Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation.

Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.

[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action.

BACKGROUND: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. RESULTS: [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·µmol-1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. CONCLUSIONS: The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.

Institutional Impact of EVAR's Incorporation in the Treatment of Abdominal Aortic Aneurysm: a 12 Years' Experience Analysis.

INTRODUCTION: Endovascular aneurysm repair (EVAR) was introduced as a less aggressive treatment of abdominal aortic aneurysms (AAA) for patients ineligible for open repair (OR). OBJECTIVE: To analyze EVAR's incorporation impact in the treatment of infra-renal abdominal aortic aneurysms in our institution. METHODS: A retrospective study of the patients with diagnostic of infra-renal AAA treated between December 2001 and December 2013 was performed. The choice between EVAR and OR was based on surgeon's experience, considering patient clinical risk and aneurysm's anatomical features. Patients treated by EVAR and by OR were analyzed. In each group, patient's and aneurysm's characteristics, surgical and anesthesia times, cost, transfusion rate, intraoperative complications, hospital stay, mortality and re-intervention rates and survival curves were evaluated. RESULTS: The mean age, all forms of heart disease and chronic renal failure were more common in EVAR group. Blood transfusion, surgical and anesthesia times and mean hospital stay were higher for OR. Intraoperative complications rate was higher for endovascular aneurysm repair, overall during hospitalization complication rate was higher for open repair. The average cost in endovascular aneurysm repair was 1448.3€ higher. Re-interventions rates within 30 days and late re-intervention were 4.1% and 11.7% for endovascular aneurysm repair versus 13.7% and 10.6% for open repair. CONCLUSIONS: Two different groups were treated by two different techniques. The individualized treatment choice allows to achieve a mortality of 2.7%. Age ≥80 years influences survival curve in OR group and ASA ≥IV in EVAR group. We believe EVAR's incorporation improved the results of OR itself. Patients with more comorbidities were treated by endovascular aneurysm repair, decreasing those excluded from treatment. Late reinterventions were similar for both techniques.

Institutional impact of EVAR's incorporation in the treatment of abdominal aortic aneurysm: a 12 years' experience analysis

Abstract Introduction: Endovascular aneurysm repair (EVAR) was introduced as a less aggressive treatment of abdominal aortic aneurysms (AAA) for patients ineligible for open repair (OR). Objective: To analyze EVAR's incorporation impact in the treatment of infra-renal abdominal aortic aneurysms in our institution. Methods: A retrospective study of the patients with diagnostic of infra-renal AAA treated between December 2001 and December 2013 was performed. The choice between EVAR and OR was based on surgeon's experience, considering patient clinical risk and aneurysm's anatomical features. Patients treated by EVAR and by OR were analyzed. In each group, patient's and aneurysm's characteristics, surgical and anesthesia times, cost, transfusion rate, intraoperative complications, hospital stay, mortality and re-intervention rates and survival curves were evaluated. Results: The mean age, all forms of heart disease and chronic renal failure were more common in EVAR group. Blood transfusion, surgical and anesthesia times and mean hospital stay were higher for OR. Intraoperative complications rate was higher for endovascular aneurysm repair, overall during hospitalization complication rate was higher for open repair. The average cost in endovascular aneurysm repair was 1448.3€ higher. Re-interventions rates within 30 days and late re-intervention were 4.1% and 11.7% for endovascular aneurysm repair versus 13.7% and 10.6% for open repair. Conclusions: Two different groups were treated by two different techniques. The individualized treatment choice allows to achieve a mortality of 2.7%. Age ≥80 years influences survival curve in OR group and ASA ≥IV in EVAR group. We believe EVAR's incorporation improved the results of OR itself. Patients with more comorbidities were treated by endovascular aneurysm repair, decreasing those excluded from treatment. Late reinterventions were similar for both techniques.