Pediatric LTx Research Articles

Outcomes of Concomitant Cardiac Surgical Procedures Performed During Pediatric Lung Transplantation in the United States.

Data on concomitant cardiac surgery (CCS) performed during pediatric lung transplantation (LTx) is limited. Therefore, we conducted a multi-institutional analysis to identify the incidence and outcomes of CCS in pediatric (< 18 years) LTx recipients by merging data (2004-2023) from the United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) databases. Of the total of 596 pediatric LTx recipients, 87 (15%) underwent CCS. The majority of these cardiac surgeries were atrial septal defect (ASD) closure (90%) followed by aortic arch/descending aortic repair (3%), atrial repair (3%), ventricular septal defect closure (2%), patent ductus arteriosus ligation (2%), and tricuspid valve repair (2%). The median age at LTx was 3years (IQR: 0-12). Pulmonary hypertension (PHT) was the predominant indication for LTx (54%). Survival to discharge was 94% and 5-years survival was 64%. Our findings indicate CCS in children undergoing LTx has acceptable outcomes.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2022 Part I: Lung Transplantation

These highlights focus on the research in lung transplantation (LTX) that has been published in the year 2022 and includes the assessment and optimization of candidates for LTX, donor optimization, the use of organs from donation after circulatory death (DCD), and outcomes when using marginal or novel donors, recipient factors affecting LTX, including age, disease, the use of extracorporeal life support (ECLS), and special situations, such as COVID-19, pediatric LTX, and retransplantation. The remainder of the article focuses on the perioperative management of LTX, including the perioperative risk factors for acute renal failure (AKI), and the incidence and management of phrenic nerve injury, delirium, and pain and the postoperative management of hyperammonemia, early postoperative infections, and the use of donor-derived cell-free deoxynucleic acid (DNA) to detect rejection.

Pediatric Lung Transplantations: New Possibilities and Challenges in Treatment of Children With End-Stage Respiratory Failure

Lung transplantation (LTx) is the last treatment option for children with end-stage respiratory failure. According to the literature, cystic fibrosis remains the most common cause of pediatric LTx. The study aimed to assess the characteristics of pediatric LTx recipients as well as the outcomes of the transplantation. Our study is a single-center retrospective review of clinical data of all 11 patients who underwent a LTx before the age of 18 years between the years 2016 and 2020. Medical records were examined for patients' characteristics, general treatment, and complications. There were a total of 11 patients (8 males) with a median age 14.5 years (range: 11-17). The primary diseases that led to LTx were: cystic fibrosis in 8 patients (72.73%), hereditary hemorrhagic telangiectasia in 2 patients (18.18%), and idiopathic pulmonary arterial hypertension in 1 patient (9.09%). Median period from qualification to LTx was 235.55 days (range: 11-748). Two patients (18.18%) underwent lung retransplantation after 3 and 5 years. One patient passed away 10 months after surgery due to noncompliance. Pediatric lung transplantation is less common than lung transplantation in adults. It also differs in fields of donors accessibility, stronger immune system response and noncompliance that may lead to graft failure.

Lung Transplantation for Pulmonary Vascular Disease in Children: A United Network for Organ Sharing Analysis.

Pulmonary vascular disease (PVD) represents an important clinical indication for lung transplant (LTx) in infants, children, and adolescents. There is limited information on LTx outcomes in these patients. We explored LTx volumes and post-LTx survival in children with PVD compared to other diagnoses. The UNOS Registry was queried from 1989 to 2020 to identify first-time pediatric LTx recipients (< 18 yo). PVD was categorized as idiopathic pulmonary arterial hypertension (IPAH) and non-idiopathic arterial hypertension (non-IPAH) and compared to all other patients as other diagnoses. Univariate and multivariate regression models were performed. 984 pediatric LTx patients (593 before 2010 and 391 during/after 2010) were identified, of which 145 (14.7%) had PVD. There has been no significant change in annual rate of all LTxs over comparative eras. However, there has been a decrease in rate of LTxs for PVD patients. Children with PVD had similar survival to other LTx groups in the early era (p = 0.2) and the latter era (p = 0.9). Univariate Cox models, showed that LTx in patients with PVD was associated with a significantly less risk of mortality for children aged 6-11years compared to younger and older cohorts (HR = 0.4 [0.17-0.98]; p = 0.045), whereas multivariate analysis showed a trend toward higher mortality in 11-17-year-olds (HR = 1.54 [0.97-2.45]; p = 0.06). For PVD patients, oxygen supplementation and ventilator support at LTx were associated with worse post-transplant survival (p = 0.029 and p = 0.01). There has been a decrease in LTx volume for pediatric patients with PVD in the modern era. Post-LTx outcomes for children with PVD are similar to those of other diagnoses in both eras, with children aged 6-11years having the best survival. Given these findings, LTx should be considered for this patient population.

Reality of DCD donor use in pediatric thoracic transplantation in the United States

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.

Extracorporeal membrane oxygenation bridge to pediatric lung transplantation: Modern era analysis.

Survival outcomes of children on extracorporeal membrane oxygenation (ECMO) at time of lung transplant (LTx) remain unclear. Pediatric first-time LTx recipients transplanted between January 2000 and December 2020 were identified in the United Network for Organ Sharing Registry to compare post-transplant survival according to ECMO support at time of transplant. For a comprehensive analysis of the data, univariate analysis, multivariable Cox regression, and propensity score matching were performed. During the study period, 954 children under 18 years of age underwent LTx with 40 patients on ECMO. We did not identify a post-LTx survival difference between patients receiving ECMO when compared to those that did not. A multivariable Cox regression model (Hazard ratio = 0.83; 95% confidence interval: 0.47, 1.45; p = .51) did not demonstrate an increased risk for death post-LTx. Lastly, a propensity score matching analysis, retaining 33 ECMO and 33 non-ECMO patients, further confirmed no post-LTx survival difference comparing ECMO to no ECMO cohorts (Hazard ratio = 0.98; 95% confidence interval: 0.48, 2.00; p = .96). In this contemporary cohort of children, the use of ECMO at the time of LTx did not negatively impact post-transplant survival.

Atrial arrhythmias following lung transplant: a single pediatric center experience.

Outcomes after lung transplant (LTx) in children have slowly improved. Although atrial arrhythmia (AA) is a common and adverse complication following LTx among adults, there is limited data on pediatric recipients. We detail our pediatric single-center experience while providing further insights on occurrence and management of AA following LTx. A retrospective analysis of LTx recipients at a pediatric LTx program from 2014 to 2022 was performed. We investigated timing of occurrence and management of AA following LTx, and its effect on post-LTx outcome. Three out of nineteen (15%) pediatric LTx recipients developed AA. The timing of occurrence was 9-10 days following LTx. Those patients in the older age group (age >12 years old) were the only ones who developed AA. Developing AA did not have a negative effect on hospital stay duration or short-term mortality. All LTx recipients with AA were discharged home on therapy that was discontinued at 6 months for those who was on mono-therapy without recurrence of AA. AA is an early post-operative complication in older children and younger adults undergoing LTx at a pediatric center. Early recognition and aggressive management can mitigate any morbidity or mortality. Future investigations should explore factors that place this population at risk for AA in order to prevent this complication post-operatively.

Worldwide organ allocation systems for pediatric lung transplantation.

Pediatric lung transplantation (LTX) remains limited by the scarcity of small donor lungs, particularly in less populated parts of the world. Optimal organ allocation, including the prioritization and ranking of pediatric LTX candidates, and the appropriate matching of pediatric donors to recipients have been crucial elements in improving pediatric LTX outcomes. We aimed to elucidate the various pediatric lung allocation practices worldwide. A global survey of current pediatric solid organ transplantation deceased donation allocation practices was conducted by the International Pediatric Transplant Association (IPTA), and these policies were subsequently analyzed if publicly available, with focus on pediatric lung transplantation. Significant variation was found in lung allocation systems worldwide both in terms of prioritization and distribution for children. Definition of pediatrics varied from <12 years of age to <18 years of age. While several countries performing LTX for young children do not have a formal system to prioritize pediatric candidates, many countries that perform LTX at higher rates do offer prioritization methods for children: including the United States, United Kingdom, France, Italy, Australia, and countries serviced by Eurotransplant. Certain lung allocation practices for pediatrics are highlighted herein, including the newly instituted Composite Allocation Score (CAS) system in the United States, pediatric matching with Eurotransplant, and pediatric prioritization in Spain. The systems highlighted here explicitly aim to provide judicious and high quality LTX care for children.

Body mass index percentage and survival in pediatric patients listed for lung transplantation: A modern-era multi-institutional analysis

Prior studies suggest that being underweight by body mass index percentiles (BMI%) or thinness grade did not affect post-transplant survival in pediatric lung transplant (LTx) recipients regardless of cystic fibrosis (CF) or non-CF diagnosis. Graft and overall survival from the time of listing was instead evaluated based on listing BMI%, the current standard of practice for BMI definitions in pediatrics, to ascertain the impact of a "severely low" subcategory. The UNOS registry was queried for children listed for LTx (aged 2 to <18 years) from January 1986 to March 2020. BMI% at listing and transplant were calculated per CDC guidelines according to age in years, sex, and reported BMI%. Patients were divided by listing BMI%: severely low (<3rd), low (3-<5th), normal (5-<85th), overweight (85-<95th), and obese (≥95th). Kaplan-Meier curves were generated to assess differences in overall survival since listing based on BMI% classes. Cox proportional-hazards models were developed to assess risk factors for overall and graft survival, including listing BMI%, transplant listing era (≥2005), and listing age, by reporting hazard ratios (HR). Listing BMI% was calculable for 1,876 patients. The proportion of patients with CF differed significantly between BMI% groups (p < 0.001). Patients listed with a non-CF diagnosis comprised 34% of those in the severely low category, and 88% of those listed with an obese BMI%. Compared to patients with a normal listing BMI%, the cohort with severely low BMI% had worse overall survival regardless of LTx (p=0.009) and graft survival (p=0.034). Compared to patients with a low BMI%, those with a severely low BMI% had significantly poorer graft survival as well (p=0.040). Mean graft survival was not significantly different between groups that remained at listing BMI% vs those that improved in category despite an overall small sample size. Independent predictors of poorer survival from the time of listing include severely low vs low-normal BMI% (HR=1.20) and listing age (HR=1.02). The proportion of children listed at severely low BMI% has steadily decreased with time, yet pediatric LTx candidates listed with a severely low BMI% had poorer graft and overall survival compared to those of normal BMI%. Severely low listing BMI% was an independent prognostic factor for higher mortality risk from the time of placement on the waitlist. BMI% may be a modifiable target for improving survival regardless of transplantation.

Late-onset Chronic Kidney Disease Over 2 Decades After Pediatric Liver Transplantation: A Single-center, Retrospective Study.

Although chronic kidney disease (CKD) after liver transplantation (LTx) is a common complication in adults, its long-term significance after pediatric LTx remains unclear. We examined the decades-long transition of renal function and revealed the risk factors for late-onset CKD after pediatric LTx in a single-center retrospective cohort of 117 pediatric LTx recipients who survived >5 y. The estimated glomerular filtration rate (eGFR) and CKD stages were calculated using serum creatinine. Risk factor analysis for late-onset CKD was performed in 41 patients whose eGFR could be evaluated at >20 y after LTx. The median age at LTx was 1.3 y, and most primary diagnoses were biliary atresia (77%). The mean pre-LTx and 1, 5, 10, 20, and >20 y post-LTx eGFRs were 180, 135, 131, 121, 106, and 95 mL/min/1.73 m 2 , respectively, with a median renal follow-up period of 15 y. The eGFR declined by 47% at >20 y after LTx ( P < 0.001). CKD was observed in 8%, 19%, and 39% of cases at 10, 20, and >20 y after LTx, respectively. In patients receiving cyclosporine, trough levels were 1.5 times higher in those with CKD up to 10 y after LTx. The multivariate analysis showed that older age at LTx (odds ratio, 1.3 by 1 y; P = 0.008) and episodes of repeated/refractory rejection (odds ratio, 16.2; P = 0.002) were independent risk factors of CKD >20 y after LTx. In conclusion, renal function deteriorates slowly yet steadily after pediatric LTx. Long-term careful surveillance is essential after pediatric LTx, especially in repeated/refractory rejection or long-term high trough-level use of cyclosporine cases.

COVID-19 in pediatric lung transplant recipients: Clinical course and outcome

COVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients. Between March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded. Nineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p=0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable. Unlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.

Monitoring practices of chronic lung allograft dysfunction in pediatric lung transplantation.

Chronic lung allograft dysfunction (CLAD) continues to negatively impact the survival of pediatric lung transplant (LTx) recipients. Current consensus guidelines are adult-focused. We sought to examine CLAD detection and monitoring practices at pediatric LTx programs. We conducted a survey among the International Pediatric Lung Transplant Collaborative. Questions consisted of practitioner's experience, LTx program demographics, and querying tests used for CLAD surveillance and detection. Investigations queried included: chest x-ray (CXR), chest computed tomography (CT), lung magnetic resonance imaging (MRI), ventilation/perfusion scanning, conventional pulmonary function testing (PFT), multiple breath washout (MBW), infant/preschool PFT, bronchoalveolar lavage, transbronchial biopsies (TBBx), or other tissue sampling techniques. Preferences for certain modalities over others were questioned based on a five-point Likert scale. Twenty-four of 25 programs responded. Chest CT and CXR are used generally for both CLAD surveillance and detection. No programs use lung MRI clinically, it may have some utility in the future. While all centers use conventional PFT, MBW, and infant/preschool PFT are used in one-fifth and one-third of centers, respectively. While the majority of programs use TBBx, only 41.7% would obtain a diagnosis based on tissue histopathology over noninvasive techniques if CLAD is suspected. Utilization of biomarkers is still limited. Our results indicate continued use of conventional PFT along with chest CT and less so CXR for CLAD detection and monitoring in the large majority of centers. Infant/preschool PFTand novel methods such as MBW are used in a few centers only. Respondents agreed there is a timely need for pediatric consensus guidelines on CLAD detection and monitoring.

Assessment of Cardiac Contribution to Exercise Intolerance in Pediatric Bilateral Lung Transplant Recipients

<h3>Purpose</h3> Exercise intolerance is common among lung transplant (LTx) recipients. However, there is limited data in pediatrics. Since the heart and lungs work in concert with each other, we aim to assess the cardiac contribution to exercise intolerance in pediatric LTx recipients by examining the prevalence of traditional cardiac risk factors (CRFs) and their performance on cardiopulmonary exercise testing (CPET). <h3>Methods</h3> All pediatric LTx recipients followed at a single center who had a resting echocardiogram (echo), were able to exercise, and had a routine CPET in the last 2 years were included. CRFs including hypertension, hyperlipidemia, diabetes mellitus (DM), body mass index (BMI), activity level, and smoking history were assessed. CPET-derived maximal oxygen consumption (VO2_max) and % predicted peak VO2 (ppVO2_max) were used to assess exercise tolerance. Left ventricular (LV) systolic and diastolic function were also assessed on resting echo. <h3>Results</h3> 11 bilateral LTx patients (7M, 4F, and median age 21 years, range 17-28 years) formed the cohort. Median time since LTx is 6 years, range 2-10 years. The majority of patients (8, 73%) had multiple CRFs: 7 (64%) had hypertension, 7 (64%) hyperlipidemia, 6 (55%) DM, 2 with BMI ≥25 kg/m², and 6 (55%) sedentary lifestyle. None had a smoking history. On resting echo, all had normal LV systolic function. 5 (45%) had LV diastolic dysfunction. On CPET, 9 (82%) had abnormal ppVO2_max ≤85%, even with maximal patient effort. None had ischemia. Surprisingly, only 2 of the 9 had a pulmonary limitation to exercise with abnormal breathing reserve (<25%) to account for abnormal ppVO2_max. 6 had a cardiac limitation to exercise attributed to inability to augment stroke volume (decreased % predicted peak O2 pulse). 1 had an abnormal respiratory exchange ratio (RER <1.10), with a normal % predicted peak O2 pulse and a chronotropic deficit (achieving 60% predicted peak heart rate). Of note, 2 patients had normal exercise tolerance with ppVO2_max >85%. <h3>Conclusion</h3> Despite maximal effort, low exercise tolerance is common among pediatric LTx recipients. The high prevalence of CRFs, diastolic dysfunction, and inability to augment stroke volume suggest a potential cardiac contribution to exercise intolerance for this cohort. Further studies are needed to define potential cardiac issues in exercise tolerance in pediatric LTx recipients.

High Volume Centers Have Lower Incidence of Acute Cellular Rejection in Pediatric Lung Transplant Recipients and Better Survival After Treatment

Purpose Acute cellular rejection (ACR) is a common form of allograft rejection in pediatric recipients after lung transplant (LTx). ACR most commonly occurs during the 1st post-transplant year. This study sought to determine if transplant center volume affected ACR-related outcomes in children after LTx. Methods The United Network for Organ Sharing (UNOS) Registry was queried for patients <18 years who underwent LTx in 1987-2020. Cohorts were patients who were treated for ACR during the 1st post-LTx year (ACR group) and who did not experience ACR (non-ACR). Survival of patients who had ACR was compared by LTx center volume defined as average of LTx/year: >5LTx/year (high), >1-≤5LTx/year (medium) and 1LTx/year (low). Results 1338 patients were included in our analysis with 271 (20.3%) identified as having ACR. Compared to non-ACR, the ACR cohort were older (median 14 [11-16] vs 13 [7-16] years, p<0.001), more commonly female (65.3% vs 57.3%, p=0.016), more commonly diagnosed with cystic fibrosis (62.3% vs 45.5%, p<0.001), and had a higher lung allocation score at LTx (37.3 [34.6-47.8] vs 35.8 [33-42.6], p=0.029). Kaplan-Meier survival of ACR vs non-ACR cohorts trended towards lower survival at 5-yr (37% vs 47%) & 10-yr (25% vs 34%) post-LTx, p=0.06. ACR occurred in 17% of patients at high (n=98/574), 18.5% (n=73/395) at medium, and 27% (n=100/369) at low volume centers. Patients treated for ACR at high volume centers had better post-transplant survival than low volume centers (p<0.001) but similar survival to those at medium volume centers (p=0.081; Figure). No significant difference in survival was observed in medium vs low volume centers (p=0.14). Conclusion ACR treated within the 1st post-LTx year influences survival of pediatric LTx recipients. ACR incidence was lowest at higher volume centers where post-ACR treatment survival outcomes were also superior. More analysis is needed to determine factors affecting differences in center outcomes regarding ACR. Acute cellular rejection (ACR) is a common form of allograft rejection in pediatric recipients after lung transplant (LTx). ACR most commonly occurs during the 1st post-transplant year. This study sought to determine if transplant center volume affected ACR-related outcomes in children after LTx. The United Network for Organ Sharing (UNOS) Registry was queried for patients <18 years who underwent LTx in 1987-2020. Cohorts were patients who were treated for ACR during the 1st post-LTx year (ACR group) and who did not experience ACR (non-ACR). Survival of patients who had ACR was compared by LTx center volume defined as average of LTx/year: >5LTx/year (high), >1-≤5LTx/year (medium) and 1LTx/year (low). 1338 patients were included in our analysis with 271 (20.3%) identified as having ACR. Compared to non-ACR, the ACR cohort were older (median 14 [11-16] vs 13 [7-16] years, p<0.001), more commonly female (65.3% vs 57.3%, p=0.016), more commonly diagnosed with cystic fibrosis (62.3% vs 45.5%, p<0.001), and had a higher lung allocation score at LTx (37.3 [34.6-47.8] vs 35.8 [33-42.6], p=0.029). Kaplan-Meier survival of ACR vs non-ACR cohorts trended towards lower survival at 5-yr (37% vs 47%) & 10-yr (25% vs 34%) post-LTx, p=0.06. ACR occurred in 17% of patients at high (n=98/574), 18.5% (n=73/395) at medium, and 27% (n=100/369) at low volume centers. Patients treated for ACR at high volume centers had better post-transplant survival than low volume centers (p<0.001) but similar survival to those at medium volume centers (p=0.081; Figure). No significant difference in survival was observed in medium vs low volume centers (p=0.14). ACR treated within the 1st post-LTx year influences survival of pediatric LTx recipients. ACR incidence was lowest at higher volume centers where post-ACR treatment survival outcomes were also superior. More analysis is needed to determine factors affecting differences in center outcomes regarding ACR.

Auto-inflammation and auto-immunity pathways are associated with emergence of BOS in pediatric lung transplantation.

Long-term survival after lung transplantation (LTx) is limited by chronic lung allograft dysfunction (CLAD). We report an analysis of cytokine profiles in bronchoalveolar lavage samples collected during a prospective multicenter non-interventional trial primarily designed to determine the impact of community-acquired respiratory viral infections (CARV) in outcomes after pediatric LTx. In this analysis, we identify potential biomarkers of auto-inflammation and auto-immunity associated with survival and risk of bronchiolitis obliterans (BOS) after LTx with cytokine analysis of bronchoalveolar lavage fluid (BALF) from 61 pediatric recipients. Higher IL-23 (p=.048) and IL-31 (p=.035) levels were associated with the risk of BOS, and lower levels of epithelial growth factor (EGF) (p=.041) and eotaxin (EOX) (p=.017) were associated with BOS. Analysis using conditional inference trees to evaluate cytokines at each visit associated with survival identified soluble CD30 (p<.001), pro-inflammatory cytokine IL-23 (p=.02), and sTNFRI (p=.01) below cutoff levels as associated with BOS-free survival. Our results indicate that post-LTx survival in children may be linked to activation of alternate pathways of the immune system that affect airway remodeling in addition to activation of "classical" pathways that have been described in adult LTx recipients. These may indicate pathways to target for intervention.

Feasibility of Real-Time Central Surgical Review for Patients with Advanced-Stage Hepatoblastoma in the JPLT3 Trial.

In the JPLT3 study, a real-time central surgical reviewing (CSR) system was employed aimed at facilitating early referral of candidates for liver transplantation (LTx) to centers with pediatric LTx services. The expected consequence was surgery, including LTx, conducted at the appropriate time in all cases. This study aimed to review the effect of CSR on institutional surgical decisions in cases enrolled in the JPLT3 study. Real-time CSR was performed in cases in which complex surgeries were expected, using images obtained after two courses of preoperative chemotherapy. Using the cloud-based remote image viewing system, an expert panel consisting of pediatric and transplant surgeons reviewed the images and commented on the expected surgical strategy or the necessity of transferring the patient to a transplant unit. The results were summarized and reported to the treating institutions. A total of 41 reviews were conducted for 35 patients, and 16 cases were evaluated as possible candidates for LTx, with the treating institutions being advised to consult a transplant center. Most of the reviewed cases promptly underwent definitive liver surgeries, including LTx per protocol.

Cardiovascular Burden Is High in Pediatric Lung Transplant Recipients.

Cardiovascular morbidity is common in adults after lung transplantation (LTx) but has not been described for pediatric LTx recipients. Early subclinical cardiovascular damage is reflected by increases in pulse wave velocity (PWV; indicating arteriosclerosis), intima-media thickness (IMT; indicating atherosclerosis), and left ventricular mass index (LVMI; indicating left ventricular hypertrophy). We annually assessed 47 pediatric LTx recipients in a prospective longitudinal study (144 observations, mean 3.1 visits/patient, range of 1-4 visits, mean follow-up 2.2 y). At inclusion, increased PWV and IMT were detected in 13% and 30%, respectively, and elevated LVMI was detected in 33%. Higher PWV was associated with male sex, longer time since LTx, higher diastolic blood pressure, and lower glomerular filtration rate. Male sex and lower hemoglobin levels were associated with higher IMT, and the presence of diabetes was associated with higher LVMI. Pediatric LTx recipients suffer from a high and sustained burden of subclinical cardiovascular damage. In light of improving long-term outcomes, cardiovascular morbidity needs to be addressed. Our analysis identified classical and nonclassical risk factors to be associated with the measures for cardiovascular damage, which could serve as targets for intervention.

Long-term Follow-up of a Randomized Trial of Tacrolimus or Cyclosporine A Microemulsion in Children Post Liver Transplantation.

Background.The aim of this study was to determine the long-term efficacy and safety of tacrolimus (Tac) and cyclosporine immunosuppression in pediatric liver transplantation (LTx).Methods.One hundred fifty-six patients who had taken part in a multicenter, randomized, open, parallel study of Tac and corticosteroids versus cyclosporine A microemulsion (CyA-ME), corticosteroids, and azathioprine. Patients were assessed at regular intervals up to 14 y after LTx. Analysis was conducted descriptively.Results.In a long-term follow-up, there was a similar incidence of acute rejection (Tac versus CyA-ME, 5 versus 8) and graft loss (5 versus 10). There were 11 deaths in the cohort, which were from infectious complications/malignancy in the Tac group (n = 2/5) and from chronic rejection/liver failure in the CyA-ME group (n = 3/6). A similar incidence of Epstein-Barr virus and posttransplant lymphoproliferative disease was observed (8 versus 8, 3 versus 3). However, there was a greater incidence of cosmetic adverse events in the CyA-ME cohort, with higher incidences of hypertrichosis (8 versus 27) and gum hyperplasia (20 versus 6). Growth improved equally in both groups. Overall, 81% of patients randomized to Tac remained on Tac therapy at study end, compared with 31% of patients randomized to CyA-ME. Common reasons for switching from CyA-ME included steroid-resistant/acute rejection (n = 12/8) and cosmetic changes (n = 8).Conclusions.This study is the first prospective, observational follow-up study of pediatric patients randomized to Tac and CyA-ME to evaluate long-term outcomes. Our analysis was limited by the degree of switchover between the cohorts; however, there were fewer deaths from chronic rejection/liver failure and reduced adverse events with Tac. Long-term use of Tac and Tac combination therapy appears to be safe and effective immunosuppression for pediatric LTx recipients.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p<.001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p<.001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p=.003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p<.001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p=.01 at 10years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p=.013), but was similar between groups for males (55% vs. 54%, p=.305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Role of Tacrolimus C/D Ratio in the First Year After Pediatric Liver Transplantation.

Background: The calcineurin inhibitor (CNI) tacrolimus (TAC) is a cornerstone agent in immunosuppressive therapy in pediatric liver transplantation (LTX). Adverse effects limit the use of CNI. In adults, calculating the individual TAC metabolism rate allows to estimate the transplant recipient's risk for therapy-associated complications.Methods: A retrospective, descriptive data analysis was performed in children who had undergone LTX in 2009–2017 and had received TAC twice daily in the first year after LTX. A weight-adjusted concentration/dose ratio (C/D ratio) was calculated [TAC trough level/(daily TAC dose/body weight)] every 3 months after LTX to estimate the average individual TAC metabolism rate. Depending on the C/D ratio, all patients were divided into two groups: fast metabolizers (FM) and slow metabolizers (SM). Clinical and laboratory parameters were analyzed as risk factors in both groups.Results: A total of 78 children (w 34, m 44, median age at LTX 2.4; 0.4–17.0 years) were enrolled in the study. FM (SM) had a mean C/D ratio of <51.83 (≥51.83) ng/ml/(mg/kg). FM were younger at the time of LTX (median age 1.7; 0.4–15.8 years) than SM (5.1, 0.4–17.0), p = 0.008. FM were more likely to have biliary atresia (20/39, 51%) compared to SM (11/39, 28%), p = 0.038, whereas SM were more likely to have progressive familial intrahepatic cholestasis (9/39, 23%) vs. in FM (1/39, 3%), p = 0.014. Epstein–Barr virus (EBV) infection occurred more frequently in FM (27/39, 69%) than SM (13/39, 33%), p = 0.002. Three FM developed post-transplant lymphoproliferative disorder. The annual change of renal function did not differ in both groups (slope FM 1.2 ± 0.6; SM 1.4 ± 0.8 ml/min/1.73 m2 per year, and p = 0.841).Conclusions: Calculation of individual, weight-adjusted TAC C/D ratio is a simple, effective, and cost-efficient tool for physicians to estimate the risk of therapy-associated complications and to initiate individual preventive adjustments after pediatric LTX. Lower TAC levels are tolerable in FM, especially in the presence of EBV infection, reduced renal function, or when receiving a liver transplant in the first 2 years of life.