Extended perioperative use of the ProtekDuo cannula for drainage in central venopulmonary-aortic ECMO for bilateral orthotopic lung transplantation.

We present the case of a 24-year-old female who was supported with ProtekDuo cannula with variations of venopulmonary (VP) extracorporeal membrane oxygenation. The patient was cannulated for acute respiratory distress syndrome and she underwent bilateral orthotopic lung transplantation. This is the first report of the ProtekDuo cannula as a drainage cannula in central (dl)VP-/AO ECMO for 5 days.

Concurrent veno-pulmonary extracorporeal membrane oxygenation cannulation with ProtekDuo parallel to an in situ veno-pulmonary single-lumen cannula.

This technical report describes the successful transition from dual lumen, single site veno-venous extracorporeal membrane oxygenation ((dl)V-V ECMO) to single lumen, dual site veno-pulmonary (V-P) ECMO, and subsequently to dual lumen, single site (dl)V-P ECMO involving temporary placement of two cannulas in the main pulmonary artery. No complications were observed during these transitions. This technique could address concerns related to cannula exchanges in VP ECMO. However, caution is warranted and constant monitoring of cannula position using real-time imaging is required when using this technique due to the risk profile.

Veno-arterial extracorporeal membrane oxygenation as bridge for fluid resuscitation in a patient with acute respiratory failure and circulatory shock two years post lung transplantation.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) continues to evolve and is recognized as an important adjunct as a bridge to recovery or a bridge to transplant. We wanted to share our experience of using veno-arterial (VA) ECMO as an adjunct to lung recovery and an aide for fluid resuscitation. CASE DESCRIPTION: We present the case of a 77-year-old man with a history of previous single lung transplant who had acute respiratory decompensation and cardiovascular collapse secondary to CMV pneumonia and septic shock. He was cannulated for VA ECMO, treated for CMV pneumonia and resuscitated with 5 L of albumin 5% and antibiotics, within 12 hours of cannulation. He required two days of VA ECMO and was ultimately decannulated and discharged to a rehabilitation facility on hospital day 73. CONCLUSION: This case emphasizes the challenging clinical scenario of fluid resuscitation in a lung transplant patient. With adequate patient selection, a multidisciplinary team and the use of VA ECMO, success can be achieved.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Exogenous connexin43-expressing autologous skeletal myoblasts ameliorate mechanical function and electrical activity of the rabbit heart after experimental infarction.

Acute myocardial infarction is one of the major causes of mortality worldwide. For regeneration of the rabbit heart after experimentally induced infarction we used autologous skeletal myoblasts (SMs) due to their high proliferative potential, resistance to ischaemia and absence of immunological and ethical concerns. The cells were characterized with muscle-specific and myogenic markers. Cell transplantation was performed by injection of cell suspension (0.5 ml) containing approximately 6 million myoblasts into the infarction zone. The animals were divided into four groups: (i) no injection; (ii) sham injected; (iii) injected with wild-type SMs; and (iv) injected with SMs expressing connexin43 fused with green fluorescent protein (Cx43EGFP). Left ventricular ejection fraction (LVEF) was evaluated by 2D echocardiography in vivo before infarction, when myocardium has stabilized after infarction, and 3 months after infarction. Electrical activity in the healthy and infarction zones of the heart was examined ex vivo in Langendorff-perfused hearts by optical mapping using di-4-ANEPPS, a potential sensitive fluorescent dye. We demonstrate that SMs in the coculture can couple electrically not only to abutted but also to remote acutely isolated allogenic cardiac myocytes through membranous tunnelling tubes. The beneficial effect of cellular therapy on LVEF and electrical activity was observed in the group of animals injected with Cx43EGFP-expressing SMs. L-type Ca(2+) current amplitude was approximately fivefold smaller in the isolated SMs compared to healthy myocytes suggesting that limited recovery of LVEF may be related to inadequate expression or function of L-type Ca(2+) channels in transplanted differentiating SMs.

Surgical treatment of non-malignant laryngotracheal stenosis.

The objectives of this study were the following: (1) to analyze the results of surgical treatment of non-malignant subglottic laryngeal and tracheal stenosis, (2) to evaluate the feasibility and technical aspects of the video mediastinoscopy for the mobilization of the mediastinal trachea, (3) to evaluate the influence of the early internal condition of the anastomosis on the development of restenosis. From 1996 up to 2013, 75 patients aged 11-78 years underwent surgery for post-intubation/tracheostomy (71 patients), post-traumatic (3 patients), and idiopathic (1 patient) subglottic laryngeal and tracheal stenosis. Twenty-three (30.7 %) patients with subglottic laryngeal and upper tracheal stenosis underwent cricotracheal resection and thyrotracheal anastomosis (group A), while 52 (69.3 %) patients with tracheal stenosis underwent tracheal resection and cricotracheal or tracheotracheal anastomosis (group B). The length of the resected segment in patients of groups A and B was 28-55 (42 ± 11) mm and 18-65 (36 ± 14) mm, respectively, (p = 0.22). Perioperative complications within 30 days occurred in eight (34.8 %) patients of group A, and in six (11.5 %) patients of group B (p = 0.04). There was one intraoperative and one postoperative death on the third day due to heart failure. The excellent results were achieved in 63 (86.3 %), satisfactory in 8 (11.0 %), and unsatisfactory in 2 (2.7 %) patients. The incidence rate of perioperative complications is related to the location of the stenosis and the type of the resection and anastomosis. Video mediastinoscopy simplifies the mobilization of the mediastinal trachea, which allows for carrying out the anastomosis with minimal tension. Early internal abnormalities of the anastomosis predict its restenosis.

Double lung en bloc procurement and back table separation of lungs.

Donor organ recovery techniques have improved with novel preservation solutions, implementation of advanced preservation systems and machine perfusion. However, surgical techniques for organ procurement have not changed. In this video tutorial, we have outlined key steps in double lung en bloc organ recovery, including introduction of pulmonoplegia, pulmonectomy en bloc and separation of the two single-lung blocks.

Bilateral orthotopic lung transplant via a clamshell thoracosternotomy from a donor with extended cold static lung preservation.

In this video tutorial, we present a comprehensive step-by-step operative technique for a bilateral orthotopic lung transplant using a bilateral transverse thoracosternotomy in a patient with idiopathic pulmonary fibrosis lung disease. The donor lungs were exposed to extended cold static ischaemic storage at 10° C for the semi-elective operation.

Conversion technique from venovenous to venopulmonary ECMO support.

We present the cannulation technique for venopulmonary extracorporeal membrane oxygenation using the ProtekDuo dual-lumen cannula in a patient who, after a bilateral orthotopic lung transplant and coronavirus disease 2019 infection, was converted from a multisite venovenous extracorporeal membrane oxygenation configuration, using the same vessel.

Dual lumen venopulmonary extracorporeal membrane oxygenation cannulation technique using the ProtekDuo.

In this video tutorial, we present the cannulation technique for venopulmonary extracorporeal membrane oxygenation using the ProtekDuo dual-lumen cannula in a patient with acute respiratory distress syndrome.

Novel Use of Ivabradine for Persistent Sinus Tachycardia in a Patient on Extracorporeal Life Support With Right Ventricular Dysfunction.

Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired. A 17-year-old male with a history of vaping developed acute respiratory distress syndrome (ARDS) and RV dysfunction, requiring extra corporal life support (ECLS). He suffered from pST. Given his RV dysfunction, a beta-blocker was avoided, and ivabradine was used safely with improvement of his pST. This case demonstrates the efficacy of ivabradine to reduce heart rate and avoid the use of beta-blockers for patients with RV dysfunction, which could be detrimental. Ivabradine was shown to lower the heart rate without altering hemodynamic parameters.

Paediatric donor lung preservation using Paragonix BAROguard.

Paediatric lung transplantation is a lifesaving option in selected patients with end-stage lung disease. Favourable long-term outcomes are limited by impaired mucus clearance, increased risk of infection resulting from immunosuppression, and chronic lung allograft dysfunction. Organ preservation techniques play an important role in the quality of donated organs. Barotrauma to donated lungs may arise from a combination of excessive recruitment manoeuvres and altitude change during air transportation. The Paragonix BAROguard Donor Lung Preservation System is an FDA-approved advanced organ recovery system that maintains continuous airway pressure of 15 cm of water during transportation of the donated lung(s) to the recipient. The Paragonix LUNGguard monitors temperature during transportation of donor lung(s), while the new BAROguard monitors both temperature and pressure during transportation of donor lung(s). In this publication, we present technical aspects of advanced preservation of paediatric donor lungs using the Paragonix BAROguard Donor Lung Preservation System.

ProtekDuo Cannula for Pre-, Intra-, and Postoperative Lung Transplantation Management.

ABSTRACT: We present a 61-year-old patient with pulmonary hypertension, acute respiratory failure, and acute severe right ventricular (RV) dysfunction. Preoperatively, a ProtekDuo® was inserted for extracorporeal membrane oxygenation (ECMO) and RV protection with venopulmonary (VP) ECMO in (dl) V-P ECMO configuration. Intraoperatively, it provided venous drainage for venoarterial (VA) ECMO in (dl) VP-/AO configuration for bilateral orthotopic lung transplantation (BOLT). Postoperatively, the patient remained on (dl) V-P ECMO for RV support and was decannulated with mild RV dysfunction after 5 days. This is the first description of the ProtekDuo® used in (dl) V-P to (dl) VP-/AO to (dl) V-P configuration for the entire perioperative period of BOLT.

Predicting Primary Graft Dysfunction in Lung Transplantation: Machine Learning-Guided Biomarker Discovery.

BACKGROUND: There is an urgent need to better understand the pathophysiology of primary graft dysfunction (PGD) so that point-of-care methods can be developed to predict those at risk. Here we utilize a multiplex multivariable approach to define cytokine, chemokines, and growth factors in patient-matched biospecimens from multiple biological sites to identify factors predictive of PGD. METHODS: Biospecimens were collected from patients undergoing bilateral LTx from three distinct sites: donor lung perfusate, post-transplant bronchoalveolar lavage (BAL) fluid (2h), and plasma (2h and 24h). A 71-multiplex panel was performed on each biospecimen. Cross-validated logistic regression (LR) and random forest (RF) machine learning models were used to determine whether analytes in each site or from combination of sites, with or without clinical data, could discriminate between PGD grade 0 ( n = 9) and 3 ( n = 8). RESULTS: Using optimal AUROC, BAL fluid at 2h was the most predictive of PGD (LR, 0.825; RF, 0.919), followed by multi-timepoint plasma (LR, 0.841; RF, 0.653), then perfusate (LR, 0.565; RF, 0.448). Combined clinical, BAL, and plasma data yielded strongest performance (LR, 1.000; RF, 1.000). Using a LASSO of the predictors obtained using LR, we selected IL-1RA, BCA-1, and Fractalkine, as most predictive of severe PGD. CONCLUSIONS: BAL samples collected 2h post-transplant were the strongest predictors of severe PGD. Our machine learning approach not only identified novel cytokines not previously associated with PGD, but identified analytes that could be used as a point-of-care cytokine panel aimed at identifying those at risk for developing severe PGD.

Outcome of Veno-Pulmonary Extracorporeal Life Support in Lung Transplantation Using ProtekDuo Cannula: A Systematic Review and Description of Configurations.

Background: Refractory end-stage pulmonary failure may benefit from extracorporeal life support (ECLS) as a bridge to lung transplantation. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) has been recommended for patients who have failed conventional medical therapy and mechanical ventilation. Veno-arterial (VA) ECMO may be used in patients with acute right ventricular (RV) failure, haemodynamic instability, or refractory respiratory failure. Peripheral percutaneous approaches, either dual-site single-lumen cannulation for veno-pulmonary (VP) ECMO or single-site dual-lumen (dl)VP ECMO, using the ProtekDuo right ventricular assist device (RVAD) cannula, has made this configuration a desirable option as a bridge to transplantation. These configurations support the right ventricle, prevent recirculation by placing the tricuspid and pulmonary valve between the drainage and return cannulas, provide the direct introduction of oxygenated blood into the pulmonary artery, and have been shown to decrease the incidence of acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT) in certain disease states. This promotes haemodynamic stability, potential sedation-weaning trials, extubation, mobilisation, and pre-transplant rehabilitation. Methods: A web-based literature search in PubMed and EMBASE was undertaken based on a combination of keywords. The PICOS and PRISMA approaches were used. Results: Four case series were identified out of 323 articles, with a total of 34 patients placed on VP ECMO as a bridge to lung transplantation. All relevant data are reviewed and integrated into the Discussion. Conclusions: Despite the limited available evidence, the use of ProtekDuo has become very promising for the management of end-stage lung disease as a bridge to lung transplantation.

Venovenous ECMO for Acute Chronic Heart Failure after Bilateral Lung Transplantation.

ABSTRACT: Venovenous (VV) ECMO is rarely used during decompensated circulatory states. Although VA ECMO is the routine option, VV ECMO may be an option in selected patients. We present a case of pulmonary edema due to acute heart failure in a patient 4- and 12-year post-lung transplantation who received VV ECMO. Using a thoughtful cannulation strategy, VV ECMO, and aggressive ultrafiltration, the patient was successfully decannulated, extubated, and discharged from the hospital. In cardiogenic pulmonary edema, VV ECMO represents an additional, and likely under-utilized tool, especially in patients who are at high risk for ventilator-associated lung injury. Cannula location and size should be given additional consideration to potentially transition to V-AV ECMO configuration if necessary.

MerTK-dependent efferocytosis by monocytic-MDSCs mediates resolution of ischemia/reperfusion injury after lung transplant.

Lung transplantation (LTx) outcomes are impeded by ischemia/reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of receptor Mer tyrosine kinase (MerTK) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from patients after LTx were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with BALB/c (WT), Cebpb-/- (MDSC-deficient), Mertk-/-, or MerTK-cleavage-resistant mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of patients with CLAD was observed compared with healthy individuals. In the murine IRI model, a significant increase in M-MDSCs, MerTK expression, and efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb-/- and Mertk-/- mice. Adoptive transfer of M-MDSCs in Cebpb-/- mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

MerTK-dependent efferocytosis by monocytic-MDSCs mediates resolution of post-lung transplant injury.

Rationale: Patients with end stage lung diseases require lung transplantation (LTx) that can be impeded by ischemia-reperfusion injury (IRI) leading to subsequent chronic lung allograft dysfunction (CLAD) and inadequate outcomes. Objectives: We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis (phagocytosis of apoptotic cells) to facilitate resolution of lung IRI. Methods: Single-cell RNA sequencing of lung tissue and BAL from post-LTx patients was analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), cebpb -/- (MDSC-deficient), Mertk -/- or MerTK-CR (cleavage resistant) mice. Lung function, IRI (inflammatory cytokine and myeloperoxidase expression, immunohistology for neutrophil infiltration), and flow cytometry of lung tissue for efferocytosis of apoptotic neutrophils were assessed in mice. Measurements and Main Results: A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients compared to healthy subjects was observed. In the murine IRI model, significant increase in M-MDSCs, MerTK expression and efferocytosis was observed in WT mice during resolution phase that was absent in cebpb -/- Land Mertk -/- mice. Adoptive transfer of M-MDSCs in cebpb -/- mice significantly attenuated lung dysfunction, and inflammation leading to resolution of IRI. Additionally, in a preclinical murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Conclusions: Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can significantly contribute to the resolution of post-LTx IRI.

Thoracoliths in Pleural Space Mimicking Lung Cancer: A Case Report.

Pulmonary nodules often present a diagnostic challenge due to their diverse etiology, ranging from benign to malignant conditions. We discuss the diagnostic journey of a 71-year-old female patient with a history of kidney stones, who was incidentally found to have a pleural-based pulmonary nodule during a CT urogram. Subsequent imaging showed nodule growth, prompting further investigations, including a PET/CT scan and CT-guided biopsy, which yielded inconclusive results. A multidisciplinary approach recommended surgical resection, revealing three mobile calcified-like nodules within the pleural space, later identified as hyalinized nodules. The absence of malignancy was reassuring. These benign, mobile pleural bodies, known as thoracoliths, are challenging to differentiate from pulmonary nodules. This case underscores the importance of considering rare benign entities in pulmonary nodule differentials and highlights the need for a multidisciplinary approach, surgical intervention, and open-mindedness in complex diagnostic scenarios.

Intralobar pulmonary sequestration presenting as recurrent left lower lobe pneumonia.

This case discusses the diagnosis and management of pulmonary sequestration. Typically discovered incidentally on imaging, it can be a cause of recurrent pulmonary infections causing severe morbidity to the patient. Surgical management is indicated when found to prevent the complications of recurrent infections, including pulmonary necrosis, abscess, or fistula formation.