Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone

Serge Tousignant : jeux d'espaces, jeux de regards : le catalogue

L'exposition qui fait l'objet de ce catalogue a malheureusement été annulée à cause de la pandémie, mais elle aurait dû se tenir au Carrefour des arts et des sciences de l’Université de Montréal du 8 avril au 12 juin 2020.Catalogue d'exposition préparé à l'hiver 2020 dans le cadre du cours HAR 6080 / MSL 6509 : Muséologie et histoire de l'art, donné par la professeure Christine Bernier.Catalogue préparé sous la direction de Christine Bernie

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

L'identité professionnelle des médecins de famille au Québec

Cet article examine les incidences des transformations organisationnelles et culturelles contemporaines sur l’identité professionnelle des médecins de famille au Québec. Il vise à rendre compte, à partir de l’analyse de trois cohortes d’insertion sur le marché du travail, des nouvelles formes de rapport au travail qui contribuent à redéfinir l’identité professionnelle des médecins de famille. En vue de comprendre les changements dans les valeurs à l’égard du travail et de la profession médicale, la présente recherche adopte une position critique envers les modes d’explication fondés sur les thèses générationnelles. Ainsi, elle relève d’autres éléments à considérer afin de mieux comprendre l’évolution des identités professionnelles, notamment les conditions d’exercice du travail professionnel, les rigidités structurelles de genre, les changements de valeurs et les nouvelles situations de vie personnelle et familiale.This article examines the impact of contemporary organizational and cultural transformations on the professional identity of family physicians in Quebec. It aims to describe, based on an analysis of three cohorts of physicians entering the Quebec labour market, new ways of relating to work that are contributing to redefining the professional identity of family physicians. In order to understand changes in values regarding work and the medical profession, this study takes a critical stance toward generational explanatory models. Rather, it looks to other factors for improving our understanding of the evolution of professional identities, in particular the conditions of practice, structural gender rigidities, and changes in values and in personal and family situations

The professional identity of family physicians in Quebec

Cet article examine les incidences des transformations organisationnelles et culturelles contemporaines sur l’identité professionnelle des médecins de famille au Québec. Il vise à rendre compte, à partir de l’analyse de trois cohortes d’insertion sur le marché du travail, des nouvelles formes de rapport au travail qui contribuent à redéfinir l’identité professionnelle des médecins de famille. En vue de comprendre les changements dans les valeurs à l’égard du travail et de la profession médicale, la présente recherche adopte une position critique envers les modes d’explication fondés sur les thèses générationnelles. Ainsi, elle relève d’autres éléments à considérer afin de mieux comprendre l’évolution des identités professionnelles, notamment les conditions d’exercice du travail professionnel, les rigidités structurelles de genre, les changements de valeurs et les nouvelles situations de vie personnelle et familiale.This article examines the impact of contemporary organizational and cultural transformations on the professional identity of family physicians in Quebec. It aims to describe, based on an analysis of three cohorts of physicians entering the Quebec labour market, new ways of relating to work that are contributing to redefining the professional identity of family physicians. In order to understand changes in values regarding work and the medical profession, this study takes a critical stance toward generational explanatory models. Rather, it looks to other factors for improving our understanding of the evolution of professional identities, in particular the conditions of practice, structural gender rigidities, and changes in values and in personal and family situations

Liens entre le sentiment d’auto-efficacité, la détresse psychologique et la parentalité chez des adultes ayant une consommation problématique

Le sentiment d’auto-efficacité parental (SAEP) et la présence de détresse psychologique chez des parents ayant une consommation problématique d’alcool ou de drogues pourraient contribuer à expliquer la relation entre la consommation et l’exercice de la parentalité. À l’aide d’un échantillon composé de 81 parents en traitement pour une dépendance, cette étude vise à vérifier si (1) le niveau de SAEP est corrélé à la gravité de la consommation (alcool et drogues), à la sévérité de la détresse psychologique, à la qualité des pratiques éducatives et à la relation parent-enfant et si (2) la sévérité de la détresse psychologique contribue à expliquer la relation entre le SAEP et les pratiques éducatives, ainsi que la relation entre le SAEP et la relation parent-enfant. Si les résultats n’indiquent pas de corrélations entre le SAEP et la gravité de la consommation, ils indiquent que le SAEP est significativement et positivement corrélé aux comportements éducatifs positifs et aux attitudes chaleureuses/affectueuses, mais significativement et négativement corrélé au sentiment dépressif, à une discipline inconstante ainsi qu’à des attitudes parentales hostiles/agressives et négligentes/indifférentes. La détresse psychologique (anxiété et dépression) est quant à elle significativement et positivement corrélée à la gravité de la consommation (alcool et drogues) et à la présence d’une discipline inconstante, mais significativement et négativement corrélée à une supervision lacunaire. Enfin, les symptômes anxieux sont significativement et positivement corrélés aux attitudes parentales hostiles/agressives et aux attitudes négligentes/indifférentes et négativement aux attitudes chaleureuses/affectueuses. À lui seul, le SAEP permet d’expliquer les comportements éducatifs positifs, ainsi que les attitudes hostiles/agressives du parent envers son enfant. En ajoutant le sentiment anxieux, les variables permettent d’expliquer conjointement la supervision lacunaire et les trois variables attitudes parentales (chaleureuses/affectueuses, négligentes/indifférentes et hostiles/agressives). Finalement, le genre du parent combiné au SAEP permet d’expliquer une partie de la variance de la discipline inconstante. Les résultats obtenus laissent croire que d’autres facteurs pourraient expliquer la qualité de la parentalité chez des parents ayant une dépendance à l’alcool et aux drogues et invitent à poursuivre les recherches en ce sens.Parental self-efficacy (PSE) and the presence of psychological distress in parents with problematic substance use may help explain the relationship between substance abuse and parenting. This study, using a sample of 81 parents in treatment for substance abuse, investigates whether (1) the level of PSE correlates with the severity of substance use, the severity of psychological distress, the quality of child-rearing practices, and the parent-child relationship, and whether (2) the severity of psychological distress helps explain the relationship between PSE and child-rearing practices, as well as the relationship between PSE and the parent-child relationship. While the results did not yield any significant correlations between PSE and severity of use, results did demonstrate that PSE was significantly and positively correlated with positive parenting behaviors and warm/affectionate attitudes, but significantly and negatively correlated with feelings of depression, inconsistent discipline, and hostile/aggressive and neglectful/indifferent parenting attitudes. Psychological distress (anxiety and depression) was significantly and positively correlated with the severity of substance use (alcohol and drugs) and the presence of inconsistent discipline, but significantly and negatively correlated with insufficient supervision. Anxiety symptoms were also significantly and positively correlated with hostile/aggressive parental attitudes and neglectful/indifferent attitudes and negatively correlated with warm/affectionate attitudes. PSE alone explains positive parenting behaviors, as well as hostile/aggressive parenting attitudes of the parent toward the child. By adding anxious feelings, the variables jointly explain the lack of supervision and the three parental attitudes variables (warm/affectionate, neglectful/indifferent, and hostile/aggressive). Finally, parent gender combined with PSE explained some of the variance in inconsistent discipline. Results suggest that other factors may explain the quality of parenting among parents with problematic alcohol and drug use. Further research in this area is needed to explore these factors.El sentimiento de autoeficacia parental (SAEP) y la presencia de sufrimiento psicológico entre los padres o madres que presentan un consumo problemático de alcohol o de drogas podría contribuir a explicar la relación entre el consumo y el ejercicio de la paternidad/maternidad. Por medio de una muestra compuesta por 81 padres y madres en tratamiento por una dependencia, este estudio apunta a verificar si 1) el nivel de SAEP se correlaciona con la gravedad del consumo (alcohol y drogas), con la severidad del malestar psicológico, con la calidad de las prácticas educativas y con la relación parental/filial y 2) si la severidad del sufrimiento psicológico contribuye a explicar la relación entre el SAEP y las prácticas educativas, así como la relación entre el SAEP y la relación parental/filial. Si los resultados no indican correlaciones entre el SAEP y la gravedad del consumo, señalan que el SAEP está significativa y positivamente correlacionado con los comportamientos educativos positivos y con las actitudes calurosas o afectuosas, pero significativa y negativamente correlacionado con el sentimiento depresivo, con una disciplina inconstante y con actitudes parentales hostiles o agresivas y negligentes o indiferentes. El sufrimiento psicológico (ansiedad y depresión) está significativa y positivamente correlacionado con la gravedad del consumo (alcohol y drogas) y la presencia de una disciplina inconstante, pero significativa y negativamente correlacionado con una supervisión lacunar. Finalmente, los síntomas ansiosos están significativa y positivamente correlacionados con las actitudes parentales hostiles o agresivas y con las actitudes negligentes o indiferentes y negativamente con las actitudes calurosas o afectuosas. Por sí mismo, el SAEP permite explicar los comportamientos educativos positivos y las actitudes hostiles o agresivas de un padre o una madre para con su hija o hijo. Al agregar el sentimiento ansioso, las variables permiten explicar conjuntamente la supervisión lacunar y las tres variables de las actitudes parentales (calurosas o afectuosas, negligentes o indiferentes y hostiles o agresivas). Finalmente, el tipo de padre o madre combinado al SAEP permite explicar una parte de la varianza de la disciplina inconstante. Los resultados obtenidos permiten pensar que otros factores podrían explicar la calidad de la parentalidad entre los padres o madres que presentan una dependencia al alcohol y a las drogas e invitan a proseguir las investigaciones en este sentido

Enhanced Renewal of Erythroid Progenitors in Myelodysplastic Anemia by Peripheral Serotonin

Summary: Tryptophan as the precursor of several active compounds, including kynurenine and serotonin, is critical for numerous important metabolic functions. Enhanced tryptophan metabolism toward the kynurenine pathway has been associated with myelodysplastic syndromes (MDSs), which are preleukemic clonal diseases characterized by dysplastic bone marrow and cytopenias. Here, we reveal a fundamental role for tryptophan metabolized along the serotonin pathway in normal erythropoiesis and in the physiopathology of MDS-related anemia. We identify, both in human and murine erythroid progenitors, a functional cell-autonomous serotonergic network with pro-survival and proliferative functions. In vivo studies demonstrate that pharmacological increase of serotonin levels using fluoxetine, a common antidepressant, has the potential to become an important therapeutic strategy in low-risk MDS anemia refractory to erythropoietin. : Sibon et al. identify a cell-autonomous serotonergic network in human and mouse erythroid progenitors. Reduced levels of serotonin lead to decreased proliferation and survival of erythroid progenitors. Increasing serotonin’s concentration through fluoxetine, commonly used to treat depression, could be a valuable therapeutic intervention to correct myelodysplastic-syndrome-related anemia. Keywords: serotonin, Tph1, erythropoiesis, myelodysplastic syndrome, anemia, SSR

Regulation of globin-heme balance in Diamond-Blackfan anemia by HSP70/GATA1

International audienc

1980

Pour vous, ou dans votre domaine, de quoi l’année 1980 est-elle le nom? Telle est ici la question posée aux chercheuses et chercheurs de la Faculté des lettres de l’Université de Lausanne. Cette aventure interdisciplinaire interroge le possible seuil que représente 1980 tant pour les historiens de la littérature qui retiennent usuellement cette date comme l’an zéro de notre contemporanéité que pour bien des sociologues qui font naître en 1980 les premiers enfants de la «génération Y», celle qui dicte aujourd’hui la norme esthétique et idéologique. La mosaïque des réponses apportées à cette question dessine une sorte de portrait chinois de l’an huitante en une cinquantaine de tesselles littéraires, artistiques, culturelles, sociales, politiques, scientifiques, technologiques, philosophiques et intellectuelles