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1.
Unraveling the Immunopathological Landscape of Celiac Disease: A Comprehensive Review.
Patt, YS, Lahat, A, David, P, Patt, C, Eyade, R, Sharif, K
International journal of molecular sciences. 2023;(20)
Abstract
Celiac disease (CD) presents a complex interplay of both innate and adaptive immune responses that drive a variety of pathological manifestations. Recent studies highlight the role of immune-mediated pathogenesis, pinpointing the involvement of antibodies against tissue transglutaminases (TG2, TG3, TG6), specific HLA molecules (DQ2/8), and the regulatory role of interleukin-15, among other cellular and molecular pathways. These aspects illuminate the systemic nature of CD, reflecting its wide-reaching impact that extends beyond gastrointestinal symptoms to affect other physiological systems and giving rise to a range of pathological landscapes, including refractory CD (RCD) and, in severe cases, enteropathy-associated T cell lymphoma. The existing primary therapeutic strategy, a gluten-free diet (GFD), poses significant challenges, such as low adherence rates, necessitating alternative treatments. Emerging therapies target various stages of the disease pathology, from preventing immunogenic gluten peptide absorption to enhancing intestinal epithelial integrity and modulating the immune response, heralding potential breakthroughs in CD management. As the understanding of CD deepens, novel therapeutic avenues are emerging, paving the way for more effective and sophisticated treatment strategies with the aim of enhancing the quality of life of CD patients. This review aims to delineate the immunopathology of CD and exploring its implications on other systems, its complications and the development of novel treatments.
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2.
Copper-assisted oxidation of catechols into quinone derivatives.
Gómez-Herrero, AC, Sánchez-Sánchez, C, Chérioux, F, Martínez, JI, Abad, J, Floreano, L, Verdini, A, Cossaro, A, Mazaleyrat, E, Guisset, V, et al
Chemical science. 2020;(6):2257-2267
Abstract
Catechols are ubiquitous substances often acting as antioxidants, thus of importance in a variety of biological processes. The Fenton and Haber-Weiss processes are thought to transform these molecules into aggressive reactive oxygen species (ROS), a source of oxidative stress and possibly inducing degenerative diseases. Here, using model conditions (ultrahigh vacuum and single crystals), we unveil another process capable of converting catechols into ROSs, namely an intramolecular redox reaction catalysed by a Cu surface. We focus on a tri-catechol, the hexahydroxytriphenylene molecule, and show that this antioxidant is thereby transformed into a semiquinone, as an intermediate product, and then into an even stronger oxidant, a quinone, as final product. We argue that the transformations occur via two intramolecular redox reactions: since the Cu surface cannot oxidise the molecules, the starting catechol and the semiquinone forms each are, at the same time, self-oxidised and self-reduced. Thanks to these reactions, the quinone and semiquinone are able to interact with the substrate by readily accepting electrons donated by the substrate. Our combined experimental surface science and ab initio analysis highlights the key role played by metal nanoparticles in the development of degenerative diseases.
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3.
Positron emission tomography-guided volumetric resection of supratentorial high-grade gliomas: a survival analysis in 66 consecutive patients.
Pirotte, BJ, Levivier, M, Goldman, S, Massager, N, Wikler, D, Dewitte, O, Bruneau, M, Rorive, S, David, P, Brotchi, J
Neurosurgery. 2009;(3):471-81; discussion 481
Abstract
OBJECTIVE Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome. METHODS PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI. RESULTS Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806). CONCLUSIONS Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.
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4.
Three-dimensional Gaussian model to define brain metastasis limits on 11C-methionine PET.
Tang, BN, Van Simaeys, G, Devriendt, D, Sadeghi, N, Dewitte, O, Massager, N, David, P, Levivier, M, Goldman, S
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2008;(3):270-7
Abstract
PURPOSE Since 11C-methionine (MET) heavily accumulates in brain tumors, PET with MET (MET-PET) is proposed for the image-guided planning of their targeted therapy. Determination of bulk tumor limits is therefore a crucial component of MET-PET image analysis. We aimed at validating a Gaussian model of tumor delineation on MET-PET. We choose MET-PET and MRI data obtained in brain metastases to adjust the model. Indeed, MRI limits of these non-infiltrative hypermetabolic brain lesions are efficiently used for their curative treatment. METHODS AND MATERIALS We developed a three-dimensional (3D) Gaussian model that relates the tumor-limit-defining threshold to maximum and mean count values in the defined tumor volume and to mean count values in a reference region. To adjust the model to experimental data, we selected 25 brain metastases following these criteria: (i) no surgery or classical radiotherapy within 6 months, (ii) no previous radiosurgery, (iii) MET-PET and MRI acquired within a 48-h interval, (vi) necrosis representing less than 25% of tumor volume on MRI. We applied a progressive thresholding procedure on MET-PET so as to match tumor limits on contrast-enhanced co-registered MRI. RESULTS In 22 tumors, a match could be reached between tumor margins on MET-PET and MRI. The relation between mean, maximum and threshold values closely fits the 3D-Gaussian model function. We found a quadratic relation between the mean-to-threshold ratio and the maximum-to-cerebellum activity ratio. CONCLUSIONS A 3D-Gaussian model may describe the limits of MET uptake distribution within brain metastases, providing a simple method for metabolic tumor delineation.
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5.
Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures.
Pirotte, B, Goldman, S, Dewitte, O, Massager, N, Wikler, D, Lefranc, F, Ben Taib, NO, Rorive, S, David, P, Brotchi, J, et al
Journal of neurosurgery. 2006;(2):238-53
Abstract
OBJECT The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. METHODS Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and L-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning-demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection-the tumor contours were displayed in the microscope's eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. CONCLUSIONS Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.
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6.
Integration of [11C]methionine-positron emission tomographic and magnetic resonance imaging for image-guided surgical resection of infiltrative low-grade brain tumors in children.
Pirotte, B, Goldman, S, Van Bogaert, P, David, P, Wikler, D, Rorive, S, Brotchi, J, Levivier, M
Neurosurgery. 2005;(1 Suppl):128-39; discussion 128-39
Abstract
OBJECTIVE To evaluate the interest of integrating positron emission tomography (PET) images with the radiolabeled tracer [(11)C]methionine (Met) into the image-guided navigation planning of infiltrative low-grade brain tumors (LGBTs) in children. METHODS Twenty-two children underwent combined Met-PET with magnetic resonance imaging (MRI) scans in the planning of a navigation procedure. These children presented an LGBT (astrocytomas, 10; oligodendrogliomas, 4; ependymomas, 4; gangliogliomas, 4) located close to functional areas. Tumor boundaries were ill-defined on MRI (including T2-weighted and fluid-attenuated inversion-recovery scans) and could not be clearly identified for allowing a complete, or at least a large, image-guided resection. The PET tracer Met was chosen because of its higher sensitivity and specificity than MRI to detect tumor tissue. The level and extension of MET uptake were analyzed to define the PET contour, subsequently projected onto MRI scans to define a final target contour for volumetric resection. The quality of tumor resection was assessed by an early postoperative MRI and Met-PET workup. RESULTS In 20 of the 22 children with ill-defined LGBTs, PET improved tumor delineation and contributed to define a final target contour different from that obtained with MRI alone. Met-PET guidance allowed a total resection of Met uptake in 17 cases that were considered total tumor resections because the operative margin left in place contained nontumor tissue. CONCLUSION These data suggested that Met-PET guidance could help to improve the number of total resections and the amount of tumor removed in infiltrative LGBTs in children.
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7.
[Homocysteine, folic acid, group B vitamins and cardiovascular risk].
Blacher, J, Czernichow, S, Horrellou, MH, Conad, J, David, P, Chadefaux-Vekemans, B, Ankria, A, Galan, P, Hercberg, S, Ducimetière, P
Archives des maladies du coeur et des vaisseaux. 2005;(2):145-52
Abstract
Although there is a high degree of proof relating plasma homocysteine levels to cardiovascular risk, the role of homocysteine as a causal cardiovascular risk factor remains controversial. Prospective long-term clinical trials in high cardiovascular risk populations usually show a positive relationship between plasma homocysteine and the degree of cardiovascular risk. However, shorter term studies and/or those carried out in populations with lower cardiovascular risk show either a weaker correlation or no relationship at all. To date no study has shown proof of the reversibility of cardiovascular risk due to hyperhomocysteinaemia; nevertheless, a number of studies using intermediate criteria support the hypothesis of a benefit due to reduction of plasma homocysteine levels. A number of therapeutic trials published with clinical criteria have not shown convincing results in either direction. A number of interventional trials are underway: notably the SUFOLOM 3 trial in France, and the question of a benefit on cardiovascular risk by reducing homocysteine levels should be answered in the next few years. In the meantime, with the exception of homocysteinuria in which therapeutic strategies have shown their efficacy in the reduction of atherothrombotic risk with high levels of proof, the authors do not recommend the treatment of mild hyperhomocysteinaemia in any clinical setting other than "clinical trials" and certain "compassionate" indications such as early and/or recurrent vascular events associated with hyperhomocysteinaemia in the absence of conventional risk factors.
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8.
Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.
Levivier, M, Massager, N, Wikler, D, Lorenzoni, J, Ruiz, S, Devriendt, D, David, P, Desmedt, F, Simon, S, Van Houtte, P, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2004;(7):1146-54
Abstract
UNLABELLED We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.
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9.
Comparison of 18F-FDG and 11C-methionine for PET-guided stereotactic brain biopsy of gliomas.
Pirotte, B, Goldman, S, Massager, N, David, P, Wikler, D, Vandesteene, A, Salmon, I, Brotchi, J, Levivier, M
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2004;(8):1293-8
Abstract
UNLABELLED We compared the contributions of the labeled tracers (11)C-methionine (Met) and (18)F-FDG for PET-guided stereotactic biopsy of brain gliomas. METHODS In 32 patients with glioma, stereotactic Met PET and (18)F-FDG PET were integrated in the planning of stereotactic brain biopsy. PET images were analyzed to determine which tracer offered the best information for target definition. The stereotactic coregistration of PET images allowed accurate comparison of the level, distribution, and extent of uptake for both tracers according to tumor location and grade. RESULTS A histologic diagnosis was obtained for all patients. All gliomas had an area of abnormal Met uptake, and 27 showed abnormal (18)F-FDG uptake. (18)F-FDG was used for target selection when its uptake was higher in tumor than in gray matter (14 gliomas). Seven were in the basal ganglia or brain stem. Met was used for target selection when there was no (18)F-FDG uptake or when (18)F-FDG uptake was equivalent to that in the gray matter (18 gliomas). Thirteen were in the cortex. Sixty-one of the 70 stereotactic trajectories obtained from the 32 patients were based on PET-defined targets and had an area of abnormal Met uptake. These 61 Met-positive trajectories always yielded a diagnosis of tumor. All nondiagnostic trajectories (n = 9) were obtained in areas with no increased uptake of Met. In all patients with increased uptake of both tracers, the focus of highest Met uptake corresponded to the focus of highest (18)F-FDG uptake. However, the extent of uptake of both tracers was variable. CONCLUSION Distributions of highest Met and (18)F-FDG uptake are similar in brain gliomas. Because Met provides a more sensitive signal, it is the molecule of choice for single-tracer PET-guided neurosurgical procedures in gliomas.
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10.
Combined positron emission tomography and magnetic resonance imaging for the planning of stereotactic brain biopsies in children: experience in 9 cases.
Pirotte, B, Goldman, S, Salzberg, S, Wikler, D, David, P, Vandesteene, A, Van Bogaert, P, Salmon, I, Brotchi, J, Levivier, M
Pediatric neurosurgery. 2003;(3):146-55
Abstract
Because brain tumors can be histologically heterogeneous, stereotactic brain biopsies (SBB) may lead to inaccurate diagnosis or grading. Positron emission tomography (PET) has been used in pediatric neuro-oncology to help in the understanding and management of brain neoplasms. We combined PET and magnetic resonance (MR) imaging in the planning of SBB in 9 children (5 males and 4 females, aged 2-14 years) with infiltrative, ill-defined brain lesions. Tracers used for PET were (18)F-2-fluoro-2-deoxy-D-glucose in 4 cases, (11)C-methionine in 2 cases and both tracers in 3 cases. Biopsy targets were selected in hypermetabolic areas. PET-guided SBB provided accurate histological diagnosis in all patients and allowed a reduction of the number of trajectories in lesions located in functional areas. It also helped in better understanding and management of complex cases. This preliminary series suggests that combining PET and MR imaging in the planning of SBB in children (1) improves the diagnostic yield of SBB in infiltrative, ill-defined brain lesions, (2) makes it possible to reduce the sampling in high-risk/functional areas and (3) improves the quality of therapeutic management of pediatric brain tumors.