Hospital- and Ventilator-associated Pneumonia early after Lung Transplantation: a prospective Study on Incidence, Pathogen Origin and Outcome.

BACKGROUND: Hospital- (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors and outcomes are not well reported. METHODS: LT recipients transplanted at our institution (07/2019-01/2020 and 10/2021-11/2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. In addition, we evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field-gel-electrophoresis (PFGE). RESULTS: In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR 7-13). 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE.Diagnosed pulmonary hypertension (HR 4.42, 95% CI 1.62-12.08) and immunosuppression use (HR 2.87, 95% CI 1.30-6.56) were pre-transplant factors associated with pneumonia.Pneumonia occurrence was associated with longer hospital stay (HR 5.44, 95% CI 2.22-13.37) and VAP with longer ICU stay (HR 4.31, 95% CI: 1.73-10.75) within the first 30 days post-transplant; 30- and 90-day mortality were similar. CONCLUSIONS: Prospectively assessed early pneumonia incidence occurred in around 10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

Immediate Versus Deferred Systemic Therapy in Patients With Mesothelioma.

BACKGROUND: The 2018 ASCO pleural mesothelioma (PM) treatment guideline states that "a trial of expectant observation may be offered" in patients with asymptomatic inoperable epithelioid mesothelioma with low disease burden. The aim of our analysis was to evaluate clinical characteristics and outcomes in PM-patients managed with initial observation and deferred treatment initiation. METHODS: We retrospectively collected clinicodemograhic and outcome data of patients with inoperable PM. Patients were assigned to 2 treatment decision groups: decision to start immediate systemic treatment (Immediate Treatment Group) versus observation and deferring treatment (Deferred Treatment group). RESULTS: Of 222 patients with advanced PM, systemic treatment was started immediately in the majority of patients (189, 85%; immediate group); treatment was deferred in 33 (15%) patients (deferred group); systemic therapy was chemotherapy-based in 91% and 79% respectively. Patients in the deferred group were older (70 vs 67 years, p = .05), less likely to have stage IV disease (28% vs. 51%, p = .08) and more often had epithelioid histology (90% vs. 70%, p = .03). Nineteen patients (58%) in the deferred group eventually received treatment. With a median follow-up time of 10.9 months median overall survival (OS) in the entire cohort was 12.4 months and was significantly longer in the deferred group (20.6 months vs. 11.5 months, p = .02). No difference in median progression-free survival (PFS) in first-line treatment between groups was seen (5.4 and 5.3 months). CONCLUSION: This real-world analysis suggests that deferral of systemic therapy and close observation may not impact OS or physician-assessed PFS in selected PM-patients.

Extension of Cold Static Donor Lung Preservation at 10°C.

BACKGROUND: Lung transplantation is performed on a 24/7 schedule to minimize organ ischemic time. Recent preclinical studies demonstrated superior graft preservation at 10°C compared with storage in an ice cooler (gold standard). METHODS: In this prospective, multicenter, nonrandomized clinical trial, we studied transplants from donors with overnight cross-clamp times (6:00 p.m. to 4:00 a.m.) that had an earliest allowed starting time of 6:00 a.m. Lungs meeting criteria for transplantation were retrieved, transported, and immediately transferred to a 10°C temperature-controlled incubator until implantation; 70 patients and 140 matched controls were included in this study. RESULTS: Total preservation times for lungs in the study group were 12 hours, 28 minutes (interquartile range, 10 hours, 14 minutes to 14 hours, 12 minutes) and 14 hours, 9 minutes (interquartile range, 12 hours, 3 minutes to 15 hours, 45 minutes) for the first and second lung implanted, respectively. Primary graft dysfunction grade 3 at 72 hours (primary outcome) was 5.7% in the study group versus 9.3% in matched controls (difference, −3.6; 95% confidence interval [CI], −10.5 to 5.3). No meaningful differences were observed in the need for postoperative extracorporeal membrane oxygenation (5.7 vs. 9.3%), median intensive care unit stay (5 vs. 5 days), or median hospital stay (25 vs. 30 days) between the two groups. One-year Kaplan­Meier survival was similar between the two groups (94 vs. 87%; hazard ratio, 0.65; 95% CI, 0.26 to 1.6). CONCLUSIONS: Extension of cold static preservation times at 10°C appears to be safe and has the potential to improve transplantation logistics and performance. (Funded by the UHN Foundation; Clinicaltrials.gov number, NCT04616365).