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The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients. [ABSTRACT FROM AUTHOR]

Copyright of Néphrologie & Thérapeutique is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An existing detailed and broadly validated kinetic scheme is augmented to capture the flame chemistry of 1-hexene under stoichiometric and fuel rich conditions including benzene formation pathways. In addition, the speciation in a premixed stoichiometric 1-hexene flame (flat-flame McKenna-type burner) has been studied under a reduced pressure of 20–30 mbar applying flame-sampling molecular-beam time-of-flight mass spectrometry and photoionization by tunable vacuum-ultraviolet synchrotron radiation. Mole fraction profiles of 40 different species have been measured and validated against the new detailed chemical reaction model consisting of 275 species and 3047 reversible elementary reactions. A good agreement of modelling results with the experimentally observed mole fraction profiles has been found under both stoichiometric and fuel rich conditions providing a sound basis for analyzing benzene formation pathways during 1-hexene combustion. The analysis clearly shows that benzene formation via the fulvene intermediate is a very important pathway for 1-hexene. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is prone to multiple complications, including cyst infection (CyI). [18F]-FDG PET/CT imaging proved useful in the diagnosis of renal and hepatic CyI. A 4-point scale comparing the uptake of [18F]-FDG in the suspected infected cyst versus the hepatic physiological background has been proposed. We performed an independent validation of this semi-quantitative scoring system. All ADPDK patients hospitalized between January 2009 and November 2019 who underwent an [18F]-FDG PET/CT for suspected CyI were retrospectively identified using computer-based databases. Medical files were systematically reviewed. CyI was conventionally defined by the combination of fever (> 38 °C), abdominal pain, increased plasma CRP levels (≥ 70 mg/L), absence of any other cause of inflammation, and favorable outcome after ≥ 21 days of antibiotics. [18F]-FDG uptake of the suspected CyI was evaluated using a 4-point scale comparing the uptake of [18F]-FDG around the infected cysts to the uptake in the hepatic parenchyma. Statistics were performed using SAS version 9.4. Fifty-one [18F]-FDG PET/CT scans in 51 patients were included, of which 11 cases of CyI. The agreement between the 4-point scale and the gold-standard criteria of CyI was significant, with an odds ratio of 6.03 for CyI in case of a score ≥ 3 (P 0.014). The corresponding sensitivity and specificity of [18F]-FDG PET/CT using the 4-point scale were 63.6% and 77.5%, respectively. Our independent validation cohort confirms the use of a semi-quantitative 4-point scoring system of [18F]-FDG PET/CT imaging in the diagnosis of CyI in patients with ADPKD. [ABSTRACT FROM AUTHOR]

Copyright of Néphrologie & Thérapeutique is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Earth System Science is an exceptionally interdisciplinary field requiring knowledge and skills from multiple scientific disciplines. Many important questions lie at the intersection of traditional disciplines and require a systems level approach. The emerging educational challenge is to train the next generation of scientists to address these topics. Here, we describe the development, delivery, and assessment of a new course in Earth System Science designed for advanced undergraduates and beginning graduate students. The course was designed to meet specific learning objectives, delivered in an inquiry-based learning environment, and assessed to determine the extent to which the learning objectives had been attained. The course consisted of readings from both texts and primary literature, lectures by UNH professors and NASA scientists, computer modeling labs, and interdisciplinary student-team research projects. Results emphasize the importance of pre-planning and resources, establishing clear and concise student learning objectives, creating of an inquiry-based learning centered environment, role-modeling how Earth System Science research is done, and meeting student demand and institutional challenges. This class can serve as a model course for upper level undergraduates and beginning graduate students to expand their disciplinary scope, skills, and readiness to address Earth System Science questions. [ABSTRACT FROM AUTHOR]

Summary: Objective: To analyse the relationship between the levels of urinary biochemical markers of type II collagen degradation and the clinical and radiological severity and progression of knee osteoarthritis (OA). Method: Seventy-five patients with primary knee OA were included in this 3-year follow-up study. Mean joint space width (JSW) of the medial compartment of the femorotibial joint was measured with a computer assisted method on standardized radiographs taken at baseline and after a 3-year follow-up. Pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities (WOMAC) were assessed at the same time points. Type II collagen peptides Coll 2-1 and Coll 2-1 NO2, as well as pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) were measured in urines at baseline, after 1 year and 3 years, with specific immunoassays. Results: At baseline, significant correlations were found between the urinary Coll 2-1 and Coll 2-1 NO2 levels and the global WOMAC score (Coll 2-1: r =0.28, P =0.01; Coll 2-1 NO2: r =0.27, P =0.02) and its subscales for pain (Coll 2-1: r =0.27, P =0.01; Coll 2-1 NO2: r =0.30, P =0.01) and function (Coll 2-1: r =0.29, P =0.01; Coll 2-1 NO2: r =0.27, P =0.02). Pyr and D-Pyr levels were not significantly correlated with the WOMAC scores. One-year change in Coll 2-1 and Coll 2-1 NO2 urinary levels were negatively correlated with a 3-year change in JSW (Coll 2-1: r =−0.31, P =0.03; Coll 2-1 NO2: r =−0.31, P =0.03), indicating that an increase of Coll 2-1 or Coll 2-1 NO2 over 1 year is predictive of subsequent joint space narrowing. Neither Pyr nor D-Pyr was correlated with radiological OA progression. Conclusions: At baseline, Coll 2-1 and Coll 2-1 NO2 urinary levels were indicative of the clinical activity of knee OA and the increase of these peptides over 1 year was predictive of the radiological progression of knee OA. [Copyright &y& Elsevier]

La tomographie par émission de positons (TEP) au [18F]fluoro-deoxy-glucose (FDG) est utile dans le diagnostic de l'infection de kyste (IK) rénal ou hépatique chez les patients atteints d'une polykystose hépato-rénale autosomique dominante (PRAD). Toutefois, la définition TEP d'une IK est floue et subjective. Dans cette étude monocentrique rétrospective observationnelle, nous caractérisons le pattern et l'intensité de l'accumulation du [18F]FDG dans les IK afin de proposer une échelle diagnostique semi-quantitative. Tous les patients PRAD hospitalisés entre 2007 et 2019 pour suspicion d'IK et ayant bénéficié d'une TEP au [18F]FDG ont été identifiés. Une IK était définie par la présence simultanée de 5 critères : fièvre > 38 ° C ; douleur abdominale ; CRP ≥ 70 mg/L ; pas d'autre cause à l'épisode infectieux ; et évolution favorable après une antibiothérapie d'au moins 21 jours. Initialement, les images de TEP au [18F]FDG ont été interprétées de façon conventionnelle. Ensuite, l'intensité de l' uptake de [18F]FDG autour du kyste suspect a été quantifiée en utilisant une échelle à 4 grades comparant l'intensité observée à celle du foie et du pool sanguin. Soixante TEP au [18F]FDG ont été réalisées chez 38 patients. Vingt-neuf épisodes correspondaient aux critères d'IK. L'interprétation conventionnelle de la TEP au [18F]FDG aboutissaient à une sensibilité de 73,1 % et une spécificité de 70,6 %. En appliquant l'échelle visuelle de 4 grades, la spécificité augmentait à 85,3 % en considérant le seuil diagnostique d'un signal kystique ≥ 3 (c.-à-d. un uptake kystique supérieur à l'activité basale du foie). En conclusion, la TEP au [18F]FDG est utile dans le diagnostic d'IK chez le patient PRAD. De plus, l'utilisation d'une échelle visuelle semi-quantitative permet d'améliorer sa performance diagnostique, avec des valeurs prédictives positives et négatives respectivement de 78,3 et 78,4 %. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. Methods: The STORI trial patients (n=115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). Results: Median serum calprotectin was 8892ng/mL (range: 410–125,000ng/mL) in Crohn disease patients as compared with 1318ng/mL (range: 215.8–3770ng/mL) in controls (P <0.0001). Serum calprotectin was significantly higher for active disease (median=19,584ng/mL) than for inactive disease (median=8353ng/mL) (P <0.0001). Serum calprotectin correlated with hsCRP (r=0.4092, P <0.0001) and CDAI (r=0.4442, P <0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r=0.6458, 0.5515, 0.2577 with P <0.0001, P <0.0001, P =0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675ng/ml), appeared complementary to hsCRP (>5mg/l) and fecal calprotectin (>250μg/g) to predict relapse after infliximab withdrawal (P =0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). Conclusions: As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal. [Copyright &y& Elsevier]