Faculty Bibliography

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.

BACKGROUND:Our objective is to assess the feasibility, safety, and outcomes for patients discharged home with a chest tube connected to a digital drainage system after robotic pulmonary resection. METHODS:A retrospective analysis of a prospectively collected database as a quality improvement initiative. All patients had planned discharge on postoperative day one (POD1) after robotic pulmonary resection. Those with an air leak were discharge home with a chest tube connected to a digital drainage system with daily communication with the surgeon. RESULTS:From January 2019 to February 2023 there were 580 consecutive robotic resections, of which 69 (12%) patients had an air leak on POD1; 38/276 (14%) after lobectomy, 24/226 (11%) after segmentectomy, and 7/78 (9%) after wedge resection. Of these 69 patients, 52 patients (75%) were discharged on POD1, 15 patients (22%) on POD2, and 2 patients (3%) on POD3. Chest tubes were removed a median outpatient chest tube duration was 4 days (IQR 3-5). Of the 69 patients sent home with a digital drainage system, there was one complication requiring readmission for increasing subcutaneous emphysema. Five patients (7%) had system malfunctions that required return to our clinic for problem solving. There were no 30 or 90-day mortalities. CONCLUSIONS:Patients who undergo robotic pulmonary resection and have an air leak can be safely and effectively discharged on the first post-operative day and managed as an outpatient by using daily texts and or videos with pulse oximetry data on a digital drainage system with limited morbidity.

BACKGROUND/UNASSIGNED:Electromagnetic navigation bronchoscopy (ENB) can help to accurately locate pulmonary nodules using a minimally invasive approach. This study sought to evaluate the clinical efficacy and safety of dye marking localization under the guidance of ENB followed by surgery. METHODS/UNASSIGNED:A retrospective analysis was performed of 61 patients who underwent ENB localization using methylene blue dye marking before surgery at Shanghai General Hospital from October 2021 to February 2022. The clinical efficacy and safety of ENB localization and the related factors affecting the navigation time of ENB location were analyzed. RESULTS/UNASSIGNED:ENB was performed on 170 pulmonary nodules in 61 patients with a median age of 60 [interquartile range (IQR), 18] years. The majority of patients (70.69%) had more than two pulmonary nodules. The median maximum nodule diameter was 10 (IQR, 8) mm, and 48.21% of the nodules were mixed ground-glass nodules. Median time for ENB navigation was 10.5 (IQR, 6) min. The navigation success rate was 92.96%, and the ENB location success rate was 95.89%. The rate of complications related to ENB localization was 1.64% (there was only one case of pulmonary hemorrhage). The multivariate analysis showed that the factors related to the navigation time included the node location (P=0.001) and location mode (P=0.04). CONCLUSIONS/UNASSIGNED:ENB-guided methylene blue injection is an effective and safe tool for localizing and marking pulmonary nodules, and can be used to assist the diagnosis and treatment of early lung cancer. The node location and location mode had significant effects on navigation time.

BACKGROUND/UNASSIGNED:Previously, stage-IIIB non-small cell lung cancer (NSCLC) has been considered inoperable. In recent years, neoadjuvant immunotherapy has shown encouraging efficacy in the treatment of advanced stage NSCLC in several trials. However, the effectiveness and safety of neoadjuvant immunotherapy in treating stage-IIIB NSCLC are still unknown. Therefore, we conducted this retrospective study to examine the outcomes of surgery after neoadjuvant immunotherapy combined with chemotherapy for stage-IIIB NSCLC. METHODS/UNASSIGNED:Thirty patients with stage-IIIB NSCLC who were treated at the Department of Thoracic Surgery of Renji Hospital from January 2019 to September 2021 were analyzed retrospectively. Neoadjuvant immunotherapy combined with chemotherapy was administered prior to surgery. The curative effect was evaluated by imaging and pathological examinations. RESULTS/UNASSIGNED:The objective response rate (ORR) and disease control rate (DCR) of the patients after neoadjuvant therapy evaluated by imaging studies were 70% and 86.7%, respectively. Of the 30 patients, 19 (63%) underwent surgical resection, in which all achieved a complete R0 resection. The median operative time was 168 minutes (range, 75-295 minutes), and the average intraoperative blood loss was 215.3±258.4 mL. The median postoperative hospital stay was 8 days (range, 4-59 days). The major pathological response (MPR) rate was 73.7% (14/19), and the pathological complete response rate was 47.4% (9/19); 2/30 patients (6.7%) had postoperative complications, including two who developed bronchopleural fistulas and one mortality, from a postoperative pulmonary infection. The treatment-related adverse reactions were mainly grades 1-2. Only two patients had grade 3 anemia, and no grade 4 adverse reactions were observed. CONCLUSIONS/UNASSIGNED:Neoadjuvant immunotherapy and chemotherapy combined with surgery in patients with stage-IIIB NSCLC is safe and feasible. The patient outcomes and optimal number of neoadjuvant treatment cycles need to be explored and studied further.