L’accompagnement par une patiente-partenaire pour des femmes diagnostiquées d’un cancer du sein : évaluation de la détresse émotionnelle, du soutien social perçu, du coping et du contrôle perçu.

National audienc

L’accompagnement par une patiente-partenaire pour des femmes diagnostiquées d’un cancer du sein : évaluation de la détresse émotionnelle, du soutien social perçu, du coping et du contrôle perçu.

National audienc

Towards operational hydrology for a thorough spatio-temporalexploration of the Critical Zone

International audienceOver the last century, the Critical Zone faced remarkable climate and land use changes increasing the pressures onthe Hydrosphere and giving rise to numerous environmental consequences in terms of water quantity and quality.From now on, the Critical Zone must face the challenge to supply 9 billion people with quality food and safedrinking water in a context of global warming. For the Hydrosphere, this challenge could be addressed with abetter understanding of the dynamics and resilience of aquatic environments (rivers, lakes, groundwaters, oceans).In view of the spatial and temporal variety and variability of flow dynamics and biogeochemical reactions occur-ring in the Hydrosphere a new investigation method is needed. This study approaches the concept of “operationalhydrology” aiming to enhance either the spatio-temporal distribution and the quality of environmental data for athorough exploration of the Hydrosphere.To illustrate our approach, we present natural and anthropogenic dissolved gas data (He, Ne, Ar, Kr, Xe, N2, O2,CO2, CH4, N2O, H2, BTEX, and some VOCs) measured in situ with a CF-MIMS (Chatton et al, 2016) installedin a mobile laboratory arranged in an all-terrain truck (CRITEX-Lab). This ongoing work focuses on groundwaterand the field investigation of residence time distributions, recharge processes (origins), water flow paths andmixing, biogeochemical reactivity and contamination (sources).The rationale behind “operational hydrology” could be applied to the field measurement at high-frequency ofmany other environmental parameters (temperature, cations, anions, isotopes, micro-organisms) not only for theinvestigation of groundwaters but also rivers, lakes and oceans.Eliot Chatton, Thierry Labasque, Jerome de La Bernardie, Nicolas Guihe neuf, Olivier Bour and LucAquilina; Field Continuous Measurement of Dissolved Gases with a CF-MIMS: Applications to the Physics andBiogeochemistry of Groundwater Flow; Environmental Science & Technology, in press, 2016

Mutation hypomorphe de SFTPB associée à des fibroses pulmonaires viables à l’âge adulte

National audienceIntroductionLe déficit en protéine B du surfactant B (SP-B) est associé à des formes fatales de détresse respiratoire néonatale avec pneumopathie interstitielle diffuse (PID). Très peu de cas de survie post-néonatale ont été décrits. Nous rapportons ici deux patients adultes présentant une mutation homozygote hypomorphe de SFTPB (NM_000542,5). Cette étude avait pour but d’étudier la pathogénicité de la mutation silencieuse c. 582G>A de SFTPB.MéthodesLa pathogénicité de la mutation c. 582G>A a été étudiée in silico, puis par étude de transcrits (RT-PCR, Sanger) après transfection d’un plasmide contenant les exons 4 à 6 dans des cellules A549. Une mutation abolissant totalement le site d’épissage a été utilisée comme contrôle (c. 582+1G>T). Parallèlement, des études en immunohistochimie utilisant un anticorps anti SP-B et SP-C ainsi que la coloration Hématoxyline et Éosine (HE) ont été réalisées sur des biopsies pulmonaires d’un des patients, et comparées à des tissus témoins (sain et nouveau-né avec mutation fatale de SFTPB).RésultatsLes deux patients (père et fils, tous deux issus d’unions consanguines) ont présenté une PID évoluant vers une fibrose pulmonaire à l’âge adulte et dès la petite enfance respectivement. La mutation c. 582G>A concerne le dernier nucléotide de l’exon 5 et entraîne un affaiblissement du site donneur d’épissage de l’intron 5 (MaxEntScan score 5,85 vs 10,07 pour la séquence usuelle). L’étude des transcrits a montré que la mutation pouvait induire un saut d’exon 5 (en phase) ou une rétention partielle de l’intron 5 induisant un décalage de cadre de lecture avec création d’un codon stop prématuré dans l’exon 6. Ces mêmes transcrits ont été mis en évidence pour l’abolition complète du site donneur. La mutation c. 582G>A permettait aussi l’existence d’une faible quantité de transcrit normal. L’analyse tissulaire a retrouvé un aspect de PID non spécifique fibrosante avec fibroblaste foci. Le marquage SP-B dans les cellules épithéliales alvéolaires de type 2 et les macrophages alvéolaires (recyclage) était très faible chez le patient comparativement aux témoins, mais était présent, contrairement aux analyses histologiques de poumons nouveau-nés présentant une mutation homozygote fatale de SFTPB.ConclusionCette étude associe pour la première fois les mutations de SFTPB à des formes viables à l’âge adulte de fibrose pulmonaire. La survie des patients est probablement due au caractère hypomorphe de la mutation d’épissage c. 582G>A permettant une expression faible de la protéine SP-B normale. Ces résultats incitent à rechercher des mutations de SFTPB chez les patients adultes présentant une forme précoce ou familiale de fibrose pulmonaire

Hypomorphic pathogenic variant in SFTPB leads to adult pulmonary fibrosis

International audienceBiallelic pathogenic variants in the surfactant protein (SP)-B gene (SFTPB) have been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We herein report the cases of two related adults with pulmonary fibrosis due to a new homozygous SFTPB pathogenic variant, c.582G>A p.(Gln194=). In vitro transcript studies showed that this SFTPB synonymous pathogenic variant induces aberrant splicing leading to three abnormal transcripts with the preservation of the expression of a small proportion of normal SFTPB transcripts. Immunostainings on lung biopsies of the proband showed an almost complete loss of SP-B expression. This hypomorphic splice variant has thus probably allowed the patients' survival to adulthood while inducing an epithelial cell dysfunction leading to ILD. Altogether, this report shows that SFTPB pathogenic variants should be considered in atypical presentations and/or early-onset forms of ILD particularly when a family history is identified

Hypomorphic mutation in SFTPB leads to adult pulmonary fibrosis

International audienceIntroductionSurfactant protein (SP)-B deficiency caused by bi-allelic mutations of SFTPB has been associated with fatal forms of interstitial lung diseases (ILD) in newborns and exceptional survival in young children. We report two related adults with pulmonary fibrosis (PF) due to a new homozygous SFTPB mutation.MethodsThe synonymous mutation c.582G>A p.(Gln194=) was predicted in silico to affected splicing, we analyzed in vitro the transcription. Constructs of genomic SFTPB sequence spanning exon 4 to 6, WT or mutated, were transiently expressed in A549 cells. cDNA obtained was analyzed by sequencing and electrophoresis. In parallel, Haematoxylin & eosin stainings and immunostaining targeting SP-B and SP-C were assessed on biopsy of native lung explant of the proband.ResultsThe proband and his son, both being born from consanguineous union, presented a progressive PF. The proband required lung transplantation at 51 year-old. In silico studies of the predicted transcripts highlighted three abnormal transcripts, however with the preservation of the expression of a small proportion of normal SFTPB transcripts Lung biopsy of proband showed a usual interstitial pneumonia pattern. Immunostainings showed an almostcomplete loss of SP-B expression and an abnormal expression of SP-C compared to healthy controls.ConclusionsWe first report two adult patients with a fibrosing ILD due to a hypomorphic splice mutation of SFTPB. The preservation of a small proportion of normal transcript may have allowed a residual SP-B production and could explain the long-term survival of the patients. This observation extends to SFTPB the surfactant related genes mutations involved in adult PF

Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction

International audienceHuman cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD. Methods This study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8 + T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated. Results At M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV + LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57 + /NKG2C + NK, and δ2 − γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2 + γδT cells is maintained, but total NK, CD57 + /NKG2C + NK, and δ2 − γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes. Conclusions CLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV + LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD

Airway complications in lung transplant recipients with telomere-related interstitial lung disease.

Patients with short telomere-related interstitial lung disease (ILD) have worse outcomes after lung transplantation. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD lung transplant population. We conducted a multi-institutional (Brigham and Women's Hospital, Groupe de Transplantation de la SPLF) retrospective cohort study of 63 recipients between 2009 and 2019 with ILD and short telomeres, compared to 4359 recipients from the Scientific Registry of Transplant Recipients with ILD and no known telomeropathy. In the short telomere cohort, six recipients (9.5%) developed dehiscence and nine recipients (14.3%) developed stenosis, compared to 60 (1.4%) and 149 (3.4%) in the control, respectively. After adjusting for age, sex, and bilaterality, the presence of short telomeres was associated with higher odds of dehiscence (odds ratio (OR) = 8.24, 95% confidence interval (CI) = 3.34 20.29, p < .001) and stenosis (OR = 4.63, 95% CI 2.21 9.69, p < .001). The association between the presence of short telomeres and post-transplant dehiscence and stenosis suggest that airway complications may be a contributor to increased morbidity and mortality in patients with telomere-related ILD

Airway complications in lung transplant recipients with telomere-related interstitial lung disease.

Patients with short telomere-related interstitial lung disease (ILD) have worse outcomes after lung transplantation. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD lung transplant population. We conducted a multi-institutional (Brigham and Women's Hospital, Groupe de Transplantation de la SPLF) retrospective cohort study of 63 recipients between 2009 and 2019 with ILD and short telomeres, compared to 4359 recipients from the Scientific Registry of Transplant Recipients with ILD and no known telomeropathy. In the short telomere cohort, six recipients (9.5%) developed dehiscence and nine recipients (14.3%) developed stenosis, compared to 60 (1.4%) and 149 (3.4%) in the control, respectively. After adjusting for age, sex, and bilaterality, the presence of short telomeres was associated with higher odds of dehiscence (odds ratio (OR) = 8.24, 95% confidence interval (CI) = 3.34 20.29, p &lt; .001) and stenosis (OR = 4.63, 95% CI 2.21 9.69, p &lt; .001). The association between the presence of short telomeres and post-transplant dehiscence and stenosis suggest that airway complications may be a contributor to increased morbidity and mortality in patients with telomere-related ILD

Clinical outcomes after lung transplantation for fibrosis in telomerase related genes mutation carriers

International audienceCarriers of telomerase related genes (TRG) mutation seem to present a worst prognosis with more common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT and identify pre-LT prognosis factors in a multicenter cohort of lung transplant recipients with TRG mutation.We retrospectively reviewed all identified patients with pathogenic TRG mutation (n=38; TERT, n=22, TERC, n=10, RTEL1, n=6) who received LT in France, Switzerland and Belgium between 2009 and 2018. The median age at LT was 54 years (46-59), 70% were male, and 60% had idiopathic pulmonary fibrosis (IPF). At diagnosis of pulmonary fibrosis, 84% had a hematological disease, including 8 with myelodysplasia, and 45% had a liver disease. After a median follow up of 2.2 years (1,2-3,7), 16 received a single LT, 22 a double LT and 2 a combined liver-LT.The overall post-LT median survival was 3.75 years (1.8-NA). Patients with myelodysplasia before LT had an increased risk of death after LT (HR= 4.12 (1.47-11.53) p=0.007). After LT, all patients showed anemia, 70% thrombocytopenia, and 60% neutropenia. Four patients showed severe liver disease: portal hypertension, cirrhosis. Sixteen patients (42%) experienced acute renal failure and 18 (47%) developed chronic renal insufficiency during follow up. Four developed chronic lung allograft dysfunction.Overall survival after LT supports LT in TRG mutation carriers. Careful evaluation at diagnosis, might limit LT indication for patients with established myelodysplasia