27 results on '"Chinnock, Richard"'
Search Results
2. Perceptions of Pediatric Endocrinologists and Neurologists on the Drivers of Telehealth Use.
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Schulson, Lucy B., Predmore, Zachary, Sousa, Jessica L., McCullough, Colleen M., Magit, Anthony, Lerner, Carlos, Chinnock, Richard, Barkley, Steven, Marcin, James P., McGuire, Troy, Browne, Michael-Anne, and Uscher-Pines, Lori
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ENDOCRINOLOGISTS ,NEUROLOGISTS ,COVID-19 ,ATTITUDES of medical personnel ,RESEARCH methodology ,PEDIATRICS ,INTERVIEWING ,QUANTITATIVE research ,TELEMEDICINE - Abstract
OBJECTIVE: To assess the extent and drivers of telehealth use variation across clinicians within the same pediatric subspecialties. METHODS: In this mixed methods study, 8 pediatric medical groups in California shared data for eleven subspecialties. We calculated the proportion of total visits delivered via telehealth by medical group for each subspecialty and identified the 8 most common International Classification of Diseases 10 diagnoses for telehealth and in-person visits in endocrinology and neurology. We conducted semi-structured interviews with 32 pediatric endocrinologists and neurologists and applied a positive deviance approach comparing high versus low utilizers to identify factors that influenced their level of telehealth use. RESULTS: In 2019, medical groups that submitted quantitative data conducted 1.8 million visits with 549,306 unique pediatric patients. For 3 subspecialties, there was relatively little variation in telehealth use across medical groups: urology (mean: 16.5%, range: 9%-23%), orthopedics (mean: 7.2%, range: 2% -14%), and cardiology (mean: 11.2%, range: 2%-24%). The remaining subspecialties, including neurology (mean: 58.6%, range: 8%-93%) and endocrinology (mean: 49.5%, range: 24%-92%), exhibited higher levels of variation. For both neurology and endocrinology, the top diagnoses treated in-person were similar to those treated via telehealth. There was limited consensus on which clinical conditions were appropriate for telehealth. High telehealth utilizers were more comfortable conducting telehealth visits for new patients and often worked in practices with innovations to support telehealth. CONCLUSIONS: Clinicians perceive that telehealth may be appropriate for a range of clinical conditions when the right supports are available. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Feasibility of a Pilot Randomized Controlled Trial.
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Grady, Kathleen L., Andrei, Adin-Cristian, Shankel, Tamara, Chinnock, Richard, Miyamoto, Shelley D., Ambardekar, Amrut V., Anderson, Allen, Addonizio, Linda, Latif, Farhana, Lefkowitz, Debra, Goldberg, Lee R., Hollander, Seth A., Pham, Michael, Van't Hof, Kathleen, Weissberg-Benchell, Jill, Yancy, Clyde, Liu, Menghan, Melody, Nichole, and Pahl, Elfriede
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Background: Young-adult heart transplant recipients transferring to adult care are at risk for poor health outcomes. We conducted a pilot randomized controlled trial to determine the feasibility of and to test a transition intervention for young adults who underwent heart transplantation as children and then transferred to adult care.Methods: Participants were randomized to the transition intervention (4 months long, focused on heart-transplant knowledge, self-care, self-advocacy, and social support) or usual care. Self-report questionnaires and medical records data were collected at baseline and 3 and 6 months after the initial adult clinic visit. Longitudinal analyses comparing outcomes over time were performed using generalized estimating equations and linear mixed models.Results: Transfer to adult care was successful and feasible (ie, excellent participation rates). The average patient standard deviation of mean tacrolimus levels was similar over time in both study arms and < 2.5, indicating adequate adherence. There were no between-group or within-group differences in percentage of tacrolimus bioassays within target range (> 50%). Average overall adherence to treatment was similarly good in both groups. Rates of appointment keeping through 6 months after transfer declined over time in both groups.Conclusions: The feasibility of the study was demonstrated. Our transition intervention did not improve outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2019
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4. Primary Transplantation for Congenital Heart Disease in the Neonatal Period: Long-term Outcomes.
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John, Mohan M., Razzouk, Anees J., Chinnock, Richard E., Bock, Matthew J., Kuhn, Michael A., Martens, Timothy P., and Bailey, Leonard L.
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Primary transplantation was developed in the 1980s as an alternative therapy to palliative reconstruction of uncorrectable congenital heart disease. Although transplantation achieved more favorable results, its utilization has been limited by the availability of donor organs. This review examines the long-term outcomes of heart transplantation in neonates at our institution. The institutional pediatric heart transplant database was queried for all neonatal heart transplants performed between 1985 and 2017. Follow-up was obtained from medical records and an annually administered questionnaire. Overall survival and time to development of complications were estimated using the Kaplan Meier method. Univariate and multivariate analyses were performed to identify independent predictors of survival. Heart transplantation was performed in 104 neonates. Median age was 17 days. Hypoplastic left heart syndrome (classic or variant) was the primary diagnosis in 77.8% of patients. Survival at 10 years and 25 years was 73.9% and 55.8%, respectively. At 20 years, freedom from allograft vasculopathy and lymphoproliferative disease was 72.0% and 81.9%, respectively. Freedom from re-transplantation was 81.4% at 20 years. Eight patients (7.6%) developed end-stage renal disease. By multivariate analysis, lower glomerular filtration rate and allograft vasculopathy were the only significant predictors of death. Neonatal heart transplantation remains a durable therapy with very acceptable long-term survival. Children transplanted in the newborn period have the potential to reach adulthood with minimal need for reintervention. [ABSTRACT FROM AUTHOR]
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- 2019
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5. Pediatric Recipient Survival Beyond 15 Post-Heart Transplant Years: A Single-Center Experience.
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Copeland, Hannah, Razzouk, Anees, Chinnock, Richard, Deming, Douglas, Hasaniya, Nahidh, and Bailey, Leonard
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Background We evaluated late survival among pediatric heart transplant patients who have lived more than 15 years. Methods This is a retrospective chart review of the pediatric patients who underwent heart transplantation (HTx) between 1985 and 1998. Multivariate and univariate analyses were examined. Results There were 183 recipients, of whom 151 are currently alive. Age at HTx ranged from 0 days to 17.48 years (median 56 days). Pretransplant diagnoses included congenital heart disease 142 (77.6%), cardiomyopathy 38 (20.8%), and tumor 3 (1.6%). Pretransplant renal dysfunction was present in 58 patients (31.7%). Perioperative peritoneal dialysis was instituted in 15 patients, all recovered. During the follow-up period (median 20.2 years), 17 (9.3%) have had renal transplants, and 2 require hemodialysis. There were 32 deaths from the following: cardiac allograft vasculopathy (CAV); 11 (34.3%); posttransplant lymphoproliferative disease 6 (18.8%); acute rejection 4 (12.5%); sepsis 2 (6.3%); multiorgan failure 1 (3.1%); and unknown 8 (25%). Immunosuppressive therapy for the living patients consists of monotherapy 25 (17.7%), dual therapy 87 (61.7%), triple therapy 24 (17%), quadruple therapy 5 (3.5%), and 10 unknown. Cardiac re-Tx was required for CAV in 30 patients and for graft failure in 6 patients. Four patients required a third transplant for CAV. For those who survived more than 15 years after HTx, actuarial survival to 20 years and 25 years is 82% and 78%, respectively. Conclusions Pediatric HTx provides acceptable long-term survival. Cardiac re-Tx and renal transplantation offer reasonable palliation for recipients who develop CAV and renal dysfunction. [ABSTRACT FROM AUTHOR]
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- 2014
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6. Pediatric Transplantation Using Hearts Refused on the Basis of Donor Quality.
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Bailey, Leonard L., Razzouk, Anees J., Hasaniya, Nahidh W., and Chinnock, Richard E.
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TRANSPLANTATION of organs, tissues, etc. in children ,HEART transplantation ,ORGAN donors ,SUPPLY & demand ,HEALTH outcome assessment ,COHORT analysis ,HOMOGRAFTS - Abstract
Background: There is always more demand than supply of organs in pediatric heart transplantation. Yet, potential donor organs are regularly declined for a variety of reasons, among them donor organ quality as determined by United Network for Organ Sharing (UNOS) refusal code 830 or its equivalent. Methods: For the study group institutional and UNOS databases (July 2000 to December 2008) were reviewed to examine outcomes of pediatric heart transplantation using donor hearts that had been previously refused one or more times because of organ quality. Variation between outcomes of this cohort and recipients who received primarily offered heart grafts in a single institution was analyzed. Results: In 29 recipients, transplantation or retransplantation was with heart grafts previously declined on the basis of quality. Recovery distances (p < 0.002) and graft cold ischemic times (p < 0.001) were significantly longer for declined hearts. Operative survival was 93% ± 5.0% (27 of 29). Seven-year actuarial survival was 74% ± 10.5%. At the present time, 24 of the 29 recipients (83%) are alive. These results do not vary statistically from those experienced by 84 recipients of 86 primarily offered donor organs during the same time. Conclusions: Despite longer distance recovery (ie, longer graft cold ischemic times), outcomes of pediatric heart transplantation using donor heart grafts refused on the basis of organ quality are highly competitive. Pediatric donor hearts should seldom be declined on the basis of organ quality (UNOS code 830). [Copyright &y& Elsevier]
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- 2009
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7. Developmental Outcomes After Pediatric Heart Transplantation
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Chinnock, Richard E., Freier, M. Catherin, Ashwal, Stephen, Pivonka-Jones, Jamie, Shankel, Tamara, Cutler, Drew, and Bailey, Leonard
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HEART transplant recipients , *PEDIATRICS , *PEDIATRIC therapy , *SURVIVAL analysis (Biometry) , *CONGENITAL heart disease in children , *DEVELOPMENTAL biology , *HEALTH outcome assessment - Abstract
Background: Pediatric heart transplantation has now been successfully performed for more than 20 years. As survival rates have improved, more attention is now focused on long-term outcomes. Methods: This report reviews the literature on developmental outcomes after pediatric heart transplantation. Results: Pediatric patients undergoing heart transplantation generally can be expected to have developmental outcomes in the low-normal range, consistent with outcomes seen in other children with complex congenital heart disease requiring surgical intervention. When these children reach school age, or return to school, most can be expected to function reasonably well in mainstream school settings. A significant minority will require additional educational assistance. Approximately 10% will have significant neurologic impairment. In school, particular attention should be paid to evaluating the child for deficits in arithmetic and verbal skills. Performance may be better than predicted from IQ testing. Behavioral issues are common, with depression, concerns about social competence, and attention difficulties most frequently endorsed. This may pre-date transplantation in those who undergo transplantation during childhood and may improve with time. Parents more often report problem behaviors than teachers. Family resources and family coping skills are also strongly correlated with the child''s emotions and coping skills. Conclusion: The pediatric heart transplant recipient''s ability to transition from childhood into a happy and productive adult life can be significantly affected by his or her cognitive abilities, learning experiences, sense of self, and emotions. Attention to these factors is an important part of caring for these children. [Copyright &y& Elsevier]
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- 2008
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8. Decreased Exercise Performance with Age in Children with Hypoplastic Left Heart Syndrome.
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Jenkins, Pamela C., Chinnock, Richard E., Jenkins, Kathy J., Mahle, William T., Mulla, Neda, Sharkey, Angela M., and Flanagan, Michael F.
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Objective: Children born with hypoplastic left heart syndrome (HLHS) may experience cardiac dysfunction after staged surgery or transplantation, which may worsen with age. We examined the hypothesis that exercise testing can address cardiovascular capacity and suggest interventions to improve quality of life. Study design: Children with HLHS ≥8 years old performed treadmill or bicycle ergometric testing at 4 centers. Results were compared with norms for age and sex. Results: Of the 42 participants, the mean age was 12.9 years (range, 8.5-17.0 years), 64% were boys, 20 had staged surgery, and 34 completed metabolic assessment. The percent of predicted maximal oxygen uptake (mVO2) was higher in younger children. Children aged 8 to 12 years achieved 70% of predicted mVO2; children aged 13 to 17 years achieved 60% of predicted mVO2 (P = .02). The percent of predicted peak heart rate trended higher in younger patients (83% versus 75%, P = .07). Electrocardiographic changes were more common in older children. In treadmill testing, patients who had a transplant had better exercise performance than patients who underwent staged surgery in percent of predicted exercise time (82% versus 54%, P < .0001) and peak rate-pressure product (241 × 10
3 versus 195 × 103 , P = .02). The percent of predicted mVO2 did not differ between patients who had a transplant (66%) and patients who underwent staged surgery (61%, P = .25). Conclusion: Children with HLHS showed considerable age-related decline in exercise performance, regardless of surgical strategy. [Copyright &y& Elsevier]- Published
- 2008
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9. Geometric Disproportion of Cardiac Structure and Graft Ischemia Affect Tricuspid Valve Regurgitation Early After Neonatal Heart Transplantation.
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Asano, Miki, Razzouk, Anees J., Chinnock, Richard E., and Bailey, Leonard L.
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ISCHEMIA ,TRICUSPID valve insufficiency ,HEART transplantation ,SURGICAL therapeutics ,SURGERY - Abstract
Background: Although tricuspid valve regurgitation (TR) after heart transplantation is a known complication, there has been little discussion of this subject in neonatal heart transplantation. We aim to elucidate the prevalence, etiology, and evolution of TR early after transplant in neonates. Methods: Eighty-five neonatal recipients were studied retrospectively by two-dimensional and Doppler echocardiography. The semiquantitative grading of TR was based on the ratio of regurgitation jet area to right atrial area. Results: Immediately after neonatal heart transplantation, TR was recognized in 47 patients (grade 1, n = 18; grade 2, n = 22; grade 3, n = 7; and grade 4, n = 0). Tricuspid regurgitation prevalence diminished from 55% to 19% with reduction in severity 1 year after transplantation. The prevalence of TR (grade 2 and grade 3) was affected by a donor/recipient body weight ratio of more than 2.0 (p = 0.004) and graft ischemia for more than 3 hours (p = 0.014). The ratio of donor and recipient right atria portion, which had a correlation with donor/recipient body weight ratio (r
2 = 0.415, p < 0.0001), separated the four subgroups in terms of TR grade immediately after transplantation (p = 0.0064) and also at 1 year after transplantation in all surviving grafts from 1.48 ± 0.54 to 0.8 ± 0.32 (p < 0.0001). The Cox model found no significance for early posttransplant TR as a risk factor for graft survival. Conclusions: Early posttransplant TR was affected by atria geometrical disproportion and by graft ischemia. Tricuspid regurgitation was not a risk factor for graft survival because of its amelioration over time, perhaps induced by recipient growth and recovery of myocardial injury relating to graft procurement. [Copyright &y& Elsevier]- Published
- 2007
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10. Total lymphoid irradiation for refractory rejection in pediatric heart transplantation.
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Asano, Miki, Gundry, Steven R., Razzouk, Anees J., del Rio, Michael J., Thomas, Melanie, Chinnock, Richard E., and Bailey, Leonard L.
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HEART transplantation ,LYMPHOID tissue ,PEDIATRIC surgery ,CORONARY arteries - Abstract
: BackgroundWe evaluated the role of total lymphoid irradiation (TLI) in the management of refractory rejection among pediatric heart transplant patients.: MethodsEleven of 298 patients underwent TLI at 6 to 195 months of age and were divided into subgroups: those who survived (group A, n = 7) and those who did not survive beyond 1 year after TLI (group D, n = 4). Non–TLI recipient data were considered as the controls.: ResultsSix out of 11 patients died eventually (54%). TLI was initiated 3 to 107 months after transplantation with a dosage of 600 to 840 cGy. The pre-TLI rejection rate (0.62 ± 0.40 per month) was higher (p < 0.0001); however, the post-TLI rejection rate (0.24 ± 0.65 per month) showed no significant difference from the control rejection rate. The Cox proportional hazard model found significance for TLI as a risk factor for development of posttransplant coronary artery disease (relative risk, 4.8; 95% CI, 1.1 to 21.3) and posttransplant lymphoproliferative disease (relative risk, 47.9; 95% CI, 1.6 to 1,475.3), respectively. Although the rejection rate decreased after TLI in both groups (group A pre/post, 0.51 ± 0.31/0.06 ± 0.08 per month; group D pre/post, 0.82 ± 0.49/0.57 ± 1.09 per month), significance was obtained only in group A (p = 0.018).: ConclusionsTLI was an effective adjunct for reversal of refractory rejection in pediatric heart transplantation by reducing the rejection rate. Great care must be taken for the risk of development of coronary artery disease or lymphoproliferative disease. [Copyright &y& Elsevier]
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- 2002
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11. COVID-19 diagnosis and testing in pediatric heart transplant recipients.
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Bock, Matthew J., Kuhn, Micheal A., and Chinnock, Richard E.
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HEART transplant recipients , *COVID-19 , *COVID-19 testing , *ANTIBODY titer , *ANTIBODY formation , *INFECTION - Abstract
Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of infection, COVID-19 is well tolerated in this population (5% admission from home; 0% mortality). A suppressed immune system does not significantly inhibit an antibody response in pediatric heart transplant recipients (>70% antibody seroconversion) and appears to persist, similar to those without transplantation (>90 days). Routine testing for COVID-19 via PCR and antibody testing enhances the ability to detect COVID-19 infection in asymptomatic patients and may help reduce unintended transmission to more susceptible individuals. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Exercise assessment in infants after cardiac transplantation
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Abarbanell, Ginnie, Mulla, Neda, Chinnock, Richard, and Larsen, Ranae
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CARDIOPULMONARY system , *HEART , *EXERCISE , *HEART transplantation , *HEART diseases - Abstract
Background: Few data describe exercise performance after cardiac transplantation during infancy. The aim of this study was to compare the cardiorespiratory response to exercise in healthy subjects with that of subjects who had undergone heart transplantation during infancy to treat hypoplastic left heart syndrome.Methods: Subjects (24 heart transplant recipients and 25 healthy controls) exercised on a treadmill using pediatric ramp protocols. We measured heart rate (HR), blood pressure, and metabolic data. Median age at transplantation was 20 days (range, 4 to 97 days). Age of recipients at exercise testing was 9.7 ± 2.3 years and in healthy subjects was 10.5 ± 1.4 years (p = not significant [NS]).Results: Exercise duration was similar in both groups (10.3 ± 2.0 minutes in recipients vs 11.1 ± 1.5 minutes in healthy subjects, (p = NS). Heart rate at rest was greater in recipients (94 ± 15 beats per minute [bpm] vs 85 ± 11 bpm, p = 0.02). Peak HR also was less in the recipient group (158 ± 15 bpm vs 189 ± 12 bpm, p < 0.001). Peak oxygen consumption was 14% less in the recipients (32.3 ± 5.6 ml/kg/min vs 36.8 ± 5.5 ml/kg/min, p < 0.01). Ventilatory anaerobic threshold was decreased in recipients, 27.6 ± 9.6 vs 32.8 ± 6.0, p < 0.05. Respiratory exchange ratio at peak exercise was equal in both groups (1.06 ± 0.06 vs 1.06 ± 0.08). Oxygen pulse index did not differ significantly, 5.5 ± 1.1 ml/beat/m2 in recipients and 6.1 ± 1.7 ml/beat/m2 in healthy subjects (p = NS).Conclusions: Overall, children who undergo cardiac transplantation in infancy have exercise capacities within the normal range. These recipients have a decreased heart rate reserve that may account for the differences in peak oxygen consumption when compared with healthy subjects. [Copyright &y& Elsevier]
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- 2004
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13. Use of sirolimus in pediatric heart transplant patients: A multi-institutional study from the Pediatric Heart Transplant Study Group.
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Rossano, Joseph W., Jefferies, John L., Pahl, Elfriede, Naftel, David C., Pruitt, Elizabeth, Lupton, Kathy, Dreyer, William J., Chinnock, Richard, Boyle, Gerard, and Mahle, William T.
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RAPAMYCIN , *HEART transplant recipients , *CARDIAC surgery , *GRAFT rejection , *FOLLOW-up studies (Medicine) - Abstract
Background Proliferation signal inhibitors, such as sirolimus, are increasingly used in solid-organ transplantation. However, limited data exist on sirolimus-treated pediatric patients. We aimed to describe sirolimus use in pediatric heart transplant patients and test the hypothesis that sirolimus use is associated with improved outcomes. Methods A retrospective review and propensity-matched analysis of the Pediatric Heart Transplant Study database was performed on patients undergoing primary heart transplantation from 2004 to 2013 with at least 1 year of follow-up comparing patients treated vs not treated with sirolimus at 1 year after transplant. The primary outcome of interest was patient survival, with secondary outcomes including cardiac allograft vasculopathy, rejection, malignancy, and renal insufficiency. Results Between 2004 and 2013, 2,531 patients underwent transplantation. At least 1 year of follow-up was available for 2,080 patients, of whom 144 (7%) were on sirolimus at 1 year post-transplant. Sirolimus-treated and non-treated patients had similar survival in the overall cohorts and in the propensity-matched analysis. The secondary outcomes measures were also similar, including a composite end point of all outcome measures. There was a trend toward increased time to cardiac allograft vasculopathy ( p = 0.09) and decreased time to infection ( p = 0.05) among sirolimus-treated patients in the overall cohort ( p = 0.19) but not in the propensity-matched cohort ( p = 0.17). Conclusions Sirolimus was used in less than 10% of patients at 1 year post-transplant. Overall outcomes of sirolimus treated and non-treated patients were similar with respect to survival and major transplant adverse events. Further study of sirolimus in pediatric heart transplant patients is needed. [ABSTRACT FROM AUTHOR]
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- 2017
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14. ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits
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Urschel, Simon, Larsen, Ingrid M., Kirk, Richard, Flett, Julie, Burch, Michael, Shaw, Nadine, Birnbaum, Julia, Netz, Heinrich, Pahl, Elfriede, Matthews, Kathleen L., Chinnock, Richard, Johnston, Joyce K., Derkatz, Kim, and West, Lori J.
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ABO blood group system , *INCOMPATIBLES (Pharmacy) , *HEART transplantation , *FOLLOW-up studies (Medicine) - Abstract
Background: Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries. Methods: Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey. Results: Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies. Conclusions: Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation. [Copyright &y& Elsevier]
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- 2013
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15. Renal function and genetic polymorphisms in pediatric heart transplant recipients
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Feingold, Brian, Brooks, Maria M., Zeevi, Adriana, Ohmann, Erin L., Burckart, Gilbert J., Ferrell, Robert E., Chinnock, Richard, Canter, Charles, Addonizio, Linda, Bernstein, Daniel, Kirklin, James K., Naftel, David C., and Webber, Steven A.
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HEART transplantation , *PEDIATRIC cardiology , *GENETIC polymorphisms , *KIDNEY function tests , *PROPORTIONAL hazards models , *IMMUNOSUPPRESSION - Abstract
Background: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. Methods: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m2. Results: Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFβ1, CYP3A5, ABCB1, and ACE. Conclusions: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFβ1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation. [Copyright &y& Elsevier]
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- 2012
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16. Has late rejection decreased in pediatric heart transplantation in the current era? A multi-institutional study
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Ameduri, Rebecca K., Zheng, Jie, Schechtman, Kenneth B., Hoffman, Timothy M., Gajarski, Robert J., Chinnock, Richard, Naftel, David C., Kirklin, James K., Dipchand, Anne I., and Canter, Charles E.
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HEART transplantation , *PEDIATRIC cardiology , *GRAFT rejection , *MEDICAL databases , *CORONARY heart disease treatment , *MORTALITY - Abstract
Background: Late (occurring >1 year) rejection (LR) has been shown to increase mortality and morbidity after pediatric heart transplantation (HTx). The incidence of rejection has decreased in the first year after pediatric HTx in the current era. We hypothesized a similar phenomenon has occurred with LR. Methods: The Pediatric Heart Transplant Study database was used to analyze the effects of era (1993 to 1998 vs 1999 to 2007) and other factors on the prevalence of LR and its relationship to mortality, moderate–severe coronary vasculopathy (CAV) and retransplantation. Results: Freedom from first LR (59% vs 69% 5-year post-HTx, p < 0.001) and recurrent LR (p < 0.001) was significantly lower in the current vs earlier era. LR was significantly (p < 0.001) associated with early rejection (ER; rejection <1 year post-HTx) in both eras. Independent risk factors for LR were: earlier era (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.25 to 1.73, p < 0.001); non-white race (HR 1.41; 95% CI 1.19 to 1.67, p < 0.001); older recipient age (HR 1.05, 95% CI 1.03 to 1.06, p < 0.001); recipient Status 2 at transplant (HR 1.21, 95% CI 1.01 to 1.45, p = 0.037); and male donor (HR 1.17; 95% CI 1.0 to 1.37, p = 0.055). Late rejectors had a similar higher risk of mortality (odds ratio [OR] 4.20, 95% CI 3.04 to 5.81, p < 0.001) and incidence of moderate–severe CAV or retransplantation (OR 2.63, 95% CI 1.78 to 3.90, p < 0.001) in both eras. Conclusions: LR has decreased in the recent era in pediatric HTx recipients. Its effect on mortality and the development of CAV has not changed over time, suggesting an ongoing need for improved primary prevention strategies. [Copyright &y& Elsevier]
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- 2012
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17. Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients
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Ohmann, Erin L., Brooks, Maria M., Webber, Steven A., Girnita, Diana M., Ferrell, Robert E., Burckart, Gilbert J., Chinnock, Richard, Canter, Charles, Addonizio, Linda, Bernstein, Daniel, Kirklin, James K., Naftel, David C., and Zeevi, Adriana
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HEART failure in children , *GENETIC polymorphisms , *IR genes , *VIRUS diseases , *CYTOKINES , *TRANSPLANTATION of organs, tissues, etc. in children ,HEART transplantation complications - Abstract
Background: Late infections are common causes of morbidity and mortality after pediatric heart transplantation. In this multicenter study from 6 centers, we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients. Methods: Late infection was defined as a clinical infectious process occurring >60 days after transplantation and requiring hospitalization, intravenous antimicrobial therapy, or a life-threatening infection requiring oral therapy. All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor, and effector molecule genes by single specific primer-polymerase chain reaction and/or sequencing. Significant associations in univariable analyses were tested in multivariable Cox regression models. Results: Late infection was common, with 48.7% of patients experiencing ≥1 late infection, 25.2% had ≥1 late bacterial infection, and 30.5% had ≥1 late viral infection. Older age at transplantation was a protective factor for late infection, both bacterial and viral (hazard ratio [HR] 0.89–0.92 per 1-year age increase, p < 0.001). Adjusting for age, race, and transplant etiology, late bacterial infection was associated with HMOX1 A+326G AG and GG genotypes (HR, 2.41, 95% confidence interval [CI] 1.35–4.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.03–2.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.00–2.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.02–2.19; p = 0.041) in univariable analysis. Conclusion: We found an association between late bacterial infection and GP of HMOX1, which may control macrophage activation. A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation. [Copyright &y& Elsevier]
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- 2010
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18. Cause of Death in Pediatric and Infant Heart Transplant Recipients: Review of a 20-year, Single-institution Cohort
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Zuppan, Craig W., Wells, Linda M., Kerstetter, Justin C., Johnston, Joyce K., Bailey, Leonard L., and Chinnock, Richard E.
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CHILD mortality , *HEART transplant recipients , *PEDIATRIC cardiology , *COHORT analysis , *HEALTH outcome assessment , *GRAFT rejection , *CARDIAC surgery - Abstract
Background: As infant and pediatric heart transplantation becomes more common, there is a growing need to better understand the causes of failure or death, if we are to continue to improve the outcome in these children. Methods: A multidisciplinary team reviewed all deaths occurring in the cohort of infants and children transplanted during the first 20 years of the Loma Linda Pediatric Heart Transplant program, with 2 additional years of follow-up beyond the 20-year accrual period, and classified them as to cause. Results: There were 169 deaths among 421 recipients, with a median follow-up of 9.7 years. Autopsy was performed in 128 cases. The causes of death, in decreasing order of frequency, included acute rejection (26.0%), infection (16.0%), cardiac allograft vasculopathy (CAV) (14.2%), technical issues (8.3%), acute graft dysfunction (6.5%), neoplasm (7.1%), chronic graft dysfunction (4.7%) and miscellaneous factors (10.1%), and in twelve deaths (7.1%) the cause was unclassified. Acute graft dysfunction and technical issues accounted for nearly two-thirds of the deaths in the first 30 days after transplant, while acute rejection resulted in the largest number of deaths after the first year (30.4%), with CAV a close second (23.5%). Conclusions: Acute graft dysfunction and technical issues were the most frequent cause of early death. Late deaths were most often due to acute rejection and CAV, which differs somewhat from the experience reported in adults. Acute rejection was the single most important cause of late mortality, and resulted in a significant number of late sudden and unexpected deaths. [Copyright &y& Elsevier]
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- 2009
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19. Late Outcomes of Pediatric Heart Transplantation Are Independent of Pre-transplant Diagnosis and Prior Cardiac Surgical Intervention
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Dionigi, Beatrice, Razzouk, Anees J., Hasaniya, Nahidh W., Chinnock, Richard E., and Bailey, Leonard L.
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HEART transplant recipients , *PEDIATRIC diagnosis , *HEALTH outcome assessment , *CARDIAC surgery , *VASCULAR diseases , *CARDIOMYOPATHIES - Abstract
Background: An increasing number of children are being referred for cardiac transplantation after (1) failing conventional corrective or palliative surgical reconstruction, (2) after stabilization with mechanical circulatory support devices, and (3) when primary graft failure or advanced cardiac allograft vasculopathy are established. Methods: The records of 417 infants and children (age range, 0–18 years) who underwent cardiac transplantation from November 1985 through December 2005 at Loma Linda University Children''s Hospital were retrospectively reviewed. The pre-transplantation diagnosis was used to divide patients into 3 groups: primary cardiomyopathy (CM), 103; hypoplastic left heart syndrome (HLHS), 154; and other complex congenital heart disease (CCHD), 160. These groups were compared and analyzed for differences in early and late morbidity and mortality. Results: Operative mortality was significantly lower in the CM group compared with the HLHS (p < 0.02;) and CCHD groups (p < 0.01). Long-term actuarial recipient survival, however, was similar for all groups. The 15-year actuarial survival was 59% for the CM Group, 57% for the HLHS Group, and 50% for the CCHD Group. Actuarial survival after retransplantation is not statistically different from that with primary cardiac transplantation. Conclusion: Although peri-operative survival was lower in infants and children with HLHS and CCHD compared with those with CM, long-term survival has been the same for all groups. Late survival after retransplantation was not statistically different than among those with primary cardiac transplantation. [Copyright &y& Elsevier]
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- 2008
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20. Postmortem Intracranial Neuropathology in Children Following Cardiac Transplantation
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McClure, Chalmer D., Johnston, Joyce K., Fitts, James A., Cortes, Josue, Zuppan, Craig W., Chinnock, Richard E., and Ashwal, Stephen
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NEUROLOGY , *DISEASES , *JUVENILE diseases , *CENTRAL nervous system - Abstract
At Loma Linda University Children’s Hospital, the medical information of 405 pediatric patients who received orthotopic cardiac transplantation were reviewed. Of those who died (n = 136), 86% (n = 117) underwent postmortem examinations, and the brain was examined in 61% (n = 82, male = 39). The number and type of intracranial lesions present were compiled, and these were matched to underlying functional cardiac disease categories. Intracranial abnormalities were present in 87%. Infarct was the most common primary central nervous system pathology in hypoplastic left heart syndrome (41%) but was also observed frequently in children with obstructive lesions (37%), cyanotic disease (31%), or cardiac shunting (29%). Secondary findings included extraparenchymal hemorrhage in obstructive lesions (31%); hypoxic changes occurred in 15% of patients with cyanotic disease and in 14% of those with cardiac shunting. Thirty-three percent of children with restrictive lesions had no neuropathology reported. Postmortem examination brain weights were matched against age and sex norms, with 29% of females and 36% of males below two standard deviations. These findings revealed that intracranial pathology was present in the majority of transplanted children who underwent postmortem examination, and that infarctive changes constituted the most common neuropathologic abnormality. Additionally, a number of children had significantly reduced brain weight. [Copyright &y& Elsevier]
- Published
- 2006
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21. Effect of oversizing cardiac allografts on survival in pediatric patients with congenital heart disease
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Razzouk, Anees J., Johnston, Joyce K., Larsen, Ranae L., Chinnock, Richard E., Fitts, James A., and Bailey, Leonard L.
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HOMOGRAFTS , *PEDIATRICS , *CONGENITAL heart disease in children , *HEART transplantation , *HEART diseases - Abstract
Background: There are few published data regarding the long-term outcome of “large” cardiac allografts in children. This study examines the effect of cardiac graft oversizing on the survival of pediatric patients with congenital heart disease (CHD).Methods: Two hundred ninety-one children, age 1 day to 17 years (median 50 days), with CHD underwent primary cardiac transplantation between 1985 and 2002. Patients were analyzed according to donor-recipient weight ratio (D-R): Group (Gp) I (n = 252) with D-R <2.5 (range 0.59 to 2.49, median 1.4), and Gp II (n = 39) with D-R ≥2.5 (range 2.5 to 4.65, median 2.78). CHD diagnoses included hypoplastic left heart syndrome (138 in Gp I, 13 in Gp II), single ventricle (29 in Gp I, 1 in Gp II) and other (85 in Gp I, 13 in Gp II). Patients with cardiomyopathy were excluded. Pre-transplant cardiac palliation was performed in 36% of Gp I and 15% of Gp II patients. The average graft ischemic times (minutes) were 266 ± 7.5 and 283 ± 18.9 for Gp I and Gp II, respectively (p < 0.2).Results: The operative mortality for Gp I was 10.3% and 10.2% for Gp II (p < 0.99). There was no significant difference between the 2 groups in length of hospital stay (p < 0.15) or duration of ventilator support (p < 0.6) post-transplantation. However, the incidence of open chest was higher (p < 0.003) in Gp II (28%) compared with Gp I (8%). The survival rates for Gp I and Gp II were: 82 ± 2.4% vs 84 ± 5.7% at 1 year; 71 ± 2.9% vs 72 ± 7.2% at 5 years; and 63 ± 3.2% vs 65% ± 7.4 at 10 years.Conclusions: Post-transplant morbidity and short- and long-term survival of pediatric recipients with CHD are not adversely influenced by the use of oversized cardiac allografts. [Copyright &y& Elsevier]
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- 2005
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22. A longitudinal perspective on neurodevelopmental outcome after infant cardiac transplantation
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Freier, M. Catherin, Babikian, Talin, Pivonka, Jamie, Burley Aaen, Tanya, Gardner, Joy M., Baum, Marti, Bailey, Leonard L., and Chinnock, Richard E.
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QUALITY of life , *HEART transplantation , *INFANT development , *MOTOR ability in children , *IMMUNOSUPPRESSIVE agents - Abstract
Background: With improvement in medical outcomes, the current research has shifted toward understanding and enhancing the quality of life after pediatric heart transplantation. Previous research has indicated that infant heart transplant recipients are generally at risk for neurodevelopmental delays; however, no longitudinal studies exploring the patterns of development within this medical population have been performed.Methods: Using the Bayley Scales of Infant Development—II, 39 children (2 to 38 months of age) who underwent heart transplantation in infancy (<1 year) at Loma Linda University Children''s Hospital were assessed consecutively over time.Results: Mean Mental Development Index (MDI) scores for all age groups were within normal limits, except for the age ranges of 18 to 23 and 24 to 35 months, which were mildly delayed. Average Psychomoter Development Index (PDI) scores for all age groups reflected mildly delayed performance, except for the 36- to 38-month age group, which was within normal limits. Repeated measures analyses of variance on a sub-set of participants with at least 4 consecutive assessments revealed within-subject effects on MDI scores (F = 5.7, p < 0.01), but not on PDI scores (F = 1.6, p = 0.22). Significant decreases in MDI scores at 18 and 28 to 36 months were noted.Conclusions: Motor development in this population was consistently mildly delayed. Age-dependent variability in cognitive skills was apparent. The delays appeared due to speech/language acquisition (18 months), and abstract reasoning/goal-directed behaviors (28 to 36 months). Possible etiologies for cognitive delays include test artifacts, auditory functioning and effects of immunosuppressive agents. Understanding risk factors in this patient population will allow for early and effective intervention. [Copyright &y& Elsevier]
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- 2004
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23. An examination of the incidence of intubation and mechanical ventilation beyond the peri-operative period in pediatric heart transplant recipients
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Checchia, Paul A., Sehra, Ruchir, Daher, Noha, Chinnock, Richard, and Bailey, Leonard L.
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- 2004
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24. Post-transplant seizures in infants with hypoplastic left heart syndrome
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Raja, Roshan, Johnston, Joyce K., Fitts, James A., Bailey, Leonard L., Chinnock, Richard E., and Ashwal, Stephen
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SPASMS , *HEART transplantation - Abstract
Seizures are common in infants undergoing cardiac transplant and are usually attributed to a non-specific “post-pump” phenomenon. In this study, we determined which variables were associated with the occurrence of post-transplant seizures in infants with hypoplastic left heart syndrome and the need for continued treatment with antiepileptic medication. Of 127 infants studied over an 11-year period, 27 (21%), ages 9 to 90 days, had post-transplant seizures. These patients were compared to 27 age-matched transplanted infants without seizures. We compared multiple variables before, during, and after transplant including growth parameters, time of diagnosis, cyclosporine levels, maternal variables, circulatory and bypass parameters, laboratory data, neuroimaging and electroencephalographic studies, neurologic examination findings, and peri-operative complications. Post-transplant seizures were associated with total cardiopulmonary bypass time and the presence of post-transplant complications. Deep hypothermic circulatory arrest time was inversely correlated with seizure severity. Pre-transplant electroencephalographic abnormalities and total bypass time were associated with seizures requiring continued use of antiepileptic therapy. Post-transplant electroencephalograms were not associated with the need for continued treatment. Identification of variables associated with the development of post-transplant seizures is essential for early intervention to reduce long-term morbidity and mortality. Future studies to reduce risk of post-transplant seizures are warranted. [Copyright &y& Elsevier]
- Published
- 2003
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25. Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients
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Kuhn, Micheal A., Deming, Douglas D., Cephus, Constance E., Mulla, Neda F., Chinnock, Richard E., Razzouk, Anees J., and Larsen, Ranae L.
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HEART transplantation , *CATHETERIZATION , *BIOPSY , *STEROIDS , *CYCLOSPORINE - Abstract
: Background:Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection.: Methods:Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient’s immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine.: Results:A total of 1,108 biopsies were performed in 269 children with a mean follow-up of 5 ± 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1) on 3-drug immunosuppressive therapy; (2) with a recipient age >1 year; and (3) with a relatively lower cyclosporine level.: Conclusions:These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up. [Copyright &y& Elsevier]
- Published
- 2003
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26. Usefulness of cardiac transplantation in children with visceral heterotaxy (asplenic and polysplenic syndromes and single right-sided spleen with levocardia) and comparison of results with cardiac transplantation in children with dilated cardiomyopathy
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Larsen, Ranae L., Eguchi, Jim H., Mulla, Neda F., Johnston, Joyce K., Fitts, James, Kuhn, Micheal A., Razzouk, Anees J., Chinnock, Richard E., and Bailey, Leonard L.
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TRANSPLANTATION of organs, tissues, etc. , *HEART diseases - Abstract
Surgical mortality is high in children with visceral heterotaxy (VH), particularly if atrioventricular valve insufficiency, ventricular dysfunction, or aortic atresia is present. This study reviews the outcome of cardiac transplantation (CT) in infants and children with VH and congenital heart disease who are at high risk for standard palliative or corrective surgery. We reviewed CT outcomes in 29 children with VH, congenital heart disease, atrioventricular valve insufficiency, ventricular dysfunction, and/or aortic atresia. Median age at CT was 3.1 years. Cardiac surgery had been performed in 20 patients (69%) before CT. Follow-up since CT has been 8.5 ± 2.2 years. Outcomes were compared with 45 children who underwent transplantation for dilated cardiomyopathy. Actuarial graft survival in the VH group at 30 days and 1, 5, and 10 years was 100%, 86%, 68%, and 50%, respectively, compared with 100%, 96%, 83%, and 68% in children who underwent transplantation for dilated cardiomyopathy (p = 0.12). Splenic status, cardiac position, age at CT, number of prior cardiac surgeries, or systemic venous anomalies were not predictors of mortality after CT. Cardiopulmonary bypass and graft ischemic times were longer in the VH group; time on the ventilator after CT, length of hospitalization, and rejection, infection, post-transplant lymphoproliferative disease, and transplant coronary artery disease rates were equal. Thus, CT is a viable alternative therapy for high-risk patients with VH, possibly offering improved survival over standard surgical management. [Copyright &y& Elsevier]
- Published
- 2002
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27. Risk factors associated with posttransplant coronary artery disease in pediatric cardiac transplant recipients
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Hasaniya, Nahidh, Bailey, Leonard, Gundry, Steven, Razzouk, Anees, Chinnock, Richard, and Checchia, Paul A.
- Published
- 2002
- Full Text
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