Pediatric Coronary Allograft Vasculopathy—A Review of Pathogenesis and Risk Factors

Coronary allograft vasculopathy is the current leading cause for late graft loss following cardiac transplantation. Its pathogenesis is multifactorial, including immune, constitutional and genetic factors, metabolism, infection, as well as potential injury from routine immunosuppressive therapy. Children represent a patient group with unique differences: their pretransplant history rarely includes ischemic heart disease and risk factors for atherosclerotic heart disease, but many are presensitized from use of allograft material during reconstructive cardiac surgeries. Compared with older children and adults, infants and young children show significantly lower rates of graft vasculopathy that may be related to the relative immaturity of their immune system. This review summarizes the current concepts of coronary allograft vasculopathy derived mainly from animal models and adult clinical observations. It provides an overview of confirmed risk factors and explains their interactions. The characteristics and unique clinical findings among pediatric transplant recipients will be explored within the context of recent, albeit limited, scientific investigations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92455/1/chd601.pd

Efficient measurements, purification, and bounds on the mutual information

When a measurement is made on a quantum system in which classical information is encoded, the measurement reduces the observers average Shannon entropy for the encoding ensemble. This reduction, being the {\em mutual information}, is always non-negative. For efficient measurements the state is also purified; that is, on average, the observers von Neumann entropy for the state of the system is also reduced by a non-negative amount. Here we point out that by re-writing a bound derived by Hall [Phys. Rev. A {\bf 55}, 100 (1997)], which is dual to the Holevo bound, one finds that for efficient measurements, the mutual information is bounded by the reduction in the von Neumann entropy. We also show that this result, which provides a physical interpretation for Hall's bound, may be derived directly from the Schumacher-Westmoreland-Wootters theorem [Phys. Rev. Lett. {\bf 76}, 3452 (1996)]. We discuss these bounds, and their relationship to another bound, valid for efficient measurements on pure state ensembles, which involves the subentropy.Comment: 4 pages, Revtex4. v3: rewritten and reinterpreted somewha

Dopamine as a potential rescue therapy for refractory proteinâ losing enteropathy in Fontanâ palliated patients

PLE is an important cause of morbidity and mortality in patients who have undergone Fontan palliation. While multiple PLE therapies have been reported, none has proved consistently effective. Patients who do not respond to â standardâ PLE therapies face poor longâ term outcomes. We report here a significant response to dopamine infusion in three patients with chronic, refractory PLE. We hypothesize that this response may be at least partially due to a dopamine effect on lymphatic receptors rather than to an augmentation of cardiac output.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137378/1/petr12925_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137378/2/petr12925.pd

Pharmacotherapy Challenges of Fontan‐Associated Plastic Bronchitis: A Rare Pediatric Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99662/1/phar1290.pd

Risk Factors and Outcome of Fontan‐Associated Plastic Bronchitis: A Case‐Control Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139068/1/jah3521.pd

Clinical significance of antiâ HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

While VAD use in pediatric patients has previously been associated with antiâ HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of antiâ HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients postâ HTx (N=1288) with preâ HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and nonâ MCS groups after stratification by PRA and age. VAD recipients were more likely to produce antiâ HLA antibodies than nonâ MCS patients (25.5% vs 10.5% had PRA>10%, P10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized nonâ MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15â month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of antiâ HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VADâ associated antibodies and early rejection is unclear and warrants further investigation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137732/1/petr12938_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137732/2/petr12938.pd

A systematic review of parent and family functioning in pediatric solid organ transplant populations

The process of pediatric solid organ transplantation (SOT) places new and increased stressors on patients and family members. Measures of family functioning may predict psychological and health outcomes for pediatric patients and their families, and provide opportunity for targeted intervention. This systematic review investigated parent and family functioning and factors associated with poorer functioning in the pediatric SOT population. Thirty‐seven studies were identified and reviewed. Studies featured a range of organ populations (eg, heart, liver, kidney, lung, intestine) at various stages in the transplant process. Findings highlighted that parents of pediatric SOT populations commonly report increased stress and mental health symptoms, including posttraumatic stress disorder. Pediatric SOT is also associated with increased family stress and burden throughout the transplant process. Measures of parent and family functioning were associated with several important health‐related factors, such as medication adherence, readiness for discharge, and number of hospitalizations. Overall, findings suggest that family stress and burden persists post‐transplant, and parent and family functioning is associated with health‐related factors in SOT, highlighting family‐level functioning as an important target for future intervention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136483/1/petr12900.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136483/2/petr12900_am.pd

The impact of ischemic time on early rejection after pediatric heart transplant

Prolonged graft ischemia may be a risk factor for early rejection postâ HTx, but this has not been well studied in children. Furthermore, factors moderating the association between IT and early rejection have not been investigated. From 2004 to 2012, pediatric HTx recipients (n = 2381) were identified from the UNOS database. A ROC curve determined the optimal IT discriminating patients by the presence of early rejection. Separate univariate analyses identified factors associated with: (i) early (prior to hospital discharge) rejection, and (ii) IT. A multivariable logistic regression assessed independent risk factors for early rejection. We included interaction terms to evaluate whether IT’s independent risk effect on early rejection is moderated via interaction with associated factors found in univariate analysis. Longer IT was associated with an increased risk of early rejection. In multivariable analysis, IT > 3.1 hours was an independent risk factor for early rejection (AOR 1.44, P = .01). No interaction terms between IT and any associated factors were significant. Longer IT is an independent risk for early rejection in pediatric HTx recipients. Better understanding the association between IT and early rejection may identify interventions to mitigate this risk.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139903/1/petr13034.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139903/2/petr13034_am.pd

Rate of increase in serum lactate level risk-stratifies infants after surgery for congenital heart disease

ObjectiveIncreased blood lactate levels reflect tissue oxygen debt and might be indicative of low cardiac output. We hypothesized that the rate of increase in serum lactate would be an ideal marker to discriminate between infants at high and low risk of a poor outcome after surgical repair of congenital heart disease using cardiopulmonary bypass.MethodsIn the present prospective, observational study in a pediatric cardiac intensive care unit, infants (aged <12 months) undergoing cardiac surgery had serial whole blood lactate levels measured with every arterial blood gas drawn for the first 24 postoperative hours. The composite poor outcome included death, the need for extracorporeal support, and dialysis.ResultsThe lactate levels were measured in 231 infants; 19 infants (8.2%) had a poor outcome. A lactate increase rate of 0.6 mmol/L/h had very good discriminatory ability (area under the curve [AUC], 0.89) with a sensitivity of 90%, specificity of 84%, positive predictive value (PPV) of 34%, and negative predictive value (NPV) of 99%. Similar results were obtained for subgroups stratified by 1- or 2-ventricle heart disease and risk adjustment for congenital heart surgery (RACHS-1) score. In neonates (age <30 days) with single-ventricle physiology (n = 43, poor outcome = 8), a lactate increase of 0.6 mmol/L/h had near perfect discriminatory ability (AUC 0.99) with a sensitivity of 100%, specificity of 51%, PPV of 32%, and NPV of 100%. In 2-ventricle neonates (n = 43, poor outcome = 5), a lactate increase of 0.6 mmol/L/h also had near perfect discriminatory ability (AUC, 0.99), with a sensitivity of 100%, specificity of 90%, PPV of 56%, and NPV of 100%.ConclusionsThe postoperative lactate increase rate allows discrimination between infants at high and low risk of morbidity and mortality after congenital heart disease surgery, and the lactate level can be followed serially for the treatment response