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Paraganglioma is a tumor developed from paraganglia, which are groups of neuroendocrine cells located along the vascular and nerve axes of the head and neck and along the spine. These tumors are benign and still localized in more than 80% of cases. Middle mediastinal paragangliomas represent less than 1% of mediastinal tumors and grow from the superior or middle mediastinal autonomic ganglion; they mostly are non-functional and are found in older patients. The often large volume and complex location of these tumors make their surgical resection challenging forcing the surgical team to resort to cardiopulmonary bypass and practice transfection of the aortic artery. We successfully operated an 80-year-old patient by clamshell incision without bypass or arterial procedure.

Upregulated p38 signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38 signaling and accelerates PA-SMC proliferation. The activity of p38 signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1). Activated p38 induces DUSP1 expression, forming a negative feedback loop. Prostacyclin IP receptor agonists (prostacyclin and selexipag) are used to treat PAH. In this study, we aimed to verify whether IP receptor agonists affect DUSP1 expression and accelerate the proliferation of PA-SMCs. PA-SMCs were treated with BMP2, ET-1, prostacyclin, and MRE-269, an active metabolite of selexipag, either alone or in combination. We quantified mRNA expressions using real-time quantitative polymerase chain reaction. Pulmonary artery specimens and PA-SMCs were obtained during lung transplantation in patients with PAH. Both prostacyclin and MRE-269 increased DUSP1 expression. Combined treatment with BMP2 and ET-1 induced cyclin D1 and DUSP1 expression and increased PA-SMC proliferation. MRE-269 attenuated BMP2/ET-1-induced cell proliferation. ET-1 increased DUSP1 expression in PA-SMCs from control patients but not in PA-SMCs from patients with PAH. This study showed that the p38/DUSP1 negative feedback loop is impaired in PAH, contributing to unregulated p38 activation and PA-SMC hyperplasia. IP receptor agonist MRE-269 increases DUSP1 expression and inhibit p38-mediated PA-SMC proliferation. Future elucidation of the detailed mechanism underlying reduced DUSP1 expression would be informative for PAH treatment.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Upregulated p38MAPK signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38MAPK signaling and accelerates PA-SMC proliferation. The activity of p38MAPK signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1). Activated p38MAPK induces DUSP1 expression, forming a negative feedback loop. Prostacyclin IP receptor agonists (prostacyclin and selexipag) are used to treat PAH. In this study, we aimed to verify whether IP receptor agonists affect DUSP1 expression and accelerate the proliferation of PA-SMCs., SCOPUS: ar.j, info:eu-repo/semantics/published

La COVID-19 est une maladie infectieuse émergente virale causée par la souche de coronavirus SARSCoV-2. Après presque deux années de pandémie, les cliniciens ont beaucoup progressé dans les connaissances des manifestations cliniques de la maladie, notamment en mettant en avant la place du glycocalyx endothélial. Ce dernier est une structure complexe micro-fibrillaire située au pôle apical de la cellule endothéliale, constituant la barrière histologique entre la cellule et la lumière vasculaire et se comportant comme un organe à part entière. L’étude physiopathologique de ce dernier a permis de mettre en évidence l’intérêt de celui-ci dans la compréhension de la COVID-19 et de ses complications. Cette revue a donc pour but d’appréhender cette maladie sous un angle différent et se propose de résumer les données pertinentes pour le clinicien que nous avons apprises depuis deux ans.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers., SCOPUS: ar.j, info:eu-repo/semantics/published

Airway stenting offers good palliation and improves the quality of life in patients with inoperable bronchotracheal stenosis. However, in some cases, the management of stenting can be life-threatening. Hence, a strategy for maintaining oxygenation and hemodynamic stability should be anticipated to avoid critical situations. Herein, we report the use of extracorporeal membrane oxygenation (ECMO) in bronchotracheal stenting management to secure oxygenation and facilitate interventions. We retrospectively reviewed all patients who underwent rigid bronchoscopy under ECMO support for the management of bronchotracheal stenting at CHU UCL Namur hospital (Belgium), between January 2009 and December 2019. We included 14 bronchoscopy cases performed on 11 patients (3 patients underwent 2 bronchoscopies) in this study; 12 were performed on males and 2 on females. The median age was 54 years. There were 11 benign and 3 malignant etiologies for the central airway obstruction/stenosis. Eight cases were supported by venovenous ECMO and six by venoarterial ECMO. The median ECMO time was 267 minutes. The weaning of ECMO support was successful in all cases. In most cases, the procedures were performed effectively and safely. Only two local complications caused by the cannulation of ECMO were reported, and anticoagulation was adapted to avoid bleeding at the operating site and clot formation in the system. Elective ECMO support was helpful and safe for the high-risk management of bronchotracheal stenting with rigid bronchoscopy and was not associated with any additional significant complications.

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media., info:eu-repo/semantics/published

PURPOSE: Following introduction of the lung allocation score (LAS) in 2011, Eurotransplant member centers can apply for an exceptional LAS (eLAS) if the calculated LAS insufficiently reflects the perceived transplant benefit for a patient, specifically in case of primary pulmonary hypertension group 1 and 4; combined lung+non-renal transplantation; rare diseases; or extracorporeal support. Each eLAS proposal is evaluated by a LAS Review Board, consisting of ≥3 lung transplant experts, which subsequently declines or approves the eLAS request in consensus of ≥3 votes. In case of a lower than accepted score, predefined business rules to assign LAS percentiles are used. METHODS: A retrospective analysis of all eLAS requests in Eurotransplant from December 2011 until September 2019. RESULTS: Overall, 5183 lung transplants (deceased donors) were performed and 420 eLAS requests were made (Germany 52%, Netherlands 18%, Austria 18%, Belgium 13%), of which 116 (28%) were approved. Most eLAS requests concerned group B/Pulmonary vascular disease (44%), followed by group C/Cystic fibrosis or immunodeficiency disorder (28%), then group D/Restrictive lung disease (15%) and finally group A/Obstructive lung disease (11%); whereas 10 patients (2%) were not classified. The proportion of accepted eLAS requests significantly differed between countries (Germany 25%, Netherlands 37%, Austria 20%, Belgium 36%) (p=0.042). eLAS requests decreased in the Netherlands following its LAS introduction in 2014 (2011-2014 mean 13/yr vs. 2015-2019 mean 4.6/yr; p=0.060). However, since 2015 an overall annual increasing number of eLAS requests is seen, with doubling of the eLAS requests in 2018 vs. 2015, but no difference in acceptance rate (2015-2018: 22.4%) (Figure). Acceptance rates were 38% for Group B, 21% for Group C, 20% for Group D and 11% for Group A. CONCLUSION: The observed variations require further investigation to optimize lung allocation for specific patient populations in Eurotransplant, SCOPUS: ar.j, info:eu-repo/semantics/published

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤45 years, P < 0.0001), were less often smokers (35% vs. 46%, P < 0.0001), had more often clear chest X-rays (82% vs. 72%, P < 0.0001), had better donor oxygenation ratios (20% vs. 26% with PaO2/FiO2 ≤ 300 mmHg, P < 0.0001), and had better lung donor score values (LDS; 28% vs. 17% with LDS = 6, P < 0.0001) compared with donors used for LTx in countries with low donation rate. Survival rates for the groups LDS = 6 and ≥7 at 5 years were 69.7% and 60.9% (P = 0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized., SCOPUS: ar.j, info:eu-repo/semantics/published

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell-based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF-expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS-purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐ purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Primary graft dysfunction (PGD) is responsible of high early mortality in lung transplanted patients. We measured the rate of surfactant proteins in the organ donor, and we observed the occurrence of lung PGD in the recipient. The co-relation between these two parameters was evaluated. Material/Methods: In this pilot study, we prospectively collected blood samples and lung biopsies in thirteen donors at the time of recovery of organs before preservation. Gene expression of SP-A, SP-B, SP-D, and CC16 was evaluated by realtime quantitative PCR. Surfactant proteins plasma levels were evaluated by ELISA. Post-transplant assessments included hemodynamic, arterial blood gas measurements, and radiographic evaluation to determine PGD and lung biopsies. Results: Nine of the thirteen recipients (69%) developed lung infiltrates and four (31%) developed PGD at either stages 2 or 3. SP-A and SP-B expressions were dramatically reduced in lung allografts of these patients, while lung expression of SP-D and CC16 remained unchanged. Plasma levels of SP-A, SP-B, SP-D, and CC16 did not differ. Conclusions: Primary graft dysfunction may be initiated in the donor. Lung allografts with low lung SP-A and SP-B gene expression prior to implantation are associated with increased incidence of lung infiltrates after transplantation.

True atherosclerotic aneurysms of superficial femoral artery (SFA) are rare and often associated with other peripheral or aortic aneurysms. We report the case of a 84-year-old patient presenting a giant degenerative ruptured aneurysm of the superficial femoral artery. The patient underwent successful aneurysm resection and bypass grafting, with a satisfying long-term follow-up and patency of the graft. The patient was also operated one year before, for a ruptured aneurysm of the abdominal aorta. This case report is rare, because we described a case of patient with multiple atherosclerotic aneurysms, who present, for the second time, a life threating ruptured aneurysm. In this report, we see extreme and rapid evolution of SFA Aneurysm before being symptomatic. Degenerative aneurysms of the lower extremity most commonly involve the popliteal artery, while they are rarely detected in the femoral region (Leon et al., 2008). In this region, aneurysms most frequently involve the common femoral artery (CFA), whereas true aneurysms of the superficial femoral artery (SFA) represent only 15% to 25% of femoral arterial aneurysms [1-5]. Degenerative aneurysms of the SFA display peculiar characteristics (in terms of clinical onset, diagnostic timing, and clinical behavior) so that they differ from other peripheral aneurysms. Because the relative rarity of this location, our case report can be useful to participate to increase the number of reported cases, and define the therapeutic approach for this rare location.

A 58-year-old woman was diagnosed with a left-sided lone internal mammary swollen lymph node on a routine follow-up computer tomography, 42 months after a left mastectomy in the context of a ductal carcinoma grade III. The suspected metastasis was successfully removed in toto using a 3-port-da Vinci robotic procedure and the patient was discharged home without any complication on the third postoperative day. Robotically assisted oncological lymph node removal is safe, easily performed and economically affordable.

BACKGROUND: Osteogenesis imperfecta is a genetic disorder of connective tissue causing mostly left-sided heart valves and aortic root pathologies, but a coronary artery involvement reflecting an increased sensitivity to cardiovascular risk factors is also suspected in this patient population. CASE PRESENTATION: We report a 38-year-old patient with an osteogenesis imperfecta and a typical presentation of an acute myocardial infarction. The coronary angiogram showed a coronary 3-vessel disease. The patient underwent a bypass grafting surgery with the internal mammary artery. The sternum was closed using four nitinol clips and had totally stabilized at 4 months with excellent bone healing. CONCLUSIONS: With the successful clinical outcome in this patient severely affected by its osteogensis imperfecta, we underline the safe use of the LIMA, if precaution is taken towards the sternal bone, and its closure with nitinol clips.

Paragangliomas are rare tumors representing a therapeutic challenge. We present a case report of surgical resection of carotid body tumor without preoperative embolization. Our therapeutic attitude is based on controversial benefits of the embolization for those tumors. The major indication for the preoperative embolization is to reduce intraoperative blood loss, but this benefit is not demonstrated. Also, because the relative rarity of this tumor, the confounding factors relative to the surgeon and radiologist experience, no randomized trial can be performed. So, our case report can be useful to participate to increase the number of reported cases, and define the therapeutic approach for this rare tumor.

The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations., info:eu-repo/semantics/published