A Thesis Submitted to the School of Graduate Studies in Partial Fulfilment of the Requirements for the Degree Master of Science in Clinical Epidemiology (Health Research Methodology) / Introduction: There is no single agreed-upon tool to forecast hydronephrosis obstruction and surgical risk in the literature. Previous scoring systems have relied on renal scan parameters for this task, which are not performed or read consistently across hospitals. We aim to determine the utility of a hydronephrosis obstruction early scoring system in identifying severe UPJO-like hydronephrosis suggestive of surgery. Methods: We reviewed a prenatal hydronephrosis database (2008-23) to identify patients with unilateral UPJO-like hydronephrosis. Patients with vesicoureteral reflux (VUR), megaureter, or other anomalies were excluded. We collected data on the first ultrasound and surgical outcome for the Society for Fetal Urology (SFU) grade, anteroposterior pelvic diameter (APD), and percent difference in renal length – the renal length index (RLI). I undertook a multivariable logistic regression to determine the predicted value of these sonographic measurements. Model development and internal validation were performed, and model performance (calibration and discrimination) was reported. Results: Of the 465 UPJO-like hydronephrosis patients, 76.1% (354) were male and had a mean age at baseline of 3.8 ± 3.8 months. 34.8% (162) had an obstructive renal scan and 27.7% (129) underwent pyeloplasty. The developed model to predict surgery using the aforementioned variables with excellent model performance (AUC 0.92). A simplified model using SFU 3-4, APD > 13mm and RLI >12% also predicted surgery with great model performance (AUC 0.89) and improved clinical user-friendliness. Conclusion: Our clinical predictive model can accurately predict surgery in both derivation and validation cohorts of patients with antenatal UPJO-like hydronephrosis. This non-invasive tool can greatly aid in patient counselling. / Thesis / Master of Health Sciences (MSc) / Hydronephrosis (HN) is a kidney condition prevalent in 1-5% of pregnancies, typically detected through third-trimester ultrasounds. Although 70% of cases resolve spontaneously, the remaining 30% are at higher risk of renal failure if unaddressed. Traditional scoring systems have depended on renal scans, which expose patients to radiation and suffer from inconsistency across healthcare facilities. Using data from pediatric patients with HN, this study identified key predictive factors for surgical management such as severe dilation of kidneys associated with thinning, affected kidney length more than 12% longer than healthy kidney and anteroposterior diameter of the renal pelvis > 13mm. A new scoring system based solely on renal ultrasound parameters was formulated. This system establishes different risk categories, which have been validated for use in daily clinical practice. This offers urologists a reliable, radiation-free tool to gauge individual surgical risks and provides a foundation for tailored patient counselling.

Une des données essentielles que recherche le clinicien ORL lors de son diagnostic concerne la fonctionnalité des fosses nasales. Dans certains cas, cette fonction n’est approchée que de manière partielle par les diverses méthodes de mesures mises à sa disposition. La prévalence des obstructions nasales chroniques dans la population générale1 (30% de la population) souligne l’intérêt que les orthodontistes doivent porter aux pathologies respiratoires. L’acquisition d’un outil de diagnostic fiable de l’obstruction nasale permettra d’effectuer un traitement plus précoce afin de guider au mieux la croissance crânio-faciale. La RAA ne peut pas être actuellement utilisée comme unique examen diagnostique, car sa corrélation avec les évaluations subjectives peut rester faible. L’objectif de ce travail est de fournir un modèle d’aide au diagnostic de l’obstruction nasale pour tous les patients. Dans les cas où la RAA ne permet pas un diagnostic certain de l’obstruction nasale, la simulation numérique permettrait, après avoir identifié les situations anatomiques particulières, d’obtenir une approche fonctionnelle objective en confirmant ou non le diagnostic de la RAA. La méthode utilisée pour ce travail de thèse consiste en une résolution complète des équations de Navier-Stokes dans des géométries reconstruites en 3D, c’est-à-dire ayant bénéficié d’un traitement numérique pour extraire les contours puis créer les maillages surfaciques et volumiques. Le développement d'outils de mesure objectifs est un enjeu capital pour déterminer les stratégies thérapeutiques optimales et pour évaluer les résultats des traitements. La modélisation par ordinateur de la dynamique des flux aériens au sein des fosses nasales à partir de reconstructions tomodensitométriques tridimensionnelles peut présenter des applications cliniques. Une de ses applications permettrait à l’ORL de visualiser l’écoulement post-opératoire virtuellement. / One of the essential data sought by the clinician in his diagnosis on the functionality of the nasal cavity. In some cases, this function is only partially approached by various measurement methods at its disposal. The prevalence of chronic nasal obstruction in the population (30% of the population) underlines the interest to orthodontists must wear respiratory disorders. The acquisition of a reliable diagnostic tool of nasal obstruction will allow for earlier treatment to guide the best craniofacial growth. The RAA can not be currently used as single diagnostic test, because its correlation with subjective assessments can remain low. The objective of this work is to provide a model for the diagnosis of nasal obstruction for all patients. In cases where the RAA does not allow a definite diagnosis of nasal obstruction, numerical simulations allow, after identifying the particular anatomical situations, to obtain a functional objective or not confirming the diagnosis of rheumatic fever. The methodology for this thesis consists of a complete resolution of the Navier-Stokes equations in geometries reconstructed in 3D, that is to say who received a digital processing to extract the contours and surface meshes and create volume. The development of objective measurement tools is a key issue in determining optimal treatment strategies and to evaluate treatment outcomes. Computer modeling of the dynamics of air flow within the nasal cavity from three-dimensional CT reconstructions may have clinical applications. One of its applications allow to visualize the flow postoperative virtually.

Dans cette thèse, on s’intéresse à des propriétés arithmétiques des variétés algébriques. Elle contient deux parties : partie géométrique (sur un corps quelconque) et partie arithmétique (sur un corps de nombres). Dans la partie géométrique, j’étudie le quotient par sa partie constante du troisième groupe de cohomologie non ramifiée des surfaces (géométriquement) rationnelles et de leurs torseurs universels. Pour les surfaces de del Pezzo de degré au moins 5, je montre que ce quotient est trivial, sauf pour des surfaces de del Pezzo de degré 8 d’un type particulier. Pour les torseurs universels ci-dessus, je montre que ce quotient est fini et je donne une condition suffisante pour qu’il soit nul, en termes de la structure galoisienne du groupe de Picard géométrique de la surface. Dans la partie arithmétique, on étudie l’obstruction de Brauer–Manin à l’approximation forte. En collaboration avec C. Demarche et F. Xu, nous établissons l’équivalence de l’obstruction de Brauer-Manin étale et de l’obstruction de descente pour les variétés quasi-projectives. Ensuite, j’établis un théorème très général sur l’approximation forte pour les variétés ouvertes munies d’une action d’un groupe linéaire connexe G et dont un ouvert est un espace homogène de G. / In this Ph.D. thesis, we investigate some arithmetic properties of algebraic varieties. The thesis consists of two parts: a geometric part (over an arbitrary field) and an arithmetic part (over a number field). The geometric part is devoted to the study of the quotient by its constant part of the third unramified cohomology group of (geometrically) rational surfaces and of their universal torsors. For del Pezzo surfaces of degree at least 5, we show that this quotient is zero, except in the case of del Pezzo surfaces of degree 8 of a special type. For universal torsors as above, we show this quotient is finite and we give a sufficient condition for it to vanish. This condition involves the Galois structure of the geometrical Picard group. The arithmetic part is devoted to the study of the Brauer-Manin obstruction to strong approximation. In collaboration with C. Demarche and F. Xu, we establish the equivalence of étale Brauer-Manin obstruction and the descent obstruction. Then I establish a general theorem about strong approximation of open varieties equipped with an action of a connected linear algebraic group G and containing a G-homogeneous space as open subset.

Summer pasture-associated recurrent airway obstruction (SPARAO) is characterized by reversible airway obstruction resulting from airway hyper-reactivity to aeroallergens, mucus accumulation, and airway inflammation. These are key clinical features that are shared with human asthma, suggesting SPARAO’s utility as an animal asthma model. SPARAO affects horses maintained on pasture in conditions of high heat and humidity. Common in the southeastern United States, the cause of SPARAO is unknown, but is presumed to reflect reactivity to seasonally inhaled pasture-associated aeroallergens. This investigation sought to identify well-characterized histopathological lesions of human asthma, collectively termed ‘asthmatic remodeling’, in lung tissue from horses with SPARAO. Two histological staining techniques were used: H&E and Movat’s Pentachrome. Similar to chronic asthma, lung tissue from horses with SPARAO demonstrates statistically significant increases in airway smooth muscle, fibrosis, airway occlusion and inflammation, goblet cell hyperplasia, and remodeling of terminal bronchioles and elastin fibers.

Introduction: Intestinal obstruction is a common cause of hospital admissions and carries a mortality rate around 5%. We hypothesized that surgical intervention reduces mortality among these patients. Methods: We conducted a retrospective cohort study using the 2006 Nationwide Inpatient Sample (NIS) to analyze patients with a diagnosis of intestinal obstruction without hernia. We used multiple variable logistic regression to calculate the odds ratio for surgery as a predictor of death after adjusting for illness severity. Results: Among 38,931 patients, 17,544 (45.1%) underwent operative intervention for intestinal obstructions. Surgical patients were slightly younger than non-surgical patients (65 vs. 68 years), and had more severe illness, as measured by the disease staging: mortality scale (115.45 vs. 97.95, p<0.001). After adjusting for illness severity, surgery was protective from mortality (adjusted odds ratio 0.617, 95% CI 0.535-0.710, p<0.001). This finding was validated with 2 other methods of severity adjustment. Among surgery patients, there were fewer days to surgery among survivors (1 day) than non-survivors (2 days), p<0.001. The risk of bowel necrosis increased as time from admission to surgery increased. A greater percentage of surgical patients (77.5%) were discharged home compared to non-surgical patients (76.3%), p=0.007. Conclusion: Surgery is associated with a reduced odds of in-hospital mortality among patients urgently or emergently admitted with intestinal obstruction without hernia. Delaying operative intervention is associated with an increased odds of bowel necrosis and death in these patients. / Clinical Research and Translational Medicine

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction and paravalvular leak (PVL) are relatively uncommon, but are serious complications of prosthetic valve replacement. CASE PRESENTATION: We present a case that displays the unique therapeutic challenges of treating a patient who developed both LVOT obstruction and mitral PVL after undergoing surgical aortic and mitral valve replacement (MVR). We also describe the use of alcohol septal ablation and albumin-glutaraldehyde (BioGlue) for septal ablation to percutaneously treat the patient's LVOT obstruction, followed by use of an Amplatzer vascular plug for percutaneous closure of an antero-medial mitral PVL associated with severe regurgitation. CONCLUSION: Percutaneous interventional management of these entities may be considered as an initial therapeutic option, especially in high-risk patients with significant morbidity and mortality of repeat surgical operations.

Bladder obstruction (neurogenic or anatomic) induces strain injury in detrusor smooth muscle cells. Signaling via strain injury in other systems has been highly studied, while in bladder obstruction, it has been quite limited to a small number of pathways. In our study we have examined the effects of strain injury using a combination of in vivo, ex vivo and in vitro models, with the aim of understanding disease pathogenesis in the bladder. Using a combination of literature searches, phospho-protein screens and pathway analysis, we uncovered three pathways activated by mechanical strain, ERK, STAT3 and mTOR, with potential for changing not only the way we understand but also the way we treat obstructive myopathies of the bladder. We found that not only were these pathways activated in response to strain and distension injury of BSMC, but they were also responsible for proliferation and sometimes de-differentiation. Included herein are three chapters, published in 2006 and 2010, on the role of ERK, STAT3 and mTOR pathways in bladder smooth muscle cell proliferation and differentiation, 8 Appendices containing the first pages of other papers and reviews published during the course of my studies.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Orientador: José Vicente Tagliarini / Resumo: CAMPOS, C. S. M. 2018. Avaliação da incidência e evolução das manifestações das doenças nasais em pacientes portadores de fibrose cística. 2018. Dissertação (Mestrado) – Faculdade de Medicina de Botucatu, Universidade Estadual Paulista “Júlio de Mesquita Filho”, Botucatu, 2018. Introdução: A fibrose cística é uma doença originada da mutação do gene responsável pela codificação da proteína CFTR. A ausência ou defeito dessa proteína leva a um transporte irregular de sal e água em células mucosas respiratórias e de glândulas exócrinas podendo resultar em diversas manifestações clínicas. As alterações otorrinolaringológicas frequentes são rinossinusite crônica e polipose nasal. Objetivo: Avaliar a incidência e a evolução de doenças nasais em pacientes portadores de fibrose cística com exame videonasolaringoscópico documentado em prontuário do período de agosto de 2015 a agosto de 2017. Casuística e Métodos: Realizou-se a coleta de dados de 65 pacientes acompanhados no ambulatório de fibrose cística do Hospital das Clínicas de Botucatu. Foram incluídos os pacientes que possuíam exames videonasolaringoscópicos realizados durante o período de acompanhamento e que concordaram em participar do estudo. Realizou-se um estudo de coorte com avaliação dos dados epidemiológicos, presença de comorbidades, achados nos exames videonasolaringoscópicos, positivação de cultura de orofaringe e resposta ao tratamento clínico. Resultados: Foram analisados 51 pacientes. A mutação delta F508 esteve pr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: CAMPOS, C.S.M. 2018. Evaluation of the incidence and evolution of the manifestations of nasal diseases in patients with cystic fibrosis. 2018. Thesis (Master) – Botucatu Medical School, Universidade Estadual Paulista “Júlio de Mesquita Filho”, Botucatu, 2018. Introduction: Cystic fibrosis is a disease originated from the mutation of the gene responsible for the coding of the CFTR protein. The absence or defect of this protein leads to an irregular transport of salt and water in respiratory mucous cells and exocrine glands, resulting in several clinical manifestations. Frequent otorhinolaryngological changes are chronic rhinosinusitis and nasal polyps. Objective: To evaluate the incidence and evolution of nasal diseases in patients with cystic fibrosis with a videonasolaryngoscopic exam documented in medical records from August 2015 to August 2017. Casuistry and Methods: Data were collected from 65 patients followed in the cystic fibrosis outpatient clinic Botucatu Medical School. Patients who had videonasolaryngoscopic examinations performed during the follow-up period and who agreed to participate in the study were included. A cohort study was conducted with epidemiological data, presence of comorbidities, findings in videonasolaryngoscopic examinations, oropharyngeal culture positivity and response to clinical treatment. Results: Fifty-one patients were analyzed. The delta F508 mutation was present in 20 patients. The comorbidities evaluated were: bronchiectasis (n = 39), p... (Complete abstract click electronic access below) / Mestre

The impact of percutaneous renal artery angioplasty and stenting (PTRAS) for treatment of atherosclerotic renal artery stenosis (ARAS) is not fully understood, especially in patients with chronic kidney disease (CKD). We performed a retrospective cohort study of patients with significant ARAS and moderate to severe chronic kidney disease (estimated GFR 15-60 ml/min/1.73m2) who were treated medically or with PTRAS. The primary endpoint of this study was change in renal function over the first year after treatment. Secondary endpoints included hemodynamic outcomes, antihypertensive medication doses, end stage renal disease (ESRD), and death. We reviewed all patients with a diagnosis of significant ARAS and impaired GFR treated between 1997-2007 in the Veterans Affairs Connecticut Healthcare System (VACHS). A total of 118 patients met inclusion criteria (71 medical treatment, 47 PTRAS), with an average follow-up of 34 months. The students t-test was used to compare baseline characteristics, as well as renal and hemodynamic endpoints between the two treatment groups. The cohort had a mean age of 73 ± 9 years and average baseline GFR of 37.2 ± 14.9 ml/min/1.73m2. Demographic, clinical and laboratory characteristics at baseline were similar between the two groups, with the exception of higher diastolic blood pressure in the stent group at baseline (75 versus 70 mmHg, p=0.028). No statistically significant difference was found between the two treatment groups for any renal endpoints. After a steady decline in GFR in both the medical treatment and stent groups during the 12 months preceding diagnosis (-4.2 versus -4.0 ml/min/1.73m2, p=0.911), GFR stabilized in both groups over the year following diagnosis (decline in GFR of -1.6 versus -1.4 ml/min/1.73m2, p=0.938). Multivariate models did not reveal an association between treatment modality and percent change in GFR during follow-up. No difference was found in blood pressure outcomes at 12 months between the medical and stent groups. Antihypertensive therapy, measured in defined daily doses (DDDs), was significantly higher in the medical treatment group at 12 months (4.5 versus 3.5 DDDs, p=0.048), but lost significance thereafter. In addition, the number of deaths was significantly higher in the stented group on univariate analysis, although this did not remain significant on multivariable Cox analysis. No difference was found between treatment groups in the development of ESRD. These data suggest that, among patients with ARAS and CKD, medical therapy and renal artery stenting are comparable in stabilizing renal function.