[Optimizing efficacy and security of CAR-T cells, and immune monitoring].

The immune system plays a critical role in the control and eradication of tumors. A better understanding of the anti-tumor immune mechanisms over the last decade has led to the development of immunotherapies, including cellular therapies such as those using CAR-T cells. These therapies have been remarkably effective in hematological malignancies.

Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed.

Epidemiological Study to Assess the Prevalence of Lung Cancer in patients with smoking-associated atherosclerotic cardiovascular diseases: PREVALUNG study protocol.

Introduction: Eligibility criteria definition for a lung cancer screening (LCS) is an unmet need. We hypothesised that patients with a history of atheromatous cardiovascular disease (ACVD) associated with tobacco consumption are at risk of lung cancer (LC). The main objective is to assess LC prevalence among patients with ACVD and history of tobacco consumption by using low-dose chest CT scan.

A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.

Background: Filaminopathies A are rare disorders affecting the brain, intestine, or skeleton, characterized by dominant X-linked filamin A (FLNA) gene mutations. Macrothrombocytopenia with functionally defective platelets is frequent. We have described a filaminopathy A male patient, exhibiting a C-terminal frame-shift FLNa mutation (Berrou et al.

New insights into regulation of αIIbβ3 integrin signaling by filamin A.

Background: Filamin (FLN) regulates many cell functions through its scaffolding activity cross-linking cytoskeleton and integrins. FLN was shown to inhibit integrin activity, but the exact mechanism remains unclear.

Objectives: The aim of this study was to evaluate the role of filamin A (FLNa) subdomains on the regulation of integrin αIIbβ3 signaling.

Kawasaki Disease Shock Syndrome vs Classical Kawasaki Disease: A Meta-analysis and Comparison With SARS-CoV-2 Multisystem Inflammatory Syndrome.

Background: The emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD)-and, more specifically, Kawasaki disease shock syndrome (KDSS)-prompted us to explore KDSS in a preamble of a systematic comparison between the 2 conditions.

Methods: We completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls.

Results: A total of 10 case-control series were included in the meta-analysis.

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

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

Purpose: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease.

Materials And Methods: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups.

Preoperative C-reactive protein predicts early postoperative outcomes after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.

Objective: To determine whether preoperative systemic inflammation (defined by C-reactive protein [CRP] levels ≥10 mg/L) is associated with worse functional and hemodynamic status and poor early outcomes postendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: This study included 159 patients who underwent pulmonary endarterectomy from 2009 to 2013 (derivation cohort) and 238 patients from 2015 to 2016 (validation cohort) with CRP data from the national CTEPH registry. The correlations between proinflammatory markers (CRP, interleukins 1 and 6, fibrinogen, and leukocytes) and hemodynamics were assessed in the derivation cohort.

Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous.

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells.

ICAM-1 promotes the abnormal endothelial cell phenotype in chronic thromboembolic pulmonary hypertension.

Background: Pulmonary endothelial cells play a key role in the pathogenesis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or the release of intercellular adhesion molecule-1 (ICAM-1) by pulmonary endothelial cells of patients with CTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH.

Methods: We studied pulmonary endarterectomy specimens from 172 patients with CTEPH and pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancer without metastasis.

Impact of the initiation of balloon pulmonary angioplasty program on referral of patients with chronic thromboembolic pulmonary hypertension to surgery.

Background: Balloon pulmonary angioplasty (BPA) is a technique proposed for inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study we aimed to determine whether initiation of the BPA program has modified the characteristics and outcome of patients undergoing pulmonary endarterectomy (PEA), and compared the characteristics of patients undergoing one or the other procedure.

Methods: This prospective registry study included all patients with CTEPH who underwent PEA in the French National Reference Center before (2012 to 2013) and after (2015 to 2016) BPA program initiation (February 2014).

Central versus peripheral cannulation of extracorporeal membrane oxygenation support during double lung transplant for pulmonary hypertension.

Objectives: Extracorporeal membrane oxygenation (ECMO) has become the standard of cardiopulmonary support during a sequential double lung transplant for pulmonary hypertension. Whether central or peripheral cannulation is the best strategy for these patients remains unknown. Our goal was to determine which is the best strategy by comparing 2 populations of patients.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension.

Background: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration.

Methods And Results: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation.

The importance of capillary density-stroke work mismatch for right ventricular adaptation to chronic pressure overload.

Objective: Mechanisms of right ventricular (RV) adaptation to chronic pressure overload are not well understood. We hypothesized that a lower capillary density (CD) to stroke work ratio would be associated with more fibrosis and RV maladaptive remodeling.

Methods: We induced RV chronic pressure overload over a 20-week period in 2 piglet models of pulmonary hypertension; that is, a shunt model (n = 5) and a chronic thromboembolic pulmonary hypertension model (n = 5).

Abnormal pulmonary endothelial cells may underlie the enigmatic pathogenesis of chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension results from chronic mechanical obstruction of the pulmonary arteries after acute venous thromboembolism. However, the mechanisms that result in the progression from unresolved thrombus to fibrotic vascular remodeling are unknown. We hypothesized that pulmonary artery endothelial cells contribute to this phenomenon via paracrine growth factor and cytokine signaling.

De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome.

Background: The impact of de-novo donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. We analyzed DSA that developed at Day 7 and Month (M) 1, M3, M6 and M12 after lung transplantation and evaluated their impact on chronic lung allograft dysfunction (CLAD) development and survival.

Methods: One hundred thirty-four patients who underwent lung transplantation at our institution between November 2007 and August 2013 were included in this study.

Single platelets seal neutrophil-induced vascular breaches via GPVI during immune-complex-mediated inflammation in mice.

Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex (IC)-mediated inflammation in mice immunodepleted in platelets and/or neutrophils or deficient in GPVI.

Pulmonary microvascular lesions regress in reperfused chronic thromboembolic pulmonary hypertension.

Background: Pulmonary microvascular disease (PMD) develops in both occluded and non-occluded territories in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and may cause persistent pulmonary hypertension after pulmonary endarterectomy. Endothelin-1 (ET-1) and interleukin-6 (IL-6) are potential PMD severity biomarkers, but it remains unknown whether they are related to occluded or non-occluded territories. We assessed PMD and ET-1/IL-6 gene expression profiles in occluded and non-occluded territories with and without chronic lung reperfusion in an animal CTEPH model.

Hemostatic disorders in a JAK2V617F-driven mouse model of myeloproliferative neoplasm.

Thrombosis is common in patients suffering from myeloproliferative neoplasm (MPN), whereas bleeding is less frequent. JAK2(V617F), the main mutation involved in MPN, is considered as a risk factor for thrombosis, although the direct link between the mutation and hemostatic disorders is not strictly established. We investigated this question using conditional JAK2(V617F) knock-in mice with constitutive and inducible expression of JAK2(V617F) in hematopoietic cells, which develop a polycythemia vera (PV)-like disorder evolving into myelofibrosis.

The mouse dorsal skinfold chamber as a model for the study of thrombolysis by intravital microscopy.

Although intravital microscopy models of thrombosis in mice have contributed to dissect the mechanisms of thrombus formation and stability, they have not been well adapted to study long-term evolution of occlusive thrombi. Here, we assessed the suitability of the dorsal skinfold chamber (DSC) for the study of thrombolysis and testing of thrombolytic agents by intravital microscopy. We show that induction of FeCl3-induced occlusive thrombosis is achievable in microvessels of DSCs, and that thrombi formed in DSCs can be visualised by intravital microscopy using brightfield transmitted light, or fluorescent staining of thrombus components such as fibrinogen, platelets, leukocytes, and von Willebrand factor.

Magnesium-deficiency does not alter calcineurin inhibitors activity in mice.

Introduction: Tacrolimus (TAC) and cyclosporin (CsA) are commonly responsible for hypomagnesemia that predisposes in turn for hypertension, renal impairment and encephalopathy.

Objective: The effects of TAC on Mg(2+)-homeostasis and of pre-existing Mg(2+)-deficiency on TAC immunosuppressive activity were compared to CsA in mice.

Methods: Mg(2+) was quantified in plasma, erythrocytes, urine, feces, and femurs from mice treated with TAC 5mg/kg/day.