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Importance: Ninety-day mortality rates after esophagectomy are an indicator of the quality of surgical oncologic management. Accurate risk prediction based on large data sets may aid patients and surgeons in making informed decisions. Objective: To develop and validate a risk prediction model of death within 90 days after esophagectomy for cancer using the International Esodata Study Group (IESG) database, the largest existing prospective, multicenter cohort reporting standardized postoperative outcomes. Design, Setting, and Participants: In this diagnostic/prognostic study, we performed a retrospective analysis of patients from 39 institutions in 19 countries between January 1, 2015, and December 31, 2019. Patients with esophageal cancer were randomly assigned to development and validation cohorts. A scoring system that predicted death within 90 days based on logistic regression ß coefficients was conducted. A final prognostic score was determined and categorized into homogeneous risk groups that predicted death within 90 days. Calibration and discrimination tests were assessed between cohorts. Exposures: Esophageal resection for cancer of the esophagus and gastroesophageal junction. Main Outcomes and Measures: All-cause postoperative 90-day mortality. Results: A total of 8403 patients (mean [SD] age, 63.6 [9.0] years; 6641 [79.0%] male) were included. The 30-day mortality rate was 2.0% (n = 164), and the 90-day mortality rate was 4.2% (n = 353). Development (n = 4172) and validation (n = 4231) cohorts were randomly assigned. The multiple logistic regression model identified 10 weighted point variables factored into the prognostic score: age, sex, body mass index, performance status, myocardial infarction, connective tissue disease, peripheral vascular disease, liver disease, neoadjuvant treatment, and hospital volume. The prognostic scores were categorized into 5 risk groups: very low risk (score, =1; 90-day mortality, 1.8%), low risk (score, 0; 90-day mortality, 3.0%), medium risk (score, -1 to -2; 90-day mortality, 5.8%), high risk (score, -3 to -4: 90-day mortality, 8.9%), and very high risk (score, =-5; 90-day mortality, 18.2%). The model was supported by nonsignificance in the Hosmer-Lemeshow test. The discrimination (area under the receiver operating characteristic curve) was 0.68 (95% CI, 0.64-0.72) in the development cohort and 0.64 (95% CI, 0.60-0.69) in the validation cohort. Conclusions and Relevance: In this study, on the basis of preoperative variables, the IESG risk prediction model allowed stratification of an individual patient's risk of death within 90 days after esophagectomy. These data suggest that this model can help in the decision-making process when esophageal cancer surgery is being considered and in informed consent.

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (&lt, 50 &micro, m 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 &lt, 300 &micro, m PA. Stages II and III were observed in 300 to 1000 &mu, m PA, and only Stage I was observed in larger-diameter PA (&gt, 1000 &mu, m). 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.

Supplemental material, sj-pdf-1-pul-10.1177_2045894020941343 for Hemodynamic trajectories and outcomes in patients with pulmonary arterial hypertension by Myriam Amsallem, Shadi P. Bagherzadeh, David Boulate, Andrew J. Sweatt, Kristina T. Kudelko, Yon K. Sung, Jeffrey A. Feinstein, Elie Fadel, Olaf Mercier, Andre Denault, Francois Haddad and Roham Zamanian in Pulmonary Circulation

Right heart failure is the leading cause of mortality in patients with pulmonary hypertension (PH). At early stage of PH the right ventricle (RV) remodels to adapt to the increased pulmonary vascular resistances. This adaptation is characterized by morphological, functional and myocardial changes. The evaluation of these changes may be applied for screening, prognosis evaluation and follow-up of patients with PH. However, the pathophysiology of the transition from adaptive to maladaptive phenotypes remains unclear; and identification of RV therapeutic targets and noninvasive methods for its evaluation remains to developed. The aim of this thesis was to evaluate non-invasive screening of PH with echocardiography and to study the pathophysiology of acute right heart failure in the setting of chronic PH by performing precise phenotyping of a new large animal model. A wide review of anatomic, embryologic and physiologic concepts was performed to help for the understanding of parameters of RV evaluation; then published and ongoing original studies were presented.In a first study, we investigated PH screening with echocardiography in patients with advanced lung disease. In this study, we showed that enlargement of the RV and of the right atrium, as well as function parameters of the RV were associated with PH. When the tricuspid regurgitation was available (52% of cases), RV morphology and function parameters did not improve PH diagnosis. Abnormal RV morphology and function without available tricuspid regurgitation provided moderate detection value; whereas 20% of patients without PH presented enlargement of the RV. In a large animal model with progressive increase in pulmonary artery mechanical obstruction, enlargement of the RV was the earliest RV parameter associated with PH development. This study highlights the need for more specific RV indices of PH.In a second study we investigated right ventricular changes in a new large animal model of acute right heart failure occurring on chronic PH; a situation associated with around 40% mid term mortality or transplantation. We characterized right ventricular changes during acute volume and pressure overload and after hemodynamic restauration in a large animal model of chronic thromboembolic PH. The RV was evaluated with parameters derived from pressure-volume loops, echocardiography, right heart catheterism and with circulating biomarkers. Pathological and proteins content analyzes of the RV around 3 hours after hemodynamic restauration showed acute subendocardial and subepicardial focal ischemic lesions as well as signs of autophagy activation. We found similar ischemic lesions in RV of 5 patients who underwent a heart-lung transplantation for PH in the setting of hemodynamic compromise. Preliminary data suggest that these lesions are associated with end-organ injury and poor overall survival after heart-lung transplantation in patients with PH.In conclusion, abnormal echocardiographic right heart metrics may be observed in patients with advanced lung disease without PH limiting their use for PH screening in this population. This highlight the need for more specific right heart metrics associated with PH. At the other extreme of the spectrum of PH severity, we described for the first time a large animal model of acute right heart failure in chronic PH. We reproduced and described the main morphological and functional features observed in acute right heart failure on PH and we showed for the first time that acute right ventricular ischemic lesions may develop within few hours despite hemodynamic restauration with dobutamine. These data provide a strong rational to develop specific biomarkers to evaluate tissue lesions of the right ventricle and determine their clinical implications., L’insuffisance cardiaque droite est la première cause de mortalité des patients atteints d’hypertension pulmonaire (HP). Au début de la maladie, le ventricule droit (VD) opère un remodelage permettant une adaptation à l’augmentation des résistances vasculaires pulmonaires. Au cours de cette adaptation, les caractéristiques morphologiques, fonctionnelles et myocardiques se modifient. L’analyse de ces modifications peut s’appliquer en clinique au niveau du dépistage, de l’évaluation pronostique et du suivi des patients atteints d’HP. Néanmoins, la physiopathologie du passage d’un état compensé à un état décompensé reste à élucider de même que l’identification de nouvelles cibles thérapeutiques ou l’élaboration de méthodes non-invasives d’évaluation du VD restent à développer. L’objectif de cette thèse était d’évaluer un moyen de dépistage de l’HP en échographie cardiaque et d’étudier la physiopathologie de la défaillance ventriculaire droite sur un cœur droit remodelé. Un large rappel des notions d’anatomie, d’embryologie et de physiologie nécessaires à la compréhension des paramètres d’évaluation du VD a été réalisé, puis des études originales publiées et en cours ont été présentées.Une première étude s’est intéressée au dépistage échocardiographique d’une HP chez des patients avec une pathologie pulmonaire avancée. Nous avons montré que la dilatation de l’oreillette droite, du VD et certains paramètres fonctionnels étaient liés à une HP. Lorsque la fuite tricuspidienne était quantifiable (chez 52% des patients), l’évaluation d’autres paramètres du VD n‘améliorait pas le dépistage d’une HP. La présence de paramètres du VD anormaux chez les patients dont la fuite tricuspidienne n’était pas quantifiable n’améliorait pas le dépistage ; 20% des patients sans HP présentaient une dilatation du VD. Une validation extrinsèque chez l’animal avec une obstruction vasculaire pulmonaire modérée et progressive confirmait que la dilatation du VD était un des paramètres les plus précoces quantifiable lors du développement d’une HP. Le développement d’indices non-invasifs du VD plus spécifique d’une l’HP est nécessaire.Une seconde étude, nous avons caractérisé les modifications du VD au cours d’une insuffisance cardiaque droite aigue survenant dans le cadre d’une HP dans une nouveau modèle animal. Le VD était évalué avec des paramètres de courbes pression-volume, d’échocardiographie, de cathétérisme cardiaque droit et par des biomarqueurs circulants. L’analyse anatomopathologique et protéique du VD, environ 3 heures après la restauration hémodynamique, retrouvait des lésions d’ischémie sous-endocardiques et sous-épicardiques et des stigmates d’activation d’autophagie. Nous avons retrouvé des lésions sous-endocardiques du VD similaires chez 5 patients avec une HP ayant bénéficié d’une transplantation cardiopulmonaire dans un contexte de défaillance hémodynamique. Des données préliminaires suggèrent que ces lésions sont associées aux défaillances rénales et hépatiques et à une altération de la survie après transplantation cardiopulmonaire.En conclusion, certains signes de remodelage du VD peuvent être présents chez des patients avec des pathologies pulmonaires avancés en l’absence d’HP, ce qui limite leur intérêt pour le diagnostic non-invasif d’une HP. A l’autre extrémité du spectre de sévérité d’une HP, nous avons modélisé pour la première fois une insuffisance cardiaque droite aigue dans un modèle animal d’HP. Nous avons démontré pour la première fois que des lésions ischémiques pouvaient se développer dans le VD en quelques heures malgré l’induction d’une restauration hémodynamique avec de la dobutamine. Ces données apportent un rationnel fort pour l’évaluation des lésions tissulaires du VD à l’aide de biomarqueurs circulant en pratique clinique dont les applications restent à établir.