Publications by authors named "Julien De Wolf"

The machine perfusion (MP) of transplantable grafts has emerged as an upcoming field in Cardiothoracic (CT) transplantation during the last decade. This technology carries the potential to assess, preserve, and even recondition thoracic grafts before transplantation, so it is a possible game-changer in the field. This technology field has reached a critical turning point, with a growing number of publications coming predominantly from a few leading institutions, but still need solid scientific evidence.

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Article Synopsis
  • Researchers have created a new ex vivo model using lung transplant methods to study how SARS-CoV-2 infects human lungs, addressing limitations of animal models and lab systems.
  • The study used single-cell RNA sequencing to determine that the virus primarily targets alveolar macrophages (AMs) and monocyte-derived macrophages (MoMacs), with MoMacs showing a stronger inflammatory response.
  • Findings indicate that the Wuhan strain of SARS-CoV-2 is more effective than the D614G variant, and understanding how the virus interacts with lung macrophages could inform prevention strategies.
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lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung.

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Introduction: Lung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known.

Methods: To address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours.

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Background: Lung cancer is more common in posttransplant recipients than in the general population. The objective of this study was to examine the chimerism donor/recipient cell origin of graft cancer in recipients of lung transplant.

Methods: A retrospective chart review was conducted at Foch Hospital for all lung transplantations from 1989 to 2020.

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In response to the increasing demand for lung transplantation, lung perfusion (EVLP) has extended the number of suitable donor lungs by rehabilitating marginal organs. However despite an expanding use in clinical practice, the responses of the different lung cell types to EVLP are not known. In order to advance our mechanistic understanding and establish a refine tool for improvement of EVLP, we conducted a pioneer study involving single cell RNA-seq on human lungs declined for transplantation.

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Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients.

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Article Synopsis
  • Lung transplantation is the only cure for severe chronic lung diseases but has a 50% survival rate after 5 years, partly due to immune responses.
  • Researchers developed a cross-circulatory platform in pigs to study how immune cells are recruited and activated in donor lungs, finding that myeloid cells were the main responders.
  • The model allows for easy tracking of immune reactions in real-time, which could help in developing better therapies to improve lung transplant outcomes.
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Introduction: The objective of this study was to determine whether computed tomography (CT) could be a useful tool for nonsolid lung nodule (NSN) treatment planning, surgery or stereotactic body radiation therapy (SBRT), by assessing the macroscopic and microscopic extension of these nodules.

Methods: The study prospectively included 23 patients undergoing anatomic resection at the Foch Hospital in 2020/2021 for NSN with a ground-glass component of more than 50%. Firstly, for each patient, both the macroscopic dimensions of the NSN were assessed on CT and during pathologic analysis.

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Endogenous production of carbon monoxide (CO) is affected by inflammatory phenomena and ischemia-reperfusion injury. Precise measurement of exhaled endogenous CO (eCO) is possible thanks to a laser spectrometer (ProCeas® from AP2E company). We assessed eCO levels of human lung grafts during the normothermic Lung Perfusion (EVLP).

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Background: Rapidly progressive interstitial lung disease (RPILD) associated with the anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5ab+) dermatomyositis (DM) is a rare but life-threatening condition despite immunosuppressive treatment. We report the case of a 44-year-old woman who was diagnosed with severe RPILD associated with anti-MDA5ab+ DM 1 week before her admission in the intensive care unit. The patient underwent a successful double-lung transplant after she failed treatment with immunosuppressive therapy, including tofacitinib.

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Background: Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes.

Methods: We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters.

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Background: Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples.

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Background: Pre-formed donor-specific antibodies (DSAs) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. A virtual crossmatch-based strategy for perioperative desensitisation protocol has been used for immunised LTx candidates since 2012 at Foch Hospital (Suresnes, France). We compared the outcome of desensitised LTx candidates with high DSA mean fluorescence intensity and those with low or no pre-formed DSAs, not desensitised.

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Fat embolism is a serious complication in patients with multiple traumatic injuries. It is often asymptomatic during the first hours of resuscitation, thus remains underdiagnosed in patients who progress to brain death. Lung transplantation issued from such grafts can lead to severe lung primary graft dysfunction, the management of which is deemed difficult.

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Objectives: The identification of the intersegmental plane during lung segmentectomies remains a practical difficulty, notably with minimally invasive approaches. The intraoperative techniques are based on demarcating either the bronchial or the vascular territories. The goal of this study was to evaluate the use of 3-dimensional reconstructions in understanding the intersegmental plane of segment 6.

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Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients.

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Background: Hanging donors are considered as marginal donors and frequently unsuitable for lung transplantation. However, there is no evidence of higher lung transplantation (LTx) morbidity-mortality with lungs providing by hanging donor.

Methods: Between January 2010 and July 2015, we performed a retrospective study at Foch hospital.

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Bronchoplasty is frequently required for radical resection of central typical carcinoid tumours. As sleeve bronchoplasty can be a complex procedure, an accurate evaluation of the tumour location is mandatory. Although the endobronchial part of the tumour can be easily evaluated by bronchoscopy, the exo-bronchial part is difficult to analyse with a standard computed tomography (CT) scan.

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Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with limited therapeutic options, requiring the development of efficient targeted therapies based on molecular phenotype of the tumor and to identify predictive biomarkers of the response.

Materials And Methods: The effect of inhibitors was investigated by cell viability assessment on primary MPM cell lines established in our laboratory from patient tumors, well characterized at the molecular level. Effects on apoptosis, cell proliferation and viability on MPM growing in multicellular spheroid were also assessed for verteporfin.

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Anterior mediastinal tracheostomy (AMT) is established after division of the retrosternal trachea following resection of extended upper airway malignancies, stomal recurrences, or cervicomediastinal exenteration. AMT is occasionally performed for nonmalignant diseases. Starting in the 1980s, the use of a pectoralis major myocutaneous island flap reduced the mortality attributable to innominate artery rupture previously reported in historical series.

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Objectives: Adrenal oligometastatic non-small-cell lung cancer is rare, and surgical management remains controversial.

Methods: We performed a multicentre, retrospective study from January 2004 to December 2014. The main objective was to evaluate survival in patients who had undergone adrenalectomy after resection of primary lung cancer.

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Background: Liver and lungs are the two most frequent sites of metastatic spread of colorectal cancer (CRC). Complete resection of liver and/or lung metastases is the only chance of cure, and several studies have reported an improved survival after an aggressive treatment. Nevertheless, CRC liver metastases (CLM) have been recognized as a pejorative factor for patients undergoing pulmonary metastasectomy.

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