The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation.

OBJECTIVE: The use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation. METHODS: The AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement. RESULTS: The expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively. CONCLUSIONS: Achieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.

Case Report: Recurrence of Acute Respiratory Distress Syndrome After Bilateral Lung Transplantation.

BACKGROUND: The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. RESULTS: After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. CONCLUSION: With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.

Extracorporeal life support as a bridge to lung transplantation: Where are we now?

The number of lung transplant procedures performed internationally is increasing but the donor organ pool is insufficient to meet demand and waiting list mortality is unacceptably high. As survival rates for patients with acute respiratory distress syndrome managed on extracorporeal life support (ECLS) have steadily improved, a potential role for ECLS to support critically ill patients awaiting a donor organ match has emerged. We explore the rapidly evolving landscape of ECLS as a bridge to lung transplantation with review of the patient selection criteria, predictors of survival, modes of pre and peri-transplant support, and the importance of a holistic multidisciplinary approach to care. Finally, we consider innovations that are envisaged to increase the accessibility, safety, and effectiveness of ECLS delivery for future lung transplant candidates.

COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report.

BACKGROUND: Autoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections. CASE PRESENTATION: A 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now). CONCLUSIONS: We report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Lung Transplantation for Acute Respiratory Distress Syndrome.

In this review, we discuss the outcomes of patients with severe acute respiratory distress syndrome (ARDS). We discuss evidence that suggests that a significant proportion of patients with ARDS develop end-stage lung disease and die of pulmonary complications. In carefully selected patients with permanent lung damage, lung transplant can be a life-saving treatment.

Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study.

BACKGROUND: Although the number of lung transplantations (LTx) performed worldwide for COVID-19 induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of most severly ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx to the pandemic are unknown. METHODS: A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-Cov-2) infection admitted between January 1, 2020 and May 30, 2021 in Austria. Patients referred to one of the two Austrian LTx centers were analyzed and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared to patients who underwent LTx for other indications. RESULTS: Between January 1, 2020 and May 30, 2021, 39.485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation, 183 received extra-corporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. With a median follow-up of 134 (47-450) days, 14/19 patients are alive. CONCLUSIONS: Early referral of ECMO patients to a LTx center is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.

[Recommendations for Extracorporeal Membrane Oxygenation (ECMO) in COVID-19 Patients]. / Empfehlungen für ECMO bei COVID-19-Patienten: Consensus Paper zur Extrakorporalen Membranoxygenierung der Medizinischen Universität Wien.

The pandemic from the SARS-CoV­2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.

BACKGROUND: Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications. METHODS: We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed. FINDINGS: Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19. INTERPRETATION: The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients. FUNDING: National Institutes of Health. VIDEO ABSTRACT.

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19.

Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called "cytokine storm", with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.

Recommendations for extracorporeal membrane oxygenation (ECMO) in COVID-19 patients : Consensus paper of the Medical University of Vienna.

The pandemic from the SARS-CoV­2 virus is currently challenging healthcare systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe working environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develop respiratory or circulatory failure that is refractory to conventional treatment, it is of utmost importance to clearly define criteria for the use of ECMO in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.