3D advanced imaging overlay with rapid registration in CHD to reduce radiation and assist cardiac catheterisation interventions.

Novel commercially available software has enabled registration of both CT and MRI images to rapidly fuse with X-ray fluoroscopic imaging. We describe our initial experience performing cardiac catheterisations with the guidance of 3D imaging overlay using the VesselNavigator system (Philips Healthcare, Best, NL). A total of 33 patients with CHD were included in our study. Demographic, advanced imaging, and catheterisation data were collected between 1 December, 2016 and 31 January, 2019. We report successful use of this technology in both diagnostic and interventional cases such as placing stents and percutaneous valves, performing angioplasties, occlusion of collaterals, and guidance for lymphatic interventions. In addition, radiation exposure was markedly decreased when comparing our 10-15-year-old coarctation of the aorta stent angioplasty cohort to cases without the use of overlay technology and the most recently published national radiation dose benchmarks. No complications were encountered due to the application of overlay technology. 3D CT or MRI overlay for CHD intervention with rapid registration is feasible and aids decisions regarding access and planned angiographic angles. Operators found intraprocedural overlay fusion registration using placed vessel guidewires to be more accurate than attempts using bony structures.

Food-Induced Anaphylaxis: an Update.

PURPOSE OF REVIEW: This review aims to provide an update of recent advances in the epidemiology, clinical features and diagnosis, and management of food-induced anaphylaxis (FIA). RECENT FINDINGS: Food allergy prevalence and FIA rates continue to rise, but FIA fatalities are stable. Basophil and mast cell activation tests promise more accurate identification of food triggers. Oral, sublingual, and epicutaneous immunotherapy can desensitize a significant portion of subjects. Epinephrine use for FIA remains sub-optimal. As the burden of food allergy continues to increase, it appears that the corresponding increase in research focused on this epidemic is beginning to bear fruit. The stable number of FIA fatalities in the face of an ongoing epidemic indicates lives have already been saved. The emergence of new diagnostic tests and interventional therapies may transform the management of FIA in the coming years.

Lower opportunity ZIP code is associated with worse outcomes after listing in pediatric heart transplantation.

BACKGROUND: The Child Opportunity Index (COI) comprehensively measures children's social determinants of health. We describe association between COI and outcomes after listing for heart transplantation. METHODS: We conducted a retrospective review of the United Network for Organ Sharing (UNOS) database for U.S. children listed for heart transplant between 2012 and 2020. ZIP codes were utilized to assign COI. Primary outcome was survival from time of listing. Secondary outcomes included waitlist survival, 1-year post-transplant survival, and conditional 1-year post-transplant survival. Cox regression was performed adjusting for payor, age, race, diagnosis, and support at listing for all outcomes except waitlist survival, for which Fine-Gray competing risk analysis was performed. RESULTS: Of 5,723 children listed, 109 were excluded due to missing ZIP codes. Race/ethnicity and payor were associated with COI (p < 0.001). Patients living in very low COI ZIP codes compared to all others had increased mortality from time of listing (HR 1.16, CI 1.03-1.32, p = 0.02) with 1-, 5-, and 9-year survival of 79.3% vs 82.2%, 66.5% vs 73.0%, and 53.6% vs 64.7% respectively, were more likely to be removed from the waitlist due to death or being too sick (subdistribution HR 1.26, 95% CI 1.10-1.42), and had increased mortality conditional on one-year post-transplant survival (HR 1.38, 1.09-1.74, p = 0.008) with 1-, 3-, and 5- year survival of 94.7% vs 97.3%, 87.0% vs 93.1%, and 78.6% vs 86.9%. CONCLUSIONS: Children living in lower opportunity ZIP codes had poorer survival from time of listing, poorer waitlist survival, and poorer conditional one-year post-transplant survival.

An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients.

PURPOSE: Obtaining direct and rapid proof of molecular activity in early clinical trials is critical for optimal clinical development of novel targeted therapies. SU11248 is an oral multitargeted kinase inhibitor with selectivity for fms-related tyrosine kinase 3/Flk2 (FLT3), platelet-derived growth factor receptor alpha/beta, vascular endothelial growth factor receptor 1/2, and KIT receptor tyrosine kinases. FLT3 is a promising candidate for targeted therapy in acute myeloid leukemia (AML), because activating mutations occur in up to 30% of patients. We conducted an innovative single-dose clinical study with a primary objective to demonstrate inhibition of FLT3 phosphorylation by SU11248 in AML. EXPERIMENTAL DESIGN: Twenty-nine AML patients each received a single dose of SU11248, escalated from 50 to 350 mg, in increments of 50 mg and cohorts of three to six patients. FLT3 phosphorylation and plasma pharmacokinetics were evaluated at seven time points over 48 h after SU11248 administration, and FLT3 genotype was determined. Study drug-related adverse events occurred in 31% of patients, mainly grade 1 or 2 diarrhea and nausea, at higher dose levels. RESULTS: Inhibition of FLT3 phosphorylation was apparent in 50% of FLT3-wild-type (WT) patients and in 100% of FLT3-mutant patients. FLT3 internal tandem duplication (ITD) mutants showed increased sensitivity relative to FLT3-WT, consistent with preclinical predictions. The primary end point, strong inhibition of FLT3 phosphorylation in >50% patients, was reached in 200 mg and higher dose cohorts. Downstream signaling pathways were also inhibited; signal transducer and activator of transcription 5 (STAT5) was reduced primarily in internal tandem duplication patients and at late time points in FLT3-WT patients, whereas extracellular signal-regulated kinase (ERK) activity was reduced in the majority of patients, independent of FLT3 inhibition. CONCLUSIONS: This novel translational study bridges preclinical models to the patient setting and provides the first evidence of anti-FLT3 activity in patients. Proof of target inhibition accomplishes a crucial milestone in the development of novel oncology therapeutics.