Hepatic and Renal Consequences of Single-Ventricle Physiology Palliated With the Fontan Operation.

Over time, long-term survival has dramatically increased for patients with complex congenital heart disease who undergo the Fontan operation. With this increased survival, it has become apparent that such a circulation has important consequences for other organ systems, particularly the liver and kidney. The adverse milieu created by chronic venous hypertension, low cardiac output, and an inflammatory state contribute to the pathologic changes observed in the liver and kidneys over the long term in Fontan patients. The clinical importance of these hepatic and renal comorbidities have only recently begun to be recognized in the context of increasing life expectancy in this population. The objectives of this review are to provide an overview of the pathophysiology of the Fontan circulation and how liver and kidney disease evolve in this setting; to summarize the current evidence base as it relates to the diagnostic approach to liver and kidney disease in Fontan patients; and to discuss the therapeutic approaches to Fontan- associated liver and kidney disease. Given that this is a very active area of research in congenital heart disease, we have identified knowledge gaps and priority research areas to improve the care of Fontan patients. These include establishing the optimal diagnostic tests to detect and track liver and kidney disease change over time, determining which treatable risk factors contribute to the development of liver and kidney disease, and evaluating therapies to prevent or slow progression of liver and kidney disease.

A text messaging intervention and quality of life in adolescents with solid organ transplants.

BACKGROUND: Facilitating communication between adolescents and HCP outside of appointments may enhance patient experience and outcomes. The purpose of this study was to determine whether SMS enhances the healthcare experience, QoL, and medication adherence in adolescent SOT patients. METHODS: This was a prospective observational study of an SMS platform (WelTel Inc) for SOT patients aged 12-19 years. QoL was assessed before and after using the PedsQL™ Transplant Module. Medication adherence was assessed with the frequency of therapeutic tacrolimus levels and variation based on control chart analysis. Patient experience and engagement was evaluated with surveys, response rate to messages, and number of clinical conversations (>2 messages). RESULTS: Twenty-three patients were included (median age 15.7 years (IQR 13.6-17.1)). Median intervention duration was 13.5 months (range 4.0-16.7 months). There was a 68% response rate (742/1095) with 375 clinical conversations. The majority of patients reported the intervention provided a positive outlook on their health (17/23), was useful (18/23), and improved their connection to HCPs (17/23). Following the intervention, there was no significant difference in the median scaled QoL scores (pre-intervention: 81 (IQR 76.5-93.3), post-intervention: 78 (IQR 76-93); p = .37), mean percentage of therapeutic tacrolimus levels (pre-intervention: 52 ± 25%, post-intervention: 65 ± 17%; p = .07), or variation on control chart analysis of tacrolimus levels. CONCLUSIONS: The WelTel messaging platform provided supplemental clinical care for a group of adolescent SOT patients that enhanced their healthcare experience. Patient QoL and adherence were unchanged following the intervention and remained at a high level.

Adolescents with solid organ transplant: Using the BRIEF2 parent-report and self-report to measure parent-child agreement and everyday executive function.

Agreement between parent and adolescent ratings of executive function (EF) is not known in adolescents with solid organ transplant (SOT), even though pressing concerns about EF deficits are being raised in this population. The current study investigated EF in adolescents with SOT using parent and self report. Twenty-five adolescents (M = 15.51 years) with SOT and their parent completed a behavior rating scale assessing EF within everyday context using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parents and their adolescents demonstrated moderate to excellent agreement across the BRIEF2 clinical and index scores, higher than previous research with a typical sample. Adolescent males had higher agreement with their parents than female adolescents. Both parents and adolescents reported significantly higher mean T scores on various BRIEF2 indices and domains, in addition to higher rates of clinically elevated executive dysfunction than their peers. Assessment of EF and targeting specific EF domains for intervention may be useful in this population.

Association of Preoperative Diuretic Use With Early Acute Kidney Injury in Infants With Biventricular Hearts Following Cardiac Surgery.

Background Diuretics are used to manage congestive heart failure in infants with congenital heart disease. Adult data indicate that preoperative diuretic use increases the risk of cardiac surgery associated acute kidney injury (CS-AKI). We have sought to understand if preoperative diuretics in infants increases the risk of CS-AKI. Methods and Results This is a single-center retrospective study of infants (1-12 months) who had CS requiring cardiopulmonary bypass between 2013 and 2018. The diagnosis and severity of CS-AKI was defined according to the Kidney Disease Improving Global Outcomes guidelines. Three hundred patients were included (mean 6 months, SD 2.4, range 1.2-12.9 months). A total of 149 (49.7%) patients were diagnosed with CS-AKI (stage 1: 80 [54%], stage 2: 57 [38%], stage 3: 12 [8%]). Logistic regression analysis showed preoperative diuretics were not associated with CS-AKI (odds ratio [OR], 0.79; 95% CI, 0.43-1.44; P=0.45). A diagnosis of tetralogy of Fallot was an independent risk factor for CS-AKI (OR, 3.49; 95% CI, 1.33-9.1, P=0.01). A diagnosis of tetralogy of Fallot (OR, 3.6; 95% CI, 1.28-10.22; P=0.02) and longer cardiopulmonary bypass (OR, 1.01; 95% CI, 1.0-1.02; P=0.04) time are risk factors for moderate to severe CS-AKI. Conclusions Preoperative diuretic use does not contribute to the risk of CS-AKI in infants early after surgery. A diagnosis of tetralogy of Fallot was the only risk factor for CS-AKI identified using multivariate analysis in our cohort. Furthermore, a diagnosis of tetralogy of Fallot and longer cardiopulmonary bypass time are risk factors for moderate to severe CS-AKI.

Fontan-Associated Liver Disease: Spectrum of Disease in Children and Adolescents.

Background Information is evolving on liver disease in pediatric patients with Fontan physiology. The purpose of this investigation is to evaluate the spectrum of liver disease in a pediatric population of patients with Fontan physiology and evaluate transient elastography (TE) as a noninvasive marker of liver disease. Methods and Results We prospectively enrolled all children with Fontan physiology. All patients underwent comprehensive liver evaluation including liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), aspartate transaminase to platelet ratio index, albumin, bilirubin, international normalized ratio, complete blood cell count, abdominal ultrasound, and TE. Transjugular liver biopsies and hemodynamic measurements were performed in a subset of patients. A total of 76 children (median, 11.7; interquartile range, 8.4-14.8 [56% male]) were evaluated, with 17 having a transjugular liver biopsy (median 14.8 years; interquartile range, 14.3-17.4). All biopsies showed pathological changes. The severity of liver pathology did not correlate with TE. There was a positive correlation between TE and time since Fontan (R=0.42, P<0.01), aspartate transaminase to platelet ratio index (R=0.29, P=0.02), aspartate transaminase (R=-0.42, P<0.01), and platelets (R=-0.42, P<0.01). Splenomegaly on abdominal ultrasound was correlated with TE (z=-2.2, P=0.03), low platelet count (z=1.9, P=0.05), low aspartate transaminase (z=1.9, P=0.02), and low alkaline phosphatase (z=2.4, P=0.02). Conclusions Liver disease was ubiquitous in our cohort of pediatric patients with Fontan Physiology. Given the correlation between TE and time from Fontan, TE shows potential as a prospective marker of liver pathology. However, individual measurements with TE do not correlate with the severity of pathology. Given the prevalence of liver disease in this population, protective measures of liver health as well as routine liver health surveillance should be implemented with consideration for hepatology consultation and biopsy in the event of abnormal liver biochemical markers or imaging.

Fontan-Associated Liver Disease: Evidence for Early Surveillance of Liver Health in Pediatric Fontan Patients.

The growing awareness of Fontan-associated liver disease (FALD) in adults with Fontan physiology has provided the impetus to better understand the natural history of FALD and develop a reliable noninvasive method to diagnose and monitor liver health in this population. Biochemical and imaging tests have been investigated to determine their association with liver pathology. The congestive hepatopathy that develops after the Fontan procedure has made interpreting these tests challenging. We have reviewed and summarized the current understanding and ongoing challenges with respect noninvasive measures of liver health in Fontan patients including biochemical tests, elastography, hepatic ultrasound, cross-sectional imaging, and hemodynamics and how they relate to liver pathology. It has been demonstrated from biopsy data that liver disease is universal and progressive in Fontan patients. Traditional biochemical tests, elastography, and imaging methods are often abnormal in Fontan patients but do not reliably indicate significant liver pathology. Although a reliable means for surveillance of FALD remains elusive, this continues to be an active area of investigation, with promising recent developments. Therapeutic options for FALD are limited, with cardiac transplant as the only option that can stabilize FALD pathology and improve symptomatology. Given the limited therapeutic options and the prevalence of liver disease in Fontan patients, there is a compelling case for early routine surveillance of liver health and promotion of global liver health.

Outcomes of Radiofrequency Perforation for Pulmonary Atresia and Intact Ventricular Septum: A Single-Centre Experience.

Percutaneous radiofrequency perforation (RFP) of the pulmonary valve is used as a primary therapy in neonates with pulmonary atresia and intact ventricular septum (PAIVS). We sought to determine the safety and efficacy of RFP for PAIVS in a single center and assess the pre-intervention anatomical parameters associated with a biventricular outcome. We retrospectively reviewed all cases of PAIVS treated with RFP at a single center from 1999 through 2012. We collected baseline imaging data, technical aspects of the procedure, adverse events and outcomes. RFP was attempted in 18 patients with 17 successful procedures. There was no mortality; one patient had an acute complication requiring surgical intervention. All were alive at the most recent follow-up (median 4.9 years; IQR = 2.0-6.8 years), 12/17 (71%) had a biventricular circulation, 2/17 (12%) had a 1½ ventricle repair, 2/17 (12%) had a univentricular repair and 1/17 was lost to follow-up. A biventricular outcome in patients with PAIVS was associated with the pre-intervention tricuspid valve/mitral valve (TV/MV) ratio and tricuspid valve (TV) z-score. The median TV/MV ratio for patients who underwent a biventricular repair and a non-biventricular repair was 0.82 (IQR = 0.71-0.90) and 0.59 (IQR = 0.39-0.76), P = 0.036, respectively. The median TV z-scores were -3.2 [(-4.9 to -2.6), and -6.8 (-9.7 to -4.8] P = 0.036 for the biventricular and non-biventricular groups, respectively. RFP is a safe primary therapy for PAIVS. With appropriate patient selection, RFP will often result in a biventricular circulation. Both the TV/MV and TV z-score were found to be a predictor of a biventricular outcome in our cohort.

Hybrid stenting for left ventricular outflow tract obstruction in congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries is commonly associated with left ventricular outflow tract obstruction. We describe a case of congenitally corrected transposition of the great arteries and previous surgical ventricular septal defect repair with recurrent left ventricular outflow tract obstruction. The patient underwent a hybrid procedure to stent the left ventricular outflow tract, which was successful with no re-intervention through 3 years of follow-up.

Effect of different single-session educational modalities on improving medical students' ability to demonstrate proper pressurized metered dose inhaler technique.

OBJECTIVE: Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students' skills over the long term. METHODS: The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. RESULTS: Video, one-on-one and the placebo groups modalities statistically improved the average medical student's score in the immediate retesting (7.5 and 7.4 vs. 4.7, p < .01, respectively). Moreover, the proportion of passing grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p < .05). CONCLUSIONS: One-on-one teaching and video education were able to improve medical students' ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

Internal return of carbon dioxide in decarboxylation: catalysis of separation and 12C/13C kinetic isotope effects.

It has been proposed that the decarboxylation of mandelylthiamin, the adduct of benzoylformate and thiamin, is uniquely catalyzed by protonated pyridines through a preassociation mechanism in which proton transfer competes with the internal return of carbon dioxide. Application of this mechanism suggests that the observed primary (12)C/(13)C kinetic isotope effect in the absence of catalyst is reduced in magnitude because diffusion of carbon dioxide is partially rate-determining. Where proton transfer blocks the internal return of carbon dioxide, the separation of carbon dioxide is facilitated, and the observed isotope effect increases toward the intrinsic value for carbon-carbon bond breaking. Headspace analysis of carbon dioxide formed over the course of the reaction shows that protonated pyridine increases the magnitude of the observed (12)C/(13)C KIE, consistent with the proposed mechanism.

Catalyzing separation of carbon dioxide in thiamin diphosphate-promoted decarboxylation.

Thiamin diphosphate-dependent decarboxylases form addition intermediates between thiamin diphosphate (ThDP) and 2-ketoacids. Although it appears that the intermediate should react without the intervention of catalysts, evidence has clearly shown that Brønsted acid catalysis occurs through a pre-associated system. This can promote separation of carbon dioxide from the residual carbanion by protonation of the carbanion. Proteins operate through pre-association and may readily promote the separation of carbon dioxide by protonating or oxidizing the nascent carbanion. Alternatively, a nucleophilic side chain may trap carbon dioxide as an unstable hemi-carbonate. Mutagenesis experiments by others have shown that enhanced activity due to the protein in the presence of thiamin diphosphate does not depend on the presence of any one proton donor, consistent with pooled activity within the active site. This form of catalysis has not been widely recognized, but should be considered an integral aspect of enzyme-promoted decarboxylation.