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Background Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non–dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. Methods We retrospectively studied all consecutive patients diagnosed with AS (peak aortic jet velocity [Vmax] ≥ 2.5 m/s) and left ventricular ejection fraction ≥ 50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018’. The estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. Results Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8–4.8) years, the mean overall rate of change in AVA was -0.077; 95%CI [-0.082; -0.073] cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P Conclusions Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

BackgroundConventional transthoracic (TTE) and transoesophageal echocardiography (TEE) parameters assessing right ventricle (RV) systolic function are daily used assuming their clinical interchangeability. RV longitudinal shortening fraction (RV-LSF) is a two-dimensional speckle tracking parameter used to assess RV systolic function. RV-LSF is based on tricuspid annular displacement analysis and could be measured with TTE or TEE.ObjectiveThe aim of the study was to determine if RV-LSFTTE and RV-LSFTEE measurements were interchangeable in the perioperative setting.MethodsProspective perioperative TTE and TEE echocardiography were performed under general anesthesia during scheduled cardiac surgery in 90 patients. RV-LSF was measured by semi-automatic software. Comparisons were performed using Pearson correlation and Bland-Altman plots. RV-LSF clinical agreement was determined as a range of −5 to 5%.ResultsOf the 114 patients who met the inclusion criteria, 90 were included. The mean preoperative RV-LSFTTE was 20.4 ± 4.3 and 21.1 ± 4.1% for RV-LSFTEE. The agreement between RV-LSF measurements was excellent, with a bias at −0.61 and limits of agreement of −4.18 to 2.97 %. All measurements fell within the determined clinical agreement interval in the Bland-Altman plot. Linear regression analysis showed a high correlation between RV-LSFTTE and RV-LSFTEE measurement (r = 0.9; confidence interval [CI] 95%: [0.87–0.94], p < 0.001).ConclusionRV-LSFTTE and RV-LSFTEE measurements are interchangeable, allowing RV-LSF to be a helpful parameter for assessing perioperative changes in RV systolic function.NCTNCT05404737. https://www.clinicaltrials.gov/ct2/show/NCT05404737.

Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy - CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs' seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels. ispartof: Sci Rep vol:9 issue:1 pages:4477- ispartof: location:England status: Published online

Background/Aims: Post-stroke neurocognitive disorders (post-stroke NCD) have been reported with a very variable prevalence. Methods: Based on a systematic literature search, hospital-based studies published between January 1990 and September 2015 were selected when they reported the prevalence of total, mild, and major post-stroke NCD diagnosed by using specified criteria. Factors affecting prevalence were assessed using meta-regression analysis. Results: Among the 7,440 references evaluated, 16 hospital-based studies were selected, corresponding to a total of 3,087 patients. The overall prevalence of total post-stroke NCD was 53.4% (95% CI: 46.9–59.8): 36.4% for mild post-stroke NCD (95% CI: 29–43.8) and 16.5% (95% CI: 12.1–20.8) for major post-stroke NCD. The overall prevalence was mainly influenced by the threshold score used for categorization (p = 0.0001) and, in the subgroup of studies using a conservative threshold (i.e., ≤7th percentile), by the recurrent stroke rate (p = 0.0005). The prevalence of major post-stroke NCD was mainly influenced by age (p = 0.003). Conclusion: More than half of stroke survivors experience post-stroke NCD, corresponding to mild post-stroke NCD in two-thirds of cases and major post-stroke NCD in one-third of cases. Harmonization of stroke assessment and cognitive score thresholds is urgently needed to allow more accurate estimation of post-stroke NCD prevalence, especially mild post-stroke NCD.

International audience; An amendment to this paper has been published and can be accessed via the original article.

Supplemental Digital Content is available in the text, The Bland–Altman (BA) and percentage error (PE) methods have been previously described to assess the agreement between 2 methods of medical or laboratory measurements. This type of approach raises several problems: the BA methodology constitutes a subjective approach to interchangeability, whereas the PE approach does not take into account the distribution of values over a range. We describe a new methodology that defines an interchangeability rate between 2 methods of measurement and cutoff values that determine the range of interchangeable values. We used a simulated data and a previously published data set to demonstrate the concept of the method. The interchangeability rate of 5 different cardiac output (CO) pulse contour techniques (Wesseling method, LiDCO, PiCCO, Hemac method, and Modelflow) was calculated, in comparison with the reference pulmonary artery thermodilution CO using our new method. In our example, Modelflow with a good interchangeability rate of 93% and a cutoff value of 4.8 L min−1, was found to be interchangeable with the thermodilution method for >95% of measurements. Modelflow had a higher interchangeability rate compared to Hemac (93% vs 86%; P = .022) or other monitors (Wesseling cZ = 76%, LiDCO = 73%, and PiCCO = 62%; P < .0001). Simulated data and reanalysis of a data set comparing 5 CO monitors against thermodilution CO showed that, depending on the repeatability of the reference method, the interchangeability rate combined with a cutoff value could be used to define the range of values over which interchangeability remains acceptable.

International audience; Contamination of natural aquatic ecosystems by Cryptosporidium is a major environmental and human health issue. In Haiti, environmental Cryptosporidium oocysts pollution has been well documented by previous studies conducted in several cities of the country. In groundwater from Les Cayes of Haiti, significant concentrations from 1 to 989 oocysts in 100 liters of filtered water were calculated. Results of these studies revealed high level of Cryptosporidium oocysts pollution in surface water and groundwater. Therefore, regarding cryptosporidiosis, contaminated water resources constitute a real sanitary risk mainly for children and immunocompromised individuals. So, it is necessary to assess the biological risk for populations served by those polluted water resources. The aim of this study is to present: (i) the steps of a procedure intended to evaluate risks to human health linked to the consumption of water from groundwater; and (ii) the results of its application on groundwater from Les Cayes, city located in southwestern Haiti. The procedure is based on a scenario that describes the existence of an uncontrolled landfill leachate which are neither collected nor treated. The refuse has a close contact with the soil making easy the transfer of various pollutants from the surface to groundwater. Moreover, latrines and septic tanks are often discharged into the unsaturated zone of the geological matrix are also retained. Risk estimation was calculated for two groups in the exposed population: immunocompetent and immunocompromised individuals. As expected, the study revealed a high risk for individuals in the immunocompromised group.; La contaminación de los ecosistemas acuáticos naturales por Cryptospridium parvum constituye una verdadera preocu-pación de salud humana e ambiental principalmente en los países en desarrollo. En Haití, los oocitos de cryptosporidios se han encontrado en muchas ciudades del país en las aguas de superficie y las aguas destinadas al consumo humano. En las aguas subterráneas en Les Cayes de Haití, concentraciones significativas de 1 a 989 oocitos en 100 litros de agua filtrada han sido determinadas. Los resultados de estos estudios han revelado un nivel elevado de polución por oocitos de Cryptosporidium en las aguas de superficie y aguas subterráneas. Por ende, los recursos en agua contaminados por oocitos constituyen un verdadero riesgo sanitario para los niños y las personas inmunodeprimidas. Así, se hace necesario evaluar el riesgo biológico para las poblaciones que se abastecen de estos recursos en agua contaminados. El objetivo de este estudio es presentar: (i) las etapas de un procedimiento destinado a evaluar los riesgos para la salud humana ligados al consumo de agua proveniente de las aguas subterráneas; et (ii) los resultados de la aplicación de este proced-imiento en las aguas subterráneas en Les Cayes, ciudad situada en el suroeste de Haití. El procedimiento está basado en un escenario que describe la existencia de una descarga violenta en donde los lixiviados no son ni recolectados ni tratados. Las basuras están directamente en contacto con el suelo y siguen los mecanismos de transferencia hacia la capa de agua subterránea. Además, las letrinas y fosas sépticas, rechazando sus efluentes en la zona no saturada de la matriz geológica, están igualmente retenidas. La estimación del riesgo ha sido calculada para dos grupos en la población expuesta: inmunodeprimida y immunocompetente. Este aparece como un riesgo elevado para los inmunodeprimidos.; La contamination des écosystèmes aquatiques naturels par Cryptospridium parvum constitue une véritable préoccupa-tion de santé hu et environnementale principalement dans les pays en développement. En Haïti, des oocytes de cryptosporidies ont été retrouvés dans plusieurs villes du pays dans les eaux de surface et dans les eaux destinées à la consommation humaine. Dans les eaux souterraines Les Cayes d'Haïti, des concentrations significatives de 1 à 989 oo-cystes dans 100 litres d'eau filtrée ont été déterminées. Les résultats de ces études ont révélé un niveau élevé de pollution par des oocystes de Cryptosporidium dans les eaux de surface et des eaux souterraines. Par conséquent, les ressources en eau contaminés par des oocystes constituent un véritable risque sanitaire principalement pour les enfants et les per-sonnes immunodéprimées. Ainsi, il apparaît nécessaire d'évaluer le risque biologique pour les populations desservies par ces ressources en eau polluées. Le but de cette étude est de présenter: (i) les étapes d'une procédure destinée à évaluer les risques pour la santé humaine liés à la consommation d'eau provenant des eaux souterraines; et (ii) les résultats de l'application de cette procédure sur les eaux souterraines Les Cayes, ville située dans le sud-ouest Haïti. La procédure est basée sur un scénario qui décrit l'existence d'une décharge sauvage où les lixiviats ne sont ni collectés, ni traités. Les déchets sont directement en contact avec le sol et suivent les mécanismes de transfert vers la nappe. En outre, les latrines et fosses septiques, rejetant leurs effluents dans la zone non saturée de la matrice géologique, sont également retenues. L'estimation du risque a été calculée pour deux groupes dans la population exposée: immunodéprimé et immunocompétent. Il apparaît comme attendu un risque élevé pour les immunodéprimés.

International audience; PurposePrimary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance.Patients and MethodsPatients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS).ResultsForty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance).ConclusionIn this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.

International audience; The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma prognosis with concomitant systemic and neurological involvement at diagnosis is poor with a high risk of relapse when treated with conventional chemotherapies alone. This retrospective study supports the feasibility and the potential benefit of a consolidative strategy with high-dose therapy followed by autologous stem cell transplantation in this subset of patients. This strategy and the best intensive chemotherapy regimen remain to be validated in prospective trials.

The primary objective of this thesis is to evaluate the added prognostic value of health-related quality of life (QoL) inoncology and to explore ils utility for routine clinical practice as well as for design of clinical trials.In a methodological point of view, we will fïrst compare statistical and clinical performances of a model based onclinico-biological variables and a model based on clinico-biological variables and QoL scores.After validation of ils prognostic value, optimal cut-off points for QoL scores will be explored and revised prognosticclassifications including QoL measures will be built. QoL could then be used to guide treatment assignment and asinclusion/exclusion criteria or as stratification criteria in randomized clinical trials.For the different types of cancer, the validation of the prognostic value of QoL for advanced cancer patients will beperformed according to standard recommendations. The following steps will be performed:> Selection of prognostic factors based on univariable Cox models.> Multivariable Cox models using stepwise procedure. The number of variables entering the multivariable modelwill be selected in such a way that the thumb rule (10 events per variable) will be respected.> If a prognostic System exists, compare its performance alone with ils performance after addition of QoL factorsas well as other clinico-biological factors not included in the prognostic System.> Verify model hypotheses.> Assess model performance using HarreH"s C-index, Schempers V statistic, The NRI (Net ReclassificationImprovement) and the IDI (Integrated Discrimination Improvement). Perform sensitivity analysis after imputation of missing QoL data. Internai validation ofnew models. Find cut-off values for QoL scales to facilitate their use in daily practice.Three type of cancer will be studied: Advanced hepatocellular carcinoma. Metastatic pancreatic adenocarcinoma. Metastatic colorectal cancer.; L'objectif principal de cette thèse est d'étudier la valeur pronostique de la qualité de vie (QdV) en cancérologie etd'explorer son utilité tant pour la pratique clinique que pour la planification des essais.Pour ce faire, nous évaluerons la significativité statistique et clinique de rapport d'un modèle de prédiction composé defacteurs cliniques et de la Qdv par rapport à un modèle de prédiction composé uniquement de facteurs cliniques.La validation statistique et clinique de cette plus-value de la Qdv en oncologie, permettrait de construire des index plusprécis en termes de pronostic vital, et mieux adapter les traitements. En fonction de sa valeur pronostic, la Qdv pourraitservir de critère de stratification dans les essais randomisés en oncologie.Pour les différentes localisations et le stade concernés, la recherche des facteurs pronostics sera réalisée selon lesrecommandations publiées dans la littérature. La procédure suivante sera utilisée :> Sélection des facteurs pronostics par un modèle univarié.> Construction d'un modèle multivarié par sélection « forward », « backward » ou « stepwise » en respectant aumieux la « règle de 10 événements par variable ».> Si existence de scores pronostics étudier l'apport de la Qdv à ces scores.> Vérifications à posteriori des hypothèses du modèle.> Mesure de la concordance entre les valeurs prédites et les valeurs observées à l'aided'indicateurs comme le C-index d'Harell, la statistique de Schemper, le NR1 (Net Reclassification Improvement) et l'IDI (Integrated Discrimation Improvement) de d'Agostino. Analyse de sensibilité par rapport aux données manquantes dans les différentes dimensions de la qualité de vie.Validation interne et/ou externe du modèle. Recherche de valeurs seuil pour les différents scores de qualité de vie dans le but d'une meilleure applicationclinique.Trois localisations seront étudiées : Carcinome hépatocellulaire en situation palliative. Cancer du pancréas métastatique. Cancer colorectal métastatique