Publications by authors named "Adwaiy Manerikar"

9 Publications

  • Page 1 of 1

Lung donation following SARS-CoV-2 infection.

Am J Transplant 2021 Jul 31. Epub 2021 Jul 31.

Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and "efficacy" of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.
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http://dx.doi.org/10.1111/ajt.16777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441925PMC
July 2021

Modern ECMO circuitry may obviate the need for continuous systemic anticoagulation.

Ann Thorac Surg 2021 May 8. Epub 2021 May 8.

Northwestern University Feinberg School of Medicine, 676 N. St Clair St, Suite 650, Chicago, IL 60611. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2021.04.073DOI Listing
May 2021

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

Lancet Respir Med 2021 05 31;9(5):487-497. Epub 2021 Mar 31.

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1016/S2213-2600(21)00077-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012035PMC
May 2021

Prophylactic Ureaplasma-directed Antimicrobials in Lung Donors Can Prevent Fatal Hyperammonemia.

Transplantation 2021 03;105(3):e35-e36

Division of Thoracic Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.

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http://dx.doi.org/10.1097/TP.0000000000003540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905692PMC
March 2021

MELD Score Predicts Outcomes in Patients Undergoing Venovenous Extracorporeal Membrane Oxygenation.

ASAIO J 2021 08;67(8):871-877

From the Department of Medicine.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is increasingly being used in the management of severe acute respiratory distress syndrome (ARDS). The Respiratory ECMO Survival Prediction (RESP) score is most commonly used to predict survival of patients undergoing ECMO. However, the RESP score does not incorporate renal and hepatic dysfunction which are frequently a part of the constellation of multiorgan dysfunction associated with ARDS. The Model for End-Stage Liver Disease (MELD) incorporates both liver and kidney dysfunction and is used in the risk stratification of liver transplant recipients as well as those undergoing cardiac surgery. The aim of this study was to assess the prognostic value of the MELD score in patients undergoing VV ECMO. Patients undergoing VV ECMO from 2016 to 2019 were extracted from our prospectively maintained institutional ECMO database and stratified based on MELD score. Baseline clinical, laboratory, and follow-up data, as well as post-ECMO outcomes, were compared. Of 71 patients, 50 patients (70.4%) had a MELD score <12 and 21 (29.6%) had a MELD score ≥12. The higher MELD score was associated with increased post-ECMO mortality but reduced risk of dialysis and tracheostomy. In multivariate analysis, higher MELD score (HR 1.35, 95% CI = 1.07-2.75), lower body surface area (HR 0.16, 0.04-0.65), RESP score (HR 0.75, 95% CI = 0.64-0.87), and platelet count (HR 0.99, 95% CI = 0.98-0.99), were significant predictors of postoperative mortality. We conclude that MELD score can be used complementarily to the RESP score to predict outcomes in patients with ARDS undergoing VV ECMO.
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http://dx.doi.org/10.1097/MAT.0000000000001321DOI Listing
August 2021

Comparative Effectiveness of Surgical Approaches for Lung Cancer.

J Surg Res 2021 07 9;263:274-284. Epub 2020 Dec 9.

Division of Thoracic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Background: The magnitude of association and quality of evidence comparing surgical approaches for lung cancer resection has not been analyzed. This has resulted in conflicting information regarding the relative superiority of the different approaches and disparate opinions on the optimal surgical treatment. We reviewed and systematically analyzed all published data comparing near- (30-d) and long-term mortality for minimally invasive to open surgical approaches for lung cancer.

Methods: Comprehensive search of EMBASE, MEDLINE, and the Cochrane Library, from January 2009 to August 2019, was performed to identify the studies and those that passed bias assessment were included in the analysis utilizing propensity score matching techniques. Meta-analysis was performed using random-effects and fixed-effects models. Risk of bias was assessed via the Newcastle-Ottawa Scale and the ROBINS-I tool. The study was registered in PROSPERO (CRD42020150923) prior to analysis.

Results: Overall, 1382 publications were identified but 19 studies were included encompassing 47,054 patients after matching. Minimally invasive techniques were found to be superior with respect to near-term mortality in early and advanced-stage lung cancer (risk ratio 0.45, 95% confidence interval [CI] 0.21-0.95, I = 0%) as well as for elderly patients (odds ratio 0.45, 95% CI 0.31-0.65, I = 30%), but did not demonstrate benefit for high-risk patients (odds ratio 0.74, 95% CI 0.06-8.73, I = 78%). However, no difference was found in long-term survival.

Conclusions: We performed the first systematic review and meta-analysis to compare surgical approaches for lung cancer which indicated that minimally invasive techniques may be superior to thoracotomy in near-term mortality, but there is no difference in long-term outcomes.
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http://dx.doi.org/10.1016/j.jss.2020.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169528PMC
July 2021

Lung transplantation for patients with severe COVID-19.

Sci Transl Med 2020 12 30;12(574). Epub 2020 Nov 30.

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19-associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonresolving COVID-19-associated respiratory failure. We performed single-molecule fluorescence in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single-cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm postmortem lung biopsies from two patients who had died from COVID-19-associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single-cell RNA sequencing data from the lungs of patients with late-stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.
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http://dx.doi.org/10.1126/scitranslmed.abe4282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050952PMC
December 2020

Lung transplantation for pulmonary fibrosis secondary to severe COVID-19.

medRxiv 2020 Oct 27. Epub 2020 Oct 27.

Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 acute respiratory distress syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-induced pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report the results of the first two successful lung transplantation procedures in patients with non-resolving COVID-19 associated acute respiratory distress syndrome in the United States. We performed smFISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. Single cell RNA-Seq of the explanted native lungs from transplant and paired warm post-mortem autopsies showed similarities between late SARS-CoV-2 acute respiratory distress syndrome and irreversible end-stage pulmonary fibrosis requiring lung transplantation. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation in either patient. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.

Single Sentence Summary: Some patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.
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http://dx.doi.org/10.1101/2020.10.26.20218636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605582PMC
October 2020

Comparative effectiveness and cost-efficiency of surgical approaches for thymectomy.

Surgery 2020 10 5;168(4):737-742. Epub 2020 Jul 5.

Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address:

Background: We compared the clinical outcomes and cost-efficiency of surgical approaches (sternotomy-open, video assisted thoracoscopic surgery, and robotic assisted thoracic surgery) for thymectomy.

Methods: This is a retrospective review of 220 consecutive patients who underwent thymectomy between January 1, 2007, and January 31, 2017. Surgical approach was determined by the surgeon, but we only included cases that could be resected using any of the 3 approaches.

Results: Open approach was used in 69 patients, whereas minimally invasive technique was used in 151 (97, video assisted thoracoscopic surgery; 54, robotic assisted thoracic surgery). Open surgery was associated with greater total hospital cost ($22,847 ± $20,061 vs $14,504 ± $10,845, P < .001). Open group also revealed longer duration of intensive care unit (1.2 ± 2.8 vs 0.2 ± 1.3 days, P < .001) and hospital stay (4.3 ± 4.0 vs 2.0 ± 2.6 days, P < .001). There were no differences in major adverse clinical outcomes. Long-term recurrence-free survival after resection of thymoma was similar between the groups.

Conclusion: Minimally invasive techniques were equally efficacious compared with the open approach in the resection of the thymus. Additionally, their use was associated with decreased hospital duration of stay and reduced cost. Hence the use of minimally invasive approaches should be encouraged in the resection of thymus.
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http://dx.doi.org/10.1016/j.surg.2020.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816338PMC
October 2020
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