Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients.

Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.

Bilateral Carotid Artery Molecular Calcification Assessed by [18F] Fluoride PET/CT: Correlation with Cardiovascular and Thromboembolic Risk Factors.

Atherosclerosis, a leading cause of mortality and morbidity worldwide, involves inflammatory processes that result in plaque formation and calcification. The early detection of the molecular changes underlying these processes is crucial for effective disease management. This study utilized positron emission tomography/computed tomography (PET/CT) with [18F] sodium fluoride (NaF) as a tracer to visualize active calcification and inflammation at the molecular level. Our aim was to investigate the association between cardiovascular risk factors and [18F] NaF uptake in the left and right common carotid arteries (LCC and RCC). A cohort of 102 subjects, comprising both at-risk individuals and healthy controls, underwent [18F] NaF PET/CT imaging. The results revealed significant correlations between [18F] NaF uptake and cardiovascular risk factors such as age (ß = 0.005, 95% CI 0.003-0.008, p < 0.01 in LCC and ß = 0.006, 95% CI 0.004-0.009, p < 0.01 in RCC), male gender (ß = -0.08, 95% CI -0.173--0.002, p = 0.04 in LCC and ß = -0.13, 95% CI -0.21--0.06, p < 0.01 in RCC), BMI (ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in LCC and ß = 0.02, 95% CI 0.01-0.03, p < 0.01 in RCC), fibrinogen (ß = 0.006, 95% CI 0.0009-0.01, p = 0.02 in LCC and ß = 0.005, 95% CI 0.001-0.01, p = 0.01), HDL cholesterol (ß = 0.13, 95% CI 0.04-0.21, p < 0.01 in RCC only), and CRP (ß = -0.01, 95% CI -0.02-0.001, p = 0.03 in RCC only). Subjects at risk showed a higher [18F] NaF uptake compared to healthy controls (one-way ANOVA; p = 0.02 in LCC and p = 0.04 in RCC), and uptake increased with estimated cardiovascular risk (one-way ANOVA, p < 0.01 in LCC only). These findings underscore the potential of [18F] NaF PET/CT as a sensitive tool for the early detection of atherosclerotic plaque, assessment of cardiovascular risk, and monitoring of disease progression. Further research is needed to validate the technique's predictive value and its potential impact on clinical outcomes.

Involvement of the Gap Junction Protein, Connexin43, in the Formation and Function of Invadopodia in the Human U251 Glioblastoma Cell Line.

The resistance of glioblastomas to treatments is mainly the consequence of their invasive capacities. Therefore, in order to better treat these tumors, it is important to understand the molecular mechanisms which are responsible for this behavior. Previous work suggested that gap junction proteins, the connexins, facilitate the aggressive nature of glioma cells. Here, we show that one of them-connexin43 (Cx43)-is implicated in the formation and function of invadopodia responsible for invasion capacity of U251 human glioblastoma cells. Immunofluorescent approaches-combined with confocal analyses-revealed that Cx43 was detected in all the formation stages of invadopodia exhibiting proteolytic activity. Clearly, Cx43 appeared to be localized in invadopodia at low cell density and less associated with the establishment of gap junctions. Accordingly, lower extracellular matrix degradation correlated with less mature invadopodia and MMP2 activity when Cx43 expression was decreased by shRNA strategies. Moreover, the kinetics of invadopodia formation could be dependent on Cx43 dynamic interactions with partners including Src and cortactin. Interestingly, it also appeared that invadopodia formation and MMP2 activity are dependent on Cx43 hemichannel activity. In conclusion, these results reveal that Cx43 might be involved in the formation and function of the invadopodia of U251 glioblastoma cells.

Echocardiography to predict tolerance to negative fluid balance in acute respiratory distress syndrome/acute lung injury.

PURPOSE: In acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), a conservative fluid management strategy improves lung function but could jeopardize extrapulmonary organ perfusion. The objective was to evaluate the diagnostic accuracy of echocardiography to predict tolerance of negative fluid balance (NFB) in patients with ARDS/ALI. MATERIALS AND METHODS: A prospective and observational study in an adult intensive care unit of a university hospital was conducted. All hemodynamically stable patients with ARDS/ALI were included. Echocardiography was performed before NFB and again after 24 hours. Tolerance of NFB was evaluated by the presence of hypotension, acute kidney injury, or need for fluid expansion. The 2 patient groups (tolerating and not tolerating NFB) were compared. RESULTS: Forty-five patients were included. Median age (Q1-Q3) was 58 (52-66) years, and the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen was 205 (163-258) mm Hg. Negative fluid balance was 1950 (1200-2200) mL within 24 hours in the tolerant group. Complications of NFB were observed in 35% cases. After univariate and multivariate logistic regression analyzes, 2 criteria was independently associates with poor tolerance: mitral inflow E wave to early diastolic mitral annulus velocities ratio (E/Ea ratio; odds ratio, 2.02 [1.02-4.02]; P = .04) and weight gain (odds ratio, 1.2 [1.03-1.4]; P = .02). The area under receiver operating characteristic curves was 0.74 for E/Ea and 0.77 for weight gain. CONCLUSIONS: The ratio of E/Ea accurately predicted tolerance of NFB in patients with ARDS/ALI.

Extracorporeal membrane oxygenation in 5 patients with bronchial fistula with severe acute lung injury.

PURPOSE: The management of bronchial fistula associated with acute lung injury raises two major concerns: (1) high ventilation pressures are necessary for lung recruitment but detrimental for fistula healing, and (2) adequate lung recruitment is prevented by large air leak. Primary surgical closure of bronchial fistula should be attempted but is rarely successful during mechanical ventilation. We sought to evaluate the efficacy of extracorporeal membrane oxygenation associated with lung-protective ventilation in case of failure of conventional management. DESCRIPTION: Arteriovenous extracorporeal membrane oxygenation was initiated by femorofemoral cannulation. A stepwise increase of extracorporeal membrane oxygenation output and a decrease of mechanical ventilation settings were simultaneously performed, aiming at lung-protective ventilation. EVALUATION: During a 1-year period, this protocol management was used in 5 patients with refractory respiratory failure associated with bronchial fistula after thoracic operations. This strategy allowed fistula healing in 3 patients. CONCLUSIONS: If correctly timed, extracorporeal membrane oxygenation can provide a therapeutic bridge to lung-protective ventilation and allow bronchial fistula healing in case of refractory respiratory failure.

Poor performances of EuroSCORE and CARE score for prediction of perioperative mortality in octogenarians undergoing aortic valve replacement for aortic stenosis.

BACKGROUND AND OBJECTIVE: Although results of cardiac surgery are improving, octogenarians have a higher procedure-related mortality and more complications with increased length of stay in ICU. Consequently, careful evaluation of perioperative risk seems necessary. The aims of our study were to assess and compare the performances of EuroSCORE and CARE score in the prediction of perioperative mortality among octogenarians undergoing aortic valve replacement for aortic stenosis and to compare these predictive performances with those obtained in younger patients. METHODS: This retrospective study included all consecutive patients undergoing cardiac surgery in our institution between November 2005 and December 2007. For each patient, risk assessment for mortality was performed using logistic EuroSCORE, additive EuroSCORE and CARE score. The main outcome measure was early postoperative mortality. Predictive performances of these scores were assessed by calibration and discrimination using goodness-of-fit test and area under the receiver operating characteristic curve, respectively. RESULTS: During this 2-year period, we studied 2117 patients, among whom 134/211 octogenarians and 335/1906 nonoctogenarians underwent an aortic valve replacement for aortic stenosis. When considering patients with aortic stenosis, discrimination was poor in octogenarians and the difference from nonoctogenarians was significant for each score (0.58, 0.59 and 0.56 vs. 0.82, 0.81 and 0.77 for additive EuroSCORE, logistic EuroSCORE and CARE score in octogenarians and nonoctogenarians, respectively, P < 0.05). Moreover, in the whole cohort, logistic EuroSCORE significantly overestimated mortality among octogenarians. CONCLUSION: Predictive performances of these scores are poor in octogenarians undergoing cardiac surgery, especially aortic valve replacement. Risk assessment and therapeutic decisions in octogenarians should not be made with these scoring systems alone.