Presurgical pulmonary function tests in the first few days of life in neonates with congenital heart disease, a pilot study.

OBJECTIVE: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. DESIGN: Infants ≥ 37 weeks gestation with critical CHD were studied within the first few days of life, prior to cardiac surgery, and compared to data from a published reference group of healthy term neonates without CHD, studied at the same institution. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. RESULTS: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). CONCLUSIONS: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Presurgical Pulmonary Function Tests in the First Few Days of Life in Neonates with Congenital Heart Disease, A Pilot Study.

Objective: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. Design: Infants > 37 weeks gestation with critical CHD were studied within the first few days of life and prior to cardiac surgery and compared to data from a published reference group. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. Results: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). Conclusions: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Short- and Mid-Term Autograft Outcomes Following the Reinforced Ross Operation.

BACKGROUND: The Ross operation for aortic valve replacement continues to be a controversial option because of concerns related to late autograft dilation and progressive neo-aortic insufficiency. In 2005, the reinforced Ross procedure was described at our institution to address this problem. We aim to analyze the short and mid-term outcomes following this procedure. METHODS: This is a retrospective study of patients who underwent the reinforced Ross operation between 2004 and 2019. A comprehensive chart review was performed. Echocardiograms were independently reviewed by an adult congenital cardiologist. The time to reintervention was evaluated with a Kaplan-Meier curve. Analysis was conducted in JMP 15.1 (SAS Inc., Cary, NC). RESULTS: Twenty-five patients underwent the reinforced Ross operation. Twenty-three patients (92%) had bicuspid aortic valve and the most common indication for surgery was a combination of aortic insufficiency and stenosis (n = 18, 72%). The mean follow-up was 6.1 ± 5.0 years. All patients were alive at the time of follow-up. Six patients (24%), from early in our experience, required subsequent aortic reintervention. Median time to reintervention was 41.8 months (0-81.5 months). Sixteen (64%) patients had less than moderate aortic insufficiency at last follow-up. Additionally, average aortic root measurements remained unchanged. CONCLUSIONS: The reinforced Ross technique was initially proposed as a way to mitigate aortic root dilation seen in the traditional Ross procedure. Our experience suggests an associated learning curve with the majority of aortic reinterventions occurring within the first few years following surgery. Continued follow-up is warranted to assess its long-term durability and functionality.

Palliative Care Involvement in Patients with Operative Mortality After Cardiac Surgery.

BACKGROUND: The aim of this study was to examine palliative care involvement in patients with operative mortality after cardiac surgery, to gain a better understanding of this high-risk population and factors influencing referral. METHODS: This is a retrospective review using data submitted to the Society of Thoracic Surgeons National Database. RESULTS: The total study population included 93 patients with operative mortality, only 30% of whom had palliative care involvement. The median time from first palliative care involvement to death was 6 days. Nearly 40% of patients had a status labeled as elective at the time of surgery. CONCLUSION: Our findings suggest that patient mortality risk for elective surgery is being underestimated, or the indications for palliative care consultation in high-risk patients is going unrecognized. Such knowledge may facilitate earlier palliative care involvement, with the goal of improved quality of life for cardiac patients.

Reinforced Ross operation and intermediate to long term follow up.

The Ross operation for aortic valve replacement continues to be a controversial option because of concerns related to late autograft dilation and progressive neo-aortic regurgitation. We described a technique in 2005 to address this problem, in which we place the entire autograft in a Dacron tube which makes it theoretically unlikely, if not impossible, for it to dilate-the reinforced Ross procedure. Since 2004, we have operated on 25 patients using this technique. Median length of follow-up in our cohort was 6 years, with 14 patients having 5 years or more of follow-up. Our data demonstrate the externally supported, or reinforced Ross technique using a straight graft is a safe and effective technique in older children, adolescents, and young adult patients. At intermediate follow-up, patients who underwent a reinforced Ross technique were less likely to have neoaortic root dilatation.

Factors Influencing Family Burden in Pediatric Hematology/Oncology Encounters.

PURPOSE: Caring for a child with cancer or hematologic disease places unique stress on a family unit. Families' subjective experience of this care-related burden mediates the relationship between cost and health-related outcomes. While financial costs are well described for families of pediatric hematology/oncology patients, it is unclear how cost and other factors each contribute to families' overall experience of care-related burden. This study identifies and groups the challenges that families report and describes their association with overall reported burden. METHODS: This mixed-methods analysis of a cross-sectional single-center study was conducted via structured, self-administered questionnaire provided to inpatient and outpatient caregivers of pediatric hematology/oncology patients. Respondents rated their perception of burden associated with that day's medical encounter on a 5-point Likert scale. The questionnaire included an open-ended prompt for caregivers about areas they deemed most burdensome. Primary themes were extracted and categorized. RESULTS: A total of 278 outpatient and 42 inpatient caregivers participated. Six thematic categories emerged: logistics, life disruption, care delivery system, parking, financial burden, and emotional burden. Outpatient caregivers reported more burden than inpatient caregivers for the first three categories, while inpatient caregivers reported more burden for the last three. Salient subthemes associated with higher and lower overall burden were identified in each theme category. CONCLUSIONS: These data establish theme categories for future study of caregiver-perceived burden in pediatric hematologic/oncologic encounters, demonstrate that certain components of cost contribute disproportionately to caregivers' overall sense of care-related burden, and identify areas within each of the 6 burden categories that can be best targeted to alleviate caregiver burden.

Amino Acid Uptake Measured by [18F]AFETP Increases in Response to Arginine Starvation in ASS1-Deficient Sarcomas.

Rational: In a subset of cancers, arginine auxotrophy occurs due to the loss of expression of argininosuccinate synthetase 1 (ASS1). This loss of ASS1 expression makes cancers sensitive to arginine starvation that is induced by PEGylated arginine deiminase (ADI-PEG20). Although ADI-PEG20 treatment is effective, it does have important limitations. Arginine starvation is only beneficial in patients with cancers that are ASS1-deficient. Also, these tumors may metabolically reprogram to express ASS1, transforming them from an auxotrophic phenotype to a prototrophic phenotype and thus rendering ADI-PEG20 ineffective. Due to these limitations of ADI-PEG20 treatment and the potential for developing resistance, non-invasive tools to monitor sensitivity to arginine starvation are needed. Methods: Within this study, we assess the utility of a novel positron emission tomography (PET) tracer to determine sarcomas reliant on extracellular arginine for survival by measuring changes in amino acid transport in arginine auxotrophic sarcoma cells treated with ADI-PEG20. The uptake of the 18F-labeled histidine analogue, (S)-2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (AFETP), was assessed in vitro and in vivo using human-derived sarcoma cell lines. In addition, we examined the expression and localization of cationic amino acid transporters in response to arginine starvation with ADI-PEG20. Results: In vitro studies revealed that in response to ADI-PEG20 treatment, arginine auxotrophs increase the uptake of L-[3H]arginine and [18F]AFETP due to an increase in the expression and localization to the plasma membrane of the cationic amino acid transporter CAT-1. Furthermore, in vivo PET imaging studies in mice with arginine-dependent osteosarcoma xenografts showed increased [18F]AFETP uptake in tumors 4 days after ADI-PEG20 treatment compared to baseline. Conclusion: CAT-1 transporters localizes to the plasma membrane as a result of arginine starvation with ADI-PEG20 in ASS1-deficient tumor cells and provides a mechanism for using cationic amino acid transport substrates such as [18F]AFETP for identifying tumors susceptible to ADI-PEG20 treatment though non-invasive PET imaging techniques. These findings indicate that [18F]AFETP-PET may be suitable for the early detection of tumor response to arginine depletion due to ADI-PEG20 treatment.

18F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors.

BACKGROUND: Noninvasively predicting early response to therapy in recurrent pediatric brain tumors provides a challenge. 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) PET/MRI has not been previously studied as a tool to evaluate early response to antiangiogenic therapy in children. The purpose of this study was to evaluate the safety and feasibility of using 18F-FDOPA PET/MRI to assess response to bevacizumab in children with relapsed brain tumors. MATERIALS AND METHODS: Six patients with recurrent gliomas (5 low-grade, 1 high-grade) planned to undergo treatment with bevacizumab were enrolled. 18F-FDOPA PET/MRI scans were obtained prior to and 4 weeks following the start of treatment, and these were compared with the clinical response determined at the 3-month MRI. The primary PET measure was metabolic tumor volume (MTV) at 10 to 15 min after 18F-FDOPA injection. For each tumor, the MTV was determined by manually defining initial tumor volumes of interest (VOI) and then applying a 1.5-fold threshold relative to the mean standardized uptake value (SUV) of a VOI in the frontal lobe contralateral to the tumor. RESULTS: 18F-FDOPA PET/MRI was well tolerated by all patients. All tumors were well visualized with 18F-FDOPA on the initial study, with peak tumor uptake occurring approximately 10 min after injection. Maximum and mean SUVs as well as tumor-to-brain ratios were not predictors of response at 3 months. Changes in MTVs after therapy ranged from 23% to 98% (n = 5). There is a trend towards the percent MTV change seen on the 4-week scan correlating with progression-free survival. CONCLUSION: 18F-FDOPA PET/MRI was well tolerated in pediatric patients and merits further investigation as an early predictor of response to therapy.

Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors.

OBJECTIVES: Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG), is a hallmark of active cancer cells that is not directly measured with standard (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. METHODS: Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF), oxygen (CMRO2) and glucose (CMRGlu) metabolism, and AG, using (15)O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. RESULTS: Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. CONCLUSIONS: Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.