Hemodynamic Analysis of Fast and Slow Aneurysm Occlusions By Flow Diversion in Rabbits

Purpose: To assess hemodynamic differences between aneurysms that occlude rapidly and those occluding in delayed fashion after flow diversion in rabbits. Methods: Thirty-six elastase-induced aneurysms in rabbits were treated with flow diverting devices. Aneurysm occlusion was assessed angiographically immediately before they were sacrificed at 1 (n=6), 2 (n=4), 4 (n=8) or 8 weeks (n=18) after treatment. The aneurysms were classified into a fast occlusion group if they were completely or near completely occluded at 4 weeks or earlier and a slow occlusion group if they remained incompletely occluded at 8 weeks. The immediate post-treatment flow conditions in aneurysms of each group were quantified using subject-specific computational fluid dynamics and statistically compared. Results: Nine aneurysms were classified into the fast occlusion group and six into the slow occlusion group. Aneurysms in the fast occlusion group were on average significantly smaller (fast=0.9 cm, slow=1.393 cm, p=0.024) and had smaller ostia (fast=0.144 cm2, slow=0.365 cm2, p=0.015) than aneurysms in the slow occlusion group. They also had a lower mean posttreatment inflow rate (fast=0.047 mL/s, slow=0.155 mL/s, p=0.0239), kinetic energy (fast=0.519 erg, slow=1.283 erg, p=0.0468), and velocity (fast=0.221 cm/s, slow=0.506 cm/s, p=0.0582). However, the differences in the latter two variables were only marginally significant. Conclusions: Hemodynamic conditions after flow diversion treatment of cerebral aneurysms in rabbits are associated with the subsequent aneurysm occlusion time. Specifically, smaller inflow rate, kinetic energy, and velocity seem to promote faster occlusions, especially in smaller and small-necked aneurysms. These results are consistent with previous studies based on clinical series

Hemodynamic analysis of fast and slow aneurysm occlusions by flow diversion in rabbits

PURPOSE: To assess hemodynamic differences between aneurysms that occlude rapidly versus those occluding in delayed fashion after flow diversion in rabbits. METHODS: Thirty six elastase induced aneurysms in rabbits were treated with flow diverting devices. Aneurysm occlusion was assessed angiographically immediately prior to sacrifice at one (n=6), two (n=4), four (n=8) or eight (n=18) weeks after treatment. Aneurysms were classified into a fast occlusion group if they were completely or near completely occluded at 4 weeks or earlier, and into a slow occlusion group if they remained incompletely occluded at 8 weeks. The immediate post-treatment flow conditions in aneurysms of each group were quantified using subject-specific computational fluid dynamics and statistically compared. RESULTS: Nine aneurysms were classified into the fast occlusion group and six into the slow occlusion group. Aneurysms in the fast occlusion group were on average significantly smaller (fast=0.9 cm, slow=1.393 cm, p=0.024), and had smaller ostia (fast=0.144 cm(2), slow=0.365 cm(2), p=0.015) than aneurysms in the slow occlusion group. They also had lower mean post-treatment inflow rate (fast=0.047 mL/s, slow=0.155 mL/s, p=0.0239), kinetic energy (fast=0.519 erg, slow=1.283 erg, p=0.0468), and velocity (fast=0.221 cm/s, slow=0.506 cm/s, p=0.0582). However, the differences of the latter two variables were only marginally significant. CONCLUSIONS: Hemodynamic conditions after flow diversion treatment of cerebral aneurysms in rabbits are associated to the subsequent aneurysm occlusion time. Specifically, smaller inflow rate, kinetic energy, and velocity seem to promote faster occlusions, especially in smaller and small-necked aneurysms. These results are consistent with previous studies based on clinical series

Nocturnal Glucose Metabolism in Type 1 Diabetes: A Study Comparing Single Versus Dual Tracer Approaches

Background: Understanding the effect size, variability, and underlying physiology of the dawn phenomenon is important for next-generation closed-loop control algorithms for type 1 diabetes (T1D). Subjects and Methods: We used an iterative protocol design to study 16 subjects with T1D on individualized insulin pump therapy for two successive nights. Endogenous glucose production (EGP) rates at 3 a.m. and 7 a.m. were measured with [6,6-(2)H(2)]glucose as a single tracer, infused from midnight to 7 a.m. in all subjects. To explore possibility of tracer recycling due to prolonged [6,6-(2)H(2)]glucose infusion, which was highly probable after preplanned interim data analyses, we infused a second tracer, [6-(3)H]glucose, from 4 a.m. to 7 a.m. in the last seven subjects to measure EGP at 7 a.m. Results: Cortisol concentrations increased during both nights, but changes in glucagon and insulin concentration were inconsistent. Although the plasma glucose concentrations rose from midnight to 7 a.m. during both nights, EGP measured with [6,6-(2)H(2)]glucose between 3 a.m. and 7 a.m. did not differ during Night 1 but fell in Night 2. However, EGP measured with [6-(3)H]glucose at 7 a.m. was higher than that measured with [6,6-(2)H(2)]glucose during both nights, thereby suggesting tracer recycling probably underestimating EGP calculated at 7 a.m. with [6,6-(2)H(2)]glucose. Likewise, EGP was higher at 7 a.m. with [6-(3)H]glucose than at 3 a.m. with [6,6-(2)H(2)]glucose during both nights. Conclusions: The data demonstrate a consistent overnight rise in glucose concentrations through increased EGP, mediated likely by rising cortisol concentrations. The observations with the dual tracer approach imply significant tracer recycling leading to underestimation of EGP measured by longer-duration tracer infusion

Physical Activity Sensors Are Superior to Heart Rate Monitoring for Real-Time Activity Detection: Implications for Closed-Loop Diabetes Control

Objective: We have recently shown that mild/moderate-grade physical activity (PA) influences glucose status in healthy individuals and age/gender matched type 1 diabetes mellitus (T1DM) using continuous subcutaneous insulin infusion. Currently in closed-loop studies, instantaneous heart rate and accelerometers are being evaluated to measure PA. We compared PA measured by accelerometers to instantaneous heart rate output. Methods: A total of 23 subjects (11 controls and 12 T1DM) underwent a carefully planned and supervised PA protocol. Where continuous glucose data were captured using Dexcom SEVEN PLUS\uae continuous glucose sensor, PA data were collected using MSR accelerometers (MSR Electronics GmbH, Seuzach, Switzerland) attached to a participant\u2019s body using an elastic belt. The heart rate data were captured on IntelliVue patient monitors (Philips Healthcare, Andover, MA) using finger clip pulse oximeters. The data were compared for two inactive (premeal and meal) bouts and two active bouts to test repeatability. Heart rate and accelerometer data were scaled to a 0% to 100% range based on the participant-specific minimum and maximum values, and intraclass coefficient (ICC) was computed for concordance measures. Results: Heart rate profiles by patient were highly variable, whereas accelerometers tracked the study protocol more closely. While the concordance, by ICC, varied considerably by patient, it did not differ statistically between T1DM and controls (p = .44). For both controls and T1DM, during active periods, both heart rate and accelerometery output varied appropriately, but during the two sedentary periods, the heart rate data showed more variability (p = .02 and p = .04, respectively). Conclusion: Highly accurate accelerometery shows more accuracy compared with instantaneous heart rate and has more potential for incorporation into closed-loop systems for T1D

Exercise effects on postprandial glucose metabolism in type 1 diabetes: A triple-tracer approach

To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V̇o(2max)) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia