Citations

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) from IGF-binding protein-2, -4, and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF-1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF-1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what’s up and what’s down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.

Abstract Assessment of x-ray angiography system performance is typically performed using stationary test objects with simple geometries such as a disk on a uniform background. However, these methods do not represent realistic imaging conditions in interventional cardiology as anatomy and devices are inherently non-stationary due to cardiac motion. In this work, a novel implementation of the channelized Hotelling observer (CHO) was used to assess the influence of motion blur on object detectability. A standard CHO model assumes imaging system stationarity whereby the detectability index of a test object is independent of location. However, real angiography systems are inherently non-stationary. While vendor correction gain factors and offset maps are used to compensate for visual non-uniformities, these corrections do not restore stationarity to the images. Methods to accommodate non-stationarity and allow assessment of the influence of motion blur on test object detectability will be presented. The effect of motion blur was quantified with the relative detectability index ( ), where the for an object when moving with constant linear velocity was compared to a low velocity ‘pseudo-stationary’ condition to account for system non-stationarity. The pseudo-stationary condition was used to isolate the influences of spatial non-stationarity and motion blur. Three different test object shapes (disks, spheres and capsules) with linear velocity in the range 0–30 cm · s −1 were tested. For 1 mm diameter objects and linear velocity 30 cm · s −1 , was degraded by 37%, 33% and 42% for the disk, sphere and capsule respectively, relative to the pseudo-stationary condition. Considering all test objects with diameter greater than 2 mm and linear velocity 30 cm · s −1 , was degraded by less than 10% due to motion. In summary, this work describes a new approach to assess performance of x-ray angiography systems using the CHO model and moving test objects.

Abstract

Abstract Purpose Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. Methods and materials Eighteen patients with high‐risk ( n = 16) and locally recurrent neuroblastoma ( n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post‐induction MIBG‐avid metastatic sites. Primary sites ( n = 18) were treated to 21–36 Gy (relative biological effectiveness [RBE]), and metastatic sites ( n = 16) were treated to 21–24 Gy (RBE). Local control and survival rates were calculated using the Kaplan–Meier method. Results With a median follow‐up of 60.2 months, two‐ and five‐year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five‐year progression‐free survival (PFS) was 64%, and the five‐year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation‐related nephropathy or hepatopathy was reported. Conclusions Excellent local control was achieved using proton therapy to the primary and post‐induction MIBG‐positive distant sites. The predominant site of failure is progression in post‐induction non‐MIBG‐avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.