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Coronary artery vasculopathy (CAV) remains the leading cause of mortality after pediatric heart transplantation (HT).Coronary angiography is the gold standard for diagnosis, though it is an invasive test. We aimed to evaluate the utility of echocardiography in the detection of CAV by comparing functional echocardiographic parameters in transplanted patients with and without CAV. A retrospective review of pediatric patients who underwent HT between January 1999 and December 2022 at our institution was performed. We matched all patients with CAV to patients without CAV by age at transplant and gender. For patients with CAV, echocardiograms obtained on the day of or just prior to their CAV diagnoses were analyzed. Echocardiograms performed at matched time since transplant were chosen for the non-CAV group. Clinical data as well as echocardiogram parameters for left ventricular (LV) and right ventricular (RV) function and tissue Doppler imaging (TDI) were collected. The median age at CAV (n = 18) diagnosis was 12.04 years with a median time since transplant of 5.81 years. The median number of rejection episodes in the CAV group was 1.94, and the mean in the non-CAV group was 0.83 (p<0.041). Demographic and clinical data are described in Table 1A. The median LV ejection fraction by Simpson biplane method was significantly lower in patients with CAV compared to non-CAV patients (56.97% vs 62.57%, p = 0.002). There were no differences in assessments of RV function as shown in Table 1C. In those with CAV, septal mitral e' velocity was significantly lower when compared to the non-CAV group (0.09 m/s vs 0.11 m/s, p = 0.015). Reduced septal mitral e' velocity may be associated with the development of CAV in pediatric HT patients. Attention to subtle reduction of trends of TDI velocities and LV function may be helpful in determining when further coronary evaluation is necessary. [ABSTRACT FROM AUTHOR]

Background: With improved survival of adults with congenital heart disease (CHD) comes a need to understand the lifelong outcomes of this population. The aim of this paper is to describe the rationale and design of Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), a study to determine long-term medical, neurocognitive, and psychosocial outcomes among adults with a history of intervention for CHD and to identify factors associated with those outcomes., Methods: CHD PULSE is a cross-sectional survey conducted from September 2021 to April 2023 among adults aged 18 and older with a history of at least one intervention for CHD at one of 11 participating U.S. centers in the Pediatric Cardiac Care Consortium. Participants with CHD were asked to complete a 99-question survey on a variety of topics including: demographics, surgeries, health insurance, health care, heart doctors, general health, height and weight, education and work history, reproductive health (for women only), and COVID-19. To construct a control group for the study, siblings of survey respondents were invited to complete a similar survey. Descriptive statistics for demographics, disease severity, center, and method of survey completion were computed for participants and controls. Comparisons were made between participants and non-participants to assess for response bias and between CHD participants and sibling controls to assess for baseline differences., Results: Among the 14,322 eligible participants, there were 3133 respondents (21.9%) from 48 U.S. states with surveys returned for inclusion in the study. Sibling contact information was provided by 691 respondents, with surveys returned by 326 siblings (47.2%). The median age of participants was 32.8 years at time of survey completion, with an interquartile range of 27.2 years to 39.7 years and an overall range of 20.1 to 82.9 years. Participants were predominantly female (55.1%) and of non-Hispanic White race/ethnicity (87.1%). There were no differences between participants and non-participants regarding severity of CHD. Compared to non-participants, participants were more likely to be female, of older age, and be of non-Hispanic White race/ethnicity. Enrolled siblings were more likely to be female and slightly younger than participants., Conclusions: With surveys from 3133 participants from across the U.S., CHD PULSE is poised to provide keen insights into the lifelong journey of those living with CHD, extending beyond mere survival. These insights will offer opportunities for informing strategies to enhance and improve future outcomes for this population of patients., (Copyright © 2024. Published by Elsevier Inc.)

Background: Elevated left ventricular outflow tract (LVOT) gradients during exercise can occur in patients with hypertrophic cardiomyopathy (HCM) as well as in athletes and normal controls. The authors' staged exercise protocol calls for imaging at rest and during each stage of exercise to evaluate the mechanism of LVOT obstruction at each stage. They investigated whether this staged approach helps differentiate HCM from athletes and normal controls., Methods: They reviewed pediatric exercise stress echocardiograms completed between January 2009 and October 2017 at their center and identified those with gene-positive HCM, athlete's heart, and normal controls. Children with inducible obstruction (those with no LVOT gradient at rest who developed a LVOT peak gradient > 25 mm Hg during exercise) were included. LVOT peak gradient, velocity time integral, acceleration time, and deceleration time were measured at rest, submaximal stages, and peak exercise., Results: Compared with athletes, HCM patients had significantly higher LVOT peak gradients at rest (P = .019), stage 1 of exercise (P = .002), and peak exercise (P = .051), as well as a significantly higher change in LVOT peak gradient from rest to stage 1 (P = .016) and from rest to peak (P = .038). The acceleration time/deceleration time ratio of the LVOT Doppler was significantly lower in HCM patients compared with normal controls at peak exercise., Conclusions: The HCM patients who develop elevated LVOT gradients at peak exercise typically manifest early obstruction in the submaximal stages of exercise, which helps to differentiate them from athletes and normal controls.

Objective: To prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer., Methods: Overall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as>2 altered markers., Results: The median age of the patients was 68 years (range: 53-82y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T≤2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%). An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation., Conclusions: Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma., Materials and Methods: Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes., Results: Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038)., Conclusions: Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To report one of the largest series of clinical and renal function outcomes of treated iatrogenic vascular lesions (IVL) after partial nephrectomy (PN). Angioembolization (AE) is the treatment of choice for patients with these lesions, but the additional renal injury conferred by this treatment has not been well described., Patients and Methods: Patients who underwent open, laparoscopic, or robot-assisted PN from 2002 to 2012 were identified and those with AE were selected. Patients' charts were reviewed, and renal function was analyzed using estimated glomerular filtration rate (eGFR) and progression of chronic kidney disease (CKD) classification before and after PN and AE., Results: There were 849 patients who underwent PN and an IVL developed in 28 (3.3%). Twenty (71%) presented with gross hematuria at a mean of 10.2 ± 7.7 days after PN and 8 (28%) needed transfusion. All patients had identifiable IVL at the time of selective AE, and technical success was achieved in 24/28 (86%), although 4 needed subsequent additional AE. The paired decrease in eGFR after PN was significant (P<0.01), while the paired change in eGFR after AE was not with either short-term (2.8 days) or intermediate-term (362 days) follow-up (P=0.50). Four patients experienced transient worsening in CKD classification after AE, although three experienced CKD stage improvement., Conclusion: Selective AE for IVL after PN is safe, efficacious, and does not lead to a significant impairment of renal function. It remains the preferred approach for the evaluation and management of post-PN hemorrhage.

Background: Bosentan, a dual endothelin-receptor antagonist, is registered for the treatment of pulmonary arterial hypertension. Little is known about the effects of bosentan in children. This study was conducted to investigate the pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension., Methods: In this 2-center, open-label study, 19 pediatric patients with pulmonary arterial hypertension were enrolled and stratified for body weight and epoprostenol use. Patients weighing between 10 and 20 kg, between 20 and 40 kg, or greater than 40 kg received a single dose of 31.25, 62.5, or 125 mg, respectively, on day 1, followed by 4 weeks of treatment with the initial dose. The dose was then up-titrated to the target dose (31.25, 62.5, or 125 mg twice daily). Pharmacokinetic and hemodynamic parameters were obtained at baseline and after 12 weeks of treatment. Six-minute walk distance and cardiopulmonary exercise testing results were measured at baseline and at week 12 in children aged 8 years or older., Results: The variability in exposure among the 3 groups was less than 2-fold after single- and multiple-dose administration. The exposure to bosentan decreased over time in all groups. The covariates body weight, gender, age, and the use of epoprostenol had no significant effect on the pharmacokinetics of bosentan. Bosentan produced hemodynamic improvement and was well tolerated. The mean change from baseline in mean pulmonary artery pressure was -8.0 mm Hg (95% confidence interval, -12.2 to -3.7 mm Hg), and that in pulmonary vascular resistance index was -300 dyne x s x m(2)/cm(5) (95% confidence interval, -576 to -24 dyne x s x m(2)/cm(5))., Conclusions: The pharmacokinetics of bosentan in pediatric patients with pulmonary arterial hypertension and healthy adults are similar, and treatment with bosentan resulted in hemodynamic improvement. These results suggest that the applied dosing regimens may be appropriate to treat pediatric patients.

The effect on plasma amino acid levels and sleep parameters of three experimental diet conditions was investigated in 12 healthy young men. A total of 71 sleep records and 715 plasma samples were analysed for %REM (TDT) and total plasma tryptophan and tyrosine respectively. The ratio of tryptophan to tyrosine was virtually the same under the fat supplement as under the nosupplement conditions. The ratio associated with the CHO load was found to be 14 per cent higher, however. A 29 per cent higher value found with the Protein load may be misleading due to the nature of the supplement used. %REM (TDT) was not found to be significantly related to any of the above conditions.

The activity of pyruvate dehydrogenase was higher in brain homogenates prepared by using a Potter-Elvehjem type homogenizer (79.0 +/- 2.38 nmol/min/mg of protein) than by using an Ultra-Turrax homogenizer (from 62.39 +/- 1.35 to 74.60 +/- 1.21 nmol/min/mg of protein). Different conditions of homogenization with the Ultra-Turrax had no significant effect on the activity of pyruvate dehydrogenase. Pyruvate dehydrogenase activity decreased significantly in brain homogenates maintained at 0 degrees C for short periods or stored at ?20 degrees C for several days. Marked differences in pyruvate dehydrogenase activities reported in earlier work have been attributed to its instability in brain homogenates. The results showed that pyruvate dehydrogenase is not a rate limiting enzyme in the metabolism of glucose in brain in vivo.

M mode echo recordings of the left ventricle (LV) were performed in 33 patients with alcoholic liver disease, 26 patients with various non-alcoholic liver diseases, and in 18 non-alcoholic controls. Groups were well matched for age and overall nutritional status (as assessed by anthropometry) and none of the subjects studied had cardiorespiratory symptoms. Alcoholics had significantly increased LV free wall thickness and LV cavity dimension at end diastole (EDD). Multiple regression analysis of the data identified alcohol abuse as the most important variable affecting EDD, and this relation could not be explained by differences in age, sex, overall nutrition, cigarette smoking, thiamine status (total blood thiamine and thiamine pyrophosphate concentration), presence of liver disease, or severity of liver disease (cirrhotic vs non-cirrhotic). The increase in LV free wall thickness was not significantly related to alcohol abuse. These results suggest that chronic alcohol abuse is an important independent risk factor for cardiac dilatation, and that increase in EDD may be an early marker of alcoholic cardiomyopathy.

1. In a study of the metabolism of l-[(35)S]methionine in vivo, the labelled sulphur compounds of rat liver and brain were separated first by ion-exchange chromatography into two fractions containing (i) free sulphur amino acids such as methionine, cystathionine, cyst(e)ine and homocyst(e)ine and (ii) glutathione. 2. Two-dimensional paper chromatography with butan-1-ol-acetic acid or propionic acid-water in the first direction and 80% acetone or acetone-ethyl methyl ketone-water in the second direction was found superior to other solvent systems for separating the sulphur amino acids. 3. At 10min. after injection of [(35)S]methionine only a small part of the (35)S was found combined in free methionine or other free sulphur amino acids. 4. Evidence was obtained of the presence of adenosyl[(35)S]methionine and adenosyl[(35)S]homocysteine in perchloric acid extracts of rat liver and brain. 5. The trans-sulphuration pathway was active in brain as well as in liver.