Publications by authors named "Cypel M"

Background: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure.

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Objective: To determine the impact of prolonged storage of donor lungs at 10°C of up to 24h on outcome after lung transplantation.

Background: An increasing body of evidence suggests 10°C as the optimal storage temperature for donor lungs. A recent study showed that cold ischemic times can be safely expanded to >12h when lungs are stored at 10°C.

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Background: To investigate through a meta-analysis of comparative studies the impact of donor type (brain death DBD vs circulatory death DCD) on the short- and long-term outcomes of lung transplantation(LTx).

Methods: Literature search (terms "lung transplantation" AND "donation after circulatory death") was performed up to July 2022 and studies comparing outcomes of LTx from DCD versus DBD were selected. Primary endpoints were early and long-term mortality.

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Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.

Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.

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The implications of a lung malignancy in a lung transplant recipient are poorly understood. Here, we linked national transplant and cancer databases to determine how lung cancer impacted prognosis in lung transplant recipients with incidentally explanted lung cancers (IELCs). Records from the Scientific Registry of Transplant Recipients and National Cancer Database were linked to identify 186 patients who received a lung transplant and were subsequently diagnosed with lung cancer.

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Significance: Standard treatments for isolated lung metastases remain a clinical challenge. lung perfusion technique provides flexibility to overcome the limitations of photodynamic therapy (PDT) by replacing the blood with acellular perfusate, allowing greater light penetration.

Aim: Using Monte Carlo-based simulations, we will evaluate the abilities of a light delivery system to irradiate the lung homogenously.

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The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee.

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Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx.

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Background: Recent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3 hours postmortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model.

Methods: After uDCD induction, donor pigs were allocated to one of the following groups: control-static lung inflation only (SLI); TC - SLI + continuous intrapleural topical cooling (TC); or TC+Sevo - SLI + TC + sevoflurane.

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Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases.

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Objectives: Hypothermic lung preservation at 10 °C has been recently shown to enhance quality of healthy donor lungs during ischemia. This study aims to show generalizability of the 10 °C lung preservation using an endotoxin-induced lung injury with specific focus on the benefits of post-transplant lung function and mitochondrial preservation.

Methods: Lipopolysaccharide (3 mg/kg) was injected intratracheally in rats to induce lung injury.

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Ischemia-reperfusion is an unavoidable step of organ transplantation. Development of therapeutics for lung injury during transplantation has proved challenging; understanding lung injury from human data at the single-cell resolution is required to accelerate the development of therapeutics. Donor lung biopsies from 6 human lung transplant cases were collected at the end of cold preservation and 2-hour reperfusion and underwent single-cell RNA sequencing.

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Objective: Previous reports showed enhanced graft function in both healthy and injured porcine lungs after preservation at 10 °C. The objective of the study is to elucidate the mechanism of lung protection by 10 °C and identify potential therapeutic targets to improve organ preservation.

Methods: Metabolomics data were analyzed from healthy and injured porcine lungs that underwent extended hypothermic preservation on ice and at 10 °C.

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Objective: Thoracic surgery is associated with one of the highest rates of chronic postsurgical pain (CPSP) among all surgical subtypes. Chronic postsurgical pain carries significant medical, psychological, and economic consequences, and further interventions are needed to prevent its development. This study aimed to determine the prevalence, characteristics, and risk factors associated with CPSP after thoracic surgery.

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Introduction: Carbon monoxide (CO) has been shown to exert protective effects in multiple organs following ischemic injury, including the lung. The purpose of this study was to examine the effects of CO administration during ex vivo lung perfusion (EVLP) on lung grafts exposed to prolonged cold ischemia.

Methods: Ten porcine lungs were subjected to 18 h of cold ischemia followed by 6 h of EVLP.

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Traditionally, lobectomy was standard for stage IA non-small-cell lung cancer (NSCLC). Recent RCTs suggest sublobar resection's comparable outcomes. Our meta-analysis, incorporating 30 studies (including four RCTs), assessed sublobar resection's efficacy.

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Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment.

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Lung transplantation results are compromised by ischemia-reperfusion injury and alloimmune responses. Ex vivo lung perfusion (EVLP) is used to assess marginal donor lungs before transplantation but is also an excellent platform to apply novel therapeutics. We investigated donor lung immunomodulation using genetically engineered mesenchymal stromal cells with augmented production of human anti-inflammatory hIL-10 (MSCs).

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The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both and organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients.

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Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included.

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Objectives: Dual-lumen cannulas for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support are typically inserted in the right internal jugular vein (RIJV); however, some scenarios can make this venous route inaccessible. This multicentre case series aims to evaluate if single-site cannulation using an alternative venous access is safe and feasible in patients with an inaccessible RIJV.

Methods: We performed a multi-institutional retrospective analysis including high-volume ECMO centres with substantial experience in dual-lumen cannulation (DLC) (defined as >10 DLC per year).

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Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung.

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