Citations

Background: The first pediatric appropriate use criteria (PAUC) were recently published for initial outpatient transthoracic echocardiography (TTE). We sought to determine the effect of release of the PAUC on the appropriateness of TTE ordering patterns of pediatric cardiologists. Methods: Data were prospectively collected from patients having initial outpatient TTE ordered prior to (Phase I, 6 mo) and 3 months after release (Phase II, 4 mo) of PAUC. Site-investigators determined the indication of the study and assigned appropriateness rating based on the PAUC document [Appropriate (A), May Be Appropriate (M), or Rarely Appropriate (R)] or "Unclassifiable" (U). Results: A total of 4562 TTEs (2655 Phase I, 1907 Phase II) were ordered by 103 physicians at 6 sites. Overall comparison of appropriateness rating for Phase I and II showed no change in the rate for A or M, but a decline in the rate of R and increase in U. Similar results were noted when comparisons were made for physicians that ordered at least 20 TTEs during each phase (N = 30/103, 29%), Table 1. There was no change in any appropriateness rating at 3 sites, a decline in R at 2, an increase in A at 1, and an increase in U at 2 sites. Overall and site-specific comparisons of rate of R TTEs are shown in Fig 1. Conclusions: The release of PAUC document had only a small impact on physician ordering behavior for initial TTEs, including a small decrease in R. Overall, these data suggest that more focused interventions are required to fully implement guideline recommendations and improve the appropriate use of pediatric TTE. This information should be helpful in designing educational interventions to reduce the rate of TTEs ordered for R indications.

BACKGROUND: For sudden collapse from out-of-hospital cardiac arrest (OHCA) in adults, bystander chest compression-only CPR (COCPR) results in equivalent or better survival compared with conventional CPR with rescue breathing. However, patients who arrest from a non-cardiac cause may also receive COCPR even though rescue breathing might benefit them. We sought to determine whether lay rescuers appropriately provided COCPR or conventional CPR depending on the suspected etiology of OHCA. METHODS: Analysis of a statewide, Utstein-style registry of adult OHCA during a large-scale campaign endorsing COCPR for adults who suddenly collapse. The relationship between bystander CPR (both COCPR and conventional CPR), presumed arrest etiology, and survival to hospital discharge were evaluated. Means and 95% confidence intervals (CI) were calculated. FINDINGS: A total of 7,652 adult OHCAs not witnessed by EMS were analyzed from 10/04 to 09/10. After exclusion of non-lay bystanders and arrests in medical facilities, presumed cardiac etiology and non-cardiac etiology OHCA totaled 4,913 and 1,202, respectively. The presumed specific non-cardiac etiologies were non-cardiopulmonary (e.g. overdose, suicide, subarachnoid hemorrhage) (57%), trauma (27%), and respiratory (16%). All-rhythm survival was 7.0% (CI: 6.3 - 7.8) for cardiac etiologies and 3.3% (CI: 2.3 - 4.3) for non-cardiac (p<0.001). Bystander CPR was provided for 33% (CI: 31.4 - 34.1) of victims with presumed cardiac causes versus 28% (CI: 25.6 - 30.7) for non-cardiac causes (p=0.002). Presumed respiratory causes of OHCA had a much lower proportion of COCPR (8.3%, CI: 4.4 - 12.2) than cardiac causes (18.0%, CI: 16.9 - 19.1, p<0.001). Survival for non-cardiac cases was: 4.4% (CI 0.9 - 7.8) for conventional CPR, 3.5% (CI: 0.9 - 6.0) for COCPR, and 3.1% (CI: 2.0 - 4.3) for no CPR (p = 0.66). CONCLUSIONS: In the setting of a large-scale, statewide public health campaign endorsing lay rescuer COCPR for adults who suddenly collapse and are not breathing normally, bystanders were much less likely to perform COCPR on OHCA victims who might benefit from rescue breathing. Furthermore, when COCPR was performed on presumed non-cardiac cause arrest victims, there was no demonstrable negative impact on survival.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

ImportanceClonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling.ObjectiveTo determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes.Design, Setting, and ParticipantsThis was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023.ExposuresCHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro–B-type natriuretic peptide), and echocardiographic indices.Main Outcome MeasureIncident AF.ResultsA total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index.Conclusions and RelevanceLarge TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

AbstractBackgroundComputed tomography (CT) is routinely used to guide cryoablation procedures. Notably, CT‐guidance provides 3D localization of cryoprobes and can be used to delineate frozen tissue during ablation. However, metal‐induced artifacts from ablation probes can make accurate probe placement challenging and degrade the ice ball conspicuity, which in combination could lead to undertreatment of potentially curable lesions.PurposeIn this work, we propose an image‐based neural network (CNN) model for metal artifact reduction for CT‐guided interventional procedures.MethodsAn image domain metal artifact simulation framework was developed and validated for deep‐learning‐based metal artifact reduction for interventional oncology (MARIO). CT scans were acquired for 19 different cryoablation probe configurations. The probe configurations varied in the number of probes and the relative orientations. A combination of intensity thresholding and masking based on maximum intensity projections (MIPs) was used to segment both the probes only and probes + artifact in each phantom image. Each of the probe and probe + artifact images were then inserted into 19 unique patient exams, in the image domain, to simulate metal artifact appearance for CT‐guided interventional oncology procedures. The resulting 361 pairs of simulated image volumes were partitioned into disjoint training and test datasets of 304 and 57 volumes, respectively. From the training partition, 116 600 image patches with a shape of 128 × 128 × 5 pixels were randomly extracted to be used for training data. The input images consisted of a superposition of the patient and probe + artifact images. The target images consisted of a superposition of the patient and probe only images. This dataset was used to optimize a U‐Net type model. The trained model was then applied to 50 independent, previously unseen CT images obtained during renal cryoablations. Three board‐certified radiologists with experience in CT‐guided ablations performed a blinded review of the MARIO images. A total of 100 images (50 original, 50 MARIO processed) were assessed across different aspects of image quality on a 4‐point likert‐type item. Statistical analyses were performed using Wilcoxon signed‐rank test for paired samples.ResultsReader scores were significantly higher for MARIO processed images compared to the original images across all metrics (all p < 0.001). The average scores of the overall image quality, iceball conspicuity, overall metal artifact, needle tip visualization, target region confidence, and worst metal artifact, needle tip visualization, iceball conspicuity, and target region confidence improved by 34.91%, 36.29%, 39.94%, 34.17%, 35.13%, and 45.70%, respectively.ConclusionsThe proposed method of image‐based metal artifact simulation can be used to train a MARIO algorithm to effectively reduce probe‐related metal artifacts in CT‐guided cryoablation procedures.

Post‐mortem analyses have identified carotid body hypertrophy in conditions of chronic hypoxemia, including sleep apnea; however, post‐mortem assessment limits the clinical relevance of such findings. We tested the hypotheses that: 1) carotid body size can be detected in living individuals by computed tomographic angiography (CTA), and 2) patients with sleep disordered breathing [Apnea Hypopnea Index (AHI) ≥ 30 events/hour] exhibit larger carotid bodies than those without sleep disordered breathing (AHI < 5 events/hour). A chart review was conducted from patients seen at the Mayo Clinic between January 2000 and February 2015 who had undergone neck CTA and polysomnography. From an initial pool of 583, 109 patients met our strict inclusion criteria. Widest axial measurements of the right and left carotid bodies were performed independently by two radiologists blinded to condition and average carotid body size was calculated for each patient of interest. Carotid body identification was possible in 81% of patients. Intra‐class correlation coefficients ranged from 0.93 to 0.95 (right carotid body: 0.93; left: 0.94; average: 0.95). From subjects with identifiable carotid bodies, widest axial measurements were greater in patients with high AHI (n=32; right: 2.9±0.2mm, left: 3.1±0.2mm, average: 3.0±0.1mm) compared to patients with low AHI (n=46; right: 2.5±0.1mm, left: 2.7±0.1mm, average: 2.6±0.1mm; p=0.04, p=0.04, p=0.02, respectively). Because participants in the high AHI group were significantly older than those in the low AHI group (65±2 years vs. 50±2 years; p<0.01), an analysis of covariance was performed to control for the influence of age on carotid body size. After adjusting for age, no differences in carotid body size were observed between the patient groups (p=0.45, p=0.59, p=0.54 for right, left, and average carotid body, respectively). Main findings are two‐fold: 1) carotid body size can be identified by CTA in approximately 80% of patients with good inter‐observer agreement, and 2) adults that exhibit sleep disordered breathing do not have larger carotid bodies when compared to controls, after adjusting for age. Support or Funding Information This work was supported by the National Institutes of Health [grant numbers T32 GM008685 (ARE), R01 DK090541 (MJJ)].

Abstract BACKGROUND Leveraging external data has the potential to increase efficiency and precision of drug development in glioblastoma by complementing or replacing data from in-trial controls. We used an external control arm (ECA) to re-analyze data of the abemaciclib, neratinib and CC-115 arms of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. METHODS INSIGhT (NCT02977780) is an ongoing phase 2 adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma with a shared control arm of patients receiving radiation therapy with concurrent and maintenance temozolomide. The initial experimental arms (abemaciclib, neratinib, CC-115) have not shown a survival benefit relative to the shared control arm. We re-analyzed the experimental arm data and replaced the shared control arm with an ECA. The ECA was developed from a collection of trial datasets and real-world data available through the Glioblastoma External (GBM-X) Data Platform (). Propensity score matching was used to adjust for possible differences between pretreatment covariates (age, sex, resection, KPS) in the ECA and shared control arm. Cox proportional hazards models were used to estimate treatment effects. RESULTS On INSIGhT, patients were randomized to abemaciclib (n = 74), neratinib (n = 80), and CC-115 (n = 12). There were 687 unmethylated MGMT patients in the GBM-X ECA. After propensity score matching, there was no significant treatment effect associated with abemaciclib (HR 1.091, 95%CI:0.834-1.433, p = 0.536), neratinib (HR = 1.043, 95%CI:0.787-1.383, p = 0.770), or CC-115 (HR 1.088, 95%CI:0.834-1.433, p = 0.794) compared to the ECA. CONCLUSION In comparison to an ECA, there was no significant survival benefit with abemaciclib, neratinib and CC-115. Treatment effects estimates were similar to the primary analyses based on the original shared control arm of INSIGhT. The use of external control arms in early phase testing of new therapies is supported by our findings and could significantly reduce costs and time to conduct trials in newly diagnosed glioblastoma.