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Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate in the coming decades. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry. This two-part review concentrates on CT-CCM as its own subspeciality of critical care and cardiothoracic surgery and provides aspirational goals for its practitioners and scientists. In part one, a list of guiding principles and a call-to-action agenda geared towards growth and promotion of CT-CCM are offered. In part two, an evaluation of selected scientific data is performed, identifying gaps in CT-CCM knowledge, and recommending direction to future scientific endeavors.

Increased senescence and expression of profibrotic genes in old lung fibroblasts contribute to disrepair responses. We reported that primary lung fibroblasts from old mice have lower expression and activity of the cystine transporter Slc7a11/xCT than cells from young mice, resulting in changes in both the intracellular and extracellular redox environments. This study examines the hypothesis that low Slc7a11 expression in old lung fibroblasts promotes senescence and profibrotic gene expression. The levels of mRNA and protein of Slc7a11, senescence markers, and profibrotic genes were measured in primary fibroblasts from the lungs of old (24 mo) and young (3 mo) mice. In addition, the effects of genetic and pharmacological manipulation of Slc7a11 were investigated. We found that decreased expression of Slc7a11 in old cells was associated with elevated markers of senescence (p21, p16, p53, and β-galactosidase) and increased expression of profibrotic genes (Tgfb1, Smad3, Acta2, Fn1, Col1a1, and Col5a1). Silencing of Slc7a11 in young cells replicated the aging phenotype, whereas overexpression of Slc7a11 in old cells decreased expression of senescence and profibrotic genes. Young cells were induced to express the senescence and profibrotic phenotype by sulfasalazine, a Slc7a11 inhibitor, whereas treatment of old cells with sulforaphane, a Slc7a11 inducer, decreased senescence without affecting profibrotic genes. Like aging cells, idiopathic pulmonary fibrosis fibroblasts show decreased Slc7a11 expression and increased profibrotic markers. In short, old lung fibroblasts manifest a profibrotic and senescence phenotype that is modulated by genetic or pharmacological manipulation of Slc7a11.

COVID-19, the clinical syndrome caused by the novel coronavirus, SARS-CoV-2, continues to rapidly spread, leading to significant stressors on global healthcare infrastructure. The manifestations of COVID-19 in solid organ transplant recipients are only beginning to be understood with cases reported to date in transplant recipients on chronic immunosuppression. Herein, we report the first case of COVID-19 in a lung transplant recipient in the immediate posttransplant period, and we describe the epidemiologic challenges in identifying the source of infection in this unique situation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Systemic arterial air embolism following a percutaneous transthoracic lung biopsy is a rare but known complication, with current literature reporting an incidence of 0.01-0.45%. A prompt diagnosis of arterial air embolism is important as complications resulting from migration of air to the systemic circulation with correspondent complications., Case Report: A 60-year-old female who presented for an elective percutaneous lung biopsy of an incidentally found pulmonary nodule. The procedure was performed, following the completion of the procedure the patient experiment syncopal symptoms and was diagnosed by CT scan with Left ventricular air embolism, subsequently transferred to Intensive care unit for medical attention, she was placed on right lateral decubitus Trendelenburg for 24 hours and administer 100% oxygen via a nonrebreather mask. Repeat chest CT the following day revealed complete resolution of her intracardiac free air., Conclusion: Although systemic arterial air embolism remains a rare complication of percutaneous lung biopsies, recognition prevents potential mortality which can develop due to neurological and cardiac complications. Close vigilance in the intensive care unit is recommended and hyperbaric chamber when appropriate.

Obliterative bronchiolitis (OB) and Bronchiolitis Obliterans Syndrome (BOS) are frequent complications in the lung transplant recipient, and are the leading cause of mortality after transplantation. The mechanisms responsible for OB remain elusive, but inflammatory and tissue remodeling responses are implicated. We hypothesized that alterations in markers of tissue remodeling in BALF of lung transplant recipients could predict development of OB. To test this, we identified 13 lung transplant recipients who developed both BOS and histologic OB (OB group) at median post-operative day (POD) 485 (range 73-2070). Bronchoalveolar lavage fluid (BALF) was obtained at median POD 387 (range 45-2205), which preceded the onset of OB and BOS by a median of 140 days (range 60-365). As a control, BALF was also obtained from a group of 21 stable recipients without OB (non-OB group) at median POD 335 (range 270-395). BALF was examined for gelatinolytic activity, fibronectin gene transcription, and transforming growth factor-beta1 (TGF-beta1) expression. Gelatin zymography of BALF from the OB group showed increased matrix metalloproteinase-9 (MMP-9) activity over that of the non-OB group (p < 0.005). Similarly, BALF from the OB group induced greater fibronectin expression in fibroblasts compared to the non-OB group (p < 0.03). The induction of fibronectin also correlated with the amount of TGF-beta1 protein in BALF (r = 0.71) from the OB group. We conclude that activation of tissue remodeling precedes the onset of OB, and analysis of gelatinolytic and/or fibronectin-inducing activity in BALF can serve as an early, pre-clinical marker for OB.

Neutrophils are sequestered in the newly transplanted lung after reperfusion or with infection, rejection, and chronic graft dysfunction. Because unopposed (free) neutrophil elastase (NE) released into bronchoalveolar secretions may injure the lung allograft and impair bacterial clearance, we assessed total neutrophil numbers, myeloperoxidase activity as an index of neutrophil influx and degranulation, alpha1-antiprotease (alpha1-AP) concentrations, and unopposed NE activity in bronchoalveolar secretions from lung transplant recipients. Unopposed NE activity was present in bronchoalveolar lavage fluid (BALF) from recipients transplanted for emphysema associated with alpha1-AP deficiency as well as recipients without such deficiency (171 of 2,137 BALF; 8%). Ten of 17 (59%) recipients with alpha1-AP deficiency who were followed for at least 1 yr after transplant with multiple surveillance and diagnostic bronchoscopies had at least one BALF containing unopposed NE, usually associated with the presence of > or = 10(5) colony forming units/ml BALF of aerobic bacteria. In contrast, 19 of 58 (33%) with emphysema not associated with alpha1-AP deficiency, 8 of 32 (25%) recipients with cystic fibrosis (CF), 6 of 16 (38%) with idiopathic pulmonary fibrosis (IPF), and 11 of 36 (31%) with other indications for transplant had unopposed NE in BALF. alpha1-AP levels were significantly elevated in the early posttransplant time period and could be augmented considerably in alpha1-AP-deficient recipients with episodes of infection or rejection. Our findings indicate that unopposed NE activity can be found in both alpha1-AP-deficient and alpha1-AP-sufficient recipients after transplantation, usually in association with endobronchial bacterial infection.

Background: A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation., Methods: Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease., Results: One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05)., Conclusions: This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.