The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

ICP Monitoring and Phase-Contrast MRI to Investigate Intracranial Compliance.

OBJECTIVE: The amplitude of intracranial pressure (ICP) can be measured by ICP monitoring. Phase-contrast magnetic resonance imaging (PCMRI) can quantify blood and cerebrospinal fluid (CSF) flows. The aim of this work was to investigate intracranial compliance at rest by combining baseline ICP monitoring and PCMRI in hydrocephalus patients. MATERIALS AND METHODS: ICP monitoring was performed before infusion testing to quantify ΔICP_rest at the basal condition in 33 suspected hydrocephalus patients (74 years). The day before, patients had had a PCMRI to assess total cerebral blood flow (tCBF), intracranial blood volume change (stroke volume SVblood), and cervical CSF volume change (the stroke volume CSV). Global (blood and CSF) intracranial volume change (ΔIVC) during each cardiac cycle (CC) was calculated. Finally, Compliance: C_rest = ΔIVC/ΔICP_rest was calculated. The data set was postprocessed by two operators according to blind analysis. RESULTS: Bland-Altman plots showed that measurements presented no significant difference between the two operators. ΔICP_rest = 2.41 ± 1.21 mmHg, tCBF = 469.89 ± 127.54 mL/min, SVblood = 0.82 ± 0.32 mL/cc, CSV = 0.50 ± 0.22 mL/cc, ΔIVC = 0.44 ± 0.22 mL, and C_rest = 0.23 ± 0.15 mL/mmHg. There are significant relations between SVblood and CSV and also SVblood and tCBF. CONCLUSIONS: During "basal" condition, the compliance amplitude of the intracranial compartment is heterogeneous in suspected hydrocephalus patients, and its value is lower than expected! This new parameter could represent new information, complementary to conventional infusion tests. We hope that this information can be applied to improve the selection of patients for shunt surgery.

Value of PET/CT 3D visualization of head and neck squamous cell carcinoma extended to mandible.

PURPOSE: To study an original 3D visualization of head and neck squamous cell carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG PET/CT imaging along with a new innovative FDG and NaF image analysis using dedicated software. The main interest of the 3D evaluation is to have a better visualization of bone extension in such cancers and that could also avoid unsatisfying surgical treatment later on. PATIENTS AND METHODS: A prospective study was carried out from November 2016 to September 2017. Twenty patients with head and neck squamous cell carcinoma extending to the mandible (stage 4 in the UICC classification) underwent [18F]-NaF and [18F]-FDG PET/CT. We compared the delineation of 3D quantification obtained with [18F]-NaF and [18F]-FDG PET/CT. In order to carry out this comparison, a method of visualisation and quantification of PET images was developed. This new approach was based on a process of quantification of radioactive activity within the mandibular bone that objectively defined the significant limits of this activity on PET images and on a 3D visualization. Furthermore, the spatial limits obtained by analysis of the PET/CT 3D images were compared to those obtained by histopathological examination of mandibular resection which confirmed intraosseous extension to the mandible. RESULTS: The [18F]-NaF PET/CT imaging confirmed the mandibular extension in 85% of cases and was not shown in [18F]-FDG PET/CT imaging. The [18F]-NaF PET/CT was significantly more accurate than [18F]-FDG PET/CT in 3D assessment of intraosseous extension of head and neck squamous cell carcinoma. This new 3D information shows the importance in the imaging approach of cancers. All cases of mandibular extension suspected on [18F]-NaF PET/CT imaging were confirmed based on histopathological results as a reference. CONCLUSIONS: The [18F]-NaF PET/CT 3D visualization should be included in the pre-treatment workups of head and neck cancers. With the use of a dedicated software which enables objective delineation of radioactive activity within the bone, it gives a very encouraging results. The [18F]-FDG PET/CT appears insufficient to confirm mandibular extension. This new 3D simulation management is expected to avoid under treatment of patients with intraosseous mandibular extension of head and neck cancers. However, there is also a need for a further study that will compare the interest of PET/CT and PET/MRI in this indication.

Impact of the point spread function on maximum standardized uptake value measurements in patients with pulmonary cancer.

Maximum standardized uptake value (SUVmax) from fluorodeoxyglucose (FDG) positron emission tomography (PET) scans is a semi quantitative measure that is increasingly used in the clinical practice for diagnostic and therapeutic response assessment purposes. Technological advances such as the implementation of the point spread function (PSF) in the reconstruction algorithm have led to higher signal to noise ratio and increased spatial resolution. The impact on SUVmax measurements has not been studied in clinical setting. We studied the impact of PSF on SUVmax in 30 consecutive lung cancer patients. SUVmax values were measured on PET-computed tomography (CT) scans reconstructed iteratively with and without PSF (respectively high-definition [HD] and non-HD). HD SUVmax values were significantly higher than non-HD SUVmax. There was excellent correlation between HD and non-HD values. Details of reconstruction and PSF implementation in particular have important consequences on SUV values. Nuclear Medicine physicians and radiologists should be aware of the reconstruction parameters of PET-CT scans when they report or rely on SUV measurements.

Fluorodeoxyglucose positron emission tomography fails to detect distant metastases at initial staging of melanoma patients with metastatic involvement of sentinel lymph node.

BACKGROUND: Positron emission tomography (PET) using fluorodeoxyglucose (FDG) has proven to be more sensitive and accurate than other imaging modalities for the detection of distant metastases in patients with melanoma. Sentinel lymph node (SLN) status is the most important prognostic factor in melanoma patients with no evidence of distant metastasis. OBJECTIVES: To assess the rate of distant metastases in patients with a positive SLN biopsy (SLNB). METHODS: Forty-six consecutive patients with a positive SLNB underwent PET or PET-computed tomography within 6 weeks of the SLNB procedure. The patients did not present any clinical sign of nodal involvement or of distant metastasis. PET findings were classified as positive, negative or nonconclusive. RESULTS: No patient had a positive PET scan for distant metastasis. Six patients (13%) had a nonconclusive PET scan; none of them presented distant metastasis within 12 months. Forty patients (87%) had a negative PET scan; among them five (12%) presented with distant metastasis within 12 months. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography failed to detect distant metastases at initial staging in patients with a positive SLNB, even in patients who presented with distant metastases within 12 months after the FDG PET scan. These results could be explained by the low prevalence of macroscopic metastatic disease at this stage and by the important delay between the onset of the spread of microscopic metastatic disease and the identification by PET scan of macroscopic metastatic disease.

[PowerVote: an evaluation tool]. / Utilisation de PowerVote pour une évaluation.

OBJECTIVE: The objective was to report the experience using PowerVote software to evaluate the teaching provided to Toulouse ophthalmology residents. SUBJECTS AND METHODS: This prospective study covers all ophthalmology residents in Toulouse during the 2006-2007 academic year. Courses were alternately given by residents and resident physicians, during a 45-minute PowerPoint presentation. At the beginning of the course, the residents answered five multiple-choice questions. A month after the end of the 12-course program, participants were tested, using PowerVote, on the content of the entire course, focusing on objectives that the residents had received at the start. RESULTS: The level of theoretical knowledge increased significantly, from 4.0/10 to 6.8/10. (P=0.0027). CONCLUSION: Tests using PowerVote allowed instantaneous correction of the answers to the test questions. Consequently, the teaching was easier to adapt to the students' knowledge. Descriptive statistics of the results obtained could be generated via the PowerVote software and displayed on an Excel spreadsheet. The use of PowerVote also allowed direct evaluation of student knowledge and adjustments in the teaching for the following courses. This interactive pedagogical tool has potential for development, particularly to evaluate practices in the context of on-going medical education.

Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients.

BACKGROUND: Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. OBJECTIVE: To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. METHODS: A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher's exact test or the two-sample t-test and the chi(2) test. Multivariable logistic regression was used to adjust for possible confounding factors. RESULTS: We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1.8 mm (interquartile range 1.1-3). Regression was observed in 23% (n = 94). SLN metastases were observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P = 0.012). The adjusted odds ratio (OR) for regressive melanoma was 0.9 [95% confidence interval (CI) 0.4-1.9; P = 0.777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1.5 to < 2.0 mm (adjusted OR 3.1; 95% CI 1.4-7.1; P = 0.006) and >or= 2.0 mm (adjusted OR 3.5; 95% CI 1.7-7.4; P = 0.001) and ulceration of the melanoma (adjusted OR 1.8; 95% CI 1.1-3.2; P = 0.03). CONCLUSION: Regression is not an independent predictor of the risk of SLN metastasis in melanoma.

Mild Alzheimer's disease: a "position paper".

Under the auspices of the Societe Francaise de Geriatrie et Gerontologie, a multi-disciplinary group of specialists in geriatrics, neurology, epidemiology, psychiatry, neuroradiology and nuclear medicine met with the aim of drawing up references on the methods for diagnosing and treating mild Alzheimer's disease. The critical analysis of international literature, conducted by Professor Bruno Vellas for the scientific committee, has served to support study of the latest knowledge in 2008. The multi-disciplinary group met on 14 and 15 May 2008 in order to set out the questions that this study must answer and to allocate draft studies. Thus, it has been possible to conduct a study focused on mild Alzheimer's disease, giving particular attention to diagnostic procedure, specific methods of treatment and the benefits of making a diagnosis.

[Management of levodopa-induced dyskinesia]. / Prise en charge des dyskinésies par la lévodopa.

There are three main therapeutic strategies to manage levodopa-induced dyskinesias in parkinsonian patients: (1) prevent the occurrence of the priming phenomenon which generates the abnormal movements, (2) avoid the expression of dyskinesias in already primed brain with antidyskinetic symptomatic interventions and (3) reverse, once primed, the changes that occurred in the basal ganglia to induce dyskinesias. To prevent, at least partly, priming for dyskinesias is attempted by the early use of dopamine D2 agonists, which delays the need for levodopa. To avoid the expression of dyskinesias in already primed patients, amantadine is presently the most efficacious symptomatic medication, while functional stereotactic surgery is required in the most severe cases. There are several ways to try to reverse, at least partly, dyskinesia priming. The strategy is to reduce as much as possible (ideally completely) the daily dose of levodopa, by the mean of adjunct interventions like high doses of oral agonists, or more efficiently, with apormorphine subcutaneous infusion or subthalamic deep brain stimulation.