A Deep Learning Framework for Predicting Patient Decannulation on Extracorporeal Membrane Oxygenation Devices: Development and Model Analysis Study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapy for patients with refractory respiratory failure. The decision to decannulate someone from extracorporeal membrane oxygenation (ECMO) often involves weaning trials and clinical intuition. To date, there are limited prognostication metrics to guide clinical decision-making to determine which patients will be successfully weaned and decannulated. OBJECTIVE: This study aims to assist clinicians with the decision to decannulate a patient from ECMO, using Continuous Evaluation of VV-ECMO Outcomes (CEVVO), a deep learning-based model for predicting success of decannulation in patients supported on VV-ECMO. The running metric may be applied daily to categorize patients into high-risk and low-risk groups. Using these data, providers may consider initiating a weaning trial based on their expertise and CEVVO. METHODS: Data were collected from 118 patients supported with VV-ECMO at the Columbia University Irving Medical Center. Using a long short-term memory-based network, CEVVO is the first model capable of integrating discrete clinical information with continuous data collected from an ECMO device. A total of 12 sets of 5-fold cross validations were conducted to assess the performance, which was measured using the area under the receiver operating characteristic curve (AUROC) and average precision (AP). To translate the predicted values into a clinically useful metric, the model results were calibrated and stratified into risk groups, ranging from 0 (high risk) to 3 (low risk). To further investigate the performance edge of CEVVO, 2 synthetic data sets were generated using Gaussian process regression. The first data set preserved the long-term dependency of the patient data set, whereas the second did not. RESULTS: CEVVO demonstrated consistently superior classification performance compared with contemporary models (P<.001 and P=.04 compared with the next highest AUROC and AP). Although the model's patient-by-patient predictive power may be too low to be integrated into a clinical setting (AUROC 95% CI 0.6822-0.7055; AP 95% CI 0.8515-0.8682), the patient risk classification system displayed greater potential. When measured at 72 hours, the high-risk group had a successful decannulation rate of 58% (7/12), whereas the low-risk group had a successful decannulation rate of 92% (11/12; P=.04). When measured at 96 hours, the high- and low-risk groups had a successful decannulation rate of 54% (6/11) and 100% (9/9), respectively (P=.01). We hypothesized that the improved performance of CEVVO was owing to its ability to efficiently capture transient temporal patterns. Indeed, CEVVO exhibited improved performance on synthetic data with inherent temporal dependencies (P<.001) compared with logistic regression and a dense neural network. CONCLUSIONS: The ability to interpret and integrate large data sets is paramount for creating accurate models capable of assisting clinicians in risk stratifying patients supported on VV-ECMO. Our framework may guide future incorporation of CEVVO into more comprehensive intensive care monitoring systems.

Respiratory extracorporeal membrane oxygenation : From rescue therapy to standard tool for treatment of acute respiratory distress syndrome?

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS) has increased substantially. With modern trials supporting its efficacy, ECMO has become an important tool in the management of severe ARDS. OBJECTIVES: The objectives of this paper are to discuss ECMO physiology and configurations used for patients with ARDS, review evidence supporting the use of ECMO for ARDS, and discuss aspects of management during ECMO. CONCLUSION: Current evidence supports the use of ECMO, combined with an ultra-lung-protective approach to mechanical ventilation, in patients with ARDS who have refractory hypoxemia or hypercapnia with severe respiratory acidosis. Furthermore, data suggest that center volume and experience are important factors in the care of patients receiving ECMO. The use of extracorporeal technologies in expanded patient populations and the optimal management of patients during ECMO remain areas of investigation. This article is freely available.

How I manage differential gas exchange in peripheral venoarterial extracorporeal membrane oxygenation.

Dual circulation is a common but underrecognized physiological occurrence associated with peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Competitive flow will develop between blood ejected from the heart and blood travelling retrograde within the aorta from the ECMO reinfusion cannula. The intersection of these two competitive flows is referred to as the "mixing point". The location of this mixing point, which depends upon the relative strengths of the native and extracorporeal pumps, will determine which regions of the body are perfused with blood ejected from the left ventricle and which regions are perfused by reinfused blood from the ECMO circuit, effectively establishing dual circulations. Because gas exchange within these circulations is dictated by the native lungs and membrane lung, respectively, oxygenation and carbon dioxide removal may differ between regions-depending on how well gas exchange is preserved within each circulation-potentially leading to differential oxygenation or differential carbon dioxide, each of which may have important clinical implications. In this perspective, we address the identification and management of dual circulation and differential gas exchange through various clinical scenarios of venoarterial ECMO. Recognition of dual circulation, proper monitoring for differential gas exchange, and understanding the various strategies to resolve differential oxygenation and carbon dioxide may allow for more optimal patient management and improved clinical outcomes.

Ex vivo lung evaluation of single donor lungs when the contralateral lung is rejected increases safe use.

OBJECTIVE: The decision to perform a single-lung transplant (SLT) when the contralateral donor lung is rejected is a challenging scenario. The introduction of ex vivo lung perfusion (EVLP) has improved donor lung assessment, and we hypothesize that it has improved SLT outcomes in this setting. METHODS: A retrospective single-center review of all SLTs performed between 2000 and 2017 was performed in which the years 2000 to 2008 were considered the "pre-EVLP era" and 2009 to 2017 the "EVLP era." Recipients of SLT lungs when the contralateral lung was declined were classified into 3 groups: (1) Pre-EVLP era, (2a) EVLP era but EVLP not used, and (2b) EVLP era and EVLP used. The outcomes of interest were survival, time-to-extubation, and intensive care unit and hospital stay. RESULTS: Among 1692 transplants between 2000 and 2017, 244 (14%) were SLT. SLT rate was similar between eras (pre-EVLP 16% vs EVLP 15%), but more SLTs were performed where the contralateral lung was declined in the EVLP era (pre-EVLP 32% vs EVLP 45%, P = .04). Lungs evaluated on EVLP had lower procurement partial pressure of oxygen and were more often from donation after cardiac death donors. Recipients were generally also sicker, with a greater proportion of rapidly deteriorating recipients. Despite this, outcomes were similar between eras with a trend towards lower 30-day mortality in the EVLP era. CONCLUSIONS: The availability of EVLP allowed for better evaluation of marginal single lungs when the contralateral was declined. This has led to increased use rates with preserved outcomes despite use of more extended criteria organs.

Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity.

BACKGROUND: Blood group O candidates have lower lung transplantation rates despite having the most common blood group. We postulated that waitlist outcomes among these candidates and those with other blood types vary with disease severity and lung allocation score (LAS). METHODS: We performed a retrospective cohort study of 32,772 waitlist candidates using the United Network of Organ Sharing registry from May 2005 to 2020. After identifying an interaction between blood group and LAS, we evaluated the association between blood group and waitlist outcomes within LAS quartiles using unadjusted and adjusted competing risk models. RESULTS: In the lowest LAS quartile, blood group O had a 20% reduced transplantation rate (SHR: 0.80, 95%CI: 0.75-0.85) and higher waitlist death/removal (1.33, 95%CI: 1.15-1.55) compared with group A. Blood group AB had a 52% higher transplantation rate (SHR: 1.52, 95%CI: 1.34-1.73) in the lowest LAS quartile compared with group A. In the highest LAS quartile, there was no difference in transplantation rates between groups O and A. In contrast, group B had a 19% reduced transplantation rate (SHR, 0.81 95%CI: 0.73-0.89) and AB had a 28% reduced transplantation rate (SHR: 0.72, 95%CI: 0.61-0.86) in the highest LAS quartile. Additionally, groups B and AB had increased risk of waitlist death/removal in the highest LAS quartile compared with A (SHR: 1.27, 95%CI: 1.08-1.48; SHR: 1.31, 95%CI: 1.00-1.72). CONCLUSIONS: Waitlist outcomes among ABO blood groups vary depending on illness severity, which is represented by LAS. Blood group O has lower transplantation rates at low LAS while groups B and AB have lower transplantation rates at high LAS.

Extracorporeal Membrane Oxygenation Support in COVID-19 Patients: A Propensity Score Analysis.

Revised guidelines clarify indications for extracorporeal membrane oxygenation (ECMO) support in Coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS). Limited data exist to compare clinical outcomes of COVID-19 ARDS patients to non-COVID-19-related ARDS patients when supported with ECMO. An observational propensity-matched study was performed to compare clinical and ECMO-related complications between COVID-19-related ARDS patients (COVID) and non-COVID-19-related ARDS (Control). COVID- patients cannulated from March 1st, 2020, through June 1st, 2021, were included and matched to patients from the historical cohort at our center from 2012 to 2020 based on age, body mass index (BMI), acute physiology and chronic health evaluation (APACHE) II score, and duration ECMO run. The primary outcome was complications during ECMO therapy. A total of 56 patients were propensity matched 1:1 with a mean age of 40.9 years, BMI 32.1 kg/m2, APACHE II score of 26.6, and duration of ECMO support of 22.6 days. In total 18 COVID-19 patients were observed to have more major bleeding complications (18 vs. 9, p = 0.03). Although not statistically significant, they also had more strokes (6 vs. 3) and required more chest tubes (13 vs. 8). Inpatient mortality was not different. ECMO support in COVID-19 patients is associated with more major bleeding complications, strokes, and chest tube placements. The use of ECMO in patients with COVID-19-related ARDS appears to be associated with an increased risk of complications.

2021: Perioperative and critical care year in review for the cardiothoracic surgery team.

For yet another year, our lives have been dominated by a pandemic. This year in review, we feature an expert panel opinion regarding extracorporeal support in the context of COVID-19, challenging previously held standards. We also feature survey results assessing the impact of the pandemic on cardiac surgical volume. Furthermore, we focus on a single center experience that evaluated the use of pulmonary artery catheters and the comparison of transfusion strategies in the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction (REALITY) trial. Additionally, we address the impact of acute kidney injury on cardiac surgery and highlight the controversy regarding the choice of fluid resuscitation. We close with an evaluation of dysphagia in cardiac surgery and the impact of prehabilitation to optimize surgical outcomes.

One Year Into the Pandemic: Evolving COVID-19 Outcomes in Lung Transplant Recipients, a Single-center Experience.

In the early months of the coronavirus disease 2019 (COVID-19) pandemic, our center reported a mortality rate of 34% in a cohort of 32 lung transplant recipients with COVID-19 between March and May 2020. Since then, there has been evolving knowledge in prevention and treatments of COVID-19. To evaluate the impact of these changes, we describe the clinical presentation, management, and outcomes of a more recent cohort of lung transplant recipients during the second surge and provide a comparison with our first cohort. Methods: We conducted a retrospective cohort study that included all consecutive lung transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. We compared baseline demographics and major outcomes between the first- and second-surge cohorts. Results: We identified 47 lung transplant recipients (median age, 60; 51% female) who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. The current cohort had a higher proportion of patients with mild disease (34% versus 16%) and fewer patients with a history of obesity (4% versus 25%). Sixty-six percent (n = 31) required hospitalization and were treated with remdesivir (90%) and dexamethasone (84%). Among those hospitalized, 77% (n = 24) required supplemental oxygen, and 22% (n = 7) required invasive mechanical ventilation. The overall 90-d mortality decreased from 34% to 17% from the first cohort to the second (adjusted odds ratio, 0.26; 95% confidence interval, 0.08-0.85; P = 0.026). Conclusions: Although COVID-19-associated mortality rate in lung transplant recipients at our center has decreased over time, COVID-19 continues to be associated with significant morbidity and mortality.

Lung Transplantation for Pulmonary Fibrosis Associated With Hermansky-Pudlak Syndrome. A Single-center Experience.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage defect with resultant bleeding diathesis, and pulmonary fibrosis. The bleeding diathesis associated with HPS had long been considered a contraindication to lung transplantation; consequently, few reports of successful lung transplantation for HPS exist. Methods: In the largest case series on lung transplant for HPS, we describe the characteristics of 11 lung transplant candidates with HPS-related pulmonary fibrosis, and the management and outcomes of 7 patients who underwent lung transplantation. Results: Of the 7 patients transplanted, 30-d survival was 85.7% (6/7). Six patients had at least 2 y of follow-up available with a 1-y survival of 83.3% and a 2-y survival of 83.3% (5/6). The median age at referral was 48 y (range 29-62 y). Eight patients (72.7%) were of Puerto Rican ancestry with confirmed type 1 HPS mutation. Six out of 7 patients received prophylaxis for bleeding diathesis, with a majority receiving desmopressin; 1 patient was administered aminocaproic acid infusion, and another received 2 units of platelets before surgery. Estimated blood loss and the amount of intraoperative blood product administered was highly variable with or without prophylaxis. Median blood loss was 400 mL (range 125-750) and estimated blood products administered was 700 mL (range 490-4043). Conclusions: HPS should not be considered a contraindication for lung transplantation. Although patients with HPS seem to have an increased risk of massive hemorrhage, the risk is unpredictable. Transplant teams should prepare a preoperative plan in consultation with hematology and consider the use of prophylactic platelet transfusion and desmopressin.

The Safety and Efficacy of Tracheostomy in Patients Diagnosed With COVID-19: An Analysis of 143 Patients at a Major NYC Medical Center.

OBJECTIVE: To determine the optimal surgical strategy for performing tracheostomy in COVID-19 patients. BACKGROUND: Many ventilated COVID-19 patients require prolonged ventilation. We do not know if tracheostomy will improve their care. Given the paucity of data on this topic, the optimal surgical approach has yet to be elucidated. METHODS: This is a cohort study of 143 ventilator dependent COVID-19 patients undergoing tracheostomy at an academic medical center from April 15th to May 15th, 2020, with follow up until June 1, 2020. We included adult patients admitted to a NYC medical center with COVID-19 who required invasive mechanical ventilation for greater than 2 weeks who were unable to be extubated and determined to have reasonable chance of recovery and fit defined tracheostomy candidate criteria. Patients underwent either a percutaneous tracheostomy (PT) or open surgical tracheostomy (ST) performed by 1 of 3 surgical services. RESULTS: One hundred forty-three patients underwent tracheostomy, 58 (41%) via a ST, and 85 (59%) via a PT. There were no significant differences in patient characteristics between the 2 groups, except that more patients who had a history of extracorporeal membrane oxygenation underwent PT (11% vs 2%, P = 0.049). There were no statistical differences observed between the PT and ST groups with regard to bleeding complications (3.5%vs 10.3%, P = 0.099), tracheostomy related complications (5.9% vs 8.6%, P = 0.528), inpatient death (12% vs 5%, P = 0.178), discharge from hospital (39% vs 36%, P = 0.751) or surgeon illness (0% vs 0%, P = 1). CONCLUSION AND RELEVANCE: The rapid formation of a multi-disciplinary team allows for the efficient evaluation and performance of a large volume of tracheostomies in a resource-limited setting. Bedside tracheostomy in COVID-19 does not cause additional harm to patients if performed after 2 weeks from intubation. It also seems to be safe for proceduralists to perform in this timeframe. The manner of tracheostomy does not change outcomes significantly if it is performed safely and efficiently.

Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.

BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

The Evolution of the Use of Extracorporeal Membrane Oxygenation in Respiratory Failure.

Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency to support patients with acute respiratory failure, most commonly, and severe forms of acute respiratory distress syndrome (ARDS). The marked increase in the global use of ECMO followed the publication of a large randomized trial in 2009 and the experience garnered during the 2009 influenza A (H1N1) pandemic, and has been further supported by the release of a large, randomized clinical trial in 2018, confirming a benefit from using ECMO in patients with severe ARDS. Despite a rapid expansion of ECMO-related publications, optimal management of patients receiving ECMO, in terms of patient selection, ventilator management, anticoagulation, and transfusion strategies, is evolving. Most recently, ECMO is being utilized for an expanding variety of conditions, including for cases of severe pulmonary or cardiac failure from coronavirus disease 2019 (COVID-19). This review evaluates modern evidence for ECMO for respiratory failure and the current challenges in the field.

Technical Aspects of Lung Volume Reduction Surgery Including Anesthetic Management and Surgical Approaches.

As palliative treatment, lung volume reduction surgery can be offered to a selected subset of chronic obstructive pulmonary disease patients. Careful adherence to established inclusion and exclusion criteria is critical to achieve good outcomes. The evolution of surgical techniques toward minimally invasive approaches has improved outcomes. The fully extrathoracic access combining a subxiphoid incision with subcostal port placement allowed a further decrease in perioperative pain, which favors spontaneous respiratory drive and early postoperative mobilization. Less aggressive resections and better match for size of the hemithorax have contributed to a short-term reduction in morbidity and continued improvements in cardiopulmonary function.

Geographic Differences in Lung Transplant Volume and Donor Availability During the COVID-19 Pandemic.

BACKGROUND: Regional variation in lung transplantation practices due to local coronavirus disease 2019 (COVID-19) prevalence may cause geographic disparities in access to lung transplantation. METHODS: Using the United Network for Organ Sharing registry, we conducted a descriptive analysis of lung transplant volume, donor lung volume, new waitlist activations, and waiting list deaths at high-volume lung transplant centers during the first 3 months of the pandemic (March 1. 2020, to May 30, 2020) and we compared it to the same period in the preceding 5 years. RESULTS: Lung transplant volume decreased by 10% nationally and by a median of 50% in high COVID-19 prevalence centers (range -87% to 80%) compared with a median increase of 10% (range -87% to 80%) in low prevalence centers (P-for-trend 0.006). Donation services areas with high COVID-19 prevalence experienced a greater decrease in organ availability (-28% range, -72% to -11%) compared with low prevalence areas (+7%, range -20% to + 55%, P-for-trend 0.001). Waiting list activations decreased at 18 of 22 centers. Waiting list deaths were similar to the preceding 5 years and independent of local COVID-19 prevalence (P-for-trend 0.36). CONCLUSIONS: Regional variation in transplantation and donor availability in the early months of the pandemic varied by local COVID-19 activity.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Crisis Standards of Care.

The coronavirus disease 2019 (COVID-19) pandemic has placed extraordinary strain on global healthcare systems. Use of extracorporeal membrane oxygenation (ECMO) for patients with severe respiratory or cardiac failure attributed to COVID-19 has been debated due to uncertain survival benefit and the resources required to safely deliver ECMO support. We retrospectively investigated adult patients supported with ECMO for COVID-19 at our institution during the first 80 days following New York City's declaration of a state of emergency. The primary objective was to evaluate survival outcomes in patients supported with ECMO for COVID-19 and describe the programmatic adaptations made in response to pandemic-related crisis conditions. Twenty-two patients with COVID-19 were placed on ECMO during the study period. Median age was 52 years and 18 (81.8%) were male. Twenty-one patients (95.4%) had severe ARDS and seven (31.8%) had cardiac failure. Fifteen patients (68.1%) were managed with venovenous ECMO while 7 (31.8%) required arterial support. Twelve patients (54.5%) were transported on ECMO from external institutions. Twelve patients were discharged alive from the hospital (54.5%). Extracorporeal membrane oxygenation was used successfully in patients with respiratory and cardiac failure due to COVID-19. The continued use of ECMO, including ECMO transport, during crisis conditions was possible even at the height of the COVID-19 pandemic.

Deceased-donor lobar lung transplant: A successful strategy for small-sized recipients.

OBJECTIVES: Lobar lung transplantation (LLTx) from deceased donors is a potential solution for donor-recipient size mismatch for small sized recipients. We reviewed our institutional experience to compare outcomes after LLTx to standard lung transplantation (LTx). METHODS: We retrospectively reviewed transplants in our institution from January 2000 to December 2017. LLTx early- and long-term outcomes were compared with LTx. Additional analysis of outcomes was performed after dividing the cohort into 2 eras (era 1, 2000-2012; era 2, 2013-2017). RESULTS: Among the entire cohort (1665), 75 were LLTx (4.5%). Compared with LTx, LLTx were more frequently bridged to transplant with extracorporeal life support or mechanical ventilation and were transplanted in a rapidly deteriorating status (respectively, 20% vs 4.4%, P = .001; 22.7% vs 7.9, P < .001; and 41.3% vs 26.5%, P = .013). LLTx had longer intensive care unit and hospital lengths of stay (respectively, median 17 vs 4 days, and 45 vs 23, both P < .001), and greater 30-day mortality (13.3% vs 4.3%, P = .001) and 90-day mortality (17.3% vs 7.2%, P = .003). In era 2, despite a significantly greater 30-day mortality (10.8% vs 2.8%, P = .026), there was no significant difference in 90-day mortality between LLTx and LTx (13.5% vs 5.1%, P = .070). Overall survival at 1, 3, and 5 years was not significantly different between LLTx and LTx (73.2% vs 84.4%, 56.9% vs 68.4% and 50.4% vs 55.8, P = .088). CONCLUSIONS: Although LLTx is a high-risk procedure, both mid- and long-term survival are comparable with LTx in all cohorts in the modern era. LLTx therefore represents a valuable surgical option for small-sized recipients.

The mononuclear phagocyte system contributes to fibrosis in post-transplant obliterans bronchiolitis.

Bronchiolitis obliterans syndrome (BOS) is a fibrotic disease that is heavily responsible for the high mortality rates after lung transplantation. Myofibroblasts are primary effectors of this fibrotic process, but their origin is still debated. The purpose of this work was to identify the precursors of mesenchymal cells responsible for post-transplant airway fibro-obliteration.Lineage-tracing tools were used to track or deplete potential sources of myofibroblasts in the heterotopic tracheal transplantation model. Allografts were analysed by histology, confocal microscopy, flow cytometry or single-cell transcriptomic analysis. BOS explants were evaluated by histology and confocal microscopy.Myofibroblasts in the allografts were recipient-derived. When recipient mice were treated with tacrolimus, we observed rare epithelial-to-mesenchymal transition phenomena and an overall increase in donor-derived myofibroblasts (p=0.0467), but the proportion of these cells remained low (7%). Haematopoietic cells, and specifically the mononuclear phagocyte system, gave rise to the majority of myofibroblasts found in occluded airways. Ablation of Cx3cR1+ cells decreased fibro-obliteration (p=0.0151) and myofibroblast accumulation (p=0.0020). Single-cell RNA sequencing revealed similarities between myeloid-derived cells from allografts and both murine and human samples of lung fibrosis. Finally, myofibroblasts expressing the macrophage marker CD68 were increased in BOS explants when compared to controls (14.4% versus 8.5%, p=0.0249).Recipient-derived myeloid progenitors represent a clinically relevant source of mesenchymal cells infiltrating the airways after allogeneic transplantation. Therapies targeting the mononuclear phagocyte system could improve long-term outcomes after lung transplantation.

COVID-19 in lung transplant recipients: A single center case series from New York City.

There are limited data describing COVID-19 in lung transplant recipients. We performed a single center, retrospective case series study of lung transplant patients followed by the Columbia Lung Transplant program who tested positive for SARS-CoV-2 between March 19 and May 19, 2020. Thirty-two lung transplant patients developed mild (16%), moderate (44%), or severe (41%) COVID-19. The median age of patients was 65 years, and the median time from lung transplant was 5.6 years. Symptoms included cough (66%), dyspnea (50%), fever (47%), and gastrointestinal upset (44%). Patients received hydroxychloroquine (84%), azithromycin (75%), augmented steroids (44%), tocilizumab (19%), and remdesivir (9%). Eleven patients (34%) died at a median time of 14 days from admission. Complications during admission included: acute kidney injury (63%), transaminitis (31%), shock (31%), acute respiratory distress syndrome (25%), neurological events (25%), arrhythmias (22%), and venous thromboembolism (9%). Compared to patients with moderate COVID-19, patients with severe COVID-19 had higher peak white blood cell counts (15.8 vs 7 × 103 /uL, P = .019), C-reactive protein (198 vs. 107 mg/L, P = .010) and D-dimer (8.6 vs. 2.1 ug/mL, P = .004) levels, and lower nadir lymphocyte counts (0.09 vs. 0.4 × 103 /uL, P = .006). COVID-19 is associated with severe illness and a high mortality rate in lung transplant recipients.