Clinical outcomes of multiple aneurysms microsurgical clipping: Evaluation of 90 patients

Background The incidence of multiple intracranial aneurysms (MIAs) among patients who are diagnosed with aneurysm is 15–45% in the literature. Treatment options depend on the patient's status, age, aneurysm location and neurosurgeon's experience. In this study outcomes of micro-surgically clipped 90 patients have been evaluated. Materials and methods Medical records of 90 (49 women and 41 men) patients of MIAs who underwent surgery by the authors, during a 3-year period from 2011 to 2013 were retrospectively reviewed of prospectively collected patients’ data. Surgically treated patients underwent a lateral supraorbital craniotomy followed by microsurgical clipping of all reachable aneurysms. Results The mean age of the sample is 50.8±11.9 (25–82) years. There were 67 patients presented with SAH. The most common complaint was severe headache of sudden onset (94%) in SAH group and migraine type headache (60.8%) in incidentally diagnosed group. According to location of the arteries; ACoA (50), MCA (R:49,L:45), ICA (R:34,L:15), PCoA (R:9,L:4), ACA (R:6,L:4), basilar artery (3) and SCA (2). Mortality rate was 13.3% (n=12), morbidity rate (new deficit was developed) was 18.8% (n=17) [7 out of them were partially/completely dependent on others for daily living activities before surgery (i.e. GOS<3)] and 67.8% (n=61) of the patients returned to their normal jobs and daily activities. Conclusions Multiple cerebral aneurysms are not associated with a less favorable outcome than are single aneurysm cases. Authors prefer microsurgical clipping of all the aneurysms, be it on the reverse side, if the aneurysm location is reachable and that includes bilaterally presenting MIAs

Modèles de dépendance hiérarchique pour l'évaluation des passifs et la tarification en actuariat

Dans cette thèse on s’intéresse à la modélisation de la dépendance entre les risques en assurance non-vie, plus particulièrement dans le cadre des méthodes de provisionnement et en tarification. On expose le contexte actuel et les enjeux liés à la modélisation de la dépendance et l’importance d’une telle approche avec l’avènement des nouvelles normes et exigences des organismes réglementaires quant à la solvabilité des compagnies d’assurances générales. Récemment, Shi et Frees (2011) suggère d’incorporer la dépendance entre deux lignes d’affaires à travers une copule bivariée qui capture la dépendance entre deux cellules équivalentes de deux triangles de développement. Nous proposons deux approches différentes pour généraliser ce modèle. La première est basée sur les copules archimédiennes hiérarchiques, et la deuxième sur les effets aléatoires et la famille de distributions bivariées Sarmanov. Nous nous intéressons dans un premier temps, au Chapitre 2, à un modèle utilisant la classe des copules archimédiennes hiérarchiques, plus précisément la famille des copules partiellement imbriquées, afin d’inclure la dépendance à l’intérieur et entre deux lignes d’affaires à travers les effets calendaires. Par la suite, on considère un modèle alternatif, issu d’une autre classe de la famille des copules archimédiennes hiérarchiques, celle des copules totalement imbriquées, afin de modéliser la dépendance entre plus de deux lignes d’affaires. Une approche avec agrégation des risques basée sur un modèle formé d’une arborescence de copules bivariées y est également explorée. Une particularité importante de l’approche décrite au Chapitre 3 est que l’inférence au niveau de la dépendance se fait à travers les rangs des résidus, afin de pallier un éventuel risque de mauvaise spécification des lois marginales et de la copule régissant la dépendance. Comme deuxième approche, on s’intéresse également à la modélisation de la dépendance à travers des effets aléatoires. Pour ce faire, on considère la famille de distributions bivariées Sarmanov qui permet une modélisation flexible à l’intérieur et entre les lignes d’affaires, à travers les effets d’années de calendrier, années d’accident et périodes de développement. Des expressions fermées de la distribution jointe, ainsi qu’une illustration empirique avec des triangles de développement sont présentées au Chapitre 4. Aussi, nous proposons un modèle avec effets aléatoires dynamiques, où l’on donne plus de poids aux années les plus récentes, et utilisons l’information de la ligne corrélée afin d’effectuer une meilleure prédiction du risque. Cette dernière approche sera étudiée au Chapitre 5, à travers une application numérique sur les nombres de réclamations, illustrant l’utilité d’un tel modèle dans le cadre de la tarification. On conclut cette thèse par un rappel sur les contributions scientifiques de cette thèse, tout en proposant des angles d’ouvertures et des possibilités d’extension de ces travaux.The objective of this thesis is to propose innovative hierarchical approaches to model dependence within and between risks in non-life insurance in general, and in a loss reserving context in particular. One of the most critical problems in property/casualty insurance is to determine an appropriate reserve for incurred but unpaid losses. These provisions generally comprise most of the liabilities of a non-life insurance company. The global provisions are often determined under an assumption of independence between the lines of business. However, most risks are related to each other in practice, and this correlation needs to be taken into account. Recently, Shi and Frees (2011) proposed to include dependence between lines of business in a pairwise manner, through a copula that captures dependence between two equivalent cells of two different runoff triangles. In this thesis, we propose to generalize this model with two different approaches. Firstly, by using hierarchical Archimedean copulas to accommodate correlation within and between lines of business, and secondly by capturing this dependence through random effects. The first approach will be presented in chapters 2 and 3. In chapter 2, we use partially nested Archimedean copulas to capture dependence within and between two lines of business, through calendar year effects. In chapter 3, we use fully nested Archimedean copulas, to accommodate dependence between more than two lines of business. A copula-based risk aggregation model is also proposed to accommodate dependence. The inference for the dependence structure is performed with a rank-based methodology to bring more robustness to the estimation. In chapter 4, we introduce the Sarmanov family of bivariate distributions to a loss reserving context, and show that its flexibility proves to be very useful for modeling dependence between loss triangles. This dependence is captured by random effects, through calendar years, accident years or development periods. Closed-form expressions are given, and a real life illustration is shown again. In chapter 5, we use the Sarmanov family of bivariate distributions in a dynamic framework, where the random effects are considered evolutionary and evolve over time, to update the information and allow more weight to more recent claims. Hence, we propose an innovative way to jointly model the dependence between risks and over time with an illustration in a ratemaking context. Finally, a brief conclusion recalls the main contributions of this thesis and provides insights into future research and possible extensions to the proposed works

MicroRNA and gene signature of severe cutaneous drug hypersensitivity reactions reveal the role of miR-483- 5p/miR-28-5p in inflammation by targeting Granulysin gene

Purpose: To build a microRNA and gene signature of severe cutaneous adverse drug reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).Methods: MicroRNA expression profiles were downloaded from miRNA expression profile of patients’ skin suffering from TEN using an array comprising of 372 miRNAs; download site: www.jacionline.org. The patient samples were eight TEN, ten SJS patients and twenty-two healthy individuals. A total of 192 microRNAs were found with unique expression patterns (overexpressed) in contrast with healthy skin controls and patients. Thereafter, the following databases were used for downstream analysis: geneMANIA, DIANA-miRPath version 3, DIANA-TarBase version 7.0, Ingenuity Pathway Analysis (IPA) as well as DAVID, STRING and GENECODIS online tools.Results: Granulysin (GNLY) geneMANIA database search yielded 21 interacting genes that were 64.6 % in physical interaction, 17 % in co-expression pattern. miRBD potential microRNAs that target the 21 genes were 79 miRs. Eighteen miRs overlap between the overexpressed miRs from SJS/TEN samples and the miRs targeting the 21 genes. Moreover, Ingenuity pathway analysis IPA revealed that the microRNAs were involved in inflammation.Conclusion: Analysis of differential microRNA expressions reveals two significant DE miRs that target Granulysin (483-5p/miR-28-5p). MiR-GNLY loop interactions in hypersensitivity reactions may function as biomarkers for SCAR including SJS and TEN.Keywords: Severe cutaneous adverse drug reactions (SCAR) Steven-Johnson Syndrome, Toxic epidermal necrolysis, Granulysin, Biomarkers, MicroRNA signatur

Pathway analysis for identification of potential biomarkers in severe cutaneous drug hypersensitivity reactions

Purpose: To construct a cluster model or a gene signature for Stevens-Johnson syndrome (SJS) using pathways analysis in order to identify some potential biomarkers that may be used for early detection of SJS and epidermal necrolysis (TEN) manifestations.Methods: Gene expression profiles of GSE12829 were downloaded from Gene Expression Omnibus database. A total of 193 differentially expressed genes (DEGs) were obtained. We applied these genes to geneMANIA database, to remove ambiguous and duplicated genes, and after that, characterized the gene expression profiles using geneMANIA, DAVID, REACTOME, STRING and GENECODIS which are online software and databases.Results: Out of 193 genes, only 91 were used (after removing the ambiguous and duplicated genes) for topological analysis. It was found by geneMANIA database search that majority of these genes were coexpressed yielding 84.63 % co-expression. It was found that ten genes were in Physical interactions comprising almost 14.33 %. There were < 1 % pathway and genetic interactions with values of 0.97 and 0.06 %, respectively. Final analyses revealed that there are two clusters of gene interactions and 13 genes were shown to be in evident relationship of interaction with regards to hypersensitivity.Conclusion: Analysis of differential gene expressions by topological and database approaches in the current study reveals 2 gene network clusters. These genes are CD3G, CD3E, CD3D, TK1, TOP2A, CDK1, CDKN3, CCNB1, and CCNF. There are 9 key protein interactions in hypersensitivity reactions and may serve as biomarkers for SJS and TEN. Pathways related gene clusters has been identified and a genetic model to predict SJS and TEN early incidence using these biomarker genes has been developed.Keywords: Steven-Johnson Syndrome, Toxic epidermal necrolysis, Differentially expressed genes, Hypersensitivity reactions, Genes, Biomarker

Enhancing contrast of magnetic resonance imaging in patients with liver cirrhosis: Conveyance times of Primovist in hepatobiliary system

Purpose: To determine transit times for excretion of gadoxetic acid (Gd-EOB-DTPA), a recent magnetic resonance imaging (MRI) contrast agent, in hepatobiliary system of patients with liver cirrhosis.Methods: Liver cirrhosis patients that underwent contrast MRI examination at Renai Hospital, Taipei City, Taiwan were included. The patients who have experienced contrast-enhanced abdominal MR examination after injection of 10 mL Gd-EOB-DTPA at 1.5-T MR from December 2009 to March 2011, were included retrospectively. The images were evaluated for the presence of contrast agent in intrahepatic bile ducts (IHD), common bile duct (CBD), gall bladder and duodenum.Results: The optimal time for arterial phase was from 15 s after injection while the optimal time for portal venous imaging was from 40 s after injection. Furthermore, the optimal time to observe changes was 20 min after contrast initiation of Gd-EOB-DTPA in 39 patients (83 %) in IHD and 37 patients (78.5 %) in CBD. Gall bladder reflux was visible in 26 patients (43 %), and duodenal excretion in 17 patients (36 %). After 30 min of contrast injection, Gd-EOB-DTPA could still be detected in 6 patients (13 %) in IHD and 7 patients (15 %) in CBD, while gall bladder reflux was visible in 10 patients (21 %), and duodenal excretion in 20 patients (55 %).Conclusion: The excretion of Gd-EOB-DTPA can be observed in liver cirrhosis patients.Keywords: Hepatocellular carcinoma, Magnetic resonance imaging (MRI), Gadoxetic acid, Common hepatic duc

Surgical treatment of preschool childhood spinal thoracic tuberculosis: Two case reports and technical note

Background: The development of paraplegia and kyphosis are two important problems related to spinal tuberculosis (Pott’s disease) in children. The current study aims to present two pediatric Pott’s disease, point out the progression of this disease in children, surgical options and surgical outcomes.Materials and methods: Two cases of childhood Pott’s disease were referred to our department with progressive neurological deficits (both of children were experienced bilateral weakness in lower extremities; grade C according to Frankel scale) during short periods (less than one month per each). Both cases’ MRIs are demonstrated abscesses in thoracic spine. Both patients are treated surgically. We discussed in this study the technical notes in both cases, especially in 2-year-old child.Results: Both cases were treated surgically after decompressing nerve roots and thecal sac posterior instrumentation was applied. Microbiological examination of both samples revealed on M.Tuberculosis. Orthoses are applied three months after operations. Antituberculosis medication protocol was applied. Preoperative paraparesis had recovered completely and muscle strengths all returned to normal in both children. There is no loss of correction during the follow-up periods.Conclusion: Spinal tuberculosis is a dynamic disease that may lead to severe deformities in childhood. Especially in cases where two or more vertebrae are affected, early surgical treatment is essential to prevent severe kyphosis. Surgical intervention accompanied with antituberculosis medications protocol is essential to cure treatment in pediatric population. In children aged ?6 years and more than one vertebrae were affected, f?bula can be used to allow growth of the child vertebral column

Comparison of the biochemical and radiological criteria for lumbar disc degeneration

Background The relationship between radiological degeneration criteria on lumbar magnetic resonance imaging (MRI) and both the keratan sulfate (KS) and chondroitin sulfate (ChS) levels was examined in disc material taken from patients undergoing lumbar disc herniation (LDH) surgery. To examine whether the biochemical and radiological degeneration criteria testing the reliability of radiological degeneration findings agreed and to evaluate the contribution of the KS/ChS ratio to disc form (protruding or extruding). Methods This was a prospective experimental cohort study. Using enzyme-linked immunosorbent assay, KS and ChS levels were measured in the degenerate nucleus pulposus taken from 71 patients with a diagnosis of LDH who underwent surgery. The degeneration levels and disc form (protruding or extruding) were determined according to the Pfirrmann five-stage grading system on preoperative T2-weighted lumbar MRIs. According to the Pfirrmann system, 28 patients were grade III and 43 were grade IV. The relationship between radiological criteria and the KS/ChS ratio was statistically evaluated. Results The KS levels (p=0.046) and the KS/ChS ratio (p=0.001) were significantly higher in grade IV patients than in grade III patients. However, there was no difference between the KS and ChS levels and the KS/ChS ratio when patients were classified as protruding or extruding according to their disc structure. Disc structure and biochemical degeneration indicators were not correlated. Conclusions The KS level and the KS/ChS ratio were high in patients with marked radiological degeneration on lumbar MRI, demonstrating the sensitivity and reliability of the Pfirrmann five-stage grading system for showing radiological degeneration