Dissertations / Theses: 'Multicentric'

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Takahashi(Mizuguchi), Aya. "Genetic features of multicentric/multifocal intramucosal gastric carcinoma." Kyoto University, 2019. http://hdl.handle.net/2433/243290.

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Lim, Stephen Chin Ming. "Asian Biblical hermeneutics as multicentric dialogue : towards a Singaporean way of reading." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/asian-biblical-hermeneutics-as-multicentric-dialogue(a5c5fd43-270c-4e07-bd6b-412442d61364).html.

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In this thesis, I propose a way of reading the Bible in the context of Singapore which is my country of origin. My understanding of context draws in what decolonial thinkers, Anibal Quijano (2007) and Walter Mignolo (2012) have argued to be the modern/colonial world system and social epistemologist, Jose Medina’s (2006) polyphonic contextualism. This allows me to better situate the contextual reader within current networks of knowledge production and argue for the goals of reading the Bible in Singapore to be transformative praxis and identity formation. With the understanding of Singapore as an epistemic terrain embedded in global and local networks of knowledge production, I outline the hermeneutical norms that control contextual reading of the Bible in chapter 2. In order to better aid the task of constructing this hermeneutic, I also survey scholarship on biblical hermeneutics in chapter 3 both in the West and Asia to distil important considerations and useful reading strategies. With these considerations in mind, I propose that reading the Bible in context requires at the metatheoretical level a negotiation between western, Asian and Singaporean standpoints in chapter 4. This is facilitated by a conscientisation framework that checks the posture of specialist readers in relation to nonspecialist readers in a specific context so as to ensure submerged voices are not silenced in favour of dominant epistemologies; and a conversation framework that facilitates understanding the Other that tries to avoid Orientalist and nativist/nationalist dangers. In chapter 5, I then test the proposed method through reading the stories of Daniel to see the discursive effects such a reading strategy has on issues I outline in the analysis of my context pertaining to praxis and identity. In my final chapter, I reflect on how the reading exercise impacts on my proposed understanding of Bible and Singapore. I show that it fundamentally shifts the understanding of the Bible to what Justin Ukpong (2002) argues to be a ‘site of struggle’ and an inclusive canon that is hospitable to the many voices, especially of the marginalised in my context of Singapore.

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Boriani, Filippo <1977&gt. "The "Orthoplastic" combined surgical approach to open tibia fractures: a multicentric prospective outcome study." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6754/4/tesidottorato22%EF%80%A212%EF%80%A22014.pdf.

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Introduction: Open fractures of the leg represent a severe trauma. The combined approach, shared between plastic and orthopaedic surgeons, is considered to be important, although this multidisciplinary treatment is not routinely performed. Aim of this study was to verify whether the orthoplastic treatment is of any advantage over the traditional simply orthopedic treatment, through a multicentric inclusion of these unfrequent injuries into a prospective study. Material and methods: The following trauma centres were involved: Rizzoli Orthopaedic Institute/University of Bologna (leading centre) and Maggiore Hospital (Bologna, Italy), Frenchay Hospital (Bristol, United Kingdom), Jinnah Hospital (Lahore, Pakistan). All patients consecutively hospitalized in the mentioned centres between January 2012 and December 2013 due to tibial open fractures were included in the study and prospectively followed up to December 2014. Demographics and other clinical features were recorded, including the type of treatment (orthopaedic or orthoplastic). The considered outcome measures included duration of hospitalization, time for bone union and soft tissue closure, Enneking score at 3, 6 and 12 months, the incidence of osteomyelitis and other complications. Results: A total of 164 patients were included in the study. Out of them 68% were treated with an orthoplastic approach, whereas 32% received a purely orthopedic treatment. All considered outcome measures showed to be improved by the orthoplastic approach, compared to the orthopaedic one: time for soft tissue closure (2 versus 25 weeks), duration of hospital stay (22 versus 55 days), time for bone union (6 versus 8.5 months) , number of additional operations (0.6 versus 1.2) and functional recovery of the limb at 12 months (27 versus 19, Enneking’s score). All results were statistically significant. Conclusion: The combined orthoplastic approach to the treatment of open tibia fractures, in particular for high grade injuries (Gustilo 3B), is proven to improve the outcome of these severe injuries.

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Boriani, Filippo <1977&gt. "The "Orthoplastic" combined surgical approach to open tibia fractures: a multicentric prospective outcome study." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6754/.

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Introduction: Open fractures of the leg represent a severe trauma. The combined approach, shared between plastic and orthopaedic surgeons, is considered to be important, although this multidisciplinary treatment is not routinely performed. Aim of this study was to verify whether the orthoplastic treatment is of any advantage over the traditional simply orthopedic treatment, through a multicentric inclusion of these unfrequent injuries into a prospective study. Material and methods: The following trauma centres were involved: Rizzoli Orthopaedic Institute/University of Bologna (leading centre) and Maggiore Hospital (Bologna, Italy), Frenchay Hospital (Bristol, United Kingdom), Jinnah Hospital (Lahore, Pakistan). All patients consecutively hospitalized in the mentioned centres between January 2012 and December 2013 due to tibial open fractures were included in the study and prospectively followed up to December 2014. Demographics and other clinical features were recorded, including the type of treatment (orthopaedic or orthoplastic). The considered outcome measures included duration of hospitalization, time for bone union and soft tissue closure, Enneking score at 3, 6 and 12 months, the incidence of osteomyelitis and other complications. Results: A total of 164 patients were included in the study. Out of them 68% were treated with an orthoplastic approach, whereas 32% received a purely orthopedic treatment. All considered outcome measures showed to be improved by the orthoplastic approach, compared to the orthopaedic one: time for soft tissue closure (2 versus 25 weeks), duration of hospital stay (22 versus 55 days), time for bone union (6 versus 8.5 months) , number of additional operations (0.6 versus 1.2) and functional recovery of the limb at 12 months (27 versus 19, Enneking’s score). All results were statistically significant. Conclusion: The combined orthoplastic approach to the treatment of open tibia fractures, in particular for high grade injuries (Gustilo 3B), is proven to improve the outcome of these severe injuries.

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Zhang, Wei Hong. "The Strengths and challenges of multicentric European epidemiological projects in the field of reproductive health." Doctoral thesis, Universite Libre de Bruxelles, 2007. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210700.

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In this dissertation, we base our experience of carrying out participation in 4 EU-funded projects: EUROFETUS (Cost-Effectiveness of ultrasound screening for congenital anomalies); MOMS-B (MOther Mortality and Severe morbidity); PERISTAT(Monitoring and evaluating perinatal health) and EUPHRATES (EUropean Project on obstetric Haemorrhage Reduction: Attitudes, Trial, and Early warning System), an online questionnaire survey for researchers and a literature review, to provide results which will help us to understand the added value and the challenges of the EU collaboration research and the challenges of EU collaboration research in improving the quality and the accessibility of reproductive healthcare.

The EUROFETUS project showed that, despite the fact that the birth prevalence of congenital anomalies has been declining during the last twenty years, they are still a major cause of perinatal mortality and childhood disability in Europe. Congenital heart defects were among the most frequent and the most severe malformations, but were the least diagnosed prenatally. There was large variation between and within countries regarding the proportion of cases diagnosed prenatally and the proportion of cases resulting in termination of pregnancy. From the data available in Eurofetus, such variation might result from the cultural differences underling policy or on ultrasonographer’s expertise, or on differing interpretation of scientific evidence in the design and implementation of screening.

The MOMS-B project allowed population-based comparisons between countries by using the standardised definition that showed the three conditions (pre-eclampsia, postpartum haemorrhage and sepsis) selected to as markers of acute severe maternal morbidity are not rare in Europe. Severe haemorrhage was the most common of severe maternal morbidity condition, but its incidence varied widely between European countries.

The PERISTAT project on the indicators of unfavourable maternal health outcome showed that the maternal mortality ratios (per 100, 000 live births) for early obstetric death ranged from 2.8 to 11.4 across European countries studied. Such variation reflected different resources and systems in place with varying level of ascertainment in addition to difference in the number of maternal deaths.

The EUPHRATES project on a survey of current practice in relation to management of the third stage of labour and the immediate management of postpartum haemorrhage in 14 European countries showed that there were considerable differences in policies for managing the third stage of labour between and within the countries studied.

The online questionnaire survey for researchers showed that almost all researchers were satisfied with their participation in EU-funded project; the main benefits for them were transfer and sharing of experience and knowledge between researchers, but the administrative procedures should be simplified in the future. The description of the process needed to obtain ethical approval for a cluster randomized trial in the EUPHRATES project showed that there was considerable variation in time required and the criteria used amongst 14 European countries, with consequential delay in research and exclusion of one country from the trial.

Overall, we conclude that Community Framework programmes offer new opportunities to connect researchers from all over Europe to share expertise and resources, including computing tools, and make a real contribution to the creation of the European research area. The added value of EU collaborative research is particularly well positioned for improving foetal and maternal health, from the perspective of harmonizing case definitions, collecting the necessary number of cases within a limited period of time, comparing data between regions and countries, meeting the specific needs of the EU and giving a common response to European reproductive health questions. On the other hand, epidemiological data from multiple countries has advanced our understanding of important health-risks and their geographical distributions across Europe and provided the evidence to help people make better decisions about healthcare in the field of reproductive health for the future research.

We focus on reproductive health but believe that this approach could be adapted to other fields when appropriate./Dans cette thèse, nous avons basé notre expérience sur notre participation dans 4 projets européens (EUROFETUS, MOMS-B, PERISTAT et EUPHRATES), un questionnaire en ligne vers les chercheurs, et une revue de la littérature pour fournir les résultats qui nous aideront à comprendre la valeur ajoutée qu’apporte la recherche collaborative et les défis de cette recherche pour l’amélioration de la qualité et de l’accessibilité de la santé reproductive.

Le projet EUROFETUS montre que, en dépit du fait que la prévalence des anomalies congénitales à la naissance diminue depuis une vingtaine d’années, elles restent une cause majeure de mortalité périnatale et de handicaps infantiles. Les malformations cardiaques congénitales sont parmi les plus fréquentes et les plus sévères des malformations, mais aussi les moins diagnostiquées. Il y a de larges différences entre et à l’intérieur des pays concernant la proportion de cas diagnostiqués en prénatal et la proportion de cas résultant en interruption de grossesse. D’après les données disponibles dans EUROFETUS, de telles variations pourraient résulter de politiques de santé différentes, reflétant des divergences culturelles, de variations dans l’expertise des échographistes, ou encore d’interprétations divergentes de preuves scientifiques dans la conception ou la mise en place du screening.

Le projet collaboratif européen sur la Mortalité et la Morbidité Maternelle sévère (MOMB-B) a permis des comparaisons en population entre pays en utilisant une définition standardisée qui a montré que les trois pathologies sélectionnées (pré-éclampsie, hémorragie, sepsis) comme marqueurs de la morbidité maternelle sévère n’étaient pas rares en Europe. L’hémorragie sévère était la pathologie la plus fréquente, mais son incidence variait très fort d’un pays à l’autre.

The PERISTAT project on the indicators of unfavourable maternal health outcome showed that the maternal mortality ratios (per 100, 000 live births) for early obstetric death ranged from 2.8 to 11.4 across European countries studied. Such variation reflected different resources and systems in place with varying level of ascertainment in addition to difference in the number of maternal deaths.

Le projet EUPHRATES, par une enquête de pratique concernant le management de la troisième phase du travail et du management immédiat de l’hémorragie du postpartum dans 14 pays européens, a montré qu’il y avait des différences considérables dans les pratiques entre et à l’intérieur des pays en Europe.

Le questionnaire en ligne auprès des chercheurs a montré que la plupart étaient satisfaits de leur participation à des projets européens, les principaux bénéfices étaient le transfert et le partage d’expériences et de connaissances entre chercheurs mais que les procédures administratives devraient être simplifiées dans le futur. La description de l’utilisation des comités d’éthique dans l’essai EUPHRATES a montré de très grandes divergences.

En général, nous concluons que les programmes-cadres européens offrent de nouvelles opportunités aux chercheurs européens de partager l’expertise et les moyens, en ce compris les outils informatiques et contribuent à la création d’un espace européen de la recherche. La valeur ajoutée de la recherche collaborative est particulièrement importante pour améliorer la santé fœtale et maternelle par l’harmonisation de la définition des cas, la collecte du nombre nécessaire de cas dans une période déterminée, la comparaison des données entre les régions et pays, pour rencontrer les besoins spécifiques de l’Union Européenne et donner une réponse commune aux questions de santé reproductive en Europe. D’autre part, les données épidémiologiques de nombreux pays ont fait avancer notre compréhension de risques importants de santé maternelle et leur distribution géographique à travers l’Europe et apporté la preuve de la nécessité d’aider les gens à prendre la meilleure décision en ce qui concerne les soins en santé reproductive pour de futures recherches.

Nous nous sommes concentrés sur la santé reproductive mais nous croyons que cette approche pourrait être adaptée à d’autres domaines.

Doctorat en Sciences de la santé publique
info:eu-repo/semantics/nonPublished

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Mongeon, Luc Roland. "The right atrial pacemaker complex: The underlying mechanisms mediating the multicentric origin of atrial depolarization." Case Western Reserve University School of Graduate Studies / OhioLINK, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=case1060777680.

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MOSCATO, GIUSELLA. "Epidemiology of nosocomial infections in intensive care units in Rome (Italy): a multicentric prospective study." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2013. http://hdl.handle.net/2108/209994.

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Objective: This study investigated BSI incidence in the Intensive Care Unit and their impact on the mortality rate compared with others causes. As primary point it has been evaluated the rate of bacteremia per year, the causative organisms, the outcome of infection, the antimicrobial susceptibility patterns, the risk factors and the prevalence of multi-drug resistant Gram-positive and Gram-negative bacilli. As secondary end point, the study evaluated the most significant predictors of mortality among the usual risk factors for acquiring BSI at the admission in the ICU. Methods and materials: The study included 1,318 patients admitted to ICUs. Demographics characteristics, SAPS II score, comorbidities and BSI isolates data were collected. Crude mortality rate compared with the overall mortality rate for all causes were evaluated. Results: 324 BSIs from 1,318 patients were evaluated with a total of 407 isolates: 48.6% were Gram + , 43.7% Gram – (GNB) and 7.6% Candida spp. Among Gram+, 69.1% were Coagulase negative Staphylococci (CoNS), 21.7% Enterococci, 6% S. aureus. Among GNB, 30.8% were K. pneumoniae, 28.8% A. baumannii, 17.4% P. aeruginosa, and 6.7% E. coli. At least one episode of BSI was developed in 175 patients (132/1000 pts/year): 139/175 pts had a monomicrobial BSI and 36/175 had polymicrobial BSI. The overall mortality rate was 25.4%: 82/175 pts with BSI died, (44.4% of pts with monomicrobial BSI vs. 61.1 % of pts with polymicrobial BSI). At univariate analysis, SAPS II score (p = 0.039, OR 1.03, 1.001-1.06 CI), cardiac illness (p = 0.015, OR 2.5, 1.20-5.42 CI), and K.pneumoniae BSI (p= 0.005, OR 2.96, 1.37-6.37 CI) were significantly associated to higher risk of death. A slightly significant association between a polymicrobial bacteremia and a higher risk of death was also found (p= 0.057, OR 2.07, 0.98-4.38 CI). At multivariate analysis, having a K. pneumoniae BSI and cardiac illness at the admission in ICU were confirmed to be significantly associated with higher mortality rate (p= 0.0162 and p= 0.0158 respectively). After stratification for outcome (survivors vs. nonsurvivors), univariate and multivariate analysis were performed. Conclusions: These data suggest that K. pneumoniae BSI , cardiovascular comorbidity and polymicrobial BSI in ICU pts are associated to a higher risk of death.

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VALENTE, ALESSIA. "Multicentre translational Trial of Remote Ischaemic Conditioning in acute ischaemic Stroke (TRICS)." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2023. https://hdl.handle.net/10281/403045.

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L’ictus rappresenta la seconda causa di morte a livello globale e la prima causa di disabilità negli anziani. A causa di alcuni limiti di impiego, le principali terapie disponibili, volte a ripristinare il flusso sanguigno attraverso fibrinolisi e/o trombectomia meccanica, possono essere usate solo nel 60% dei pazienti con eziologia ischemica. Per tale motivo, la ricerca preclinica cerca di identificare target terapeutici utili per definire nuovi trattamenti ed estendere l’accesso alle cure. Nessuna nuova strategia terapeutica identificata negli studi preclinici ha però confermato la sua efficacia nei trial clinici. I problemi di traslazionalità dipendono da alcuni limiti degli studi preclinici, come l’uso di un ridotto numero di animali, che non rappresentano le condizioni reali dei pazienti o la mancata replicazione dei risultati ottenuti dai singoli laboratori, introducendo così bias metodologici, tra cui la mancanza di protocolli armonizzati. Il presente studio origina dalla necessità di migliorare il valore traslazionale della ricerca preclinica nell’ictus ischemico attraverso la definizione di un multicentre preclinical randomised controlled trial (pRCT), il progetto TRICS, che ha l’obiettivo di valutare l’azione neuroprotettiva del remote ischemic conditioning (RIC) dopo l’evento ischemico. Perché il RIC raggiunga una neuroprotezione significativa, l’outcome primario è che induca un miglioramento dei deficit sensorimotori a 48 ore dall’evento ischemico, calcolati attraverso il De Simoni neuroscore. Lo score valuta i deficit generali, che indicano lo stato di salute dell’animale e i deficit focali selettivamente associati alle conseguenze neurologiche dell’ischemia. Per ridurre al minimo i bias tecnici, il nostro studio ha previsto una prima fase di armonizzazione della valutazione comportamentale tra i centri, mediante analisi della concordanza tra i rater che eseguivano la misura, definita come interrater agreement. Questo è stato calcolato come intraclass correlation coefficient, ICC=0, nessun accordo, a ICC=1, accordo perfetto. Ci siamo posti l’obiettivo di raggiungere un interrater agreement con un ICC≥ 0.60. Una buona concordanza tra i centri è infatti una condizione indispensabile per garantire che tutti applichino lo stesso metodo di valutazione, assicurando l’oggettività, la trasparenza e la riproducibilità dei risultati. Dopo un training sull’esecuzione del De Simoni neuroscore, ogni centro ha indotto l’ischemia cerebrale nell’animale mediante l’occlusione transiente dell’arteria cerebrale media (tMCAo). A 48 ore dall’operazione, tutti gli animali sono stati filmati durante l’esecuzione del test e i video sono stati inviati al centro coordinatore, che li ha randomizzati e inoltrati ai centri. Un rater per ogni centro ha eseguito in cieco il De Simoni neuroscore sui video e sulle valutazioni è stata eseguita l’analisi statistica. Il risultato ottenuto dall’interrater agreement è stato di ICC=0.50 (0.22-0.77) per i topi e ICC=0.49 (0.210.77) per i ratti; non siamo riusciti a raggiungere l’obiettivo prefissato. Questi risultati sono dipesi da alcuni errori nell’esecuzione del test e dall’attribuzione sbagliata dei punteggi. È stata organizzata una seconda fase di training per superare le differenze di valutazioni più evidenti e preparati nuovi animali ischemici con cui sostituire i video che presentavano errori. Il risultato ottenuto dall’interrater agreement del secondo trial è stato di ICC=0.64 (0.37 – 0.85) per i topi e ICC=0.69 (0.44 - 0.88) per i ratti, soddisfacendo quindi il criterio per iniziare la fase interventistica dello studio. La fase di armonizzazione rappresenta un nuovo ed originale approccio nella ricerca preclinica e dovrebbe rappresentare lo schema di lavoro di base per pianificare uno studio pRCT al fine di renderlo solido e predittivo.
In view of fostering transferability of pre-clinical data on the efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, we designed two multi-centre translational trials in mice and rats of both sexes. We defined to model ischaemic stroke by the transient occlusion of the middle cerebral artery (tMCAo). The improvement of sensorimotor deficits at 48h after tMCAo in RIC-treated animals was defined as the primary outcome. This work presents the harmonization phase relative to the evaluation of sensorimotor deficits by De Simoni neuroscore. Each centre performed different tMCAo durations - 30, 45, 60 min - allowing sufficient variability in the outcome. Animals were monitored post-surgery according to the ARRIVE and IMPROVE guidelines and data was registered into an electronic case report form on RedCap. All animals were video recorded during the neuroscore and the videos (n=11 per species) were distributed and evaluated blindly by raters at all centres. The interrater agreement of neuroscore was described using intraclass correlation coefficient (ICC), ranging between ICC=0 (equivalent to chance) and ICC=1 (perfect agreement), setting a target of ICC≥0.60 as satisfactory. We obtained moderate agreement for mice (ICC=0.50 [0.22-0.77]) and rats (ICC=0.49 [0.21-0.77]). Errors were identified in animal handling and test execution. We thus performed a second training followed by a new blind evaluation replacing the videos with poor experimental execution. The interrater agreement improved for mice (ICC=0.64 [0.37-0.85]) and rats (ICC=0.69 [0.44-0.88]). In conclusion, two dedicated training on the neuroscore allowed us to reach the agreement target for both species and thus next proceed with the interventional phase of the project.

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Klimek, Martin. "Neuroinformatika a sdílení dat z lékařských zobrazovacích systémů." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2010. http://www.nusl.cz/ntk/nusl-218660.

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The presented master's thesis deals with the issue of storing and sharing data from medical imaging systems. This thesis, inter alia, consists of organizational and informatics aspects of medical imaging systems data in multicentric studies containing MRI brain images. This thesis also includes technical design of a web-based application for image data sharing including a web interface suitable for manipulation with the image data stored in a database.

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Pavan, Tatiana Liliane Rossi. "Concentrações séricas das citocinas Interleucina-2 (IL-2), Interleucina-6 (IL-6), Interleucina-10 (IL-10), Fator de Necrose Tumoral Alfa (TNF-) e Proteína Quimiotática de Monócitos-1 (MCP-1) em cães com linfoma multicêntrico." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-20062016-153112/.

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Linfomas representam um grupo de neoplasias que tem em comum a origem em células linforreticulares, manifestando-se geralmente em tecidos linfóides. Em sua evolução há uma reação generalizada contra as alterações sistêmicas que comprometem a homeostase, conhecida como resposta de fase aguda. Citocinas são proteínas relacionadas à imunidade inata e adquirida que medeiam diversas funções e estão envolvidas na resposta inflamatória e são produzidas em resposta a vários estímulos. Foram objetivos desse estudo, verificar se existem diferenças no perfil das citocinas interleucina-2, interleucina-6, interleucina-10, MCP-1 e TNF-alfa nos animais com linfoma multicêntrico ao diagnóstico, quando comparados a um grupo controle e verificar se existe diferença entre os níveis apresentados no momento do diagnóstico e na 6ª semana, momento em que se avalia a remissão. Os grupos do estudo foram constituídos por 20 cães com linfoma (experimental) e 19 cães clinicamente normais (controle) sendo excluídos do estudo cães que apresentavam tratamento prévio e/ou doença concomitante. A quantificação das variáveis estudadas foi realizada utilizando-se kit comercial CCYTOMAG 90K (Milliplex®), sendo as mesmas determinadas no grupo controle uma única vez e no grupo experimental, quando do diagnóstico e na 6ª semana de tratamento. A análise estatística foi realizada através de teste não paramétrico de Mann-Whitney não pareado para o grupo controle e diagnóstico, bem como o diagnóstico e a 6ª semana de tratamento, enquanto que a análise de variância simples (ANOVA) não paramétrico Kruskal-Wallis foi aplicada na comparação dos três grupos (controle, ato do diagnóstico e 6ª semana de tratamento) para todas as citocinas. Foi observada diferença significante nos níveis de IL-10 entre o grupo controle e o experimental ao diagnóstico (p= 0,0033). Os valores do grupo linfoma ao diagnóstico foram elevados em relação ao controle, sem diferença significante entre os momentos do diagnóstico e 6ª semana. As IL-2 e IL-6 mostraram diferenças significantes entre o grupo controle e o grupo linfoma ao diagnóstico (p= 0,0037 e p=0,0017, respectivamente), mas os valores do controle apresentaram-se elevados em relação ao momento do diagnóstico e não houve diferença entre o diagnóstico e 6ª semana. As citocinas TNF-α e MCP-1 não apresentaram diferença significativa. Concluiu-se que os animais com linfoma no diagnóstico apresentaram níveis séricos mais elevados de IL-10, quando comparados ao diagnóstico e ao grupo controle e seus níveis mantiveram-se elevados na 6ª semana de tratamento. As concentrações de IL-2 e IL-6 estiveram mais elevadas no grupo controle quando comparadas aos animais do grupo experimental e as concentrações de TNF-α e de MCP-1 não apresentaram diferença significativa
Lymphomas belongs to a group of malignancies that have in common the origin in lymphoreticular cells, and is generally manifested in lymphoid tissues. In its evolution there is a generalized reaction against the systemic changes that compromise the homeostasis, known as acute phase response. Cytokines are proteins related to innate and acquired immunity which mediate several functions and are involved in inflammatory response and produced in response to several stimulant. This study was designed to verify if there are differences in the profile of cytokines interleukin-2, interleukin-6, interleukin-10, MCP-1 and TNF-alpha in dogs with multicentric lymphoma when compared to a control group and see if there is difference between the levels at the time of diagnosis and at the 6th week, when remission is achieve. The study group consisted of 20 dogs with lymphoma (experimental) and 19 clinically healthy dogs (control). We excluded patients who had previous treatments and/ or concomitant disease. For measurements of cytokines we use a commercial kits CCYTOMAG 90K (Milliplex®), the same being determined in the control group only once and in the experimental group at diagnosis and at 6 week of treatment. Statistical analysis was performed using nonparametric Mann-Whitney unpaired test for the control group and diagnosis, and the diagnosis and 6 week of treatment, while the simple analysis of variance (ANOVA) nonparametric Kruskal-Wallis test was applied when comparing the three groups (control, diagnosis and act 6th week of treatment) for all cytokines. There was a significant difference in IL-10 levels between the control group and the experimental diagnosis (p = 0.0033). The values of the lymphoma group at diagnosis were higher than the control, without significant difference between the time of diagnosis and 6th week. IL-2 and IL-6 showed significant differences between the control and lymphoma groups at diagnosis (p = 0.0037 and p = 0.0017, respectively), but the control had higher levels than the lymphoma group and there was no difference between diagnosis and 6th week. The TNF-α and MCP-1 cytokines showed no significant difference. It was concluded that animals with lymphoma had higher serum levels of IL-10 when compared to control and their levels remained high at 6 weeks of treatment. IL-2 and IL-6 concentrations were higher in the control group compared to lymphoma group and the concentrations of TNF-α and MCP-1 were not significantly different

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Proença, Ana Rita dos Santos Gonçalves. "Linfoma maligno multicêntrico canino." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2009. http://hdl.handle.net/10400.5/1406.

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Dissertação de Mestrado Integrado em Medicina Veterinária
O linfoma maligno canino é um grupo heterogéneo de neoplasias com origem nas células linfóides, podendo atingir praticamente todas as regiões do organismo. A presente dissertação refere-se ao período de Setembro de 2008 a Junho de 2009, durante o qual foi desenvolvida a componente prática do Estágio Curricular de Mestrado Integrado, no Hospital Escolar da FMV, de Setembro 2008 a Fevereiro de 2009. Durante este período procedeu-se ao estudo de linfoma maligno multicêntrico em 8 canídeos que evidenciaram linfadenomegália ao exame físico e/ou exames citológicos ou histológicos positivos para linfoma maligno. O diagnóstico da doença foi realizado por análise citológica de linfonodo (n=7), baço (n=2) e medula óssea (n=1) e por exame histológico hepático (n=1). Adicionalmente realizaram-se exames complementares, nomeadamente a radiografia (n=6) e a ultrasonografia (n=6). Os 8 canídeos foram distribuídos pelos estadios clínicos da OMS sendo que 4 se enquadravam no estadio III, 3 no estadio IV e 1 no estadio V. Os sinais e sintomas clínicos mais consistentes com doença foram a linfadenomegália (n=7), perda de peso acentuada (n=5) e anorexia (n=4). Relativamente às alterações hematológicas, 4 canídeos apresentavam anemia. O tratamento quimioterápico baseado no protocolo CHOP de 19 semanas foi realizado em 4 canídeos. Dos restantes 4 animais, 3 foram submetidos a prednisolona e 1 não recebeu qualquer tipo de terapêutica. A mortalidade e morbilidade foram bastante elevadas nos 4 últimos casos. As alterações hematológicas foram a causa mais prevalente para o adiamento de algumas sessões de quimioterapia. Contudo, apesar da presença de efeitos secundários para o animal e dos possíveis riscos para a saúde pública, os efeitos benéficos do uso de quimioterápicos parece sobrepor-se aos potenciais riscos envolvidos. Duma maneira geral, os canídeos responderam bem à terapêutica quimioterápica mais complexa e os proprietários demonstraram-se satisfeitos com os resultados obtidos. Assim, tendo em conta que o linfoma maligno canino é dos tumores mais gratificantes de abordar com quimioterapia deve ser estabelecida uma correcta relação com os proprietários, de forma a aumentar a adesão ao tratamento.
ABSTRACT - MALIGNANT MULTICENTRIC LYMPHOMA IN DOG - The canine malignant lymphoma is a heterogeneous group of neoplasias whose origin is in lymphoreticular cells and can virtually reach every region of the organism. This thesis covers the period September 2008 to June 2009, during which took place the curricular training of the Integrated Master degree in Veterinary Medicine, at the FMV Teaching Hospital, September 2008 to February 2009. During this period there has been a study of malignant multicentric lymphoma in 8 dogs, these showed lymphadenomegaly at the physical exam and/or were positive to cytologic or histologic examination for malignant lymphoma. The diagnosis of the disease was made by cytological examination of lymph nodes (n = 7), spleen (n = 2), bone marrow (n = 1) and liver histology (n = 1). They were made some additional tests, including radiography (n = 6) and ultrasound (n = 6). The 8 dogs were distributed by the WHO clinical stage, 4 of which were in stage III and the other in stage IV. The clinical signs and symptoms more consistent with the disease were lymphadenomegaly (n = 7), severe weight loss (n = 5) and anorexia (n = 4). Anemia was found in 4 dogs at CBC count. The CHOP chemotherapy protocol of 19 weeks was conducted in 4 dogs. In the remaining 4 animals, 3 were submitted to prednisolone and 1 did not receive any therapy. The rate of mortality and morbidity was high in the last two cases. The hematologic toxicity was the most prevalent cause for the postponement of some chemotherapy sessions. However, despite the presence of side effects to the animal and possible risks to public health, the beneficial effects of the use of chemotherapy seems to overlap the potential risks involved. In general, dogs had a good response to chemotherapy and owners seemed to be satisfied with the results. The canine malignant lymphoma is one of the most rewarding tumors to treat with chemotherapy. Therefore, a proper relationship with the owners is very important in order to increase adherence to treatment.

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GENOVA, Pietro. "ROBOTIC VERSUS LAPAROSCOPIC INTRACORPOREAL ANASTOMOSIS IN RIGHT COLON CANCER SURGERY: ANALYSIS OF PATIENTS’ OPERATIVE OUTCOMES AND OPERATORS’ CURRENT ATTITUDES BY MEANS OF A MONOCENTRIC CLINICAL PROSPECTIVE STUDY AND A EUROPEAN MULTICENTRIC RETROSPECTIVE STUDY." Doctoral thesis, Università degli Studi di Palermo, 2022. http://hdl.handle.net/10447/533657.

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Background. Whereas laparoscopy proved to have better operative outcomes than open surgery over the years, robotic surgery provided no clear advantages over laparoscopy despite its more advanced technical features. However, robotic technology might help to achieve some advantageous procedures which are generally regarded as challenging, such as performing an intracorporeal anastomosis during a right colectomy. The objectives of this research project were: 1) to compare the outcomes of laparoscopic and robotic surgery in the case of a right colectomy with intracorporeal anastomosis for colon cancer; 2) to find any factors influencing surgical decisions and outcomes. Methods. First, we conducted a meta-analysis comparing the outcomes of laparoscopic and robotic right colectomy, providing subgroup analyses for both extracorporeal and intracorporeal anastomosis. Second, we conducted a monocentric prospective clinical study comparing laparoscopic and robotic right colectomy with intracorporeal anastomosis only. Thereby, we participated in the European mul-ticentric retrospective study MERCY (Minimally invasivE surgery for oncologic Right ColectomY). This study investigated the most relevant issues of minimally invasive right colectomy, such as the comparison between extracorporeal and intracorporeal anastomosis, the search for predictors of surgical outcomes and factors influencing the choice of surgical approach and type of anastomosis, the description of current trends in the minimally invasive surgery of right colon cancer, and the comparison between robotic and laparoscopic right colectomy with intracorporeal anastomosis. Results. We performed the largest meta-analysis on laparoscopic vs robotic right colectomy currently available, providing the first subgroup analysis for intracorporeal anastomosis only. In the pooled data analysis, the better results of robotic surgery are presumably attributable to the clear prevalence of the intracorporeal anastomosis in the robotic group rather than to the surgical approach itself. The subgroup analysis for intracorporeal anastomosis found a shorter hospital stay after robotic right colectomy, but the retrospective nature of almost all included studies cannot be excluded as an explanation. However no higher rate of anastomotic leak was found after laparoscopic surgery, suggesting that laparoscopy is as effective and safe as robotic surgery in fashioning an intracorporeal anastomosis. Our clinical research found no differences comparing 24 laparoscopic vs 40 robotic right colectomies with intracor-poreal anastomosis, except a longer operative time in the robotic group. Thereby, the MERCY study found that age, male gender, BMI, ASA score, robotic surgery, and intracorporeal anastomosis were significant predictors of surgical outcomes when performing a right colectomy for cancer. Moreover, the intracorporeal anastomosis has become increasingly widespread over the years. In this regard, age > 90 years, ASA IV, stage cT4, multivisceral resection and intraoperative hemodynamic instability were identified as factors influencing the choice of the type of anastomosis to perform. The comparison between robotic and laparoscopic right colectomy with intracorporeal anastomosis did not find any difference in terms of short-term outcomes and survivals supporting robotic surgery over laparoscopy. Conclusions. The robotic surgery is not superior to laparoscopy in performing a right colectomy with intracorporeal anastomosis for cancer. However, the debate should be directed towards the definition of ever more effective criteria for selecting patients for a specific minimally invasive approach and a specific type of anastomosis. Finally, the evidence collected throughout our research was summarized and formalized in the elaboration of the 2021 guidelines for robotic right colectomy of the Association Française de Chirurgie (AFC), in which we have taken an active part.

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Sierra, Matiz Oscar Rodrigo [UNESP]. "Avaliação do C-MYC, BCL2, KI67 e índice mitótico como fatores prognósticos em cães com linfoma difuso de grandes células B." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/137862.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O linfoma difuso de grandes células B (LDGCB) é o tipo de linfoma mais comum em cães e humanos, caracterizado por seu comportamento agressivo e por promover tempos de sobrevida variáveis, mesmo quando se utiliza a mesma abordagem terapêutica. Atualmente, poucos fatores prognósticos tem sido associados especificamente com LDGCB canino. A imunoexpressão de C-MYC e Bcl2 é reconhecida em humanos como fator prognóstico, devido a relação desses oncogenes com proliferação celular e evasão da apoptose nessa doença. O objetivo desse estudo foi avaliar a imunomarcação dos anticorpos C-MYC, Bcl2, e marcadores de proliferação celular Ki67 e índice mitótico (IM) em cães com LDGCB tratados com protocolo CHOP 19 semanas e correlacioná-la com o tempo de sobrevida e estadiamento clínico visando defini-los como possíveis fatores prognósticos. Trinta amostras de linfonodos de cães diagnosticados com LDGCB foram avaliadas. Para determinar a marcação de C-MYC, Bcl2 e Ki67 foi realizada a técnica de imuno-histoquímica utilizando-se os anticorpos C-MYC, Bcl2 (Santa Cruz Biotechnology) e MIB-1 (Dako), respetivamente. O IM foi calculado como descrito para outras neoplasias. A interpretação dos resultados da imuno-histoquímica para C-MYC e Bcl2, foi calculada no porcentagem de área do número de células marcadas, enquanto a contagem de Ki67 foi realizada com auxílio de uma gratícula, contando-se células positivas por área de 1 cm². Foram estabelecidos pontos de corte, calculando-se a média para todos os marcadores, e posteriormente os valores do C-MYC, Bcl2, Ki67 e a IM foram classificados e definidos como “baixo” ou “alto”. Amostras classificadas como alto C-MYC e alto Bcl2, concomitantemente, foram definidas como alvo duplo MYC/Bcl2. A média de C-MYC foi de 21 (intervalo: 2,5-53,5), de Bcl2 foi de 32,5 (intervalo: 16,9 – 76,8), de Ki67 foi de 107 (intervalo: 1 – 446) e de IM foi de 21 (intervalo: 0-73). Quando comparados os tempos de sobrevida para cada marcador, observou-se que o Ki67 apresentou diferença significativa entre as médias dos grupos baixo (281 dias) e alto (91 dias) (p<0,05). Não houve relação do alvo duplo MYC/Bcl2 com tempos de sobrevida (p>0,05), assim como não houve associação entre a imunomarcação dos anticorpos com o estadiamento clínico. Porém, houve correlação positiva entre C-MYC e Bcl2 (p<0,05) e entre Ki67 e IM (p<0,0001). A expressão imuno-histoquímica dos anticorpos C-MYC e Bcl2, individualmente ou em alvo duplo, não parece constituir um fator prognóstico em cães com LDGCB. Porém, valores acima de 107 células positivas de Ki67 podem estar associados com tempos de sobrevida mais curtos em cães com LDGCB tratados com protocolo CHOP 19 semanas.
Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma in dogs and humans, being characterized by its aggressive behavior with variable survival times, even when same therapeutic approach is used. Currently, few prognostic factors are described in the literature regarding canine DLBCL. Immunoexpression of C-MYC and Bcl2 is recognized in humans as a prognostic factor in DLBCL, product of the relationship between these oncogenes with cellular proliferation and apoptosis escape. The objective of this study is to evaluate the immunolabeling of C-MYC, Bcl2, and markers of cellular proliferation Ki67 and mitotic index (MI) in dogs with DLBCL treated with 19 weeks CHOP protocol and correlate them to survival times and clinical stage in order to identify new prognostic factors. Thirty lymphnode samples of dogs diagnosed with DLBCL were evaluated. For immunoexpression of C-MYC, Bcl2 and Ki67, we perform immunohistochemistry using the antibodies C-MYC, Bcl2 (Santa Cruz Biotechnology) and MIB-1 (Dako), respectively. MI was calculated as previously discussed in other tumors. The interpretation of the immunohistochemistry results for C-MYC and Bcl2 was based on the expression level of the area of positive cells, whereas a grid reticle was used for counting Ki67 positive cells in a total area of 1 cm². Cutoff values for all markers were established calculating the mean value and then the C-MYC Bcl2, Ki67 and MI values were classified and defined as “low” and “high”. Cases classified as high C-MYC and high Bcl2, were defined as double target MYC/Bcl2. Mean values were 21 (range: 2,5-53,5) for C-MYC, 32,5 (range: 16,9-76,8) for Bcl2, 107 (range: 1-446) for Ki67 and 21 (range: 0-73) for MI. Only Ki67 immunoexpression was found to be statistical different when survival times were compared between groups low and high (281 days vs 91 days). When double target MYC/Bcl2 was analyzed, no relationship was identified with survival times (p>0,05). Additionally, an association between the antibodies immunoexpression and clinical staging was not identified. However, a positive correlation between C-MYC and Bcl2 (p<0,05) and, Ki67 and MI (P<0,0001) was established. The immunohistochemistry expression of the antibodies C-MYC and Bcl2, individually or in double target, does not appear to constitute a prognostic factor in dogs with DLBCL, whereas a value of Ki67>107 positive cells can be used in dogs with DLBCL to foresee shorter survival times when treated with 19 weeks CHOP protocol.

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Lehmann, Markus [Verfasser]. "Multicentric Standardization of a Bioassay for Thyroid Receptor Stimulating Antibodies = Multizentrische Standardisierung eines Bioassays zum Nachweis von Schilddrüsen-stimulierenden Antikörpern / Markus Lehmann." Mainz : Universitätsbibliothek Mainz, 2020. http://d-nb.info/1214255930/34.

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Macedo, Thais Rodrigues. "Avaliação das concentrações de superóxido dismutase e da fragilidade osmótica eritrocitária em cães com linfoma multicêntrico com e sem anemia." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-09022011-162444/.

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Linfomas são as neoplasias hematopoiéticas mais comumente relatadas em cães, podendo ocorrer em qualquer idade. A etiologia ainda é desconhecida, porém se aceita que seja multifatorial. São classificadas de acordo com sua localização anatômica, estadio clínico da Organização Mundial de Saúde (OMS), critérios cito-histológicos e imunofenotípicos. A anemia é a anormalidade hematológica mais observada em pacientes com câncer e manifesta-se em cerca dois terços dos cães com linfoma. Os radicais livres de oxigênio produzidos pelas células tumorais aumentam o estresse oxidativo, sendo este demonstrado por mudanças na atividade das enzimas antioxidantes, podendo ocorrer oxidação de proteínas de DNA, aumento da peroxidação de lipídeos e alterações da fragilidade osmótica eritrocitária, acarretando a diminuição da meia vida das hemácias e, sendo essa diminuição um dos fatores que pode levar à anemia nos casos de linfoma. A superoxido dismutase (SOD) é uma enzima antioxidante que catalisa a dismutação do radical superóxido em oxigênio e peróxido de hidrogênio, protegendo as células dos danos induzidos por estes radicais livres. O objetivo deste estudo foi determinar as concentrações eritrocitárias de superóxido dismutase, além de substâncias reativas ao ácido tiobarbitúrico (MDA), o estado antioxidante total (TAS) e a fragilidade osmótica eritrocitária, em cães hígidos e com linfoma multicêntrico com e sem anemia, para avaliar a influência desses mecanismos no desenvolvimento das anemias associadas a essa neoplasia. Amostras de sangue foram obtidas de 24 cães com linfoma multicêntrico, sendo 10 sem anemia e 14 com anemia, e 20 cães saudáveis. Foi observada diferença significante no estado antioxidante total entre os grupos controle, grupos experimentais com linfoma multicêntrico com anemia e sem anemia (p < 0,0001). Não houve diferença significante quando os cães com linfoma com anemia e sem anemia foram comparados, assim como na avaliação das concentrações plasmáticas do MDA entre o grupo controle, grupo experimental com linfoma multicêntrico com anemia e grupo experimental com linfoma multicêntrico sem anemia (p = 0,823). A diferença também não foi significante quando se comparou o grupo controle e o grupo dos animais doentes (p=0,671). A diferença não foi significante na avaliação das concentrações eritrocitárias de superoxido dismutase entre o grupo controle, grupo experimental com linfoma multicêntrico com anemia e grupo com linfoma multicêntrico sem anemia (p=0,0748.). Entretanto, foi observada diferença significante entre o grupo controle e o grupo experimental com linfoma multicêntrico (p=0,0168). Não foi observada diferença na fragilidade osmótica eritrocitária dos cães com linfoma multicêntrico com anemia e sem anemia, as concentrações de NaCl em que observou-se 50% de hemólise estavam dentro dos valores postulados por Jain, 1963. Os resultados obtidos indicam um aumento do estresse oxidativo em cães com linfoma e que a anemia observada nos pacientes com linfoma não esta relacionada diretamente a diminuição das defesas antioxidantes eritrocitárias ou à alterações nas propriedades de membrana secundarias a peroxidação lipídica, que poderiam interferir na fragilidade do eritrócito
Lymphoma is hematopoietic malignancies most commonly reported in dogs can occur at any age. The etiology is still unknown, but is accepted to be multifactorial. They are classified according to their anatomic location, clinical stage of the World Health Organization (WHO), cytological and histological criteria and immunophenotype. Anemia is the most commonly observed hematologic abnormalities in patients with cancer and manifests itself in about two thirds of dogs with lymphoma. The oxygen free radicals produced by tumor cells increases oxidative stress, which is demonstrated by changes in antioxidant enzyme activities, protein and DNA oxidation, increased lipid peroxidation and alterations of erythrocyte osmotic fragility, leading to a decrease in half life of red blood cells and this decrease is one factor that can lead to anemia in cases of lymphoma. The superoxide dismutase (SOD) is an antioxidant enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, protecting cells from damage induced by these free radicals. The aim of this study was to determine erythrocyte superoxide dismutase, and thiobarbituric acid reactive substances (MDA), total antioxidant status (TAS) and erythrocyte osmotic fragility, and in healthy dogs with multicentric lymphoma with and without anemia, to evaluate the influence of these mechanisms in the development of anemia associated with this neoplasia. Blood samples were obtained from 24 dogs with multicentric lymphoma, 10 and 14 with anemia without anemia and 20 healthy dogs. Significant difference was observed in total antioxidant status between the control group, experimental groups with multicentric lymphoma with anemia and without anemia (p <0.0001). There was no significant difference when dogs with lymphoma with anemia and without anemia were compared no significant difference in assessment of plasma concentrations of MDA between the control group, experimental group with multicentric lymphoma with anemia and experimental group with multicentric lymphoma without anemia (p=0.823). The difference was not significant when comparing the control group and the group of sick animals (p = 0.671). The difference was not significant in the evaluation of erythrocyte superoxide dismutase concentrations between the control group, experimental group with multicentric lymphoma with anemia and patients with multicentric lymphoma without anemia (p = 0.0748).. However, significant difference was observed between the control and experimental group with multicentric lymphoma (p = 0.0168). No difference was observed in erythrocyte osmotic fragility of dogs with multicentric lymphoma with anemia and without anemia, the concentrations of NaCl in which there was 50% hemolysis were within the range postulated by Jain, 1963. The results indicate an increased oxidative stress in dogs with lymphoma and that the anemia observed in patients with lymphoma is not directly related to the decrease in erythrocyte antioxidant defenses or the changes in properties of secondary membrane lipid peroxidation, which could interfere with the fragility of erythrocyte

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Macarrão, Jéssica Andreia Coelho. "Linfoma multicêntrico canino." Master's thesis, Universidade de Évora, 2021. http://hdl.handle.net/10174/30644.

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O presente relatório de estágio foi elaborado no âmbito da conclusão do Mestrado Integrado em Medicina Veterinária da Universidade de Évora, estando dividido em duas partes. A primeira parte engloba a análise estatística de toda a casuística presenciada pela autora ao longo do estágio curricular realizado no Hospital Veterinário do Porto (HVP), desde 1 de setembro de 2020 a 28 de fevereiro de 2021. A segunda parte inclui uma monografia sobre o tema “Linfoma Multicêntrico Canino”, seguindo-se a descrição e discussão de um caso clínico. A prevalência tumoral tem vindo a aumentar ao longo dos anos, sendo uma das maiores causas de morte nos animais de companhia. O linfoma multicêntrico é o tumor mais comum na espécie canina. Devido ao grande impacto na saúde e bem-estar animal, surgiu a necessidade de adquirir um conhecimento mais amplo e rigoroso da doença; Canine Multicentric Lymphoma Abstract: The present internship report was elaborated to conclude the master’s degree in Veterinary medicine from the University of Évora and it is divided in two parts. The first part includes statistical analysis of all followed clinical cases during the internship on Hospital Veterinário do Porto, from 1st of September of 2020 to 28th of February of 2021. The second part consist of a monograph about “Canine multicentric lymphoma” followed by the presentation and discussion of a clinical case. Tumor prevalence has increased over the years, being one of the biggest causes of death in domestic animals. Multicentric lymphoma is the most common tumor in the canine species. Due to the major impact on animal health and welfare, there is a growing need to acquire a broader and more rigorous knowledge of the disease.

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Frazão, Inês Regina Bento. "Clínica e cirurgia de animais de companhia. Linfoma multicêntrico canino." Master's thesis, Universidade de Évora, 2020. http://hdl.handle.net/10174/26691.

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O presente relatório surge na sequência do estágio curricular, realizado no Hospital veterinário da Associação Zoófila Portuguesa, entre 17 de setembro de 2018 e 31 de janeiro de 2019, sendo este necessário ao término do curso no Mestrado Integrado de Medicina Veterinária na Universidade de Évora. O relatório encontra-se dividido em duas partes, a primeira refere-se às atividades desenvolvidas na área de clínica e cirurgia de animais de companhia e à casuísta a que a autora teve oportunidade de acompanhar. A segunda inclui uma monografia onde é abordado o tema “Linfoma multicêntrico canino”, com apresentação de dois casos clínicos. O linfoma multicêntrico é o tipo de linfoma mais comum em cães, a sua classificação de Linfoma de células tipo B ou Linfoma de células do tipo T é feita principalmente através de imunofenotipagem e o prognóstico varia segundo a classificação histológica do tumor, sendo que os linfomas das células T são, normalmente, mais raros e de pior prognóstico. O tratamento baseia-se na utilização de quimioterápicos em diferentes protocolos; SMALL ANIMAL MEDICINE AND SURGERY- CANINE MULTICENTRIC LYMPHOMA ABSTRACT: The present report follows the externship performed at Hospital Veterinário da Associação Zoófila Portuguesa, between the period September 17th of 2018 and January 31st of 2019, this being necessary to conclude the master’s degree in veterinary medicine at Universidade de Évora. This report is mainly divided into two parts. The first part refers to the developed activities in small animal practice and to the cases that the author had the opportunity to follow. The second includes a monography about “Canine multicentric lymphoma”, with the presentation of two clinical cases. The multicentric lymphoma is the most frequent in dogs, the classification between B-cell lymphoma or T-cell lymphoma is made mainly through immunophenotyping and the prognosis is variable according to the histological grade of the tumor, being that the t-cell lymphoma are usually rarer and of worse prognosis. The treatment is based on the use of chemotherapeutics in different protocols.

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Speicher, David Jeremiah. "Detection and Genotyping of HHV-8 in Australia and Kenya: Disease Associations with Special reference to Kaposi's Sarcoma and Castleman's Disease." Thesis, Griffith University, 2012. http://hdl.handle.net/10072/367862.

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HHV-8, the aetiological agent of Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL) has been characterised in several parts of the world but largely overlooked in Australia, perhaps because highly active antiretroviral therapy (HAART) has drastically reduced the incidence of HHV-8-associated diseases in the most at-risk population, namely those with HIV disease. Previously, Australian researchers have looked briefly at the sexual behaviours associated with risk of transmission of HHV-8, at molecular methods for detecting the presence of this virus, and have genotyped just eight clinical isolates. Now, the re-emergence of HHV-8 disease associated with increased lifespan in HIV-positive individuals has created a need to better understand the biological importance of this virus, including in Australia and in the developing world. While report of KS and HHV-8 have been previously published from Australia, this project establishes the first research group devoted to the understanding of HHV-8 from an Australian perspective, develops validated quantitative molecular detection methods for HHV-8 in blood and oral fluids, and then characterises the viruses detected via phylogenetic analyses.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Dentistry and Oral Health
Griffith Health
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Ubukata, Rodrigo. "Avaliação do estado oxidante / antioxidante sistêmico e das defesas antioxidantes eritrocitárias em cães com linfoma multicêntrico com e sem anemia." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-11012012-135001/.

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Anemia é a anormalidade hematológica mais comum em pacientes com câncer. Aproximadamente 30% dos cães com linfoma são anêmicos. A anemia pode ocorrer devido substituição da medula óssea por células tumorais, sangramentos ou hemólise, porém mais frequentemente é associada à doença crônica. Estudos realizados em seres humanos com neoplasias hematopoiéticas demonstraram que a diminuição das defesas antioxidantes eritrocitárias e aumento na concentração de marcadores de peroxidação lipídica no plasma são responsáveis pelo estresse oxidativo e ocorrência da anemia. Foram objetivos deste estudo determinar as concentrações eritrocitárias de glutationa reduzida e as atividades das enzimas antioxidantes eritrocitárias glutationa redutase, glutationa peroxidase, além de substâncias reativas ao ácido tiobarbitúrico e o estado antioxidante total em cães hígidos e com linfoma multicêntrico com e sem anemia, para avaliar a influência dos mecanismos oxidativos no desenvolvimento das anemias associadas a essa neoplasia. Foram observadas reduções significativas nas concentrações eritrocitárias de glutationa reduzida e glutationa peroxidase nos cães com linfoma multicêntrico e com anemia (p < 0,001 e p < 0,01, respectivamente). Não houve diferença significativa na avaliação das concentrações eritrocitárias de glutationa redutase e substâncias reativas ao ácido tiobarbitúrico, entretanto as concentrações plasmáticas de substâncias reativas ao ácido tiobarbitúrico eram maiores no grupo de cães com linfoma multicêntrico e com anemia (0,94 mol/L ± 0,72; média ± desvio padrão). Os valores do estado antioxidante total foram significativamente menores (p < 0,001) nos cães com linfoma multicêntrico e com anemia (0,60 mol/L ± 0,12) do que nos animais hígidos (0,87 mol/L ± 0,11). Os resultados obtidos indicam um aumento do estresse oxidativo principalmente nos cães com linfoma multicêntrico e com anemia pela diminuição das defesas antioxidantes, representadas pelo estado antioxidante total e glutationa reduzida intraeritrocitária e pela tendência a maior aumento das concentrações plasmáticas de substâncias reativas ao ácido tiobarbitúrico, podendo estas alterações contribuir para a ocorrência de anemia em cães com linfoma multicêntrico.
Anemia is the most common hematological abnormality in cancer patients. Approximately 30% of dogs with lymphoma are anemic. Anemia can occur due to bone marrow replacement by tumor cells, bleeding or hemolysis, but more often is associated with chronic disease. Researches in human hematopoietic malignancies demonstrated that reduction of erythrocyte antioxidant defenses and increased concentrations of markers of lipid peroxidation in the plasma are responsible for the occurrence of oxidative stress and anemia. This study was designed to measure the concentration of erythrocyte reduced glutathione and antioxidant enzyme activities of erythrocyte glutathione reductase, glutathione peroxidase, and thiobarbituric acid reactive substances and total antioxidant status in healthy dogs and with multicentric lymphoma with or without anemia, to evaluate the influence of oxidative mechanisms in the development of anemia associated with this neoplasia. Significant reductions were observed in erythrocyte concentrations of reduced glutathione and glutathione peroxidase in dogs with multicentric lymphoma and anemia (p < 0.001 and p < 0.01, respectively). There was no significant difference in the assessment of concentrations of erythrocyte glutathione reductase and thiobarbituric acid reactive substances, although concentrations of plasma thiobarbituric acid reactive substances were higher in dogs with multicentric lymphoma and anemia (0.94 mol/L ± 0.72, mean ± standard deviation). The values of total antioxidant status were significantly lower (p < 0.001) in dogs with multicentric lymphoma and anemia (0.60 mol/L ± 0.12) than in healthy animals (0.87 mmol/L ± 0.11). The results indicate an increased oxidative stress, especially in dogs with multicentric lymphoma with anemia and the decrease of antioxidant defenses, represented by the total antioxidant status and intraerythrocytic reduced glutathione and the trend to greater increase in plasma thiobarbituric acid reactive substances and may these changes contribute to the occurrence of anemia in dogs with multicentric lymphoma.

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Sbihi, Zineb. "Immunopathologie de la Maladie de Castleman Multicentrique associée à l'infection par HHV-8. Altérations des Cellules iNKT et Lymphocytes B." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066221/document.

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Le Virus Humain Herpès 8 (HHV-8) est un Herpèsvirus lymphotrope proche du virus d’Epstein Barr (EBV). Au cours de la lymphoprolifération B qu’est la Maladie de Castleman Multicentrique (MCM) HHV-8 est spécifiquement associé à une profifération de plasmablastes monotypiques IgM/. Ces cellules expriment des facteurs de transcription qui suggèrent que ces cellules sont au stade plasmablastique ou pré-plasmocytaire de la différenciation B.Les cellules invariantes Natural Killer (iNKT) sont des cellules innées qui jouent un rôle dans l’immunité antivirale, en particulier dans le contrôle des Herpèsvirus. Une diminution de ces cellules est associée à l’infection VIH ou l’âge, deux situations associées aux pathologies tumorales associées à HHV-8. Dans la première partie du travail nous avons analysés les iNKT chez des patients MCM et montrés des anomalies de fréquence et de prolifération de ces cellules. Les anomalies des cellules sont associées à des anomalies de répartition des sous populations B mémoires dans le sang circulants et la rate de ces patients. Des expériences de co-cultures montrent que les cellules iNKT pourraient être nécessaires au maintien de ces populations BDans la seconde partie de ce travail, nous avons démontré que la MCM HHV-8 est associée pendant les poussées de a maladie à une circulation dans le sang périphérique de cellules présentant les caractéristiques typiques des plasmablastes décrits jusqu’à présent uniquement dans les tissus lymphoïdes. Nous avons ensuite analysé le profil d’expression génique des cellules B infectées par HHV-8 par rapport à celui de sous populations B normales. Nos résultats montrent clairement que les cellules infectées par HHV-8 présentent un profil d’expression génique très différent de celui des sous populations B normales. Leur profil est par ailleurs caractéristique de plasmablastes. De plus, ces cellules sont en prolifération, modulent négativement l’expression de beaucoup de gènes associés à l’immunité et l’adhésion cellulaire. Enfin, nous confirmons que les cellules B infectées par HHV-8 de la MCM sont bien polyclonales même dans le sang circulant et sans mutations somatiques.Au total, ces résultats nous permettent de proposer un modèle de la physiopathologie de la MCM associée à l’infection HHV-8
Human Herpesvirus-8 is a B-lymphotropic \γ-herpesvirus closely related to the Epstein-Barr virus (EBV). He is specifically associated with monotypic (IgM/λ) plasmablasts in Multicentric Castleman disease (HHV-8 MCD), which is a B lymphoproliferative disorder. These cells express transcription factors suggesting they are at the plasmablast or pre-pasma cell stage of differentiation. Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV infection, both situations associated with HHV-8-related diseases. We demonstrated that iNKT cell abnormalities are associated with HHV-8 MCD. These iNKT cell alterations were found to be associated with an imbalance in the frequency of circulating and splenic B cell subsets, and results of Coculturing experiments indicate that iNKT cells may be required for maintaining this cell population. In the second part of our work thesis, we demonstrate that HHV-8 MCD is associated with a unique population of circulating plasmablasts detected during the flare of the disease, with the typical phenotype of the MCD HHV-8-infected plasmablasts in MCD lesions. Then, we used gene expression profile analysis (about 48 000 genes) to further define the phenotype of this MCD HHV-8-infected cells and to investigate the lymphoma relationship to normal B cell subpopulations. The results showed that MCD HHV-8-infected cells displayed a common gene expression profile that is clearly distinct from all the normal B cell subpopulations. The gene expression profile of MCD HHV-8-infected cells was defined as plasmablastic. Moreover, the transcriptomic pattern of MCD HHV-8-infected cells demonstrates that these cells are proliferating and escaping the immune system. Finally, we determined the clonality and the cellular origin of the monotypic circulating plasmablasts by studying the rearranged immunoglobulin heavy genes in LANA+ HHV-8-infected B cells from patients with HHV-8 MCD. Our results show that these cells are polyclonal without somatic mutation. Altogether our results allowed us to elaborate a model of MCD physiopathology

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MARIANI, JACOPO. "MULTICENTRE AND MULTISPECIES PRECLINICAL TRIAL OF REMOTE ISCHEMIC CONDITIONING IN ANIMAL MODEL OF ACUTE ISCHEMIC STROKE (TRICS–BASIC)." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2023. https://hdl.handle.net/10281/403043.

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Il condizionamento ischemico remoto (RIC) risulta essere un candidato ideale per essere investigato in uno studio multicentrico volto al trattamento dell'ictus ischemico acuto (AIS). L’ efficacia terapeutica del RIC è stata dimostrata a livello preclinico, come riportato da precedenti studi ottenuti da singoli laboratori; ciò nonostante, gli studi clinici di fase II-III non hanno ancora fornito risultati soddisfacenti. TRICS Basic è definita come la fase preclinica del progetto TRICS, un Trial traslazionale multicentrico di Condizionamento Ischemico Remoto in modelli animali di Ictus Ischemico Acuto, sostenuto dell’Organizzazione Italiana sull’ictus (ISO), che ha previsto la collaborazione di 7 università e centri di ricerca italiani. TRICS Basic è uno studio preclinico multicentrico, randomizzato e consistente, oltre ad essere orientato alla pratica traslazionale. Lo studio include due specie animali (ratti e topi) ed entrambi i generi (maschi e femmine) sono ugualmente rappresentati. Lo scopo di questo progetto è quello di studiare l'efficacia del trattamento RIC in modelli preclinici di ictus ischemico acuto. Tutti gli animali allocati nel gruppo MCAo+ (soggetti ad ictus) sono stati sottoposti allo stesso tempo di occlusione (60min nei topi; 100min nei ratti). In particolare, il trattamento è stato applicato bloccando l'arteria femorale ipsilaterale per 10 minuti nei topi e 20 nei ratti. La valutazione dei risultati è stata eseguita in cieco, sia per quanto riguarda l’outcome funzionale dicotomizzato (risultato primario), che per la quantificazione del volume dell'infarto (risultato secondario) a 48 ore. Anche le analisi statistiche sono state eseguite in cieco e secondo un paradigma intention–to–treat. Durante la fase sperimentale iniziale, è stata effettuata una fase di armonizzazione, includendo tutti i centri coinvolti, al fine di ridurre le differenze di valutazione durante la valutazione neurocomportamentale. Dopo aver raggiunto l'obiettivo di interclass correlation (ICC)=0.60, imposto a priori dal protocollo pre–pubblicato, la vera fase sperimentale ha avuto inizio. La coorte sperimentale è composta da n=206 animali (n=110 topi e n=96 ratti) ma solo n=152 sono stati inclusi nell’analisi finale per il gruppo MCAo+ (n=81 topi; n=71 ratti). I risultati ottenuti hanno dimostrato che il RIC ha un effetto positivo a livello dell’outcome funzionale (+20% nei topi; +18% nei ratti) ed è in grado di ridurre l'area della lesione ischemica (-4,3% nei topi; -26,6% nei ratti) in entrambe le specie analizzate. Nonostante il consistente numero di animali utilizzati in questo studio, rispetto ai precedenti studi preclinici su questo trattamento, non abbiamo raggiunto la significatività statistica nei nostri due outcome principali, se confrontiamo le singole specie animali. Al contrario, analizzando tutti gli animali come un’unica specie, abbiamo ottenuto un risultato significativo in entrambi gli outcome. Ciò suggerisce che, analogamente agli studi clinici, una maggiore dimensione della popolazione avrebbe portato a risultati più significativi per quanto riguarda il miglioramento del deficit neurologico e la riduzione del volume dell’infarto, analizzando le singole specie.
Remote ischemic conditioning (RIC) represents an ideal candidate to enter a multicenter trial for acute ischemic stroke (AIS) treatment, since previous results from single laboratories support its efficacy, but unfortunately phase II–III clinical trials still provided inconclusive results. TRICS–Basic is the preclinical trial in the TRICS project, a multicentre translational Trial of Remote Ischemic Conditioning in Acute Ischemic Stroke from the Italian Stroke Organization (ISO) Basic Science network, which consisted in the collaboration of 7 Italian institution. TRICS–Basic is a robust, translationally oriented, multicentre, randomized preclinical trial, which includes two animal species (rats and mice) and both male and female sexes are equally represented. The aim of this project was to investigate the efficacy of RIC treatment in AIS experimental models. All the animals in the MCAo+ groups were subjected to the same time of occlusion (60 min in mice; 100 min in rats). The treatment was applied by clamping the ipsilateral femoral artery for 10 min in mice and 20 min in rats. Blinded outcomes assessment was performed both for dichotomized functional neuroscore (primary outcome) and for infarct volume (secondary outcome) at 48 hours. Statistical analyses were performed in a blind status and according to an intention–to–treat paradigm. During the initial experimental period, we carried out a harmonization phase, including all the involved centres, in order to reduce the assessment bias during the neurobehavioral test evaluation. After we have reached the target of Inter class correlation (ICC) 30.60 imposed a priori by the protocol paper, we started the real experimental phase. The experimental cohort was composed by n=206 animals (n=110 mice and n=96 rats) but only n=168 were allocated in the MCAo+ groups (n=88 mice; n=80 rats) and n=152 animals were included in the study (n=78 mice; n=74 rats). The obtained data showed that RIC improve the good functional outcome (+20% in mice; +18% in rats) and reduce the area of ischemic injury (-4.3% in mice; -26.6% in rats) in both species. Despite the large number of animals used in this study and as compared to previous preclinical studies on RIC treatment, we did not reach the statistical significance in our two major outcomes, if we compare the single species alone. On the contrary, if we combine together all the animals, we obtained a significant result in both the analysed outcomes. This suggest that, similarly to clinical trials, a larger sample size would have resulted in more significant results in the functional and the infarct size outcomes single species analyses.

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Grasso, Marica. "“Transcutaneous laryngeal ultrasonography: a reliable, non-invasive and inexpensive preoperative method in the evaluation of vocal cords motility. A prospective multicentric analysis on a large series and an analysis of Literature”." Doctoral thesis, Universita degli studi di Salerno, 2019. http://elea.unisa.it:8080/xmlui/handle/10556/4504.

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2017 - 2018
INTRODUCTION Benign and malignant thyroid diseases affect a large population worldwide. Total Thyroidectomy is one of the most commonly performed intervention in general surgery. The most feared and dangerous complication of thyroidectomy is the paresis or paralysis of the recurrent laryngeal nerve (RLN). Therefore, endocrine surgeons have been prompted to include, among the preoperative examinations, the evaluation of vocal cords function through flexible fiberoptic laryngoscopy (FFL). RLN injuries have a low incidence in referral center with experienced surgeons and, a routine FFL could be uncomfortable for patients and leads to unjustifiable increase of health care costs. Transcutaneous laryngeal ultrasonography (TLUS) has been proposed as a noninvasive and painless indirect examination of vocal cords function as alternative to direct FFL. TLUS is an easy and feasible technique and is a non-invasive, inexpensive, rapid, painless, repeatable and well tolerated by the patient. The aim of this study is to assess TLUS reliability as an alternative method to direct FFL in the evaluation vocal folds function in patients candidate to thyroid surgery. MATHERIAL and METHOD We conducted a prospective observational multicentric cohort study on 396 consecutive patients diagnosed with benign and malignant thyroid disease referred to the Thyroid Surgery Division of the University of Campania "Luigi Vanvitelli" and to the General and Specialistic Surgery Division of the “A. Cardarelli” Hospital. Patients were stratified into 2 groups according to BMI in a non-overweight group (BMI <25) and in an overweight or obese group (BMI ≥25). Transcutaneous laryngeal ultrasonography was performed for each patients by and experienced surgeon trained in ultrasound examination and, after TLUS, all patients underwent routine preoperative FFL by a blinded experienced otolaryngologist. Findings were classified as normal or impaired vocal cord function. RESULTS Sensitivity was equal to 100% (98 – 100%), specificity was 99,5% (98 – 99,9%), positive predictive value 66,7 % (61,8 – 71,3%), negative predictive value 100% (98 – 100%). The probability of a vocal cord alteration in case of negative TLUS was 0% (0 – 10,4%) and if it resulted positive was 66,7% (60,7 – 72,3%). In our series, no False Negative have been observed. The prevalence of VCP in our series was 1% (0,3 – 2,7%). The results showed a concordance between TLUS and FL of 99,5%, with a Cohen’s K value of 0,798. DISCUSSION Thanks to the standardization of the ultrasound technique, we registered a high overall assessability rate was 96.46%, a sensitivity of 100%, a specificity of 99.5%, a positive predictive value of 66.7% and a negative predictive value of 100% in the identification of vocal cords alterations. Our results showed a concordance between TLUS and FL of 99.5%, with a Cohen’s K value of 0.798. These encouraging data allowed us to consider TLUS as part of the routine preoperative screening, as it is absolutely reliable in identifying healthy patients without paresis of the vocal cords. In case of doubts on the motility of the vocal cords, however, TLUS allowed to select patients that should be addressed to FFL. Our study confirmed some difficulty in identifying the vocal cords in male patients with hypertrophy of the thyroid cartilage without calcification. This difficulty was solved thanks to adoption of a different acoustic window in lateral approach, as our investigator had undergone specific training in ultrasound of the cervical region. CONCLUSION TLUS is a valid non-invasive and painless alternative method in the preoperative assessment of vocal cords for a selected population, such as pediatric patients, cardiopathic patients, patients who do not tolerate invasive exams, patients with no diagnosis or suspicion diagnosis of malignancy and patients who do not have voice changes. It could save a high percentage of patients from FFL and in the same time could accurately select patients candidate to second level examinations. [edited by Author]
XVII n.s. (XXXI ciclo)

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Kovalčík, Tomáš. "Neuroinformatika: metody kalibrace v multicentrické MR studii." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2010. http://www.nusl.cz/ntk/nusl-218769.

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Work deals with methods of calibration of multi-center study of magnetic resonance imaging. Magnetic resonance is the phenomenon of the substance in a magnetic field of induction B0 delivers energy in the form of RF pulse with the Larmor frequency and thus to excite particles to higher energy levels. Calibration can be performed using the distinctive and homogeneous RF phantoms. Furthermore, we can perform calibration using image registration. To calibrate the images by registering the work described in the classical linear (affine) and nonlinear. Listed below are the simulators, which are also useful for modeling various artifacts.

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Barbosa, Marcelo Joaquim. "Prevalência de Neisseria gonorrhoeae e Chlamydia trachomatis em homens atendidos em clínicas de DST de seis capitais brasileiras." Universidade Federal do Espírito Santo, 2010. http://repositorio.ufes.br/handle/10/5922.

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Made available in DSpace on 2016-12-23T13:56:05Z (GMT). No. of bitstreams: 1 Marcelo Joaquim Barbosa.pdf: 493310 bytes, checksum: 1cc616c331737b5497291791ef93fb83 (MD5) Previous issue date: 2010-07-12
Objetivos: Determinar a prevalência de Neisseria gonorrhoeae (NG) e Chlamydia trachomatis (CT) e identificar fatores demográficos, comportamentais e clínicos correlacionados a essas infecções em homens atendidos em seis clínicas de DST no Brasil. Métodos: Estudo multicêntrico, em corte transversal realizado em homens que procuraram atendimento em clínicas de DST. O estudo incluiu clínicas de DST em seis cidades distribuídas nas cinco macrorregiões do Brasil, 2004/2005. Metodologia: Coletou-se 20 ml do primeiro jato de urina para testar NG e CT por DNA-PCR. Resultados: Um total de 767 (92,9%) homens foi incluído no estudo. A mediana de idade foi de 24 (DIQ21 30) anos. A prevalência de infecção por CT foi 13,1% (IC95% 10,7%-15,5%) e por NG 18,4% (IC95% 15,7%-21,1%). A prevalência de coinfecção foi 4,4% (IC95% 2,95%-5,85%). Os fatores identificados como sendo independentemente associados com a infecção por clamídia no modelo final de regressão logística foram: ser jovem (15-24 anos) [OR=1,4 (IC95% 1,01-1,91)], apresentar corrimento uretral ao exame [OR=4.8 (IC95% 1,52-15,05)], verrugas genitais [OR=3,0 (IC95% 1,49-5,92)] e história prévia de corrimento uretral [OR=2,4 (IC95% 1,11-5,18)]. As variáveis associadas com gonorréia foram: ser jovem (15-24 anos) [OR=1,5 (IC95% 1,09-2,05)], apresentar corrimento uretral ao exame [OR=9,9 (IC95% 5,53-17,79)], verrugas genitais [OR=18,3 (IC95% 8,03-41,60)] e úlcera ao exame clínico [OR=4,9 (IC95% 1,06-22,73)]. Conclusões: Estes resultados mostram implicações importantes na realização de diagnóstico e tratamento precoces para evitar a transmissão, complicações e implementação de medidas de educação em saúde direcionadas aos homens e deve ser estimulado o oferecimento de testes para DST na rotina dos nos serviços.
Objectives: To determine the prevalence of Neisseria gonorrhoeae(NG) and Chlamydia trachomatis (CT) infections and identified demographic, behavioral, and clinical correlates of these infections in men attending six STI clinics in Brazil. Methods: Multicentric, cross-sectional study performed among men attending STI clinics in Brazil. The study included STD clinics in six diverse cities in the five geographic regions of Brazil in 2005. Patients provided 20 ml of first catch urine for testing for NG and CT by DNA-PCR. Results: A total of 767 (92.9%) men were included in the study. The median age was 24 (IQR 21 30) years old. Prevalence of Chlamydia infection was 13.1% (95%CI 10.7%-15.5%) and gonorrhea was 18.4% (95%CI 15.7%-21.1%). Coinfection prevalence was 4.4% (95%CI 2.95%-5.85%) in men who sought assistance in STI clinics. Factors identified as being independently associated with Chlamydia trachomatis in the final multiple logistic model were being younger (15-24) [OR=1.4 (95%CI 1.01-1.91)], present urethral discharge [OR=4.8 (95%CI 1.52-15.05)], genital warts [OR=3.0 (95%CI 1.49-5.92)] and previous history of urethral discharge [OR=2.4 (95%CI 1.11-5.18)]. Variables associated with gonorrhea were being younger (15 to 24) [OR=1.5 (95%CI 1.09-2.05)], presence of urethral discharge [OR=9.9 (95%CI 5.53-17.79)], genital warts [OR=18.3 (95%CI 8.03-41.60)] and ulcer in clinical examination [OR=4.9 (95%CI 1.06-22.73)]. Conclusions: These findings have important implications for implementing education and prevention efforts directed toward men at risk of HIV/STD. A venue-based approach to offer routinely testing to men in STD clinic should be stimulated.

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Gountouna, Viktoria-Eleni. "Multicentre structural and functional MRI." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9536.

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Neuroimaging techniques are likely to continue to improve our understanding of the brain in health and disease, but studies tend to be small, based in one imaging centre and of uncertain generalisability. Multicentre imaging studies therefore have great appeal but it is not yet clear under which circumstances data from different scanners can be combined. The successful harmonisation of multiple Magnetic Resonance Imaging (MRI) machines will increase study power, flexibility and generalisability. I have conducted a detailed study of the performance of three research MRI scanners in Scotland under the name CaliBrain, with the aims of developing reliable, valid image acquisition and analysis techniques that will facilitate multicentre MRI studies in Scotland and beyond. Fourteen healthy volunteers had two brain scans on each of three 1.5T MRI research machines in Aberdeen, Edinburgh and Glasgow. The scans usually took place 2-3 weeks apart. Each scan was performed using an identical scanning protocol consisting of a detailed structural MRI (sMRI) and a range of functional MRI (fMRI) paradigms. The quality assurance (QA) of scanner performance was monitored in all three sites over the duration of the study using a three-part protocol comprising a baseline assessment, regular measures and session specific measures. The analyses have demonstrated that the data are comparable but also that within- and between-scanner variances are evident and that harmonisation work could enhance the level of agreement. The QA data suggest that scanner performance was similar between and within machines over the course of the study. For the structural MRI scans an optimised methodology was utilised to minimise variation in brain geometry between scanners and fit all the scanned brains into a common stereotactic space, such that repeated measures analyses yielded no significant differences over time for any of the three scanners. I examined the reproducibility of the fMRI motor task within and between the three sites. Similar results were obtained in all analyses; areas consistently activated by the task include the premotor, primary motor and supplementary motor areas, the striatum and the cerebellum. Reproducibility of statistical parametric maps was evaluated within and between sites comparing the activation extent and spatial agreement of maps at both the subject and the group level. The results were within the range reported by studies examining the reproducibility of similar tasks on one scanner and reproducibility was found to be comparable within and between sites, with between site comparisons often exceeding the within site measures. A components of variance analysis showed a relatively small contribution of the factor site with subject being the main source of variation. Similar results were obtained for the working memory task. The analysis of the emotional face processing task showed poor reproducibility both within and between sites. These findings suggest that multicentre structural and functional MRI studies are feasible, at least on similar machines, when a consistent protocol is followed in all participating scanning sites, a suitable fMRI task is employed and appropriate analysis methods are used.

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Caskey, D. "Multicentre dialysis outcomes research in Europe." Thesis, University of Aberdeen, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.592228.

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This thesis describes a prospective study of health outcomes in chronic dialysis patients in ten centres across Europe. There are five main aims: - To describe and compare patients entering chronic dialysis programmes across Europe; - To examine the effect of referral to a nephrologist and transition onto dialysis on early QOL; - To establish the contraindications to haemodialysis and peritoneal dialysis and identify a cohort of comparable patients for comparative studies; - To overcome variations in defining and recording new ESRD patients in different countries; - To compare health outcomes among the ten participating dialysis centres. Among incident patients (n=361), a smooth transition onto dialysis was associated with better early QOL, highlighting the importance of reducing the proportion of patients followed by a nephrologist who require an urgent first dialysis. In the subset of patients suitable for both haemodialysis and peritoneal dialysis, approximately equal numbers choose each modality. In this homogeneous cohort no difference in physical or mental QOL was found in baseline between the two modes of dialysis. However, follow up of these patients found general QOL and mental QOL to improve significantly in patients commencing treatment on haemodialysis, while no significant change was observed in QOL of those beginning on peritoneal dialysis. Incident dialysis patients in west European centres were older and more co-morbid than in central and east European centres. After adjusting for differences in casemix differences in health outcomes were found, with one centre, Thessaloniki, having significantly better QOL, haemoglobin and hospitalisation rates than the reference centre, Aberdeen. The heterogeneity of the centres makes linking single processes of care to improve outcomes difficult, but this study found no link between staffing levels and better health outcomes. Further research into how the health and culture of general populations influences outcomes in dialysis patients is now necessary.

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RELLA, VALERIA. "AMILOIDOSI CARDIACA ANALISI DI PREVALENZA IN DUE STUDI MULTICENTRICI ITALIANI." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2022. http://hdl.handle.net/10281/366496.

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Tra i pazienti con diagnosi iniziale di cardiomiopatia ipertrofica afferiti a Centri di Riferimento per le Cardiomiopatie, l’AC è la malattia non riconosciuta più comune con una prevalenza complessiva del 9%, e che aumenta con l'età (dall'1% nella fascia di età tra i 40-49 anni al 26% sopra gli 80 anni). Nella popolazione generale ≥55 anni più del 7% ha almeno un reperto ecocardiografico suggestivo di AC e l’ispessimento del setto interatriale è quello più frequente. I pazienti con elevato sospetto di AC (≥3 reperti) rappresentano l’1% della popolazione generale e il 4,9% di quelli con cuore non dilatato, ipertrofico e con FE normale.
Among patients with initial diagnosis of HCM, cardiac amiloidosis has a prevalence of 9% and it increases with age. In the general population > 55 yo more than 7% has echocardiographic suspicion of the disease and echocardiography has an important role in the early diagnosis of the disease

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De, Bellis Silva Gerson. "Projeto multicentrico em fisiologia do exercicio : etapa de calibração de cicloergometros." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/275169.

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Orientador: Luiz Eduardo Barreto Martins
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação Fisica
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Resumo: Nesse projeto multicêntrico em fisiologia do exercício - etapa de calibração de cicloergômetros foi desenvolvido um calibrador de cicloergômetros que pode ser utilizado com modelos diferentes de cicloergômetros. A partir de sua calibração estática constatou-se que o mesmo foi capaz de mensurar potencia em cicloergômetros com precisão de 0,85 W. Foi realizada a calibração dinâmica de três cicloergômetros de mesmo modelo que são utilizados pelos laboratórios de fisiologia do exercício da Faculdade de Educação Física da UNICAMP, do Departamento de Fisioterapia da UFSCar e do Departamento de Clinica Médica da USP de Ribeirão Preto. O experimento de calibração testou a resistência, estabilidade e a robustez dos cicloergômetros, além de fornecer a equação que relaciona a potencia real e a potencia indicada pelos cicloergômetros nas rotações de 45, 60 e 75 rpm. As inclinações calculadas pelas regressões foram 0.992, 0.991 and 0.977 respectivamente. Aplicaram-se testes ergoespirométricos em três voluntários nas potencias corrigidas de 60 e 120 W por 10 minutos em cada um dos laboratórios citados. Os valores de consumo de oxigênio, produção de CO2, ventilação e freqüência cardíaca foram calculados no regime permanente e suas medianas comparadas. Os resultados foram diferentes (p<0.05) para as comparações diretas, porém suas variações entre os dois níveis de esforço foram semelhantes. Os testes possibilitaram a observação de que a magnitude da variabilidade biológica dos dados fisiológicos se sobrepõe a precisão mecânica dos ergômetros utilizados nestes testes. Conclui-se que os cicloergômetros calibrados estão adequados ao propósito de um projeto multicêntrico, porém os procedimentos experimentais que envolvem a variabilidade biológica ainda necessitam de padronização para tornar possível agrupar dados coletados nos diferentes Laboratórios
Abstract: In the Multicenter Exercise Physiology Project: cycle ergometer calibration phase a multiple kind cycle ergometer calibrator was developed. The exercise physiology laboratories comprising the multicenter project were from Faculty of Physical Education- UNICAMP, Department of Physical Therapy UFSCar and Department of internal medicine- USPRP. Its static calibration gave an accuracy of 0.85 W for cycle ergometer workload readout. An experimental setup for testing stability, resistance and robustness of cycles was carried out in three identical model cycle ergometers. The dynamical calibration was executed to provide the linear regression equation between actual and indicated workloads for 45, 60 and 77 rpm. The computed regressions slopes were 0.992, 0.991 and 0.977 respectively. Ergospirometric tests with 60 and 120 W of workload were applied to three volunteers for 10 min in each laboratory. Oxygen uptake, CO2 production, ventilation and heart rate were computed for steady state and their medians tested for statistical significance (P<0.05). The results were different for direct testing of variables, although their between exercise levels variations were equal. Though, the biological variability overlaps the mechanical accuracy of ergometers. In conclusion, the calibration procedure of ergometers allows the constitution of a multicenter project but biological variability associated with the ergospirometric tests needs standardization to permit the grouping of data from different Laboratories
Mestrado
Biodinamica do Movimento Humano
Mestre em Educação Física

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Borghi, Claudia <1980&gt. "Ruolo dell'elettrocardiogramma standard nella stratificazione prognostica della cardiomiopatia ipertrofica. Studio multicentrico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5384/1/borghi_claudia_tesi.pdf.

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Lo scopo di questo studio è di valutare il significato prognostico dell'elettrocardiogramma standard in un'ampia casistica di pazienti affetti da cardiomiopatia ipertrofica. In questo studio multicentrico sono stati considerati 841 pazienti con cardiomiopatia ipertrofica (66% uomini, età media 48±17 anni) per un follow-up di 7.1±7.1 anni, per ognuno è stato analizzato il primo elettrocardiogramma disponibile. I risultati hanno dimostrato come fattori indipendentemente correlati a morte cardiaca improvvisa la sincope inspiegata (p 0.004), il sopraslivellamento del tratto ST e/o la presenza di onde T positive giganti (p 0.048), la durata del QRS >= 120 ms (p 0.017). Sono stati costruiti due modelli per predire il rischio di morte improvvisa: il primo basato sui fattori di rischio universalmente riconosciuti (spessore parietale >= 30 mm, tachicardie ventricolari non sostenute all'ECG Holter 24 ore, sincope e storia familiare di morte improvvisa) e il secondo con l'aggiunta delle variabili sopraslivellamento del tratto ST/onde T positive giganti e durata del QRS >= 120 ms. Entrambi i modelli stratificano i pazienti in base al numero dei fattori di rischio, ma il secondo modello risulta avere un valore predittivo maggiore (chi-square da 12 a 22, p 0.002). In conclusione nella cardiomiopatia ipertrofica l'elettrocardiogramma standard risulta avere un valore prognostico e migliora l'attuale modello di stratificazione per il rischio di morte improvvisa.
The purpose of this study was to investigate the prognostic significance of standard electrocardiogram (ECG) in a large cohort of patients with hypertrophic cardiomyopathy (HCM). In this multicenter study 841 HCM patients (66% men, mean age 48±17 yrs) were followed for 7.1±7.1 years and the first collected ECG was considered for the analysis. The results showed that independent predictors of sudden cardiac death were unexplained syncope (p 0.004), ST segment elevation and/or giant positive T waves (p 0.048), QRS duration >= 120 ms (p 0.017). Two models has been contructed to predict the risk of sudden death: the first based on the already well known established risk factors (wall thickness >= 30 mm, non-sustained ventricular tachycardia on ECG Holter monitoring, syncope and family history of sudden death) and the second with the addition of ST segment elevation/giant positive T waves and QRS duration >= 120 ms. Whereas both models stratified patients according to the number of risk factors, the second model showed a higher predictive power (chi-square from 12 to 22, p 0.002). In conclusion in HCM standard ECG has a prognostic value and improves the current risk stratification model.

30

Borghi, Claudia <1980&gt. "Ruolo dell'elettrocardiogramma standard nella stratificazione prognostica della cardiomiopatia ipertrofica. Studio multicentrico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5384/.

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Lo scopo di questo studio è di valutare il significato prognostico dell'elettrocardiogramma standard in un'ampia casistica di pazienti affetti da cardiomiopatia ipertrofica. In questo studio multicentrico sono stati considerati 841 pazienti con cardiomiopatia ipertrofica (66% uomini, età media 48±17 anni) per un follow-up di 7.1±7.1 anni, per ognuno è stato analizzato il primo elettrocardiogramma disponibile. I risultati hanno dimostrato come fattori indipendentemente correlati a morte cardiaca improvvisa la sincope inspiegata (p 0.004), il sopraslivellamento del tratto ST e/o la presenza di onde T positive giganti (p 0.048), la durata del QRS >= 120 ms (p 0.017). Sono stati costruiti due modelli per predire il rischio di morte improvvisa: il primo basato sui fattori di rischio universalmente riconosciuti (spessore parietale >= 30 mm, tachicardie ventricolari non sostenute all'ECG Holter 24 ore, sincope e storia familiare di morte improvvisa) e il secondo con l'aggiunta delle variabili sopraslivellamento del tratto ST/onde T positive giganti e durata del QRS >= 120 ms. Entrambi i modelli stratificano i pazienti in base al numero dei fattori di rischio, ma il secondo modello risulta avere un valore predittivo maggiore (chi-square da 12 a 22, p 0.002). In conclusione nella cardiomiopatia ipertrofica l'elettrocardiogramma standard risulta avere un valore prognostico e migliora l'attuale modello di stratificazione per il rischio di morte improvvisa.
The purpose of this study was to investigate the prognostic significance of standard electrocardiogram (ECG) in a large cohort of patients with hypertrophic cardiomyopathy (HCM). In this multicenter study 841 HCM patients (66% men, mean age 48±17 yrs) were followed for 7.1±7.1 years and the first collected ECG was considered for the analysis. The results showed that independent predictors of sudden cardiac death were unexplained syncope (p 0.004), ST segment elevation and/or giant positive T waves (p 0.048), QRS duration >= 120 ms (p 0.017). Two models has been contructed to predict the risk of sudden death: the first based on the already well known established risk factors (wall thickness >= 30 mm, non-sustained ventricular tachycardia on ECG Holter monitoring, syncope and family history of sudden death) and the second with the addition of ST segment elevation/giant positive T waves and QRS duration >= 120 ms. Whereas both models stratified patients according to the number of risk factors, the second model showed a higher predictive power (chi-square from 12 to 22, p 0.002). In conclusion in HCM standard ECG has a prognostic value and improves the current risk stratification model.

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MATARAZZO, LORENZA. "“STUDIO MULTICENTRICO PER LA CARATTERIZZAZIONE GENOTIPICA E FENOTIPICA DELLE COLESTASI EREDITARIE”." Doctoral thesis, Università degli Studi di Trieste, 2020. http://hdl.handle.net/11368/2961248.

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La colestasi intraepatica è una sindrome clinica e bioumorale secondaria a disturbi congeniti o acquisiti della formazione e secrezione canalicolare degli acidi biliari. Le colestasi progressive familiari intraepatiche (PFIC) rappresentano la causa di colestasi nel 10-15% dei casi e mutazioni in tre geni sono state classicamente identificate: le PFIC tipo 1 e 2, causate da mutazioni nei geni ATP8B1 e ABCB11, caratterizzate da livelli normali di GGT e la PFIC di tipo 3, causata da mutazioni nel gene ABCB4, con GGT elevate. Negli ultimi anni, le tecniche di Next Generation Sequencing hanno permesso di identificare e caratterizzare nuovi geni coinvolti nelle colestasi ereditarie sia nella forme a GGT normali (TJP2, FXR, MYO5B), che elevate (CLDN1, DCDC2). A partire da tali premesse, è stato condotto uno studio multicentrico, retrospettivo e prospettico, con l’obiettivo di arruolare pazienti affetti da colestasi e caratterizzarli fenotipicamente e genotipicamente. I pazienti sono stati studiati mediante sequenziamento dell’esoma e conferma con tecnica Sanger nei probandi e, qualora disponibili, nei genitori. Sono stati arruolati 25 pazienti con i seguenti risultati: una predominanza del sesso maschile (19/25, 76%) ed un’età mediana all’esordio di 0.8 anni (range 0 - 15.1). Il 68% dei pazienti (17/25) era di origine italiana. La durata media del follow-up è stata di 3.7 anni (range 0.1 - 25.6). Le manifestazioni cliniche all’esordio comprendevano epatomegalia (68%), ittero (57%), prurito (43%), scarsa crescita (33%), feci ipocoliche (33%) e splenomegalia (28%). Il valore mediano delle ALT era 184 U/L (range 54 - 650), della bilirubina totale e diretta rispettivamente 5.5 mg/dl e 3.2 mg/dl. Gli acidi biliari erano aumentati nell’81% dei pazienti. Una lieve predominanza delle forme a GGT elevate (64%) è stata riscontrata. La biopsia epatica, eseguita in 16/25 (64%) pazienti, mostrava un’ istologia compatibile con colestasi intraepatica nelle forme a GGT normali e con colangiopatia per le forme a GGT elevate.La terapia medica all’esordio consisteva nell’utilizzo di acido ursodesossicolico, supplementazione con vitamine liposolubili e trattamento del prurito. Quattro pazienti (16%) hanno ricevuto trapianto epatico. I risultati completi delle analisi genetiche, disponibili per 8 pazienti, hanno mostrato una prevalenza di mutazioni a carico del gene della miosina 5B (MYO5B), presenti in 6 pazienti; 2 pazienti avevano mutazioni a carico del gene ABCB4 (PFIC tipo 3), mentre per i restanti pazienti le analisi genetiche sono ancora in corso.

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ALLONI, MARTA. "Studio multicentrico di valutazione multiparametrica cardiovascolare ultrasonografica nella predizione della coronaropatia." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/45258.

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Ad oggi la malattia cardiovascolare aterosclerotica rimane la principale causa di morbidità e mortalità (58% di morte per tutte le cause, di cui il 75% per coronaropatia e il 25% per ictus e ischemia cerebrale), e sarà la principale causa di mortalità nel 2015 secondo un rapporto della WHO. Il problema principale è legato al lungo tempo che intercorre tra l’inizio dello sviluppo di aterosclerosi nel giovane adulto e la sua manifestazione alcune decadi dopo. E’ di primaria importanza quindi poter identificare i soggetti a rischio di eventi cardiovascolari con progetti di prevenzione primaria in ogni paese, come raccomandato da diverse linee guida, comprese quelle della Società Europea di Cardiologia per la prevenzione del rischio cardiovascolare nella pratica clinica. Sono stati proposti diversi modi per stratificare il rischio cardiovascolare: fra i più importanti è stato sviluppato il Framngham risk score, che calcola la probabilità di mortalità coronarica a 10 anni a seconda della presenza dei seguenti fattori di rischio: età, presenza di diabete, fumo, pressione arteriosa, colesterolemia totale e LDL. Esistono dunque vari modi di stratificare il rischio in un soggetto asintomatico, tra carte del rischio (Framingham Risk score, SCORE, Progetto Cuore in Italia) e diversi indici bioumorali (ad esempio PCR e fibrinogeno) e strumentali: questi si adattano bene come predittori sulla popolazione generale, ma nessuno è utile nello stimare il rischio reale del singolo paziente per eventi cardiovascolari. Infatti, il rischio soggettivo è dato anche dal rischio complessivo della popolazione in cui il soggetto vive. Anche l’identificazione precoce del danno d’organo subclinico, come indicato dalle linee guida ESH/ESC, è uno degli obiettivi più importanti di prevenzione e trattamento del rischio cardiovascolare.Infatti la presenza di ipertrofia ventricolare sinistra, ispessimento medio-intimale carotideo, microalbuminuria, aumentata stiffness arteriosa aumentano il rischio cardiovascolare, indipendentemente dalla pressione arteriosa, in presenza o assenza di trattamento. Quindi parità di valori pressori, pazienti che presentano danno d’organo hanno un maggior rischio cardiovascolare e necessitano di una terapia più aggressiva e precoce. L’uso dell’ultrasonografia si adatta bene come screening del rischio cardiovascolare di popolazioni non selezionate, perché a basso costo rispetto a metodiche a maggior impatto rischio /beneficio,a maggior costo e a maggior esposizione di radiazioni come la TAC e la RMN cardiaca, inoltre è una metodica non invasiva. Infatti per eseguire uno screening bisogna che gli strumenti utilizzati siano validati, precisi, facili da utilizzare e soprattutto non invasivi. Inoltre è necessario che vi sia personale esperto, a basso costo per il sistema sanitario nazionale, la metodica non dovrebbe avere effetti biologici negativi ed essere giustificata dai risultati. L’ecografia può permettere di studiare i parametri che per primi si modificano nel processo aterosclerotico come la rigidità arteriosa e lo spessore mio intimale carotideo, i parametri di funzione longitudinale ventricolare sinistra (strain e strain rate), la velocità basale di flusso della coronaria interventricolare anteriore ed infine l’accumulo di calcio a livello delle strutture cardiache (valvole, muscoli papillari, radice aortica).

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Borsato, Emerson Paulo. "Modelo multicentrico para elaboraçăo, coleta e pesquisa de dados em protocolos eletrônicos /." oai:ufpr.br:217897, 2005. http://200.17.209.5:8000/cgi-bin/gw_42_13/chameleon.42.13a?host=localhost%201111%20DEFAULT&sessionid=VTLS&function=CARDSCR&search=KEYWORD&pos=1&u1=12101&t1=217897.

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Orientador: Antonio Carlos Ligocki Campos
Co-orientador: Jorge Eduardo Fouto Matias
Inclui apendices
Tese (doutorado) - Universidade Federal do Paraná, Setor de Cięncias da Saúde, Programa de Pós-Graduaçăo em Clínica Cirúrgica. Defesa: Curitiba, 2005
Inclui bibliografia

34

PIAZZA, ELENA. "Multicentre prospective study in patients affected by Dravet Syndrome." Doctoral thesis, Università degli studi di Pavia, 2018. http://hdl.handle.net/11571/1214868.

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Dravet syndrome (DS) is a rare and severe form of epilepsy, associated with mutations of SCN1A gene, encoding for the sodium channel voltage-dependent Nav.1.1. Epilepsy appears in the first year of life in an otherwise healthy infant. The disease is progressive and during its course neurological signs change, comorbidities appear and cognitive deficits become highly disabling. Nowadays, only few prospective longitudinal studies have been reported. Aims of this study are to perform a multicentre prospective evaluation of a group of Italian Dravet patients, carrying a SCN1A mutation, followed from the first year of life, in order to: Describe the epileptological onset and evolution, Describe neurological features, Identify the onset of a neurodevelopmental impairment, Evaluate the presence of associated behavioural disorders, Perform a correlation analysis between genetic determinants and cognitive evolution, Perform a correlation analysis between the cognitive evolution and epileptological variables. Aims of the second part of the study are to perform a prospective evaluation of a sample of Dravet patients and a control group followed in a tertiary neurological centre, followed from seizure onset in order to: Compare clinical and electrophysiological features during the first years of life, Define etiologic determinants in the control group to reach an early diagnosis and to give targeted treatment. In the first part of the study 17 Dravet patients, all carrying a mutation in SCN1A, were enrolled. The analysis of the data collected, allowed us to highlight the following remarks: the onset of febrile and/or prolonged seizures within the 6th month in a previously healthy child represents one of the typical features of Dravet Syndrome: in our series the first seizure occurred within the sixth month in 88% of the infants. Most of patients of the sample (75%), presented one or more convulsive status within the 12th month of age. Interictal myoclonus represents a common neurological sign: in our sample this already appeared at the 12th month. The association of these early findings, in an otherwise healthy patient, especially when associated with a normal EEG, can be considered a useful tool to recognize early the disease. We performed neuropsychological assessments, from the first months of the disease in order to follow its evolution. A progressive slowing appeared between the 12th and the 18th month in most of the patients. The correlation analysis between genetic determinants and cognitive evolution did not provide any evidence for a correlation between the type of mutation and the cognitive outcome. The correlation between the epilepsy course and the cognitive outcome highlighted that an early onset of seizures represents a negative prognostic factor for cognitive evolution. It’s conceivable that epileptic phenotype may play a role in determining the final cognitive outcome, but, it does not seem that a more early and targeted treatment can really modify the natural history of the disease. So other genetic and environmental factors need to be considered. In the second part of the study we performed a prospective evaluation of a sample of Dravet patients with a control group. These observations confirm what we stated above: The early onset of the seizures may lead the clinical diagnosis towards Dravet Syndrome, in our control group, only 2 patients out of 9 experienced their first seizures within the 6th month of age. The occurrence of the seizures and the status epilepticus during the first years of life can be observed in Dravet Syndrome and in other forms of genetic epilepsy, but the persistence of polymorphic, drugs-resistant seizures is more common in Dravet Syndrome. A steep decrease in the General Quotient is usually observed in Dravet Syndrome, whereas patients with other forms of genetic epilepsy show a milder decrease despite often presenting a lower GQ from the beginning.

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Matheus, Wagner Eduardo. "Carcinoma urotelial invasivo de bexiga primario versus progressivo : analise multicentrica de sobrevida global." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312203.

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Orientadores: Ubirajara Ferreira, Fernandes Denardi
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O melhor tratamento para o carcinoma urotelial invasivo de bexiga é a cirurgia de cistectomia radical. O objetivo principal desse estudo foi de comparar a taxa de sobrevida global dos tumores músculo invasivos primários dos tumores invasivos progressivos. O objetivo secundário foi comparar a taxa de sobrevida global dos subgrupos pT3/4, acometimento linfonodal e presença de metástases, dos tumores primários e invasivos. Nesse estudo multicêntrico retrospectivo, foram avaliados 242 pacientes submetidos à cistectomia radical, no período de 1992 a 2005, para tratamento de carcinoma urotelial invasivo de bexiga. Os pacientes foram divididos em dois grupos: Grupo I ¿ 185 pacientes com tumor invasivo primário e Grupo II - 57 pacientes com carcinoma urotelial invasivo progressivo. Além disso, conforme achados histopatológicos, ambos os grupos foram divididos em subgrupos: pT2 (invasão de musculatura vesical), pT3/4 (invasão de gordura perivesical e órgãos ou tecidos adjacentes), N+ (acometimento de linfonodos) e M+ (presença de metástases). Para análise estatística foram aplicados os testes de qui-quadrado, Mann-Whitney, Kaplan-Meier e Wilcoxon (Breslow). A média e mediana de seguimento foram de 98 e 90 meses para o Grupo I, e 96 e 88 meses para o Grupo II, respectivamente, e sem diferença estatística significativa (p = 0.0734). No seguimento, foram observadas as seguintes taxas de sobrevida global: no primeiro ano, 77% para o Grupo I e 84% para o Grupo II; no terceiro ano, 59% e 74% e, no quinto ano, 52% e 58% para os grupos I e II, respectivamente, sem diferença estatística significativa. Quando analisados separadamente, os três subgrupos: tumores PT3/T4, acometimento linfonodal e presença de metástases, também não foram observadas diferenças estatísticas significativas nos grupos I e II. No presente estudo, não houve diferença significativa de sobrevida global dos pacientes portadores de tumores vesicais invasivos primários e progressivos, no seguimento de cinco anos. Também não houve diferença significativa na sobrevida global, quando analisados separadamente os subgrupos: PT3/4, com acometimento linfonodal e presença de metástases
Abstract: The best treatment for all-invasive bladder cancer is radical cystectomy. The main purpose of this study was to compare the overall survival rate of primary muscle-invasive urothelialbladder carcinoma (UC) to the progressive muscle-invasive bladder carcinoma. A secondary aim was to compare the survival rate of the subgroups pT3/4, lymph nodes involvement and the presence of metastasis in primary and invasive bladder carcinomas. A retrospective multicentric analysis was performed studying a total of 242 patients who underwent radical cystectomy for invasive TCCB from 1992 to 2005. The patients were divided into two groups. There were 185 patients in Group I with progressive invasive TCCB, while Group II had 57 patients with primary invasive TCCB. Both groups were further divided according to the pathological findings in pT2 (muscle invasion), pT3/4 (perivesical fat and/or adjacent organs/structure invasion), N+ (positive lymphaticnodes) and M+ (distant organ metastasis). Several tests were employed for the statistical analysis: qui-square, Mann-Whitney, Kaplan-Meier method and Wilcoxon (Breslow). The average and median follow-ups were, respectively, 98 and 90 months in Group I and 96 and 88 months in Group II, without a significant statistical difference (p = 0.0734). The 1-year survival rate was 77% in Group I and 84% in Group II. After 3 years of follow-up the survival rate fell to 59% in Group I and 74% in Group II. Finally, the 5-year survival rate was 52% in Group I and 58% in Group II, without a significant statistical difference. When the three subgroups were analyzed separately for tumors pT3/T4, invasivelymphatic nodes and the presence of metastasis, no significant statistical differences were found in either Group I or Group II. In the present study, patients with primary invasive and progressive invasive TCCB showed a similar 5-year global survival rate. Pathological stage (PT, N and M) and patient demography did not interfere with the results
Doutorado
Cirurgia
Doutor em Cirurgia

36

Zanardi, Francesca <1979&gt. "Studio caso-controllo multicentrico su distacco di retina e movimentazione manuale di carichi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5728/1/zanardi_francesca_tesi.pdf.

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Obiettivo Valutare l’ipotesi secondo cui la movimentazione manuale di carichi possa essere un fattore di rischio per il di distacco di retina. Metodi Si è condotto uno studio caso-controllo ospedaliero multicentrico, a Bologna, (reparto di Oculistica del policlinico S. Orsola Malpighi, Prof. Campos), e a Brescia (reparto di oculistica “Spedali Civili” Prof. Semeraro). I casi sono 104 pazienti operati per distacco di retina. I controlli sono 173 pazienti reclutati tra l’utenza degli ambulatori del medesimo reparto di provenienza dei casi. Sia i casi che i controlli (all’oscuro dall’ipotesi in studio) sono stati sottoposti ad un’intervista, attraverso un questionario strutturato concernente caratteristiche individuali, patologie pregresse e fattori di rischio professionali (e non) relativi al distacco di retina. I dati relativi alla movimentazione manuale di carichi sono stati utilizzati per creare un “indice di sollevamento cumulativo―ICS” (peso del carico sollevato x numero di sollevamenti/ora x numero di anni di sollevamento). Sono stati calcolati mediante un modello di regressione logistica unconditional (aggiustato per età e sesso) gli Odds Ratio (OR) relativi all’associazione tra distacco di retina e vari fattori di rischio, tra cui la movimentazione manuale di carichi. Risultati Oltre alla chirurgia oculare e alla miopia (fattori di rischio noti), si evidenzia un trend positivo tra l’aumento dell’ICS e il rischio di distacco della retina. Il rischio maggiore si osserva per la categoria di sollevamento severo (OR 3.6, IC 95%, 1.5–9.0). Conclusione I risultati, mostrano un maggiore rischio di sviluppare distacco di retina per coloro che svolgono attività lavorative che comportino la movimentazione manuale di carichi e, a conferma di quanto riportato in letteratura, anche per i soggetti miopi e per coloro che sono stati sottoposti ad intervento di cataratta. Si rende quindi evidente l’importanza degli interventi di prevenzione in soggetti addetti alla movimentazione manuale di carichi, in particolare se miopi.
Background/Objectives To investigate the hypothesis that repeated lifting tasks could be a risk factor for retinal detachment. Methods Case-control study (case definition: surgically treated retinal detachment. Cases were identified among patients operated for retinal detachment in two large urban hospital in Bologna and Brescia. Controls were drawn from outpatients attending an eye clinic in the same catchment area. 104 cases and 173 controls (blind to the study hypothesis) responded to a structured questionnaire regarding individual, pathological and work-related factors possibly related to retinal detachment, including past/present occupational lifting tasks. Three lifting categories were defined based on the median “cumulative lifting index” (product of load, manoeuvres/hour and lifting-years) among manual workers: no lifting (reference category); light lifting; heavy lifting. Odds ratios for retinal detachment associated with “heavy”, “moderate” or “light” occupational lifting in an unconditional logistic regression model (adjusted for age and sex) were obtained. Results In addition to ocular surgery and myopia (known risk factors), an independent associations were recorded for heavy lifting (odds ratio 3.6, 95% confidence interval, 1.5 to 9.0). Likelihood ratio tests did not reveal interactions between heavy lifting, ocular/cataract surgery and myopia. Conclusions The results support the plausible hypothesis that heavy occupational lifting (involving Valsalva’s manoeuvre) may be a relevant risk factor for retinal detachment. Moreover these preliminary results confirmed, as reported in literature, an increased risk of retinal detachment for myopic subjects and for those who have undergone cataract surgery. Our observations emphasize the importance of prevention especially in subjects involved in the manual handling of loads, particularly if short-sighted.

37

Zanardi, Francesca <1979&gt. "Studio caso-controllo multicentrico su distacco di retina e movimentazione manuale di carichi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5728/.

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Abstract:

Obiettivo Valutare l’ipotesi secondo cui la movimentazione manuale di carichi possa essere un fattore di rischio per il di distacco di retina. Metodi Si è condotto uno studio caso-controllo ospedaliero multicentrico, a Bologna, (reparto di Oculistica del policlinico S. Orsola Malpighi, Prof. Campos), e a Brescia (reparto di oculistica “Spedali Civili” Prof. Semeraro). I casi sono 104 pazienti operati per distacco di retina. I controlli sono 173 pazienti reclutati tra l’utenza degli ambulatori del medesimo reparto di provenienza dei casi. Sia i casi che i controlli (all’oscuro dall’ipotesi in studio) sono stati sottoposti ad un’intervista, attraverso un questionario strutturato concernente caratteristiche individuali, patologie pregresse e fattori di rischio professionali (e non) relativi al distacco di retina. I dati relativi alla movimentazione manuale di carichi sono stati utilizzati per creare un “indice di sollevamento cumulativo―ICS” (peso del carico sollevato x numero di sollevamenti/ora x numero di anni di sollevamento). Sono stati calcolati mediante un modello di regressione logistica unconditional (aggiustato per età e sesso) gli Odds Ratio (OR) relativi all’associazione tra distacco di retina e vari fattori di rischio, tra cui la movimentazione manuale di carichi. Risultati Oltre alla chirurgia oculare e alla miopia (fattori di rischio noti), si evidenzia un trend positivo tra l’aumento dell’ICS e il rischio di distacco della retina. Il rischio maggiore si osserva per la categoria di sollevamento severo (OR 3.6, IC 95%, 1.5–9.0). Conclusione I risultati, mostrano un maggiore rischio di sviluppare distacco di retina per coloro che svolgono attività lavorative che comportino la movimentazione manuale di carichi e, a conferma di quanto riportato in letteratura, anche per i soggetti miopi e per coloro che sono stati sottoposti ad intervento di cataratta. Si rende quindi evidente l’importanza degli interventi di prevenzione in soggetti addetti alla movimentazione manuale di carichi, in particolare se miopi.
Background/Objectives To investigate the hypothesis that repeated lifting tasks could be a risk factor for retinal detachment. Methods Case-control study (case definition: surgically treated retinal detachment. Cases were identified among patients operated for retinal detachment in two large urban hospital in Bologna and Brescia. Controls were drawn from outpatients attending an eye clinic in the same catchment area. 104 cases and 173 controls (blind to the study hypothesis) responded to a structured questionnaire regarding individual, pathological and work-related factors possibly related to retinal detachment, including past/present occupational lifting tasks. Three lifting categories were defined based on the median “cumulative lifting index” (product of load, manoeuvres/hour and lifting-years) among manual workers: no lifting (reference category); light lifting; heavy lifting. Odds ratios for retinal detachment associated with “heavy”, “moderate” or “light” occupational lifting in an unconditional logistic regression model (adjusted for age and sex) were obtained. Results In addition to ocular surgery and myopia (known risk factors), an independent associations were recorded for heavy lifting (odds ratio 3.6, 95% confidence interval, 1.5 to 9.0). Likelihood ratio tests did not reveal interactions between heavy lifting, ocular/cataract surgery and myopia. Conclusions The results support the plausible hypothesis that heavy occupational lifting (involving Valsalva’s manoeuvre) may be a relevant risk factor for retinal detachment. Moreover these preliminary results confirmed, as reported in literature, an increased risk of retinal detachment for myopic subjects and for those who have undergone cataract surgery. Our observations emphasize the importance of prevention especially in subjects involved in the manual handling of loads, particularly if short-sighted.

38

Hardy, Rebecca Jane. "Meta-analysis techniques in medical research : a statistical perspective." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1995. http://researchonline.lshtm.ac.uk/682268/.

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Meta-analysis is now commonly used in medical research. However there are statistical issues relating to the subject that require investigation and some are considered here, from both a methodological and a practical perspective. Each of the fixed effect and the random effects models for meta-analysis are based on certain assumptions and the validity of these is investigated. A formal test of the homogeneity assumption made in the fixed effect model may be performed. Since the test has low power, simulation was used to investigate the power under various conditions. The random effects model incorporates a between-study component of variance into the model. A likelihood based method was used to obtain a confidence interval for this variance and also to provide an interval for the overall treatment effect which takes into account the fact that the between-study variance is estimated, rather than assuming it to be known. In order to obtain confidence intervals for the treatment effect for both the fixed effect and the random effects models, distributional assumptions of normality are usually made. Such assumptions may be checked using q-q plots of the residuals obtained for each trial in the meta-analysis. In both meta-analysis models it is assumed that the weight allocated to each study is known, when in fact it must be estimated from the data. The effect of estimating the weights on the overall treatment effect estimate, its confidence intervals, the between-study variance estimate and the test statistic for homogeneity, is investigated by both analytic and simulation methods. It is shown how meta-analysis methods may be used to analyse multicentre trials of a paired cluster randomised design. Meta-analysis techniques are found to be preferable to previously published methods specifically developed for the analysis of such designs, which produce biased and potentially misleading results when a large treatment effect is present.

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Duarte, Rosemarie. "Multicentro de desarrollo social y difusión cultural : Comuna Estación Central." Tesis, Universidad de Chile, 2005. http://repositorio.uchile.cl/handle/2250/100685.

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Se trata de desarrollar un Centro comunitario de capacitación, de desarrollo social y difusión cultural, que de respuesta a los cambios educativos, sociales y económicos de la comuna; dónde la tecnología, la interacción y la Inter.-disciplina son elementos fundamentales

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Roca, Vincent. "Harmonisation multicentrique d'images IRM du cerveau avec des modèles génératifs non-supervisés." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS060.

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L'imagerie par résonance magnétique (IRM) permet l'acquisition d'images du cerveau pour l'étude de maladies neurologiques et psychiatriques. Les images IRM sont de plus en plus utilisées dans des études statistiques pour identifier des biomarqueurs et pour des modèles de prédiction. Pour gagner en puissance statistique, ces études agrègent parfois des données acquises avec différentes machines, ce qui peut introduire de la variabilité technique biaisant les analyses des variabilités biologiques. Ces dernières années, des méthodes d'harmonisation ont été proposées pour limiter l'impact de ces variabilités dans les analyses. De nombreuses études ont notamment travaillé sur des modèles génératifs basés sur de l'apprentissage profond non-supervisé. Le travail de thèse s'inscrit dans le cadre de ces modèles qui constituent un champ de recherche prometteur mais encore exploratoire. Dans la première partie de ce manuscrit, une revue des méthodes d'harmonisation rétrospective est proposée. Différentes méthodes de normalisation appliquées au niveau de l'image, de translation de domaines ou de transfert de style y sont décrites en vue de comprendre leurs enjeux respectifs, avec une attention particulière portée aux modèles génératifs non-supervisés. La deuxième partie porte sur les méthodes d'évaluation de l'harmonisation rétrospective. Une revue de ces méthodes est d'abord réalisée. Les plus communes reposent sur des sujets “voyageurs” pour présumer des vérités terrain à l'harmonisation. La revue présente également des évaluations employées en l'absence de tels sujets : étude de différences inter-domaine, de motifs biologiques et de performances de modèles prédictifs. Des expériences mettant en avant des limites de certaines approches couramment employées et des points d'attention nécessaires à leur utilisation sont ensuite proposées. La troisième partie présente un nouveau modèle d'harmonisation d'images IRM cérébrales basé sur une architecture CycleGAN. Contrairement aux précédents travaux, le modèle est tridimensionnel et traite les volumes complets. Des images IRM provenant de six jeux de données variables en termes de paramètres d'acquisition et de distribution d'âge sont utilisées pour expérimenter la méthode. Des analyses de distributions d'intensités, de volumes cérébraux, de métriques de qualité d'image et de caractéristiques radiomiques montrent une homogénéisation efficace entre les différents sites de l'étude. À côté de ça, la conservation et le renforcement de motifs biologiques sont montrés avec une analyse de l'évolution d'estimations de volumes de matière grise avec l'âge, des expériences de prédiction d'âge, la cotation de motifs radiologiques dans les images et une évaluation supervisée avec un jeu de données de sujets voyageurs. La quatrième partie présente également une méthode d'harmonisation originale avec des modifications majeures de la première en vue d'établir un générateur “universel” capable d'harmoniser des images sans connaître leur domaine d'origine. Après un entraînement exploitant des données acquises avec onze scanners IRM, des expériences sur des images de sites non-vus lors de l'entraînement montrent un renforcement de motifs cérébraux liés à l'âge et à la maladie d'Alzheimer après harmonisation. De plus, des comparaisons avec d'autres approches d'harmonisation d'intensités suggèrent que le modèle est plus efficace et plus robuste dans différentes tâches subséquentes à l'harmonisation. Ces différents travaux constituent une contribution significative au domaine de l'harmonisation rétrospective d'images IRM cérébrales. Les documentations bibliographiques fournissent en effet un corpus de connaissances méthodologiques pour les futurs études dans ce domaine, que ce soit pour l'harmonisation en elle-même ou pour la validation. De plus, les deux modèles développés sont deux outils robustes accessibles publiquement qui pourraient être intégrés à de futures études multicentriques en IRM
Magnetic resonance imaging (MRI) enables the acquisition of brain images used in the study of neurologic and psychiatric diseases. MR images are more and more used in statistical studies to identify biomarkers and for predictive models. To improve statistical power, these studies sometimes pool data acquired with different machines, which may introduce technical variability and bias into the analysis of biological variabilities. In the last few years, harmonization methods have been proposed to limit the impact of these variabilities. Many studies have notably worked on generative models based on unsupervised deep learning. The doctoral research is within the context of these models, which constitute a promising but still exploratory research field. In the first part of this manuscript, a review of the prospective harmonization methods is proposed. Different methods consisting in normalization applied at the image level, domain translation or style transfer are described to understand their respective issues, with a special focus on unsupervised generative models. The second part is about the methods for evaluation of retrospective harmonization. A review of these methods is first conducted. The most common rely on “traveling” subjects to assume ground truths for harmonization. The review also presents evaluations employed in the absence of such subjects: study of inter-domain differences, biological patterns and performances of predictive models. Experiments showing limits of some approaches commonly employed and important points to consider for their use are then proposed. The third part presents a new model for harmonization of brain MR images based on a CycleGAN architecture. In contrast with the previous works, the model is three-dimensional and processes full volumes. MR images from six datasets that vary in terms of acquisition parameters and age distributions are used to test the method. Analyses of intensity distributions, brain volumes, image quality metrics and radiomic features show an efficient homogenisation between the different sites of the study. Next, the conservation and the reinforcement of biological patterns are demonstrated with an analysis of the evolution of gray-matter volume estimations with age, experiments of age prediction, ratings of radiologic patterns in the images and a supervised evaluation with a traveling subject dataset. The fourth part also presents an original harmonization method with major updates of the first one in order to establish a “universal” generator able to harmonize images without knowing their domain of origin. After a training with data acquired on eleven MRI scanners, experiments on images from sites not seen during the training show a reinforcement of brain patterns relative to age and Alzheimer after harmonization. Moreover, comparisons with other intensity harmonization approaches suggest that the model is more efficient and more robust to different tasks subsequent to harmonization. These different works are a significant contribution to the domain of retrospective harmonization of brain MR images. The bibliographic documentations indeed provide a methodological knowledge base for the future studies in this domain, whether for harmonization in itself or for validation. In addition, the two developed models are two robust tools publicly available that may be integrated in future MRI multicenter studies

41

Tiani, Carolina <1981&gt. "Dati preliminari dello studio multicentrico caso-controllo "Grave danno epatico acuto indotto da farmaci"." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6387/1/tiani_carolina_tesi__.pdf.

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Il danno epatico indotto dall'assunzione di farmaci viene comunemente indicato con il termine inglese DILI (Drug-Induced Liver Injury). Il paracetamolo rappresenta la causa più comune di DILI, seguito da antibiotici, FANS e farmaci antitubercolari. In particolare, i FANS sono una delle classi di farmaci maggiormente impiegate in terapia. Numerosi case report descrivono pazienti che hanno sviluppato danno epatico fatale durante il trattamento con FANS; molti di questi farmaci sono stati ritirati dal commercio in seguito a gravi reazioni avverse a carico del fegato. L'ultimo segnale di epatotossicità indotto da FANS è associato alla nimesulide; in alcuni paesi europei come la Finlandia, la Spagna e l'Irlanda, la nimesulide è stata sospesa dalla commercializzazione perché associata ad un'alta frequenza di epatotossicità. Sulla base dei dati disponibili fino a questo momento, l'Agenzia Europea dei Medicinali (EMA) ha recentemente concluso che i benefici del farmaco superano i rischi; un possibile aumento del rischio di epatotossicità associato a nimesulide rimane tuttavia una discussione aperta di cui ancora molto si dibatte. Tra le altre classi di farmaci che possono causare danno epatico acuto la cui incidenza tuttavia non è sempre ben definita sono gli antibiotici, quali amoxicillina e macrolidi, le statine e gli antidepressivi.Obiettivo dello studio è stato quello di determinare il rischio relativo di danno epatico indotto da farmaci con una prevalenza d'uso nella popolazione italiana maggiore o uguale al 6%. E’ stato disegnato uno studio caso controllo sviluppato intervistando pazienti ricoverati in reparti di diversi ospedali d’Italia. Il nostro studio ha messo in evidenza che il danno epatico da farmaci riguarda numerose classi farmacologiche e che la segnalazione di tali reazioni risulta essere statisticamente significativa per numerosi principi attivi. I dati preliminari hanno mostrato un valore di odds ratio significativo statisticamente per la nimesulide, i FANS, alcuni antibiotici come i macrolidi e il paracetamolo.
Drug-induced liver injury (DILI) is a term that describes abnormalities in liver function tests related to medication intake. Acetaminophen is the most common cause of DILI followed by antibiotics, NSAIDs, and antitubercular medications. NSAIDs represent one of the most widely used classes of drugs. Numerous case reports have described patients who develop fatal liver injury while taking NSAIDs. Several NSAIDs were withdrawn from the market because of hepatic ADRs. The latest warning signal for hepatotoxicity induced by a NSAID is related to nimesulide. In some European countries, Finland, Spain, and Ireland, nimesulide was suspended from the market because of an associated high frequency of hepatotoxicity. In contrast, a recent referral of the EMEA concluded that the benefits of the drug outweigh its risks. However, the full extent of the risk of nimesulide-induced liver injury is still a much debated issue within the EMEA. Primary objectives was to estimate the relative risk of liver injury induced by drugs with a prevalence of use in the Italian population > or = 6% This study is designed as a multicenter case–control study where cases and controls will all be recruited among patients seen in a hospital context in various parts of Italy. Information regarding demographic data, medical history, coexisting illnesses, lifestyles and dietary habits, alcohol, tobacco and coffee intake, use of herbal products, and drug use (including doses taken and indication for use on each day of exposure) will be collected directly from all patients through a structured interview. Preliminary results of this study confirm a significant relative risk (Odds Ratio) of liver injury associated with the use of nimesulide, NSAIDs, some antibiotics like macrolides and paracetamol. The results of this study could strongly affect regulatory decisions within the National Health Service.

42

Tiani, Carolina <1981&gt. "Dati preliminari dello studio multicentrico caso-controllo "Grave danno epatico acuto indotto da farmaci"." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6387/.

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Abstract:

Il danno epatico indotto dall'assunzione di farmaci viene comunemente indicato con il termine inglese DILI (Drug-Induced Liver Injury). Il paracetamolo rappresenta la causa più comune di DILI, seguito da antibiotici, FANS e farmaci antitubercolari. In particolare, i FANS sono una delle classi di farmaci maggiormente impiegate in terapia. Numerosi case report descrivono pazienti che hanno sviluppato danno epatico fatale durante il trattamento con FANS; molti di questi farmaci sono stati ritirati dal commercio in seguito a gravi reazioni avverse a carico del fegato. L'ultimo segnale di epatotossicità indotto da FANS è associato alla nimesulide; in alcuni paesi europei come la Finlandia, la Spagna e l'Irlanda, la nimesulide è stata sospesa dalla commercializzazione perché associata ad un'alta frequenza di epatotossicità. Sulla base dei dati disponibili fino a questo momento, l'Agenzia Europea dei Medicinali (EMA) ha recentemente concluso che i benefici del farmaco superano i rischi; un possibile aumento del rischio di epatotossicità associato a nimesulide rimane tuttavia una discussione aperta di cui ancora molto si dibatte. Tra le altre classi di farmaci che possono causare danno epatico acuto la cui incidenza tuttavia non è sempre ben definita sono gli antibiotici, quali amoxicillina e macrolidi, le statine e gli antidepressivi.Obiettivo dello studio è stato quello di determinare il rischio relativo di danno epatico indotto da farmaci con una prevalenza d'uso nella popolazione italiana maggiore o uguale al 6%. E’ stato disegnato uno studio caso controllo sviluppato intervistando pazienti ricoverati in reparti di diversi ospedali d’Italia. Il nostro studio ha messo in evidenza che il danno epatico da farmaci riguarda numerose classi farmacologiche e che la segnalazione di tali reazioni risulta essere statisticamente significativa per numerosi principi attivi. I dati preliminari hanno mostrato un valore di odds ratio significativo statisticamente per la nimesulide, i FANS, alcuni antibiotici come i macrolidi e il paracetamolo.
Drug-induced liver injury (DILI) is a term that describes abnormalities in liver function tests related to medication intake. Acetaminophen is the most common cause of DILI followed by antibiotics, NSAIDs, and antitubercular medications. NSAIDs represent one of the most widely used classes of drugs. Numerous case reports have described patients who develop fatal liver injury while taking NSAIDs. Several NSAIDs were withdrawn from the market because of hepatic ADRs. The latest warning signal for hepatotoxicity induced by a NSAID is related to nimesulide. In some European countries, Finland, Spain, and Ireland, nimesulide was suspended from the market because of an associated high frequency of hepatotoxicity. In contrast, a recent referral of the EMEA concluded that the benefits of the drug outweigh its risks. However, the full extent of the risk of nimesulide-induced liver injury is still a much debated issue within the EMEA. Primary objectives was to estimate the relative risk of liver injury induced by drugs with a prevalence of use in the Italian population > or = 6% This study is designed as a multicenter case–control study where cases and controls will all be recruited among patients seen in a hospital context in various parts of Italy. Information regarding demographic data, medical history, coexisting illnesses, lifestyles and dietary habits, alcohol, tobacco and coffee intake, use of herbal products, and drug use (including doses taken and indication for use on each day of exposure) will be collected directly from all patients through a structured interview. Preliminary results of this study confirm a significant relative risk (Odds Ratio) of liver injury associated with the use of nimesulide, NSAIDs, some antibiotics like macrolides and paracetamol. The results of this study could strongly affect regulatory decisions within the National Health Service.

43

Saracino, Laura. "Coordinamento di Trial Clinici multicentrici finalizzati allo studio e all'ottimizzazione dell'outcome del trapianto epatico." Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423830.

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Introduction. Despite being recognized a clinical application for almost thirty years, data are very scarce regarding liver transplant patients’ long term health issues. Patient survival surpasses the 10 year threshold in increasing numbers, exposing this population to risks from chronic use of immunosuppressive drugs. Methods. The Liver Transplantation Centre of Padua coordinated two spontaneous multricentric studies: a longitudinal observational retrospective multicentre (12 Italian Liver Transplant Centres,) assessing long term survival and main characteristics of the recipient population; and EPOCAL, a spontaneous Phase II Interventional Multicentric (7 Italian Liver Transplantation Centres) Open-label Randomized Control Trial, assessing acute rejection and graft loss within 3 months of liver transplantation, renal function, incidence of adverse events. Results. Data on 3008 liver transplantations performed in Italy between 1983–1999 were documented by an eCRF. Data of 2846 patients with sufficient follow-up were used for further analysis. 20 years patient survival was estimated at 51 %. A total of 139 patients were enrolled in the EPOCAL study, 92 in the study group and 47 in control group. We did not find any significant difference between the two groups prior intervention. The primary end-point in the study group was achieved: biopsy-proven acute rejection was under 25 % (under 14 %) (p < 0.05). Renal function was significantly better in the study group at 3 months (p < 0.05). Conclusion. These studies show an Italian long term liver transplantation cohort with excellent survival proﬁles. We show efficacy and safety of an immunosuppressive protocol with minimization of calcineurin inhibitor (tacrolimus) and early introduction of everolimus. Together, we have a path towards long term survival of patients with sustainable immunosuppressive protocols.
Introduzione. Nonostante sia un'applicazione clinica da quasi trent'anni, i dati relativi allo stato di salute a lungo termine dei pazienti trapiantati di fegato sono scarsi. Il numero dei pazienti che raggiungono la soglia di sopravvivenza a 10 anni è in aumento, esponendo questa popolazione al rischi associati all'uso cronico degli immunosoppressori. Metodi. Il Centro Trapianti di Fegato di Padova ha coordinato due studi multicentrici spontanei: uno studio retrospettivo, osservazionale, longitudinale, multicentrico (12 Centri Trapianto di Fegato italiani) che valuta la sopravvivenza a lungo termine e le principali caratteristiche della popolazione ricevente; e EPOCAL uno studio spontaneo di Fase II, interventistico, multicentrico (7 Centri Trapianto di Fegato italiani), in aperto, randomizzato, controllato che valuta il rigetto e la perdita del graft a 3 mesi dal trapianto, la funzione renale e l'incidenza degli eventi avversi. Risultati. I dati su 3008 trapianti di fegato effettuati in Italia dal 1993 al 1999 sono stati registrati in un eCRF. I dati di 2846 pazienti con un sufficiente follow-up sono stati usati per le analisi successive. La sopravvivenza a 20 anni dal trapianto è stata stimata al 51%. Un totale di 139 pazienti è stato arruolato nello studio EPOCAL, 92 nel gruppo di studio e 47 nel gruppo di controllo. Non abbiamo trovato differenze significative tra i due gruppi prima all'arruolamento. L'end-point primario dello studio è stato raggiunto: i rigetti acuti confermati da biopsia erano meno del 25 % (sotto 14 %) (p < 0,05). La funzione renale a tre mesi era significativamente migliore nel gruppo di studio (p < 0,05). Conclusioni. Questi studi presentano un profilo di sopravvivenza eccellente della coorte di pazienti italiani trapiantati di fegato da lungo tempo. Mostriamo sicurezza ed efficacia di un protocollo immunosoppressivo con minimizzazione degli inibitori della calcineurina (tacrolimus), e l'introduzione precoce di everolimus. L'insieme dei risultati mostra una strada verso la sopravvivenza a lungo termine dei pazienti con protocolli immunosoppressivi sostenibili.

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Cosendey, Marly Aparecida Elias. "Analise da implantacao do programa farmacia basica: um estudo multicentrico em cinco estados do Brasil." Rio de Janeiro : [s.n.], 2000. http://teses.cict.fiocruz.br/pdf/cosendeymaed.pdf.

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MAKIL, ELHASSAN. "Progetto Multicentrico Italiano Sonno e Scompenso (ProMISeS-II): “Disturbi Respiratori Nel Sonno e Scompenso Cardiaco”." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241151.

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Background: I disturbi respiratori nel sonno (DRS) sono altamente prevalenti in pazienti con scompenso cardiaco cronico (SCC), come dimostrato anche nello studio ProMISeS-I. Nonostante sia ben nota la valenza prognostica delle apnee nel sonno nello SCC, pochi studi hanno analizzato in dettaglio i diversi fenotipi respiratori nel sonno, cercando di identificarne i predittori clinico-strumentali. Scopi: determinare in un’ampia popolazione di pazienti con SCC le caratteristiche e la prevalenza dei diversi fenotipi respiratori nel sonno (DRS), verificare e descrivere l’associazione tra essi (DRS-Outcome) e uno o più predittori (clinico-strumentali). Materiali e metodi: Tra febbraio 2014 e febbraio 2017 sono stati consecutivamente arruolati all’interno del progetto multicentrico ProMISeS-II 830 pazienti con SCC. Per ogni paziente sono stati acquisiti, tra gli altri, un esame polisonnografico notturno (refertato secondo AASM 2007). Sono stati identificati sulla base delle caratteristiche della meccanica ventilatoria nel sonno (cut-off AHI ≥ 5 eventi/ora) 5 fenotipi respiratori notturni principali: 1.apnee prevalentemente ostruttive (pOSA) (OAHI/AHI > 0.5), 2.apnee prevalentemente centrali (pCSA) (CAHI/AHI > 0.5), 3.prevalenti ipopnee (pHY) (HY/AHI > 0.5), 4.pattern ventilatorio misto (pMIX) senza netta prevalenza di uno dei precedenti pattern, 5.assenza di alterazioni respiratorie nel sonno (NoDRS con AHI < 5). L’associazione tra DRS e loro predittori è stata analizzata mediante modelli lineari generalizzati (GLM) Risultati: la coorte era composto maggiormente da uomini (578 (88%)), l’età media era 65(11) (media (DS)) anni, il BMI 27.8 [25.2-31.1] (mediana [range interquartile]), e l’AHI mediana era 21 [6 – 37.6]. In circa il 25% dei pazienti era presente la fibrillazione atriale e il 50% risultava sedentario. L’ 81% dei pazienti (n 529) mostrava valori di FE <40% mentre il 19% (n 127) mostrava valori di FE ≥ 40%. La prevalenza globale di DRS (DRSg) osservata era del 78% (n 509) e quella dei diversi fenotipi: i) pOSA (14%, n=93) (apnee prevalentemente ostruttive); ii) pCSA (23%, n=153) (apnee prevalentemente centrali); ii) pHI (28%, n 186) (prevalenti ipopnee); v) pMIX (12%, n 77) (pattern ventilatorio misto senza netta prevalenza di uno dei precedenti pattern). Le stime del PR ottenute tramite il modello di Poisson mostrano come il genere maschile sia positivamente associato agli eventi pHI e pCSA rispetto alle femmine (PR 1.59, 95%IC 1.17-2.17 per pHI e PR 2.28, 95%IC 1.44-3.63 per pCSA) mentre non si osserva alcuna differenza per gli altri eventi. All’aumentare unitario dell’età aumenta la prevalenza di tutti gli eventi tranne pOSA, in particolare gli incrementi variano tra 1% per pHI al 4% per pMIX. Un dato inatteso riguarda i risultati relativi alla sedentarietà: l’essere sedentario, infatti, la prevalenza degli eventi pHI, pMIX e pCSA è inferiore negli individui sedentari rispetto ai non sedentari (PR 0.70 95%IC 0.58-0.84 per pHI, PR 0.22 95%IC 0.12-0.39 per pMIX e PR 0.52 95%IC 0.41-0.67 per pCSA). Per tutti gli eventi considerati, all’aumentare unitario dei livelli di BMI incrementa anche la prevalenza degli eventi di una percentuale che varia tra 1% per pCSA al 4% per pMIX. Infine, la presenza di la prevalenza di pMIX e pCSA è maggiore nei pazienti affetti fibrillazione atriale (PR 1.37, 95%IC 1.06-1.78 per pMIX e PR 1.38, 95%IC 1.14-1.68 per pCSA) e pCSA nei pazienti con bassi livelli di frazione di eiezione rispetto ai pazienti con alti livelli (PR 1.41 95%IC 1.09-1.82). Conclusioni: Lo studio ProMISeS-II, con significativo ampliamento della casistica rispetto alla prima analisi, conferma l’elevata prevalenza dei DRS nei pazienti con SCC. Ci ha permesso inoltre di meglio caratterizzare i diversi pattern respiratori sonno-correlati, studiando oltre ai fenotipi classici di pCSA e pOSA, anche ipopnee o pattern misti.
Background: sleep related breathing disorders (SRBD) are highly prevalent among congestive heart failure (CHF) patients, as indicated by the previously published ProMISeS-I study. Despite the well-known prognostic significance of SRBD in CHF patients, only few studies have performed a detailed characterization of different types of SRBD among these subjects. Aim: The aims of the present analysis, conducted in a large population of CHF patients were: 1) To explore the characteristics and prevalence of different SRBD, 2) To explore possible associations between SRBD (Outcome) and demografic, clinical characteristics (predictors). Materials and methods: A total of 830 CHF patients were consecutively enrolled in the frame of the multicentric ProMISeS-II project between february 2014 and february 2017. In all participants demographic and echocardiographic data were available for analyses. Cardio-respiratory polysomnography was performed and its results interpreted according to 2007 AASM recommendations. According to ventilatory patterns and considering an AHI ≥5 events/hour, subjects were classified into 5 different categories: 1) Prevalent Obstructive Sleep Apnea (pOSA OAHI/AHI > 0.5); 2) Prevalent Central Sleep Apnea (pCSA, CAHI/AHI > 0.5); 3) Prevalent hypopnea (pHY, HY/AHI > 0.5), 4) Mixed ventilatory pattern (pMIX) without a neat prevalence of any of the former patterns; and 5) Absence of ventilatory alterations during sleep (No SRBD, AHI < 5). The association between SRBD and their potential predictors was explored by means of generalized linear models (GLM). Results: The final cohort of the study consisted of 656 CHF patients, mostly men (n=578, 88%), mean age 65 ±11 years, median BMI 27.8 (25.2-31.1 IQR). Main identifiable causes of CHF were ischemic (56%), idiopatic (26%), other causes (11%), hypertensive (4%), and valvular (4%). An EF <40% was present in 81% of patients and atrial fibrillation was present in about 25%. The Median AHI was 21 [6 – 37.6 IQR] and the global prevalence of SRBD was 78%. Prevalence (RP) was also estimated for specific SRBDs: i) pOSA (14% n 93), ii) pCSA (23% n 153), iii) pHY (28% n 186) and v) pMIX (12% n 77). Of note, the relative prevalence of pHI (PR 1.59, 95%IC 1.17-2.17) and pCSA (PR 2.28, 95%IC 1.44-3.63) was significantly higher in men compared to women. No gender-related differences in the prevalence of pOSA nor in pMIX, were observed. In linear generalized models age was directly associated with the prevalence of all types SRBD but pOSA. In particular, each year increase in age was associated with a variable increase in the prevalence of SRBD ranging from 1% for pHI to 4% for pMIX. An unexpected result of our study regards the association of sedentarism (prevalence of 50% in our study population) with SRBDs. Compared to non-sedentary subjects, a lower relative prevalence of SRBDs was observed among sedentary subjects being 0.70 (95% IC 0.58-0.84) for pHI, 0.22 (95%IC 0.12-0.39) for pMIX, and 0.52 (95%IC 0.41-0.67) for pCSA. When evaluating the relationship between body weight and SRBDs, each unit increase in BMI was associated with a variable increase in the prevalence of SRBDs (ranging from 1% for pCSA to 4% for pMIX). Finally, the prevalence of pMIX (RP 1.37, 95%IC 1.06-1.78) and pCSA (RP 1.38, 95%IC 1.14-1.68) was significantly higher among patients with atrial fibrillation, and the prevalence of pCSA was higher (RP 1.41, 95% CI 1.09-1.82) among patients with an EF < 40%. Conclusions: the present analysis (ProMISeS-II study), conducted in a higher number of subjects (n=656) compared to the first report of the ProMISeS-I study (n=370), comfirms the extremely high prevalence of SRBD among CHF patients. In the present report SRBDs have been better characterized by identifying not only classical phenotypes such as pCSA e pOSA, but also assessing two additional categories namely pHI and mixed ventilatory patterns.

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Familusi, Mary Ajibola. "Analysis of clustered competing risks with application to a multicentre clinical trial." Master's thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/23763.

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The usefulness of time-to-event (survival) analysis has made it gain a wide applicability in statistically modelling research. The methodological developments of time-to-event analysis that have been widely adopted are: (i) The Kaplan-Meier method, for estimating the survival function; (ii) The log-rank test, for comparing the equality of two or more survival distributions; (m) The Cox proportional hazards model, for examining the covariate effects on the hazard function; and (iv) The accelerated failure time model, for examining the covariate effects on the survival function. Nonetheless, in time-to-event endpoints assessment, if subjects can fail from multiple mutually-exclusive causes, data are said to have competing risks. For competing risks data, the Fine and Gray proportional hazards model for sub-distributions has gained popularity due to its convenience in directly assessing the effect of covariates on the cumulative incidence function. Furthermore, sometimes competing risks data cannot be considered as independent because of a clustered design; for instance, in registry cohorts or multi-centre clinical trials. The Fine and Gray model has been extended to the analysis of clustered time-to-event data, by including random-centre effects or frailties in the sub-distribution hazard. This research focuses on the analysis of clustered competing risks with an application to the investigation of the management of pericarditis clinical trial (IMPI) dataset. IMPI is a multi- centre clinical trial that was carried out from 19 centres in 8 African countries with the principal objective of assessing the effectiveness and safety of adjunctive prednisolone and Mycobacterium indicus pranii immunotherapy, in reducing the composite outcome of death, constriction or cardiac tamponade, requiring pericardial drainage in patients with probable or definite tuberculous pericarditis. The clinical objective in this thesis is therefore to analyse time to these outcomes. In addition, the risk factors associated with these outcomes were determined, and the effect of the prednisolone and M. indcus pranii was examined, while adjusting for these risk factors and considering centres as a random effect. Using Cox proportional hazards model, it was found that age, weight, New York Heart Association (NYHA) class, hypotension, creatinine, and peripheral oedema show a statistically significant association with the composite outcome. Furthermore, weight, NYHA class, hypotension, creatinine and peripherial oedema show a statistically significant association with death. In addition, NYHA class and hypotension show a statistically significant association with cardiac tamponade. Lastly, prednisolone, gender, NYHA class, tachycardia, haemoglobin level, peripheral oedema, pulmonary infiltrate and HIV status show a statistically significant association with constriction. A value of 0.1 significance level was used to identify variables as significant in the univariate model using forward stepwise regression method. The random effect was found to be significant in the incidence of composite outcomes of death, cardiac tamponade and constriction, and in the individual outcome of constriction, but this only slightly changed the estimated effect of the covariates as compared to when the random effect was not considered. Accounting for death as a competing event to the outcomes of cardiac tamponade or constriction, does not affect the effect of the covariates on these outcomes. In addition, in the multivariate models that adjust for other risk factors, there was no significant difference in the primary outcome between patients who received prednisolone, and those who received placebo, or between those who received M. indicus pranii immunotherapy, and those who received placebo.

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CUTTINI, MARINA. "LA COMUNICAZIONE TRA PERSONALE SANITARIO E GENITORI IN TERAPIA INTENSIVA NEONATALE. RISULTATI DI UNA RICERCA MULTICENTRICA." Doctoral thesis, Università degli studi di Trieste, 1994. http://thesis2.sba.units.it/store/handle/item/12864.

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Balducci, Anna <1978&gt. "Effetto dell’allenamento fisico sulla capacità cardiopolmonare in pazienti adulti con ventricolo destro sistemico: studio europeo multicentrico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3868/1/Balducci_Anna_tesi.pdf.

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49

Balducci, Anna <1978&gt. "Effetto dell’allenamento fisico sulla capacità cardiopolmonare in pazienti adulti con ventricolo destro sistemico: studio europeo multicentrico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3868/.

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50

Salsi, Ginevra <1986&gt. "Ruolo della risonanza magnetica prenatale in feti con ventricolomegalia isolata nell'era della neurosonografia: uno studio multicentrico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9618/1/Tesi%20dottorato%20Ginevra%2020_10%20con%20abstract%20e%20frontespizio%20giusto.pdf.

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Obiettivi: Analizzare, in feti con riscontro all’ecografia prenatale di ventricolomegalia isolata, il ruolo della risonanza magnetica fetale (RM) nell’identificazione di ulteriori anomalie cerebrali associate. Determinare se l’incidenza di tali anomalie associate sia correlata al grado ed alla lateralità della ventricolomegalia; stimare l’incidenza di anomalie associate diagnosticabili solo dopo la nascita e non identificate dalle metodiche di diagnostica prenatale (RM ed ecografia). Metodi: Studio multicentrico, retrospettivo, di coorte, in 15 centri in Italia, Regno Unito e Spagna. su gravide sottoposte a RM dopo riscontro alla neurosonografia multiplanare di ventricolomegalia isolata, fra gennaio 2010 e marzo 2019. Scopo principale: stabilire la prevalenza di anomalie del sistema nervoso centrale (SNC) individuabili esclusivamente tramite RM. Scopo secondario: stimare l’incidenza di anomalie aggiuntive identificate esclusivamente alla nascita. Risultati: sono stati inclusi 556 feti con diagnosi ecografica di ventricolomegalia isolata. Epoca gestazionale media al momento della RM: 26.7±4.4 settimane. Dei feti inclusi nello studio, il 36.5% (95% CI 32.6-40.4; 203/556) era affetto da VM bilaterale, il 63.5% (95% CI 59.4-67.4; 353/556) monolaterale. La VM è apparsa lieve (10-12 mm) nell’80.0% dei casi (95% CI 76.5-83.2; 445/556) e moderata (13-15 mm) nel 20.0% (95% CI 16.9- 23.5; 111/556). I risultati della regressione logistica hanno evidenziato che BMI materno (OR: 0.85, 95% CI 0.7- 0.99, p= 0.030), presenza di VM moderata (OR: 5.8, 95% CI 2.6-13.4, p<0.001) ed esecuzione di RM dopo la 24^ settimana (OR: 4.1, 95% CI 1.1-15.3, p= 0.038) correlano in maniera indipendente con l’individuazione di anomalie aggiuntive alla RM. Conclusioni: Fra i feti con ventricolomegalia apparentemente isolata valutati mediante neurosonografia, la percentuale di anomalie associate riscontrate esclusivamente alla risonanza magnetica fetale è risultata più bassa di quanto riportato finora. La maggior parte dei difetti evidenziati tramite RM rientra nelle categorie dei disordini della migrazione neuronale e delle emorragie, particolarmente difficili da diagnosticare all’ecografia.
Objectives: To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild and moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound (US) evaluation of fetal brain. Methods: Multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, United Kingdom, and Spain. Inclusion criteria: fetuses affected by isolated VM on US, undergoing detailed assessment of fetal brain via a multiplanar approach. Primary outcome: to report the rate of additional CNS anomalies detected exclusively at prenatal MRI and missed at US; secondary aim: to estimate the incidence of additional anomalies detected exclusively after birth and missed at prenatal imaging. Results: 556 fetuses with a prenatal diagnosis of isolated fetal VM on US were included. Additional structural anomalies were detected at prenatal MRI and missed at US in 5.4% (95% CI 3.8-7.6) of cases. Fetuses with an associated anomaly detected only at MRI were more likely to have moderate compared to mild VM (60.0% vs 17.7%, p<0.001), while there was no significant difference between the proportion of cases with bilateral VM between the two groups (p=0.2). The results of the logistic regression analysis showed that maternal body mass index (OR: 0.85, 95% CI 0.7-0.99, p= 0.030), presence of moderate VM (OR: 5.8, 95% CI 2.6-13.4, p<0.001) and gestational age at MRI ≥24 weeks of gestation (OR: 4.1, 95% CI 1.1-15.3, p= 0.038) were independently associated with the probability of detecting associated anomalies at MRI. Associated anomalies were detected exclusively at birth and missed at prenatal imaging in 3.8% of cases. Conclusions: The rate of associated fetal anomalies missed at US and detected only at fetal MRI in fetuses with isolated mild and moderate VM undergoing neurosonography is lower than that previously reported. The large majority of these anomalies are difficult to detect on ultrasound

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