Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach

Évaluation de la ventilation non invasive à domicile chez le sujet âgé

La population âgée dans les pays développés est en augmentation constante depuis plusieurs décennies et est marquée par une prévalence importante de l'insuffisance respiratoire chronique. La ventilation non invasive au long cours est un traitement efficace de l'IRC au stade d'hypoventilation alvéolaire mais nécessite une bonne coopération du sujet pouvant faire défaut chez les patients âgés. A partir des données d'une étude de cohorte multicentrique nous avons analysé la tolérance de la VNI chez les patients de 75 ans et plus. Cinquante quatre patients étaient âgés de 75 ans et plus à l'inclusion. L'étiologie majoritaire de l'IRC sur l'ensemble de la cohorte et parmi les patients les plus âgés est le syndrome obésité/hypoventilation alvéolaire. Sur l'ensemble de la cohorte le taux de désappareillage est faible et l'observance est satisfaisante. L'analyse comparative montre que l'observance et la qualité de vie chez les patients âgés ne diffère pas du reste de la cohorte. En revanche, il existe un risque plus important de désappareillage chez les patients âgés de 80 ans et plus. Une altération sévère des fonctions cognitives à l'initiation de la VNI semble être un facteur péjoratif pour l'observance et la tolérance au long cours. En revanche le statut de vie en couple n'a pas d'influence dans cette population. Finalement la VNI semble avoir un effet bénéfique à deux ans de suivi sur les fonctions cognitives des patients de plus de 75 ans.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Comparison of models to analyze mortality data and derive concentration-time response relationship of inhaled chemicals

International audienceThe derivation of thresholds for lethal effects for inhaled chemicals is a key issue in accidental risk management because they largely determine the outcome of land use planning, among which localization of habitations in the vicinity of a factory. This derivation is generally performed on the basis of rodent lethality data analyzed by statistical models able to extrapolate effects for different times and concentrations of exposure. A model commonly used in France is the standard probit model. In this model, effects is related to exposure concentration and duration according to the Haber's law and considers that individual thresholds, corresponding to the maximum tolerated effects before dying, are log-normally distributed among the population. This approach has been criticized for its lack of biological parameters and its inability to treat data characterized by only one time of exposure. In order to improve the current state of modeling, we proposed three alternative models. Two of them (DEBtox and Haber-TKTD models) incorporate the kinetics of the chemicals. The third one (Loguniform model) is a linearization of the standard probit model. We evaluated their performance by analyzing real data and simulated data generated with each model. For data characterized by several times of exposure, the standard probit model outperformed all other models in terms of goodness of fits and estimation of parameters. For data characterized by only one time of exposure, only DEBtox model was able to fit the data and estimate parameters, provided we dispose of several observation times, typically just after exposure and a long period afterwards

Internal Tides Energy Transfers and Interactions with the Mesoscale Circulation in Two Contrasted Areas of the North Atlantic

International audienceAbstract The energy budget of the internal tide and its life cycle is investigated with a high resolution numerical simulation and a vertical normal mode decomposition. Two areas of interest are considered: the Azores Islands over the mid Atlantic ridge and the Gulf Stream offshore the North of the US East coast shelf break. Low mode (1 and 2) internal tides are found to propagate from 100 km (mode 2) to 1000 km (mode 1) away from their generation sites. Waves loose a significant portion of their energy as they propagate through the Gulf Stream, in contrast to the Azores domain. In the Gulf Stream domain, the mesoscale circulation is responsible for energy transfers from low to high modes internal tides, while the topographic scattering is dominant in the Azores area. This transfer of energy toward high modes favours energy dissipation. The mesoscale is significant in the energy budget of modes higher than mode 1 for both domains, and for all baroclinic modes in the Gulf Stream area. The internal tide is found to extract or loose energy toward the mesoscale circulation, but this accounts for less than 14%, of the energy scattered from low internal tide modes to higher ones once summed over all contributions of the modal energy budget

NonTuberculous Mycobacteria infection and lung transplantation in cystic fibrosis: a worldwide survey of clinical practice

Abstract Background In people with cystic fibrosis infection with NonTuberculous Mycobacteria is of increasing prevalence. Mycobacterium abscessus complex is of particular concern and has been associated with adverse clinical outcomes. Optimal treatment usually requires multiple antibiotics for over 12 months. When considering lung transplantation for patients with NonTuberculous Mycobacteria potential benefits must be balanced against the risks of uncontrolled infection post-transplant and significant side-effects associated with treatment. In this survey we assessed current international practice with regard to assessing and listing patients for lung transplantation. Methods We designed a questionnaire enquiring about local practice regarding screening for NonTuberculous Mycobacteria infection, specific contra-indications to transplantation, management and segregation of patients pre- and post-transplant. The survey was sent via e-mail to 37 paediatric and adult lung transplant centres across Europe, North America and Australia. Results We gathered complete questionnaires from 21 centres (57% response rate). Few centres (29%) have a clear written policy regarding NonTuberculous Mycobacteria. Sixteen (76%) centres require molecular identification of NonTuberculous Mycobacteria species. Only four centres would consider infection with M. abscessus complex in itself a contra-indication for listing, however 76% regard it as a relative contra-indication. Eighty-six percent require treatment pre-transplantation. Finally, only 61% of centres had a clear policy regarding segration of patients pre-transplant and 48% post-transplant. Conclusions The issue of NonTuberculous Mycobacteria infection in people with cystic fibrosis requiring lung transplantation is well-recognized however current international recommendations are not detailed and there is variation in practice between centres. There is an urgent requirement for high quality clinical data to inform decision-making

Early Identification of Chronic Lung Allograft Dysfunction: The Need of Biomarkers

International audienceA growing number of patients with end-stage lung disease have benefited from lung transplantation (LT). Improvements in organ procurement, surgical techniques and intensive care management have greatly increased short-term graft survival. However, long-term outcomes remain limited, mainly due to the onset of chronic lung allograft dysfunction (CLAD), whose diagnosis is based on permanent loss of lung function after the development of irreversible lung lesions. CLAD is associated with high mortality and morbidity, and its exact physiopathology is still only partially understood. Many researchers and clinicians have searched for CLAD biomarkers to improve diagnosis, to refine the phenotypes associated with differential prognosis and to identify early biological processes that lead to CLAD to enable an early intervention that could modify the inevitable degradation of respiratory function. Donor-specific antibodies are currently the only biomarkers used in routine clinical practice, and their significance for accurately predicting CLAD is still debated. We describe here significant studies that have highlighted potential candidates for reliable and non-invasive biomarkers of CLAD in the fields of imaging and functional monitoring, humoral immunity, cell-mediated immunity, allograft injury, airway remodeling and gene expression. Such biomarkers would improve CLAD prediction and allow differential LT management regarding CLAD risk

Pour en finir avec les paradis du campagnol terrestre : de la compréhension des pullulations dans les prairies à l’action

International audienc

Évaluation de l'état des habitats benthiques du Rhône. Campagnes de terrain sur 10 stations réparties sur le Rhône. OSR6 | Axe C - Action C1 | Rapport scientifique intermédiaire

L’état du fond caillouteux des cours d’eau représente une composante importante de la qualité hydromorphologique car il sert de substrat et de support à de nombreuses espèces aquatiques (animales et végétales). Il joue dès lors un rôle majeur sur la préservation de la biodiversité du cours d’eau. L’objectif de cette action est de déterminer quel est l’état interstitiel du fond caillouteux du lit des Vieux Rhône dans les secteurs restaurés et non restaurés, concourant à mieux évaluer la qualité des habitats benthiques et hyporhéiques, ainsi que l’effet des actions de restauration sur l’état de ce fond.Pour répondre à cet objectif, un suivi temporel à haute fréquence sur dix stations a débuté en septembre 2021. Le choix des stations s’est opéré dans un souci d’obtenir une diversité de contextes géographiques et une diversité en termes de fonctionnement hydro-sédimentaire (e.g. secteurs rechargés en sédiments, secteurs de référence à fort transport solide et secteurs pavés). La technique utilisée consiste à prélever un échantillon du fond du lit à l’aide d’un « échantillonneur Mc Neil ». Ainsi, l’évaluation du colmatage se base sur la détermination de la composition granulométrique de la zone hyporhéique et plus particulièrement sur la part de sédiments fins (< 2 mm) de l’échantillon. Au terme des trois premières campagnes de mesures, les premiers résultats confirment que les stations de référence possèdent bien les pourcentages de sédiments fins les plus faibles (entre 1 et 7 %). Les stations pavées montent un pourcentage de fines plus variable, avec notamment deux stations qui dépassent le seuil de 20 % (Belley et Pierre-Bénite). Quant aux stations situées en aval des recharges sédimentaires, elles comportent entre 6 et 13 % de fines, et montrent peu d’évolution sur la période étudiée malgré l’occurrence de crues morphogènes