Modélisation de l’ablation radiofréquence pour la planification de la résection de tumeurs abdominales

The outcome of radiofrequency ablation (RFA) of abdominal tumors is challenged by the presence of blood vessels and time-varying thermal conductivity, which make patient-specific planning extremely difficult. By providing predictive tools, biophysical models may help clinicians to plan and guide the procedure for an effective treatment. We introduce a detailed computational model of the biophysical mechanisms involved in RFA of hepatic tumors such as heat diffusion and cellular necrosis. It simulates the extent of ablated tissue based on medical images, from which patient-specific models of the liver, visible vessels and tumors are segmented. In this thesis, a new approach for solving these partial differential equations based on the Lattice Boltzmann Method is introduced. The model is first evaluated against clinical data of patients who underwent RFA of liver tumors. Then, a comprehensive pre-clinical experiment that combines multi-modal, pre- and post-operative anatomical and functional images, as well as the interventional monitoring of the temperature and delivered power is presented. This enables an end-to-end validation framework that considers the most comprehensive data set for model validation. Then, we automatically estimate patient-specific parameters to better predict the ablated tissue. This personalization strategy has been validated on 7 ablations from 3 clinical cases. From the pre-clinical study, we can go further in the personalization by comparing the simulated temperature and delivered power with the actual measurements during the procedure. These contributions have led to promising results, and open new perspectives in RFA guidance and planning.L'ablation par radiofréquence (ARF) de tumeurs abdominales est rendue difficile par l’influence des vaisseaux sanguins et les variations de la conductivité thermique, compliquant la planification spécifique à un patient donné. En fournissant des outils prédictifs, les modèles biophysiques pourraient aider les cliniciens à planifier et guider efficacement la procédure. Nous introduisons un modèle mathématique détaillé des mécanismes impliqués dans l’ARF des tumeurs du foie comme la diffusion de la chaleur et la nécrose cellulaire. Il simule l’étendue de l’ablation à partir d’images médicales, d’après lesquelles des modèles personnalisés du foie, des vaisseaux visibles et des tumeurs sont segmentés. Dans cette thèse, une nouvelle approche pour résoudre ces équations basée sur la méthode de Lattice Boltzmann est introduite. Le modèle est d’abord évalué sur des données de patients qui ont subi une ARF de tumeurs du foie. Ensuite, un protocole expérimental combinant des images multi-modales, anatomiques et fonctionnelles pré- et post-opératoires, ainsi que le suivi de la température et de la puissance délivrée pendant l'intervention est présenté. Il permet une validation totale du modèle qui considère des données les plus complètes possibles. Enfin, nous estimons automatiquement des paramètres personnalisés pour mieux prédire l'étendu de l’ablation. Cette stratégie a été validée sur 7 ablations dans 3 cas cliniques. A partir de l'étude préclinique, la personnalisation est améliorée en comparant les simulations avec les mesures faites durant la procédure. Ces contributions ont abouti à des résultats prometteurs, et ouvrent de nouvelles perspectives pour planifier et guider l’ARF

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Medical-Data-Models.org:A collection of freely available forms (September 2016)

MDM-Portal (Medical Data-Models) is a meta-data repository for creating, analysing, sharing and reusing medical forms, developed by the Institute of Medical Informatics, University of Muenster in Germany. Electronic forms for documentation of patient data are an integral part within the workflow of physicians. A huge amount of data is collected either through routine documentation forms (EHRs) for electronic health records or as case report forms (CRFs) for clinical trials. This raises major scientific challenges for health care, since different health information systems are not necessarily compatible with each other and thus information exchange of structured data is hampered. Software vendors provide a variety of individual documentation forms according to their standard contracts, which function as isolated applications. Furthermore, free availability of those forms is rarely the case. Currently less than 5 % of medical forms are freely accessible. Based on this lack of transparency harmonization of data models in health care is extremely cumbersome, thus work and know-how of completed clinical trials and routine documentation in hospitals are hard to be re-used. The MDM-Portal serves as an infrastructure for academic (non-commercial) medical research to contribute a solution to this problem. It already contains more than 4,000 system-independent forms (CDISC ODM Format, www.cdisc.org, Operational Data Model) with more than 380,000 dataelements. This enables researchers to view, discuss, download and export forms in most common technical formats such as PDF, CSV, Excel, SQL, SPSS, R, etc. A growing user community will lead to a growing database of medical forms. In this matter, we would like to encourage all medical researchers to register and add forms and discuss existing forms

Obesity-induced chronic inflammation in C57Bl6J mice, a novel risk factor in the progression of renal AA amyloidosis?

Background: Compelling evidence links obesity induced systemic inflammation to the development of chronic kidney disease (CKD). This systemic inflammation may result from exacerbated adipose inflammation. Besides the known detrimental effects of typical pro-inflammatory factors secreted by the adipose tissue (TNF-α, MCP-1 and IL-6) on the kidney, we hypothesize the enhanced obesity-induced secretion of serum amyloid A (SAA), an acute inflammatory protein, to play a key role in aggravating obesity-induced CKD. Methods: Groups of male C57Bl/6J mice (n = 99 in total) were fed a low (10% lard) or high (45% lard) fat diet for a maximum of 52 weeks. Mice were sacrificed after 24, 40 and 52 weeks. Whole blood samples, kidneys and adipose tissues were collected. The development of adipose and renal tissue inflammation was assessed on gene expression and protein level. Adipocytokine levels were measured in plasma samples. Results: A distinct inflammatory phenotype was observed in the adipose tissue of HFD mice prior to renal inflammation, which was associated with an early systemic elevation of TNF-α, leptin and SAA (1A-C). With aging, sclerotic lesions appeared in the kidney, the extent of which was severely aggravated by HFD feeding. Lesions exhibited typical amyloid characteristics (2A) and pathological severity positively correlated with bodyweight (2B). Interestingly, more SAA protein was detected in lesions of HFD mice. Conclusion: Our data suggest a causal link between obesity induced chronic inflammation and AA amyloidosis in C57Bl/6J mice. Though future studies are necessary to prove this causal link and to determine its relevance for the human situation, obesity may hence be considered a risk factor for the development and progression of renal AA amyloidosis in the course of CKD. (Figure Presented)

30th European Congress on Obesity (ECO 2023)

This is the abstract book of 30th European Congress on Obesity (ECO 2023

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations

Epidemiology of Injury in English Women's Super league Football: A Cohort Study

INTRODUCTION: The epidemiology of injury in male professional football has been well documented (Ekstrand, Hägglund, & Waldén, 2011) and used as a basis to understand injury trends for a number of years. The prevalence and incidence of injuries occurring in womens super league football is unknown. The aim of this study is to estimate the prevalence and incidence of injury in an English Super League Women’s Football squad. METHODS: Following ethical approval from Leeds Beckett University, players (n = 25) signed to a Women’s Super League Football club provided written informed consent to complete a self-administered injury survey. Measures of exposure, injury and performance over a 12-month period was gathered. Participants were classified as injured if they reported a football injury that required medical attention or withdrawal from participation for one day or more. Injuries were categorised as either traumatic or overuse and whether the injury was a new injury and/or re-injury of the same anatomical site RESULTS: 43 injuries, including re-injury were reported by the 25 participants providing a clinical incidence of 1.72 injuries per player. Total incidence of injury was 10.8/1000 h (95% CI: 7.5 to 14.03). Participants were at higher risk of injury during a match compared with training (32.4 (95% CI: 15.6 to 48.4) vs 8.0 (95% CI: 5.0 to 10.85)/1000 hours, p 28 days) of which there were three non-contact anterior cruciate ligament (ACL) injuries. The epidemiological incidence proportion was 0.80 (95% CI: 0.64 to 0.95) and the average probability that any player on this team will sustain at least one injury was 80.0% (95% CI: 64.3% to 95.6%) CONCLUSION: This is the first report capturing exposure and injury incidence by anatomical site from a cohort of English players and is comparable to that found in Europe (6.3/1000 h (95% CI 5.4 to 7.36) Larruskain et al 2017). The number of ACL injuries highlights a potential injury burden for a squad of this size. Multi-site prospective investigations into the incidence and prevalence of injury in women’s football are require