vein access. RESULTS/UNASSIGNED:From May 2019 to April 2024, five consecutive patients (3 men, 2 women; aged 11, 29, 37, 40, and 74 years) presented with a mid-to-distal tracheal cancer. All underwent right robotic mid-distal tracheal resections on VV ECMO for primary tracheal cancers. All patients had an end-to-end tracheal anastomosis and R0 resection and all avoided: systemic heparinization, suprahyoid release maneuvers and a postoperative guardian chin stitch. Median operative time was 258 min (range 227-292). All patients tolerated the operations well and were discharged home on the morning of postoperative day 1. There was no minor or major morbidity, no 30 or 90-day mortality, and no re-admissions. Two patients complained of cough. All had R0 resections and to date none have evidence of recurrent disease or stricture. CONCLUSION/UNASSIGNED:Resection of mid-to-distal primary tracheal cancers can be performed safely and efficiently via a right robotic approach while on VV ECMO with little to no morbidity or mortality and require only an overnight hospital stay. The techniques used to perform the operation and achieve these results are described.

The benefits of bilateral lung transplantation (BLT) versus single lung transplantation (SLT) are still debated. One impediment to clinical recommendations is that BLT vs. SLT advantages may vary based on underlying disease. Since both options are clinically tenable in patients with emphysema, we conducted a comprehensive assessment of lung allograft survival in this population. Using U.S. registry data, we studied time to all-cause allograft failure in 8,092 patients 12 years or older transplanted from 2006 to 2022, adjusting for recipient, donor, and transplant factors by inverse propensity weighting. Median allograft survival was 6.6 years in BLT compared to 5.3 years in SLT, a 25% risk-adjusted survival advantage of _0.81.3_1.8 years. Risk-adjusted bilateral survival advantages varied between 0.9 and 2.4 years across eleven subgroups. Median allograft survival in BLT was 1.2 years greater than right SLT and 2.0 years greater than left SLT. During the 16-year study period, allograft survival steadily improved for BLT but not for SLT. Although the 25% BLT survival advantage pre-dated the pandemic, COVID-19 may have contributed to an apparent SLT survival decline. Recognizing the possible influence of residual confounding due to selection biases, these findings may aid offer decision-making when both donor lungs are available.

We describe the case of a 36-year-old woman who underwent redo lung transplantation AFTER a heart-lung transplant 3.5 years prior. The retransplantation was performed through sequential left posterolateral thoracotomy followed by right anterior thoracotomy, without sternal division and without the use of extracorporeal membrane oxygenation or cardiopulmonary bypass support. The patient was found to have undergone an extensive pericardiectomy at the time of the initial heart-lung transplant. The patient recovered uneventfully and complete healing of the airway anastomosis was demonstrated. This novel technique avoids some potential pitfalls of redo lung transplantation after heart-lung transplant.

Primary graft dysfunction (PGD) is a major source of morbidity and mortality following lung transplantation, presenting as acute lung injury within 72 hours post-transplantation. Despite advances in surgical techniques and perioperative care, the complex interplay of donor, recipient, and perioperative factors contributes to its development, underscoring the multifactorial nature of PGD. Clinical management of recipients with PGD relies on supportive care strategies, including lung-protective ventilation, inhaled nitric oxide, and extracorporeal membrane oxygenation (ECMO). Severe cases of PGD may result in significant short- and long-term adverse outcomes, including early mortality. Even for patients who recover from PGD, there is also an associated increased risk of chronic lung allograft dysfunction, further compounding its clinical impact. This review provides a brief review of current knowledge regarding PGD, detailing risk factors, diagnostic criteria, and management approaches while identifying critical gaps in understanding its pathophysiology. Ongoing research is essential to develop innovative therapeutic strategies and improve outcomes for lung transplant recipients.

RATIONALE/BACKGROUND:Lower airway enrichment with oral commensals has been previously associated with grade 3 severe primary graft dysfunction (PGD) after lung transplantation (LT). We aimed to determine whether this dysbiotic signature is present across all PGD severity grades, including milder forms, and whether it is associated with a distinct host inflammatory endotype. METHODS:Lower airway samples from 96 LT recipients with varying degrees of PGD were used to evaluate the lung allograft microbiota via 16S rRNA gene sequencing. Bronchoalveolar lavage (BAL) cytokine concentrations and cell differential percentages were compared across PGD grades. In a subset of samples, we evaluated the lower airway host transcriptome using RNA sequencing methods. RESULTS:Differential analyses demonstrated lower airway enrichment with supraglottic-predominant taxa (SPT) in both moderate and severe PGD. Dirichlet Multinomial Mixtures (DMM) modeling identified two distinct microbial clusters. A greater percentage of subjects with moderate-severe PGD were identified within the dysbiotic cluster (C-SPT) than within the no PGD group (48 and 29%, respectively) though this difference did not reach statistical significance (p=0.06). PGD severity associated with increased BAL neutrophil concentration (p=0.03) and correlated with BAL concentrations of MCP-1/CCL2, IP-10/CXCL10, IL-10, and TNF-α (p<0.05). Furthermore, microbial signatures of dysbiosis correlated with neutrophils, MCP-1/CCL-2, IL-10, and TNF-α (p<0.05). C-SPT exhibited differential expression of TNF, SERPINE1 (PAI-1), MPO, and MMP1 genes and upregulation of MAPK pathways, suggesting that dysbiosis regulates host signaling to promote neutrophilic inflammation. CONCLUSIONS:Lower airway dysbiosis within the lung allograft is associated with a neutrophilic inflammatory endotype, an immune profile commonly recognized as the hallmark for PGD pathogenesis. This data highlights a putative role for lower airway microbial dysbiosis in the pathogenesis of this syndrome.

OBJECTIVE/UNASSIGNED:Anticoagulation monitoring in patients supported on extracorporeal membrane oxygenation is challenging given the risks of both bleeding and thrombotic complications. Based on our early clinical experience, we revised our heparin protocol by reducing our target anti-factor Xa assay from 0.3 to 0.7 U/mL to 0.15 to 0.5 U/mL, while instituting a partial thromboplastin time cutoff of 70 seconds. We evaluated the impact of this change on bleeding/thrombotic complications. METHODS/UNASSIGNED:A single-center retrospective study of adult patients on extracorporeal membrane oxygenation support was conducted from January 2015 to August 2022. Patients were stratified into groups based on protocol revision: Pre-Revision (2015-2018) or Post-Revision (2019-2022). Our primary end point was the incidence of bleeding/thrombotic complications. Time in therapeutic range was calculated to determine protocol adherence. Poisson regression was performed to correlate time in therapeutic range with the likelihood of complication. RESULTS/UNASSIGNED:008). CONCLUSIONS/UNASSIGNED:A modified heparin monitoring protocol defined by a lower therapeutic anti-factor Xa assay target and a set partial thromboplastin time cutoff correlated with decreases in bleeding/thrombotic complications in patients on extracorporeal membrane oxygenation.