Publications by authors named "Elie Fadel"

271 Publications

Pulmonary endarterectomy in Patients with Myeloproliferative Neoplasms.

Chest 2021 Sep 16. Epub 2021 Sep 16.

Cardiothoracic intensive care unit; Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson. France; University Paris-Saclay, Faculty of Medicine, Kremlin-Bicêtre, France; INSERM U999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.09.007DOI Listing
September 2021

Outcomes after pulmonary lobectomy in patients with history of head and neck carcinoma.

Respir Med Res 2021 Aug 25;80:100857. Epub 2021 Aug 25.

Marie Lannelongue Hospital, Groupe Hospitalier Paris Saint-Joseph, Department of Thoracic Surgery, Le Plessis-Robinson, France.

Background: We aimed to determine whether video assisted thoracic surgery (VATS) was associated with better short-term outcomes compared to open approach and to determine factors affecting long term survival after lobectomy in patients with history of head and neck carcinoma (HNC).

Methods: We performed a retrospective monocentric analysis of consecutive standard lobectomies performed for lung cancer in patients with history of HNC between 2010 and 2017. Patients' characteristics, surgical approach, lung tumor histology, in-hospital and 90-days morbi-mortality and long term survival were analyzed; VATS and open lobectomy groups were compared.

Results: Among 85 patients, 52 underwent an open lobectomy and 33 a VATS lobectomy. There was no significant difference between the two groups regarding age, preoperative characteristics, pathology and stage of lung cancer (All p = NS). In the VATS group, there was a significant decrease in proportion of in-hospital postoperative life-threatening complications requiring hospitalization in intensive care unit (12/52 vs. 1/33, p = 0.01). The 90-days postoperative comprehensive complication index was significantly increased in the open thoracotomy group (median (interquartile range):33.5 (0-53.5) vs. 8.7 (0-34.1), p = 0.018). Long term survival was not significantly different between the 2 groups - Log-rank test comparison, p = NS). Patients with squamous cell histology presented a significantly poorer survival (both Log-rank test comparison, p < 0.01).

Conclusions: Minimally invasive approach improved in-hospital and 90-days outcomes compared to open surgery for lung cancer resection in patients with history of HNC. The poor long-term results in patients with squamous cell carcinoma highlight the need to improve therapeutic strategies for this subset of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resmer.2021.100857DOI Listing
August 2021

Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT.

J Heart Lung Transplant 2021 Aug 3. Epub 2021 Aug 3.

Pulmonary Hypertension and CTEPH Research Program, Temple Heart and Vascular Institute, Temple University, Lewis Katz School of Medicine, Philadelphia, Pennsylvania.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.07.020DOI Listing
August 2021

Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry.

ERJ Open Res 2021 Jul 16;7(3). Epub 2021 Aug 16.

Royal Papworth Hospital, Cambridge, UK.

Background: Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.

Methods: 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation-perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation.

Results: Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA).

Conclusions: The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00850-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365143PMC
July 2021

Fully Integrated Quantitative Multiparametric Analysis of Non-Small Cell Lung Cancer at 3-T PET/MRI: Toward One-Stop-Shop Tumor Biological Characterization at the Supervoxel Level.

Clin Nucl Med 2021 09;46(9):e440-e447

Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay.

Introduction: The aim of this study was to study the feasibility of a fully integrated multiparametric imaging framework to characterize non-small cell lung cancer (NSCLC) at 3-T PET/MRI.

Patients And Methods: An 18F-FDG PET/MRI multiparametric imaging framework was developed and prospectively applied to 11 biopsy-proven NSCLC patients. For each tumor, 12 parametric maps were generated, including PET full kinetic modeling, apparent diffusion coefficient, T1/T2 relaxation times, and DCE full kinetic modeling. Gaussian mixture model-based clustering was applied at the whole data set level to define supervoxels of similar multidimensional PET/MRI behaviors. Taking the multidimensional voxel behaviors as input and the supervoxel class as output, machine learning procedure was finally trained and validated voxelwise to reveal the dominant PET/MRI characteristics of these supervoxels at the whole data set and individual tumor levels.

Results: The Gaussian mixture model-based clustering clustering applied at the whole data set level (17,316 voxels) found 3 main multidimensional behaviors underpinned by the 12 PET/MRI quantitative parameters. Four dominant PET/MRI parameters of clinical relevance (PET: k2, k3 and DCE: ve, vp) predicted the overall supervoxel behavior with 97% of accuracy (SD, 0.7; 10-fold cross-validation). At the individual tumor level, these dimensionality-reduced supervoxel maps showed mean discrepancy of 16.7% compared with the original ones.

Conclusions: One-stop-shop PET/MRI multiparametric quantitative analysis of NSCLC is clinically feasible. Both PET and MRI parameters are useful to characterize the behavior of tumors at the supervoxel level. In the era of precision medicine, the full capabilities of PET/MRI would give further insight of the characterization of NSCLC behavior, opening new avenues toward image-based personalized medicine in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000003680DOI Listing
September 2021

Surgical Resection of Tumors Invading the Inferior Vena Cava at the Hepatic Vein and Thoracic Levels.

World J Surg 2021 10 3;45(10):3174-3182. Epub 2021 Jul 3.

Department of Thoracic and Vascular Surgery and Lung and Heart-Lung Transplantation, Marie Lannelongue Hospital, 133 avenue de la Résistance, 92350, Le Plessis Robinson, France.

Background: Our aim was to describe the results of our program of surgical resection of tumors invading the inferior vena cava (IVC) at the hepatic and thoracic levels. We hypothesized that similar surgical outcomes may be obtained compared to tumor resection below the hepatic vein level if the liver function was preserved.

Methods: We performed a single-center retrospective study of 72 consecutive patients who underwent surgical resection from 1996 to 2019 for tumors invading the IVC. We compared two groups based on tumor location below (group I/II) or above (group III/IV) the inferior limit of hepatic veins.

Results: Tumor histology was similarly distributed between groups. In group III/IV (n = 35), sterno-laparotomy was used in 83% of patients, cardiopulmonary bypass in 77%, and deep hypothermic circulatory arrest in 17%; 23% underwent liver resection. Corresponding proportions in group I/II were 3%, 0%, 0%, and 8%. In group III/IV, 4 patients required emergency resection. Mortality on day 30 was 17% (n = 6) in group III/IV and 0% in group I/II (P = 0.01). There was no liver failure among the 66 postoperative survivors and 5 out of 6 patients who died postoperatively presented a preoperative or postoperative liver failure (P < 0.001). Overall survival was not significantly different between groups with a median follow-up of 15.1 months. R0 resection was achieved in 66% of group I/II and 49% of group III/IV patients (P = 0.03).

Conclusion: Surgical resection of tumors invading the inferior vena cava at hepatic vein and thoracic levels should be reserved to carefully selected patients without preoperative liver failure to minimize postoperative mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-021-06227-9DOI Listing
October 2021

Right Ventricle Remodeling Metabolic Signature in Experimental Pulmonary Hypertension Models of Chronic Hypoxia and Monocrotaline Exposure.

Cells 2021 06 21;10(6). Epub 2021 Jun 21.

Faculté de Médecine, Université Paris-Saclay, 91191 Gif-sur-Yvette, France.

Introduction: Over time and despite optimal medical management of patients with pulmonary hypertension (PH), the right ventricle (RV) function deteriorates from an adaptive to maladaptive phenotype, leading to RV failure (RVF). Although RV function is well recognized as a prognostic factor of PH, no predictive factor of RVF episodes has been elucidated so far. We hypothesized that determining RV metabolic alterations could help to understand the mechanism link to the deterioration of RV function as well as help to identify new biomarkers of RV failure.

Methods: In the current study, we aimed to characterize the metabolic reprogramming associated with the RV remodeling phenotype during experimental PH induced by chronic-hypoxia-(CH) exposure or monocrotaline-(MCT) exposure in rats. Three weeks after PH initiation, we hemodynamically characterized PH (echocardiography and RV catheterization), and then we used an untargeted metabolomics approach based on liquid chromatography coupled to high-resolution mass spectrometry to analyze RV and LV tissues in addition to plasma samples from MCT-PH and CH-PH rat models.

Results: CH exposure induced adaptive RV phenotype as opposed to MCT exposure which induced maladaptive RV phenotype. We found that predominant alterations of arginine, pyrimidine, purine, and tryptophan metabolic pathways were detected on the heart (LV+RV) and plasma samples regardless of the PH model. Acetylspermidine, putrescine, guanidinoacetate RV biopsy levels, and cytosine, deoxycytidine, deoxyuridine, and plasmatic thymidine levels were correlated to RV function in the CH-PH model. It was less likely correlated in the MCT model. These pathways are well described to regulate cell proliferation, cell hypertrophy, and cardioprotection. These findings open novel research perspectives to find biomarkers for early detection of RV failure in PH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10061559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235667PMC
June 2021

Superior vena cava prosthetic replacement for non-small cell lung cancer: is it worthwhile?

Eur J Cardiothorac Surg 2021 Jul 1. Epub 2021 Jul 1.

Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital and Paris Saclay University, Le Plessis-Robinson, France.

Objectives: Direct involvement of the superior vena cava (SVC) by non-small cell lung cancer (NSCLC) requires en-bloc tumour resection with complete vascular clamping and prosthetic replacement. We report the outcomes of this highly demanding procedure in the largest patient cohort to date.

Methods: We searched our institution's database for patients who underwent complete en-bloc resection of NSCLC invading the SVC followed by prosthetic SVC replacement, between 1980 and 2018. Patients with cN2, cN3 or distant metastases were not eligible.

Results: We identified 48 patients (38 males, 10 females; mean age of 57 years; tumour size, 1.9-17 cm). Neoadjuvant therapy was administered to 17 and adjuvant therapy to 31 patients. R0 resection was achieved in 41 (85%) patients; lymph node involvement was pN0 in 8, pN1 in 23, pN2 in 14 and pN3 in 3 patients. Five patients died within 30 days of surgery. Right pneumonectomy was significantly associated with postoperative death (P = 0.02). Postoperative complications developed in 13 other patients. No neurologic events related to SVC clamping occurred. Graft thrombosis developed in 2 patients. Median survival was 24 months; 3-, 5- and 10-year survival rates were 45%, 40% and 35%, respectively; and corresponding disease-free survival rates were 37%, 37% and 30%, respectively. By univariable analysis, only margin-free (R0) resection was associated with better survival (P = 0.02).

Conclusions: In highly selected patients with NSCLC involving the SVC, mortality is acceptable after complete en-bloc resection and prosthetic replacement done in an expert centre. SVC involvement should not preclude consideration of curative resection in selected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ejcts/ezab248DOI Listing
July 2021

A Ten-year Single-center Surgical Experience With Symptomatic Complete Vascular Rings.

Ann Vasc Surg 2021 Jun 25. Epub 2021 Jun 25.

Department of Thoracic and Vascular Surgery, Hôpital Marie Lannelongue, Groupe hospitalier Paris Saint Joseph, Université Paris Saclay, Paris, France.

Background: Limited data exist on the management of complete vascular rings (CVR) in adults. We reviewed our institution's surgical experience in the management of these patients.

Methods: Between 2010 and 2019, all adult patients that underwent a thoracotomy for a CVR repair were identified. We performed a retrospective medical record review of these patients to characterize their demographics and outcomes.

Results: Among the 5 patients identified (3 females, 2 males; Mean age 50 ± 9 years), anatomic variants were right arch and Kommerell diverticulum (KD) in 3 (60%) and double aortic arch in 2 (40%) patients. Indications for operation included dysphagia in 4 (80%), respiratory symptoms in 3 (60%) and aneurysmal KD in 1 (20%) patient. Two right aortic arch exclusion, 1 ligamentum arteriosum (LA) division, 1 LA division combined with a KD resection and 2 aortic reconstructions with interposition Dacron graft under partial cardiopulmonary bypass, were performed. Two carotid-subclavian artery transpositions prior to the thoracotomy were done. The postoperative length of stay was 10.0 (IQR 7.3-14.8) days. One reoperation for chylothorax and 1 for symptoms recurrence were performed for the same patient. Over a follow-up period of 1.4 (IQR 0.4-7.0) years, no mortality or major postoperative complications occurred. At their last follow-up visit, all patients reported no related remaining symptoms, except for persisting mild asthma in 1 patient.

Conclusions: Open repair of CVR in adults can be performed safely with low complication rate. Symptoms improved in all patients after definitive repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2021.04.036DOI Listing
June 2021

Risk of Lung Allograft Dysfunction Associated With Infection.

Transplant Direct 2021 Mar 18;7(3):e675. Epub 2021 Feb 18.

Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.

We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD).

Methods: We retrospectively reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD.

Results: During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for ; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1-44). Median time from transplantation to first -positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively. (n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval [CI], 1.61-8.73; < 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively ( < 0.01, logrank test).

Conclusions: Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TXD.0000000000001128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184025PMC
March 2021

Can MRI differentiate surrounding vertebral invasion from reactive inflammatory changes in superior sulcus tumor?

Eur Radiol 2021 May 15. Epub 2021 May 15.

Department of Radiology, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, Villejuif, 94800, Paris, France.

Objectives: Vertebral invasion is a key prognostic factor and a critical aspect of surgical planning for superior sulcus tumors. This study aims to further evaluate MRI features of vertebral invasion in order to distinguish it from reactive inflammatory changes.

Methods: Between 2000 and 2016, a retrospective study was performed at a single institution. All patients with superior sulcus tumors undergoing surgery, including at least two partial vertebrectomies, were included. An expert radiologist evaluated qualitative and quantitative MRI signal intensity characteristics (contrast-to-noise ratio [CNR]) of suspected involved and non-involved vertebrae. A comparison of CNR of invaded and sane vertebrae was performed using non-parametric tests. Imaging data were correlated with pathological findings.

Results: A total of 92 surgical samples of vertebrectomy were analyzed. The most specific sequences for invasion were T1 and T2 weighted (92% and 97%, respectively). The most sensitive sequences were contrast enhanced T1 weighted fat suppressed and T2 weighted fat suppressed (100% and 80%). Loss of extrapleural paravertebral fat on the T1-weighted sequence was highly sensitive (100%) but not specific (63%). Using quantitative analysis, the optimum cut-off (p < 0.05) to distinguish invasion from reactive inflammatory changes was CNR > 11 for the T2-weighted fat-sat sequence (sensitivity 100%), CNR > 9 for contrast-enhanced T1-weighted fat-suppressed sequence (sensitivity 100%), and CNR < - 30 for the T1-weighted sequence (specificity 97%). Combining these criteria, 23 partial vertebrectomies could have been avoided in our cohort.

Conclusion: Qualitative and quantitative MRI analyses are useful to discriminate vertebral invasion from reactive inflammatory changes.

Key Points: • Abnormal signal intensity in a vertebral body adjacent to a superior sulcus tumor may be secondary to direct invasion or reactive inflammatory changes. • Accurate differentiation between invasion and reactive inflammatory changes significantly impacts surgical planning. T1w and T2w are the best sequences to differentiate malignant versus benign bone marrow changes. The use of quantitative analysis improves MRI specificity. • Using contrast media improves the sensitivity for the detection of tumor invasion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-08001-wDOI Listing
May 2021

Video-Assisted Thoracoscopic En Bloc Vertebrectomy for Spine Tumors: Technique and Outcomes in a Series of 33 Patients.

J Bone Joint Surg Am 2021 Jun;103(12):1104-1114

Orthopedic and Trauma Surgery Department, Kremlin Bicêtre Hospital and Paris Saclay University, Le Kremlin Bicêtre, France.

Background: In en bloc vertebrectomy, the posterior approach is associated with limited access to anterior structures (vertebral body, esophagus, aorta, azygos vein). Video-assisted thoracoscopic surgery (VATS) might prove to be advantageous during thoracic en bloc vertebrectomy by allowing a combined anterior-posterior access in the prone position. We describe the technique and review the outcomes of 33 cases of video-assisted thoracoscopic en bloc vertebrectomy.

Methods: A retrospective, single-center cohort study included all cases of VATS with a minimum follow-up of 1 year. A team of thoracic and orthopaedic surgeons performed the surgical procedure with the patient in a single, prone position. Anterior release was carried out thoracoscopically, followed by posterior en bloc tumor removal.

Results: From 2003 to 2019, 33 patients were included. Nine patients underwent total vertebrectomy (8 had single-level and 1 had 3-level), and 24 patients underwent partial vertebrectomy (1 had single-level, 8 had 2-level, 13 had 3-level, and 2 had 4-level). Ten patients had pulmonary resection. Histology revealed 18 cases (55%) of primary bone tumors, 6 cases (18%) of lung cancer invading the spine, 6 cases (18%) of solitary metastasis, and 3 other cases (9%). The margins were tumor-free in 28 cases (85%). The median operative time was 240 minutes (range, 150 to 510 minutes), with a median blood loss of 1,200 mL (range, 400 to 6,700 mL), and there were 2 cases of conversion to thoracotomy. A total of 33 complications occurred in 18 patients (55%), and these were predominantly pulmonary. One death was surgery-related (infection). One patient had a persistent monoplegia. At a median follow-up of 63 months (range, 12 to 156 months), there were 21 surviving patients (64%) with 2 local recurrences and 1 distant recurrence, and 2 patients (6%) were lost to follow-up. The survival rates were 94% at 1 year, 71% at 2 years, and 68% at 5 years.

Conclusions: VATS en bloc vertebrectomy may be indicated for T2-to-T11 spine tumors with the exception of massive tumors, substantial chest wall and/or mediastinal invasion, and lung cancer exceeding 7 cm. The technique yielded satisfactory surgical and oncologic outcomes.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2106/JBJS.20.01417DOI Listing
June 2021

Lung and heart-lung transplantation for children with PAH: Dramatic benefits from the implementation of a high-priority allocation program in France.

J Heart Lung Transplant 2021 07 26;40(7):652-661. Epub 2021 Mar 26.

Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardio-pulmonaire, Groupe hospitalier Marie-Lannelongue -Saint Joseph, Le Plessis-Robinson, France; Université Paris-Saclay, Le Kremlin Bicêtre, France; UMR_S 999, Université Paris-Sud, INSERM, Groupe hospitalier Marie-Lannelongue -Saint Joseph, Le Plessis-Robinson, France.

Purpose: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx.

Methods: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively.

Results: Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; p = 0.02).

Conclusion: HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.03.013DOI Listing
July 2021

Transplantation for pulmonary arterial hypertension with congenital heart disease: Impact on outcomes of the current therapeutic approach including a high-priority allocation program.

Am J Transplant 2021 10 5;21(10):3388-3400. Epub 2021 Aug 5.

UMR-S 999, Inserm, Hôpital Marie Lannelongue, Faculté de Médecine Paris-Saclay, Université Paris-Saclay, Plessis-Robinson, France.

Patients with end-stage pulmonary arterial hypertension due to congenital heart disease have limited access to heart-lung transplantation or double-lung transplantation. We aimed to assess the effects of a high-priority allocation program established in France in 2007. We conducted a retrospective study to compare waitlist and posttransplantation outcomes before versus after implementation of the high-priority allocation program. We included 67 consecutive patients (mean age at listing, 33.2 ± 10.5 years) with pulmonary arterial hypertension due to congenital heart disease listed for heart-lung transplantation or double-lung transplantation from 1997 to 2016. At one month, the incidences of transplantation and death before transplantation were 3.5% and 24.6% in 1997-2006, 4.8% and 4.9% for patients on the regular list in 2007-2016, and 41.2% and 7.4% for patients listed under the high-priority allocation program (p < .001 and p = .0001, respectively). Overall survival was higher in patients listed in 2007-2016 (84.2% and 61.2% at 1 and 10 years vs. 36.8% and 22.1%, p = .0001). Increased incidence of transplantation, decreased waiting list mortality, and improved early and long-term outcomes were observed in patients with pulmonary arterial hypertension due to congenital heart disease listed for transplantation in the recent era, characterized by implementation of a high-priority allocation program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16600DOI Listing
October 2021

Retraction notice to ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELL PHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION.

J Heart Lung Transplant 2021 04;40(4):318

Université de Montpellier, Montpellier, France.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. This request follows an examination by The Editors of the uncut gels provided by the authors, which led the Editors to conclude that data were compromised in the following western blot images: Figure 3C, Figure 5B and Figure 6B. Duplicated data for the beta actin images were found in Figures 5 and 6. Examination of the raw data used for the western blot quantification also revealed frequent duplicated data. The microscopy data in Figure 5A also has features compatible with compromised data although the raw data were not available to the Editors due to the regrettable death of Dr. Saadia Eddahibi. All of the remaining authors agree with the retraction and apologize to the Editors and the readers of The Journal for difficulties this issue has caused.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2021.01.1563DOI Listing
April 2021

Immunomodulation Therapy Using Tolerogenic Macrophages in a Rodent Model of Pulmonary Hypertension.

Stem Cells Dev 2021 05 16;30(10):515-525. Epub 2021 Apr 16.

Transplant and Stem Cells Immunobiology (TSI) Lab, University Heart Center of Hamburg, Hamburg, Germany.

Inflammation plays a major role in the pathogenesis of pulmonary hypertension (PH). We sought to investigate the effects of a cell-based immunomodulation in a dysimmune model of PH. PH was induced in athymic nude rats using semaxinib (Su group,  = 6). Tolerogenic macrophages (toM) were generated from monocyte isolation and then injected either the day before semaxinib injection (Prevention group,  = 6) or 3 weeks after (Reversion group,  = 6). Six athymic nude rats were used as controls. In vivo trafficking of toM was investigated with bioluminescence imaging showing that toM were mainly located into the lungs until 48 h after injection. Right ventricular (RV) end-systolic pressure and RV systolic function were assessed at 4 weeks using echocardiography. Morphometric analysis and RNA sequencing of the lungs were realized at 4 weeks. Rats treated with toM (Prevention and Reversion groups) had a significantly lower RV end-systolic pressure at 4 weeks (respectively, 25 ± 8 and 30 ± 6 mmHg vs. 67 ± 9 mmHg,  < 0.001), while RV systolic dysfunction was observed in Su and Reversion groups. Mean medial wall thickness of small arterioles was lower in Prevention and Reversion groups compared with the Su group (respectively, 10.9% ± 0.8% and 16.4% ± 1.3% vs. 28.2% ± 2.1%,  < 0.001). Similarly, cardiomyocyte area was decreased in rats treated with toM (150 ± 18 and 160 ± 86 μm vs. 279 ± 50 μm,  < 0.001). A trend toward upregulation of genes involved in pulmonary arterial hypertension pathobiology was found in Su rats, while was significantly downregulated (fold-change = 9.8,  < 0.001). Injection of toM was associated with a less severe phenotype of PH in rats exposed to angioproliferative stress. Preserved expression of may explain the protective effect of toM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/scd.2021.0007DOI Listing
May 2021

Cannabis use and lung cancer: time to stop overlooking the problem?

Eur Respir J 2021 05 20;57(5). Epub 2021 May 20.

Thoracic Surgery and Pneumology Dept, Marie Lannelongue Hospital, Paris Saint Joseph Hospital and Paris Saclay University, Le Plessis-Robinson, France

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.04132-2020DOI Listing
May 2021

Lung transplantation for sarcoidosis: outcome and prognostic factors.

Eur Respir J 2021 08 5;58(2). Epub 2021 Aug 5.

Dept of Respiratory Medicine, Hannover Medical School, Hanover, Germany.

Study Question: In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation.

Patients And Methods: We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres.

Results: Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications.

Answer To The Study Question: Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.03358-2020DOI Listing
August 2021

Serum and pulmonary uric acid in pulmonary arterial hypertension.

Eur Respir J 2021 08 5;58(2). Epub 2021 Aug 5.

School of Medicine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

Previous studies have suggested an association between uric acid (UA) and the severity of pulmonary arterial hypertension (PAH), but it is unknown whether UA contributes to disease pathogenesis.The aim of this study was to determine the prognostic value of circulating UA in the era of current management of PAH and to investigate the role of UA in pulmonary vascular remodelling.Serum UA levels were determined in idiopathic, heritable or anorexigen PAH at baseline and first re-evaluation in the French Pulmonary Hypertension Network. We studied protein levels of xanthine oxidase (XO) and the voltage-driven urate transporter 1 (URATv1) in lungs of control and PAH patients and of monocrotaline (MCT) and Sugen/hypoxia (SuHx) rats. Functional studies were performed using human pulmonary artery smooth muscle cells (PA-SMCs) and two animal models of pulmonary hypertension (PH).High serum UA levels at first follow-up, but not at baseline, were associated with a poor prognosis. Both the generating enzyme XO and URATv1 were upregulated in the wall of remodelled pulmonary arteries in idiopathic PAH patients and MCT and SuHx rats. High UA concentrations promoted a mild increase in cell growth in idiopathic PAH PA-SMCs, but not in control PA-SMCs. Consistent with these observations, oxonic acid-induced hyperuricaemia did not aggravate MCT-induced PH in rats. Finally, chronic treatment of MCT and SuHx rats with benzbromarone mildly attenuated pulmonary vascular remodelling.UA levels in idiopathic PAH patients were associated with an impaired clinical and haemodynamic profile and might be used as a non-invasive indicator of clinical prognosis during follow-up. Our findings also indicate that UA metabolism is disturbed in remodelled pulmonary vascular walls in both experimental and human PAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00332-2020DOI Listing
August 2021

Immunodynamics of explanted human tumors for immuno-oncology.

EMBO Mol Med 2021 01 29;13(1):e12850. Epub 2020 Dec 29.

Institut Gustave Roussy, Villejuif, France.

Decision making in immuno-oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno-assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti-PD-1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/emmm.202012850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799366PMC
January 2021

Hemodynamic trajectories and outcomes in patients with pulmonary arterial hypertension.

Pulm Circ 2020 Oct-Dec;10(4):2045894020941343. Epub 2020 Dec 6.

Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.

The relative pulmonary to systemic pressure ratio (mean pulmonary arterial pressure/mean arterial pressure) has been proven to be valuable in cardiac surgery. Little is known on the prognostic value of baseline and trajectory of mean pulmonary arterial pressure/mean arterial pressure in pulmonary arterial hypertension. Patients with confirmed idiopathic, familial, drug and toxins, or connective tissue disease-related pulmonary arterial hypertension and at least one complete right heart catheterization were included and prospectively followed-up for 5.9 ± 4.03 years. Correlates of the primary end point (i.e. death or lung transplant need) during follow-up were determined using Cox regression modeling. Results showed that among the 308 patients included, 187 had at least one follow-up catheterization (median time between catheterizations: 2.16 (1.16-3.19) years). In the total cohort (mean age 47.3 ± 14.9 years, 82.8% of female and 58.1% in New York Heart Association class 3 or 4), mean pulmonary arterial pressure/mean arterial pressure (1.38 (1.07-1.77)) was associated with outcome ( = 0.01). Mean pulmonary arterial pressure/mean arterial pressure was incremental to a basic model (including right atrial pressure, systolic blood pressure, New York Heart Association class 3 or 4, and connective tissue disease) for outcome prediction, while mean pulmonary arterial pressure was not. In the 187 patients with a follow-up catheterization, both delta mean pulmonary arterial pressure and delta mean pulmonary arterial pressure/mean arterial pressure were associated with outcome (1.32 (1.11-1.58) and 1.31 (1.1-1.57) respectively,  < 0.01). Mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean arterial pressure were both incremental to the basic model, while worsening in mean pulmonary arterial pressure or mean pulmonary arterial pressure/mean arterial pressure did not reach significance. In conclusion, mean pulmonary arterial pressure/mean arterial pressure at baseline prognosticates long-term outcome with a significant, albeit modest, incremental value to basic variables.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2045894020941343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724418PMC
December 2020

ERS statement on chronic thromboembolic pulmonary hypertension.

Eur Respir J 2021 06 17;57(6). Epub 2021 Jun 17.

Université Paris-Saclay; Inserm UMR_S 999, Service de Pneumologie, Hôpital Bicêtre (AP-HP), Le Kremlin-Bicêtre, France.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.02828-2020DOI Listing
June 2021

Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.

Eur Respir J 2021 04 8;57(4). Epub 2021 Apr 8.

Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, Stanford, CA, USA.

No prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.High levels of hepatocyte growth factor (HGF), stem cell growth factor-β, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk of heart failure who warrant closer follow-up and intensified therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.02428-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029214PMC
April 2021

Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension.

Biomedicines 2020 Nov 11;8(11). Epub 2020 Nov 11.

School of Medicine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 μm PA, and only Stage I was observed in larger-diameter PA (>1000 μm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines8110493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696066PMC
November 2020

Our current understanding of and approach to the management of lung cancer with pulmonary hypertension.

Expert Rev Respir Med 2021 03 17;15(3):373-384. Epub 2021 Feb 17.

Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital GHPSJ, Institut d'Oncologie Thoracique and Paris Saclay University, France.

Introduction: Lung cancer is a frequent pathology for which the best curative treatment is pulmonary resection. Pulmonary arterial hypertension is a rare disease but pulmonary hypertension associated with parenchymal disease or left heart disease is frequently observed in these patients. The diagnosis of pulmonary hypertension before lung resection makes the perioperative management of these patients more difficult and sometimes leads to rejecting patients for surgery.

Areas Covered: We performed a review of literature on PubMed on Pulmonary hypertension associated lung resection, preoperative assessment of lung resection and perioperative management of PH patients, including guidelines and clinical trials.In this review, we summarize the current state of knowledge regarding the pre and perioperative management of patients with suspected or confirmed PH who can benefit from surgical treatment of lung cancer.

Expert Opinion: Management of PH patients before lung resection should include a very careful workup including at least right heart catheterization with evaluation of the targeted PH treatment in an expert center and evaluation of other comorbidities. Perioperative management must be carried out in a specialized center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17476348.2021.1842202DOI Listing
March 2021

Long-term Results and Functional Outcomes After Surgical Repair of Benign Laryngotracheal Stenosis.

Ann Thorac Surg 2021 06 6;111(6):1834-1841. Epub 2020 Oct 6.

Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital and Paris Saclay University, Le Plessis-Robinson, France. Electronic address:

Background: Laryngotracheal resection and anastomosis (LTRA) is a reliable treatment for benign subglottic laryngotracheal stenosis (BSLTS), but data on functional outcomes are scarce. We assessed the surgical and functional outcomes of LTRA in BSLTS.

Methods: We retrospectively reviewed consecutive patients who underwent LTRA for BSLTS in 2007 to 2018. The 30-day outcomes were mortality, complications, and success rate. At the last follow-up, patients completed functional questionnaires (visual analog scale [VAS] and modified Medical Research Council scale for dyspnea, a VAS for swallowing, and the Voice Handicap Index) and assessed quality of life.

Results: Of 43 patients with BSLTS, 28 underwent the modified Pearson technique, and 15 Grillo's procedure. During the first 30 days, no patients died, the postoperative complication rate was 44%, and the success rate was 95%. After a mean follow-up of 53 months in 38 patients (88%), 7 patients had restenosis and 36 had late surgical success (95%). In the 34 patients who completed the questionnaires (79%), mean VAS dyspnea scores decreased significantly during rest (-5.4 ± 4.2) and exercise (-5.6 ± 4.4) (P < .001). A trend toward a decrease in modified Medical Research Council scale was found (P = .057; grade 0 in 62% of patients). The Voice Handicap Index indicated that voice impairment was absent to moderate in 30 patients (88%) and severe in 4 (12%). The VAS dysphagia scores were not significantly different before and after surgery. Quality of life gains were reported by 85% of patients.

Conclusions: Laryngotracheal resection and anastomosis for BSLTS is safe and provides excellent surgical and functional outcomes with an improved quality of life. Laryngotracheal resection and anastomosis is a valid treatment option for BSLTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2020.07.046DOI Listing
June 2021

Decreased expression of miR-29 family associated with autoimmune myasthenia gravis.

J Neuroinflammation 2020 Oct 8;17(1):294. Epub 2020 Oct 8.

Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology, UMRS 974, Paris, France.

Background: Myasthenia gravis (MG) is a rare autoimmune disease mainly mediated by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction. The thymus is the effector organ, and its removal alleviates the symptoms of the disease. In the early-onset form of MG, the thymus displays functional and morphological abnormalities such as B cell infiltration leading to follicular hyperplasia, and the production of AChR antibodies. Type-I interferon (IFN-I), especially IFN-β, is the orchestrator of thymic changes observed in MG. As Dicer and miR-29 subtypes play a role in modulating the IFN-I signalization in mouse thymus, we investigated their expression in MG thymus.

Methods: The expression of DICER and miR-29 subtypes were thoroughly investigated by RT-PCR in human control and MG thymuses, and in thymic epithelial cells (TECs). Using miR-29a/b-1-deficient mice, with lower miR-29a/b-1 expression, we investigated their susceptibility to experimental autoimmune MG (EAMG) as compared to wild-type mice.

Results: DICER mRNA and all miR-29 subtypes were down-regulated in the thymus of MG patients and DICER expression was correlated with the lower expression of miR-29a-3p. A decreased expression of miR-29 subtypes was similarly observed in MG TECs; a decrease also induced in TECs upon IFN-β treatment. We demonstrated that miR-29a/b-1-deficient mice were more susceptible to EAMG without higher levels of anti-AChR IgG subtypes. In the thymus, if no B cell infiltration was observed, an increased expression of Ifn-β associated with Baff expression and the differentiation of Th17 cells associated with increased expression of Il-6, Il-17a and Il-21 and decreased Tgf-β1 mRNA were demonstrated in miR-29a/b-1-deficient EAMG mice.

Conclusions: It is not clear if the decreased expression of miR-29 subtypes in human MG is a consequence or a causative factor of thymic inflammation. However, our results from the EAMG mouse model indicated that a reduction in miR-29a/b1 may contribute to the pathophysiological process involved in MG by favoring the increased expression of IFN-β and the emergence of pro-inflammatory Th17 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-020-01958-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545844PMC
October 2020

Carotid webs management in symptomatic patients.

J Vasc Surg 2021 04 1;73(4):1290-1297. Epub 2020 Sep 1.

Vascular Center, Hôpital Marie Lannelongue, Groupe Hospitalier Paris Saint Joseph, Université Paris Saclay, Paris, France. Electronic address:

Background: Atypical fibromuscular dysplasia (AFMD), also known as carotid web, is a rare underdiagnosed shelf-like fibrous tissue arising from the posterior carotid artery bulb that is a cause of cryptogenic stroke of the anterior cerebral vascularization. Despite the recurrence and severity of strokes caused by embolization associated with AFMD, there are no recommendations on the best strategy to manage single and bilateral lesions, which have unsatisfactory outcomes when treated with medical treatment exclusively.

Methods: From January 2016 to April 2019, 365 patients were operated on for a carotid stenosis in our institution. This cohort included 11 patients (3%), with a median age of 41 years (range, 39-51 years), referred by a stroke unit, treated for a symptomatic (10 strokes and 1 recurrent transient ischemic attack) AFMD lesion. Preoperative workup revealed a contralateral similar lesion in 45% of patients (5/11), which all also underwent surgery during a subsequent hospitalization. The diagnosis was confirmed by histologic examination when open surgery was performed. The 30-day and 1-year outcomes were retrospectively reviewed.

Results: Of the 16 AFMD lesions operated, 13 were treated by open surgery (2 by classic endarterectomy and 11 by internal carotid resection-anastomosis) and 3 by carotid artery stenting, respectively, with a mean delay of 85.5 days and 20.5 days after the latest stroke. There was one complication after stenting (external iliac rupture) that was treated by a covered stent, and no perioperative complications after open surgery. The follow-ups at 30 days and 1 year were uneventful for all patients, without any deaths or stroke recurrences.

Conclusions: Symptomatic AFMD is a rare cause of cryptogenic stroke. Bilateral lesions are frequent. Early intervention is associated with favorable perioperative and 1-year outcomes. Open surgery is the first-line therapeutic option in this young patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2020.08.035DOI Listing
April 2021

Long-term Outcomes of Oral Vinorelbine in Advanced, Progressive Desmoid Fibromatosis and Influence of Mutational Status.

Clin Cancer Res 2020 12 1;26(23):6277-6283. Epub 2020 Sep 1.

Department of International Patients Care, Gustave Roussy Cancer Institute, Villejuif, Paris, France.

Purpose: Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression to avoid the short- and long-term complications of local treatments.

Experimental Design: We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute (Villejuif, Paris, France). Only patients with documented progressive disease according to RECIST v1.1 for more than 3 months (±2 weeks) before treatment initiation were included.

Results: From 2009 to 2019, 90 out of 438 patients with DF were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34 patients, for a median duration of 6.7 months. A partial response was observed in 29% and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women [HR, 2.16; 95% confidence interval (CI), 1.06-4.37; = 0.03). Among 64 patients with documented mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared with p.T41A or wild-type tumors (HR, 2.78; 95% CI, 1.23-6.27; = 0.04). Toxicity profile was favorable, without grade 3-4 toxicity, except for one grade 3 neutropenia.

Conclusions: Oral vinorelbine is an effective, affordable, and well-tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring p.S45F or p.S45P mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-1847DOI Listing
December 2020
-->