Le cancer épithélial de l’ovaire (CEO) est une cause majeure de mortalité parcancer gynécologique. Il est associé à un mauvais pronostic car il est souventdécouvert à un stade tardif. Mieux comprendre les causes et les mécanismesmoléculaires et cellulaires associés à la progression de ce cancer représente unenjeu majeur.Les deux chimiokines CXCL12/SDF-1 et fractalkine (FKN)/CX3CL1 ont étéimpliquées dans diverses tumeurs. La chimiokine SDF-1, a un effetimmunosuppresseur dans le CEO. Elle est aussi impliquée dans l’angiogenèsetumorale. L’effet de SDF-1 médié par CXCR4 est également impliqué dans larégulation de la prolifération, la survie, la migration et l'invasion des cellulescancéreuses. La FKN, a largement été mise en évidence dans les tissusépithéliaux et dans divers cancers où elle peut avoir soit un rôle anti-tumoral soitun rôle pro-tumoral. Jusqu’à présent la FKN n’a pas été étudié dans le CEO.Dans notre étude, nous avons démontré l’expression de SDF-1 et de la FKNdans l’épithélium de surface de l’ovaire sain et dans les tumeurs bénignes etmalignes. Ces résultats montrent que l’expression de SDF-1 et de la FKNpréexiste à la tumorigenèse. Nous avons démontré une expression hétérogènedes deux chimiokines dans les cellules du CEO. Les niveaux d’expression deSDF-1 dans les cellules tumorales sur une cohorte de 183 patientes n’ont aucunevaleur pronostique sur la survie globale et sur la survie sans progressiontumorale des patientes atteintes par le CEO. L’étude de la corrélation del’expression de la FKN avec les deux marqueurs de prolifération, Ki-67 etGILZ, sur une autre cohorte de 54 patientes, complétée par des expériences invitro, a montré que GILZ augmente l’expression de la FKN et d’autre part que laFKN elle-même augmente la prolifération. Cette étude contribue à élucider lerôle de SDF-1 et de la FKN dans le CEO. / Little is known about the molecules that contribute to tumor growth ofepithelial ovarian carcinomas (EOC) that remains the most lethal gynecologicalneoplasm in women.The two chemokines CXCL12/SDF-1 and fractalkine (FKN)/CX3CL1 havebeen widely studied in tumorigenesis. In epithelial ovarian cancer (EOC), SDF-1enhances tumor angiogenesis and contributes to the immunosuppressivenetwork. SDF-1 also acts on tumor cell proliferation and survival and, throughits main receptor CXCR4, governs the migration of malignant cells and theirinvasion of the peritoneum. The chemokine FKN has been documented inepithelial tissues and in various cancers. FKN have paradoxical effects intumors: anti-tumoral effect in some tumor entities and pro-tumoral effect inother tumor entities.In our study, we demonstrated the expression of SDF-1 and FKN on thesurface epithelium of normal ovaries and benign and malignant tumors,suggesting that the expression of these chemokines preexists to tumorigenesis.We also demonstrated an heterogeneous expression of both chemokines in EOC.In our large and homogeneous cohort (183 specimens of EOC), SDF-1expression levels had no effect on overall survival or progression-free survival.Thus, SDF-1 expression by tumor epithelial cells is not in itself a valuableprognostic factor in patients with advanced EOC. FKN immunostaining scores(in 54 specimens of EOC) correlated positively with the two proliferationmarkers : Ki-67 and GILZ. In vitro, we demonstrated that GILZ increases theexpression of FKN and that FKN itself increased proliferation. This studycontributes in elucidating the role of the two chemokines SDF-1 and FKN inEOC.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p < 0.0001; diastolic: OR = 3.82, p < 0.0001), elevated fasting plasma glucose levels (OR = 8.84, p < 0.0001), hypertriglyceridaemia (OR = 22.16, p = 0.001), and obesity (body mass index OR = 0.89, p < 0.0001). Assessment of resting heart rate in clinical practice had minimal and non-significant additional prognostic value compared to established cardiovascular risk factors as judged by C statistics (C = 0.001, p = 0.979). Conclusion: The measurement of resting heart rate in the daily routine of primary care does not provide incremental prognostic information for cardiovascular risk stratification.

The scientific novelty of the study A large number of reports have demonstrated that depressed heart rate variability after myocardial infarction (MI), left ventricular dysfunction and arrhythmias are powerful predictors of mortality. Nevertheless there is a lack of detailed assessment of heart rate variability in the acute period of MI, especially during the first 24 hours, from long-term (24-h) recordings, and the value of different parameters of heart rate variability in predicting dangerous complications of MI was not fully evaluated. The indications of complex and constant monitoring of heart rate variability, left ventricular function, arrhythmias in acute MI are not based on scientific studies as well as their value in predicting the effect of different methods of management, course and outcomes of critical cardiac conditions. Thus, the current study differs from all the earlier studies in that we assessed heart rate variability in the very early period of myocardial infarction (the first and the third day) using long time recordings (24 h), both – time-domain and frequency-domain –methods, and evaluated its changes in relation to arrhythmias and left ventricular function, using not only conventional 2D-echocardiography but also left ventricular long axis function assessment by M-mode and tissue Doppler imaging. The aim of the study The aim of the study was to determine the association between heart rate variability, cardiac arrhythmias and left ventricular... [to full text]

Le niveau de risque dans l'HTA est lié en partie au niveau de pression artérielle systolique (PAS) et diastolique (PAD) mais également aux atteintes d'organes cibles infracliniques. Les objectifs de ce travail sont de rechercher des facteurs pronostiques concernant le remodelage du ventricule gauche et de l'aorte dans le cadre des pathologies cardiovasculaires. Les résultats ont été obtenus à partir de la cohorte historique OLD-HTA constituée au début des années 1970 et des patients pris en charge actuellement dans le service de cardiologie. Concernant le remodelage ventriculaire gauche, nous démontrons que l'onde R aVL sur l'ECG est corrélé à l'hypertrophie ventriculaire gauche en s'appuyant sur l'IRM cardiaque comme gold standard et qu'elle permet de prédire la mortalité toute cause et cardiovasculaire dans l'HTA. D'autre part, nos résultats permettent de mieux appréhender la valeur pronostique de la PAD qui devient un élément protecteur pour une PAS donnée en cas d'athérome aortique. Enfin, nous démontrons que la présence d'athérome aortique ou de calcifications aortiques est un élément prédicteur d'événements cardiovasculaires dans les suites d'un remplacement valvulaire aortique percutané et lorsque la fréquence cardiaque est élevée chez le patient hypertendu. L'ensemble de ces éléments pronostiques permettra à l'avenir de mieux stratifier le risque cardiovasculaire de nos patients en évaluant afin de leur proposer les thérapeutiques les plus adaptées / Risk stratification in hypertension is related to the level of systolic blood pressure (SBP) and diastolic blood pressure (DBP) but also to the presence of subclinical target organ damages. The aims of the studies conducted were to determine the prognostic values of left ventricular and aortic remodeling in the clinical setting of cardiovascular disease. Results were obtained in our historic OLD-HTA cohort started in the 70’s and with patients currently treated in our cardiology department. Regarding left ventricular remodeling, we demonstrated that R wave in aVL lead from the electrocardiogram is a robust index of left ventricular hypertrophy using cardiac MRI and this index is also a powerful predictor of all-cause and cardiovascular mortality in hypertension. Moreover, our results indicated that at a specific level of SBP, a low DBP is harmful in the presence of aortic atheroma. Therefore, aortic atherosclerosis or aortic calcifications are a major predictor of cardiovascular events after transcutaneous aortic valve implantation and in hypertensive patients with high resting heart rate. Taken together these data emphasize the interplay between aorta and the heart and provide some new hints to improve risk stratification particularly in hypertension

Kranskärlssjukdom (CAD) är den ledande dödsorsaken. Sjukdomen startar med plackbildning i ett eller flera kranskärl, vilket kan leda till bröstsmärta samt andra symtom. Diagnostik av CAD inkluderar undersökningarna arbetsprov (AP) och myokardscintigrafi (MPI). Båda undersökningarnas prognostiska värde påverkas dock av parametrar som elektrokardiogram (EKG), EKG-triggning, Dukes löpbands index (DTS) och Metaboliska ekvivalenter (MET). Litteraturstudiens syfte var att jämföra den prognostiska prestandan hos AP jämfört med MPI. Detta genom att studera de nämnda parametrarnas prognostiska påverkan på respektive undersökning. De använda artiklarna uppfyllde samtliga inklusionskriterier: engelska, peer-reviewed samt etiskt godkänd eller inhämtat samtycke. Databasen Pubmed, snowballsmetod samt relaterade artiklar användes vid litteraturinsamlingen. Enligt resultatet ökar ovannämnda parametrar det prognostiska värdet hos både AP och MPI. Dock visades att patienter som uppnår olika MET samt DTS-värden bättre kan riskkategoriseras med MPI. Dessutom visades MPI kunna skilja de med sämre prognos bland patienter med positiva AP-resultat, men även bland de med negativa AP-resultat. Därmed drog författarna slutsatsen att MPI har ett ökat mervärde gällande prognostik hos patienter med CAD. Fler studier som samtidigt jämför AP och MPI behövs dock för en mer fullständig slutsats. / Coronary artery disease (CAD) is the leading cause of death. This disease starts with plaque buildup in one or more coronary vessels, which can lead to chest pain among other symptoms. Diagnostics include the exercise stress test (AP) and myocardial scintigraphy (MPI). The prognostic value of both examinations depends on parameters such as electrocardiogram (ECG), ECG-gating, Duke treadmill score (DTS) and Metabolic equivalents (MET). The purpose of this study was to compare the prognostic performance of AP with MPI, by studying the prognostic effect of the mentioned parameters in each study. The used articles met all inclusion criterias: English, peer-reviewed, and ethically accepted or obtained consent. Pubmed database, snowball method and related articles were used for literature collection. According to the results, the above-mentioned parameters increase the prognostic value of AP and MPI. However, patients achieving different MET and DTS scores are better categorized with MPI. MPI was shown to differentiate those with poorer prognosis among patients with positive AP-results and those with negative AP-results. The authors concluded that MPI has an added value regarding prognosis forpatients with CAD. However, more studies comparing AP and MPI at the same time are needed to obtain a more complete conclusion.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p < 0.0001; diastolic: OR = 3.82, p < 0.0001), elevated fasting plasma glucose levels (OR = 8.84, p < 0.0001), hypertriglyceridaemia (OR = 22.16, p = 0.001), and obesity (body mass index OR = 0.89, p < 0.0001). Assessment of resting heart rate in clinical practice had minimal and non-significant additional prognostic value compared to established cardiovascular risk factors as judged by C statistics (C = 0.001, p = 0.979). Conclusion: The measurement of resting heart rate in the daily routine of primary care does not provide incremental prognostic information for cardiovascular risk stratification.

No description available.

Introduction: Auditory neuropathy spectrum disorder (ANSD) is a disorder characterized by impaired temporal coding of acoustic signals due to a deficiency in neural synchrony or neural transmission. Despite variations in speech perception outcomes within both patients and studies, current evidence demonstrates that children with ANSD, who use hearing aids (HAs) or cochlear implants (CIs), generally achieve speech perception performance comparable to peers with sensorineural hearing loss (SNHL). However, limited studies have reported factors that have prognostic value for auditory intervention outcomes. The objectives of this doctoral thesis, consisting of three consecutive associated projects on children with ANSD, were (1) to determine factors with predictive value for post-intervention (CIs and/or HAs) outcomes through a retrospective study, (2) to systematically summarize and critically appraise existing evidence of the prognostic value of early auditory electrophysiologic tests and MRI findings for CI outcomes through a systematic review (SR), and (3) to systematically overview, summarize, and critically appraise evidence of CI outcomes through an umbrella review of current SRs (overview of SRs). -- Methods: For the first project, the records of 38 children with ANSD between 5 and 18 years old, 63.20% males, who used CIs (71%) and/or HAs, identified at the Children's Hospital of Eastern Ontario (CHEO) were reviewed. For the second and third projects, the SRs were guided by the PRISMA 2020 statement, and electronic databases were searched without restrictions on language, publication status, or year of publication. In the second project, studies on children with ANSD (including those with cochlear nerve deficiency [CND]), cochleovestibular nerve (CVN) abnormalities, or SNHL reporting the relevance of preoperative and/or postoperative electric compound action potential (eCAP), electric auditory brainstem response (eABR), and/or MRI results to CI outcomes were included. The methodological quality and strength of evidence were assessed using the Crowe Critical Appraisal Tool (CCAT) and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool, respectively. In the third project, all SRs that reported CI outcomes in children with ANSD were included. The methodological quality of the selected SRs was evaluated using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist, and the risk of bias in evidence was assessed using the Risk of Bias in Systematic Reviews (ROBIS) tool. -- Results: In the retrospective chart review (first project), ages at HL diagnosis and CI activation and the length of follow-up with CI/HA showed a significant relationship with open-set speech perception outcomes (i.e., the scores of Phonetically Balanced Kindergarten [PBK] test with word and phoneme speech materials and Hearing in Noise Test [HINT] in quiet and noise conditions). Using a Forward Linear Multiple Regression Model, the length of follow-up with CI/HA and bilateral amplification showed prognostic value for speech perception performance. In the second project, 25 papers were included in the review. While it was difficult to draw a firm conclusion about the eCAP findings, current evidence strongly supports the prognostic value of eABR and MRI for post-CI speech perception outcomes. According to the eight SRs selected for the third project, children with ANSD achieve CI outcomes comparable to their peers with SNHL. However, in children with postsynaptic ANSD (i.e., those with CND), cochlear nerve hypoplasia is associated with better speech recognition outcomes compared to cochlear nerve aplasia, especially in the absence of additional disabilities and/or medical comorbidities (ADs/MCs). -- Conclusion: Children with ANSD, especially those without cochlear nerve aplasia and ADs/MCs, achieve speech perception outcomes comparable to their peers with SNHL. In addition, age at HL diagnosis, age at CI activation, the length of follow-up with CI/HA, bilateral amplification, and eABR and MRI findings are associated with or have predictive value for intervention outcomes. The findings of the SRs should be interpreted with caution given the low quality of evidence and risk of bias in the studies selected for SRs.