BackgroundLate-onset cardiovascular complications are of serious concerns for even asymptomatic pediatric cancer survivors (PCS). We investigated whether cardiopulmonary exercise testing (CPET) can delineate the underlying pathophysiology of preclinical cardiovascular abnormalities in PCS.
MethodsWe examined CPET data via cycle ergometer in asymptomatic PCS with normal echocardiogram and age-matched controls. Peak and submaximal parameters were analyzed.
ResultsFifty-three PCS and 60 controls were studied. Peak oxygen consumption (VO2), peak work rate (WR), and ventilatory anaerobic threshold (VAT) were signi cantly lower in PCS than controls (1.86 ± 0.53 vs. 2.23 ± 0.61 L/min, 125 ± 45 vs. 154 ± 46 watt, and 1.20 ± 0.35 vs. 1.42 ± 0.43 L/min, respectively; all p < 0.01), whereas peak heart rate (HR) and ventilatory e ciency (a slope of minute ventilation over CO2 production or DVE/DVCO2) were comparable. Peak respiratory quotient (RQ) was signi cantly higher in PCS (p = 0.0006). Stroke volume (SV) reserve was decreased in PCS, indicated by simultaneous higher dependency on HR (higher ΔHR/ΔWR) and lower peak oxygen pulse (OP) at the peak exercise. Twelve PCS with high peak RQ (≥ 1.3) revealed lower pVO2 and VAT than the rest of PCS despite higher ventilatory e ciency (lower DVE/DVCO2), suggesting fundamental de ciency in oxygen utilization in some PCS.
ConclusionsPoor exercise performance in PCS is mainly attributed to limited stroke volume reserve, but the underlying pathophysiology is multi-factorial. Combined assessment of peak and submaximal CPET parameters provided critical information in delineating underlying exercise physiology of PCS.
Osteons are the repeating unit throughout cortical bone, consisting of canals filled with blood and nerve vessels surrounded by concentric lamella of hydroxyapatite-containing collagen fibers, providing mechanical strength. Creating a biodegradable scaffold that mimics the osteon structure is crucial for optimizing cellular infiltration and ultimately the replacement of the scaffold with native cortical bone. In this study, a modified air-gap electrospinning setup was exploited to continuously wrap highly aligned polycaprolactone polymer nanofibers around individual 1393 bioactive glass microfibers, resulting in a synthetic structure similar to osteons. By varying the parameters of the device, scaffolds with polymer fibers wrapped at angles between 5–20° to the glass fiber were chosen. The scaffold indicated increased cell migration by demonstrating unidirectional cell orientation along the fibers, similar to recent work regarding aligned nerve and muscle regeneration. The wrapping decreased the porosity from 90% to 80%, which was sufficient for glass conversion through ion exchange validated by inductively coupled plasma. Scaffold degradation was not cytotoxic. Encapsulating the glass with polymer nanofibers caused viscoelastic deformation during three-point bending, preventing typical brittle glass fracture, while maintaining cell migration. This scaffold design structurally mimics the osteon, with the intent to replace its material compositions for better regeneration.
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