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Intermediate-risk pulmonary embolisms (PE) represent a heterogeneous group at the high end of hemodynamically stable patients, characterized by a higher mortality rate. This challenging population gathers many unsolved question regarding its therapeutic management. The purpose of this review is to provide an updated overview of the literature regarding further risk stratification and treatment options in this population.If anticoagulation represents the undisputed first line of treatment, some patients especially in the intermediate-high risk subgroup may necessitate or could benefit from therapeutic escalation with reperfusion therapies. This includes systemic thrombolysis (ST) or catheter-directed therapies (CDT). ST, despite its high efficacy, is not recommended in this population because of prohibitive bleeding complications. Therefore, reduced-dose ST appears to be a promising option and is actually under evaluation. CDT are percutaneous reperfusion techniques developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially improved safety compared to ST.Great progress has been made in the recent years providing a wide range of therapeutic options. Optimal selection of patients who could benefit from these treatments is the key and is based on clinical, biological and radiological parameters evaluating right ventricle function and allowing accurate risk stratification. Pulmonary Embolism Response Team represents an efficient modality for therapeutic management especially in the intermediate-high risk subgroup.

BRCA1 and BRCA2 (BReast CAncer susceptibility genes) are two tumor-suppressor genes associated with the hereditary breast and ovarian cancer susceptibility syndrome. Recent studies also suggest an increased lung adenocarcinoma risk in carriers.We conducted a multi-center retrospective study in 18 different French pulmonology and/or oncology departments on medico-administrative and clinical data prospectively collected in the Clinical Data Warehouse (CDW) of Greater Paris University Hospitals (Assistance Publique-Hôpitaux de Paris, AP-HP). Clinical characteristics and outcomes of patients with LC and a previously known BRCA1/2gl variant were retrospectively evaluated.17 patients with LC and known BRCA1/2gl variant were included. Patients were most women, former smokers with localized disease and BRCA2 variants. All LC were adenocarcinoma. For patients with medical history of cancer, median time from the first cancer in the BRCA spectrum and the LC occurrence was 20 years. Median disease-free survival (DFS) and overall survival (OS) in localized tumor (Stage I and II) was not reached and 78.6 months, respectively. In advanced cancer (Stade III and IV) median progression free survival was 9.7 months and median OS was 17.8 months. Univariate OS and DFS/PFS analyses by BRCA status did not find significant differences.Results seem to show particular LC features in carriers of BRCA2 variants: adenocarcinoma subtype, woman, former or non-smoker.

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Introduction Using immune-checkpoint inhibitors (ICIs) to manage cancer is associated with various immune-related adverse events. Central and/or peripheral neurological disorders are rare and potentially serious. We analyzed the characteristics of non-small–cell lung cancer (NSCLC) patients who developed immune-related encephalitis under anti–programmed-death protein-1 or its ligand (PD-1/PD-L1). Methods Clinical, biological and radiological characteristics of ICI-treated NSCLC patients with immune-related encephalitis, from 6 centers, were evaluated retrospectively. Results The 6 centers included 9 patients: all men, all smokers, median (range) age 67 (48–77) years, 78% adenocarcinomas, first- or second-line ICI for 5 and 4 patients, respectively. Two patients had non-active cerebral metastases at ICI onset. A median of 5 (1–22) ICI infusions preceded neurological symptoms, the most frequent being confusion (78%), fever (45%) and cerebellar ataxia (33%). CSF analyses revealed a median white blood cell count of 22/mm3 (1–210/mm3), with hyperlymphocytosis in 8 patients and high protein levels in all. All bacteriological and virological analyses were negative. Cerebral MRI was considered normal for 5 patients; 4 patients had FLAIR hypersignals consistent with brain parenchyma inflammation. Three patients required intensive care. All patients received corticosteroids (different doses), a median of 8.5 (6–18) days post-onset. Corticosteroids achieved rapid symptom regression without sequelae in 8 patients. The last patient, with the longest time until corticosteroid introduction, died. ICIs were never restarted in any patient. Conclusion Immune encephalitis, a rare but serious complication of anti–PD-1/PD-L1 therapy, carries a good prognosis when managed with early corticosteroids.

Introduction BRCA1 et BRCA2 (BReast CAncer susceptibility genes) sont 2 genes consideres comme ayant une fonction « suppresseur de tumeur » du fait de leur role dans la reparation des cassures double brin de l’ADN. Les mutations germinales des genes BRCA1 et BRCA2 ont une prevalence dans la population estimee entre 0,2 et 0,3 % et sont des facteurs de risques reconnus de developper des cancers du sein, de l’ovaire, de la prostate et du pancreas. L’association avec le CBP n’est pas reconnue. L’objectif de cette etude est de decrire le phenotype du CBP chez des personnes presentant une mutation germinale de BRCA 1/2. Methodes Etude retrospective monocentrique portant sur l’ensemble des patients suivis dans le service de pneumologie de l’hopital Tenon pour un CBP entre 2012 et 2018. Nous avons identifie les personnes presentant une mutation de BRCA 1/2 et presentons leurs caracteristiques cliniques, histologiques, moleculaires, et evolutives. Resultats Neuf cas de CBP survenant chez des personnes presentant une mutation de BRCA1/2 ont ete inclus. Les patients etaient principalement de sexe feminin (7/9), et fumeurs (6/9). Les mutations de BRCA2 (5/9) etaient preponderantes et la majorite des malades avait un antecedent de cancer du sein (5/9). L’âge median au diagnostic du CBP etait de 59 ans (45–72). Le type histologique de CBP le plus frequent etait l’adenocarcinome (7/9). Le CBP etait le plus souvent diagnostique au stade localise ou localement avance (6/9). Des mutations somatiques de KRAS ont ete retrouvees dans 2/8 CBP sans autres anomalies chez les autres. L’expression de PDL-1 etait positive dans 1/4 tumeur. Six patients ont beneficie d’une chirurgie, 2 d’une chimiotherapie (CT) et 1 d’une radio-CT. La mediane de survie sans progression (SSP) des patients operes etait de 70 mois (11–204) et 5 mois sous CT. Deux des 3 patients ont presente une reponse partielle sous sel de platine. Un 2nd CBP est survenu chez 3/6 patients operes avec une mediane de survenue de 6 ans (1–12). Conclusion Cette serie suggere que le sous-groupe des personnes porteuses d’une mutation germinale BRCA 1/2 presentant un CBP aurait un âge au diagnostic plus jeune que dans la population generale des CBP et se presenterait plus frequemment sous des formes localisees avec un risque de survenu d’un second cancer pulmonaire important. Une plus large cohorte francilienne est en cours d’analyse pour preciser ces resultats.

Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, β 4 ( PLCB4 ) and guanine nucleotide binding protein (G protein), α inhibiting activity polypeptide 3 ( GNAI3 ) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development. Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients. Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.