Pediatric Transplant Patients Research Articles

#2300 Validation study of the 4-variable kidney failure risk equation for prediction of allograft loss in a group of pediatric kidney transplant recipients

Abstract Background and Aims Emerging evidence suggests that the 4-variable Kidney Failure Risk Equation (KFRE) can be used to predict the risk of graft failure in adult transplant recipients. However, research studies in pediatric patients are lacking. This study aimed to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [uACR]) for prediction of the 2- and 5-year risk of graft failure in a group of pediatric transplant patients. Method A retrospective observational study involving 59 pediatric patients who underwent kidney transplant between January 2007 and December 2017 was conducted. The KFRE risk scores were calculated with data collected at 1-year post-transplantation. The area under the receiver operating characteristic curves (AUC) and calibration plots were used to assess the discrimination and calibration properties of the 4-variable KFRE in predicting the risk of graft failure at 2 and 5 years from the point of the 1-year post-transplantation measurements. Results Among the 59 patients, 41 (69.5%) were male, with median age of 12.8 years (interquartile range 9.2-15.7) at the time of the kidney transplant. Eleven (18.6%) were living donor recipients. Median eFGR at 1-year post-transplantation was 62.0 mL/min/1.73 m2 (50.0-76.5); 1 (1.7%) and 3 (5.1%) patients developed graft failure within 2 and 5 years from the point of the 1-year post-transplantation measurements, respectively. The 4-variable KFRE showed excellent discrimination for the 2-year risk (AUC 0.966, 95% confidence interval [CI] 0.914-1.000) and very good discrimination for the 5-year risk (AUC 0.887, 95% CI 0.732-1.000). Calibration plots however showed imprecise calibration. A discernible trend was apparent in this sample, suggesting that living donor recipients have increased probability of experiencing graft failure in the first 5 years (p = 0.069). Conclusion The 4-variable KFRE may be of interest in predicting kidney failure progression in pediatric kidney transplant recipients using data at 1-year post-transplant, however to substantiate these findings and ensure the robustness of conclusions, larger-scale studies should be conducted.

NPP-669, a prodrug of cidofovir, is highly efficacious against human adenovirus infection in the permissive Syrian hamster model.

Human adenoviruses can cause serious, disseminated infections in immunocompromised patients. For pediatric allogeneic stem cell transplant patients, the case fatality rate can reach 80%. Still, there is no available antiviral drug that is specifically approved by the Food and Drug Administration for the treatment of adenovirus infections. To fill this pressing medical need, we have developed NPP-669, a prodrug of cidofovir with broad activity against double-stranded DNA viruses, including adenoviruses. Here, we report on the in vivo anti-adenoviral efficacy of NPP-669. Using the immunosuppressed Syrian hamster as the model, we show that NPP-669 is highly efficacious when dosed orally at 1 mg/kg and 3 mg/kg. In a delayed administration experiment, NPP-669 was more effective than brincidofovir, a similar compound that reached Phase III clinical trials. Furthermore, parenteral administration of NPP-669 increased its efficacy approximately 10-fold compared to oral dosing without apparent toxicity, suggesting that this route may be preferable in a hospital setting. Based on these findings, we believe that NPP-669 is a promising new compound that needs to be further investigated.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

Timing of intubation of pediatric hematopoietic cell transplant patients: an international survey.

Retrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician's decisions surrounding timing of intubation of pediatric HCT patients. We validated and distributed a brief survey exploring potential factors that may influence clinician's decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI). One hundred and four of the 869 PALISI Network's members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation. Our survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient's poor prognosis as a common reason for delayed intubation.

Clinical analysis of air-leak syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.

Air-leak syndrome (ALS) is considered as an independent risk factor for poor prognosis in adult patients who had received hematopoietic stem cell transplantation (HSCT), and the 5-year overall survival (OS) of ALS is less than 30%. However, the clinical features of ALS among post-transplant pediatric patients have rarely been explored. We retrospectively reviewed 2206 pediatric patients who had received an allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in prognosis following HSCT. In our research, ALS was divided into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). Following treatment of the ALS, 18 patients survived (18/28, 64.3%), and 10 patients died of respiratory failure or infection (10/28, 35.7%). The OS of ALS in Hebei Yanda Lu Daopei Hospital is significantly higher than others, and they were cited to be related to early diagnosis and timely FAM treatment in previous reports.

The Effect of Neurodevelopmental Disorders on the Prognosis of Children Undergoing Heart Transplantation: A Retrospective Analysis of the National Inpatient Sample 2011–2019

Background: Many international governing bodies recommend against heart transplantation in patients with severe cognitive-behavioral disabilities, however no clear criteria are offered to define severity. Patients with neurodevelopmental disorders may face systematic discrimination when being evaluated for transplant. We set out to investigate whether children with neurodevelopmental disorders that undergo heart transplantation have poorer in-hospital outcomes compared to neurotypical children. Methods: A retrospective analysis of the National Inpatient Sample database was conducted to identify pediatric patients with neurodevelopmental disorders who underwent heart transplantation from 2011–2019. Baseline characteristics and in-hospital outcomes between patients were compared. Binary logistic regression was used to investigate the association between the documented presence of a neurodevelopmental disorder and in-hospital outcomes in children undergoing heart transplantation. Results: We identified a weighted sample of 3770 pediatric cardiac transplant patients, of whom 245 (6.5%) had a documented diagnosis of neurodevelopmental disorder. There was no significant difference in the odds of major adverse cardiovascular events (all-cause mortality, stroke complications or myocardial infarction), surgical complications, infection, venous thromboembolic events, delirium/restraint use, or cardiac dysrhythmia. Patients with neurodevelopmental disorders had lower overall length of stay (44.0 days interquartile range (IQR): 16.0–90.0 vs. 57.08 days IQR: 22.0–112.0, p < 0.050), and cost of stay ($956,031 IQR: 548,559.0–1,801,412.0 vs. $1,074,793 IQR: 599,089.8–2,129,086.0, p < 0.050). Patients with neurodevelopmental disorders had significantly lower odds of acute transplant complications (adjusted odds ratio (aOR): 0.39, 95% confidence interval (CI): 0.21–0.74, p < 0.050) vascular complications (aOR: 0.36, 95% CI: 0.19–0.66, p < 0.050) and acute kidney injury (AKI) (aOR: 0.52, 95% CI: 0.33–0.83, p < 0.050). Conclusions: These data suggest that patients with neurodevelopmental disorders have overall similar if not potentially improved post-transplant outcomes in the acute setting compared to neurotypical patients, possibly secondary to selection bias in the patient selection process.

A novel approach to reducing hepatotoxicity related to fungal prophylaxis in pediatric lung transplant recipients.

Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first-line agent, has been shown to cause hepatotoxicity. We describe a single-center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post-transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post-operative course. This is a retrospective review of patients in the age 0-18 who received a lung transplant from June 2016-May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results. Forty-two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post-operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post-transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post-transplant, but this difference was not found to be statistically significant (p = .507). An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post-lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post-lung transplant are warranted.

Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications. We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa. We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa. Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients.

(1419) - Outcomes of Combined Liver-Lung Transplant in Pediatric Patients with Cystic Fibrosis: An ISHLT Study

(1419) - Outcomes of Combined Liver-Lung Transplant in Pediatric Patients with Cystic Fibrosis: An ISHLT Study

The association of Torque Teno viral load with CMV and BKV infection in pediatric and adolescent kidney transplant patients.

Background: Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. Objectives: To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. Study design: This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014–2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4–8 weeks at routine follow-up visits. Results: 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15–4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. Conclusions: This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care.

Gut Immunomodulation with Vedolizumab prior to Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Inflammatory Bowel Disease

Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied. Here we describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and during allogeneic HSCT. The study involved a retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab at 6 weeks, 4 weeks, and 1 week before undergoing HSCT. The conditioning regimen consisted of treosulfan, fludarabine, and cyclophosphamide with rabbit antithymocyte globulin, and GVHD prophylaxis included tacrolimus and steroids. Eleven patients (6 females) with a median age of 5 years (range, .4 to 14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools, and blood in stools. Four patients had developed a perianal fistula, and 1 patient had a rectal prolapse. One patient had both a gastrostomy tube and a jejunal tube in situ. Treatment of IBD before HSCT included steroids in 11 patients, anakinra in 2, infliximab in 4, sulfasalazine in 2, mesalazine in 2, and vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools, or blood in stools. Graft sources for HSCT were unrelated donor cord in 5 patients (2 with a 5/8 HLA match, 2 with a 7/8 match, and 1 with a 6/8 match), peripheral blood stem cells in 5 patients (2 haploidentical, 1 with a 9/10 HLA match, and 2 with a 10/10 match), and bone marrow in 1 patient (10/10 matched sibling donor). The median number of vedolizumab infusions was 4 (range, 3 to 12) before HSCT and 1 (range, 1 to 3) after HSCT, and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade I skin GVHD only. Chronic GVHD occurred in 1 patient and again was limited to the skin. There was no gut GVHD. Three patients experienced cytomegalovirus viremia, and 2 patients had Epstein-Barr virus viremia. At the time of this report, all patients were alive with no evidence of IBD at a median follow-up of 15 months (range, 3 to 39 months). Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for the prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as a pre-HSCT comorbidity.

Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8-15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < -1.645; n = 12), restrictive defects (TLC < 80% predicted, FEV1 and FVC z-scores < -1.645; n = 7) and non-specific pattern (FEV1 and FVC z-score< -1.645, FEV1/FVC z-score > -1.645, and TLC > 80% predicted; n = 8). HCT for malignant disease was the only factor associated with LONIPC (P = 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

Outcomes for Pediatric Oncology and Hematopoietic Stem Cell Transplantation Patients Who Undergo Tracheostomy Placement: A Pediatric Health information System Database Cohort Study, 2009-2020.

To describe the epidemiology, surgical complications, and long-term outcomes after tracheostomy in pediatric oncology and/or hematopoietic stem cell transplantation (HSCT) patients in U.S. Children's Hospitals. Retrospective cohort from the Pediatric Health information System (PHIS) database, 2009-2020. The PHIS dataset incorporates data from 48 pediatric hospitals in the Children's Hospital Association. Patients 0-21 years old with an oncologic diagnosis and/or underwent HSCT, received a tracheostomy, and were discharged from hospital between January 1, 2009, and December 31, 2020. None. There were 1061 patients included in the dataset, and 217 (20.5%) had undergone HSCT. The annual prevalence in tracheostomy usage did not change over the study period. The majority of patients (62.2%) underwent tracheostomy early (< 30 d) in the admission and those who underwent the procedure later (> 90 d) had a significant increase in mortality (52.6% vs. 17.6%; p < 0.001) and mechanical ventilation (MV) at discharge (51.9% vs. 24.5%; p < 0.001) compared with the early tracheostomy patients. Complications reported included tracheostomy site bleeding (< 1%) and infection (24%). The overall rate of MV at discharge was 32.6% and significantly associated with chronic lung (adjusted odds ratio [OR], 1.54; 95% CI, 1.03-2.32) and acute lung disease (OR, 2.18; 95% CI, 1.19-3.98). The overall rate of mortality was 19.6% within the cohort and significantly associated with HSCT (OR, 5.45; 95% CI, 3.88-7.70), diagnosis of sepsis (OR, 2.09; 95% CI, 1.28-3.41), and requirement for renal replacement therapy (OR, 2.76; 95% CI, 1.58-4,83). This study demonstrated a static prevalence of tracheostomy placement in the cohort population relative to the increasing trends in other reported groups. Regardless of underlying diagnosis, the study patients incurred substantial morbidity and mortality. However, tracheostomy specific complication rates were comparable with that of the general pediatric population and were not associated with increased odds of mortality within this population.

Caregiver self-efficacy providing nutritional support for pediatric patients undergoing hematopoietic stem cell transplant is associated with psychosocial factors.

Caregiver self-efficacy in providing nutritional support to pediatric hematopoietic stem cell transplantation (HSCT) patients has been little studied despite the increased risk of these children potentially being over- or under-nourished after HSCT, and nutritional status could possibly affect treatment outcomes. The current study aimed to describe caregiver dietary self-efficacy and its associated psychosocial factors and barriers to following dietary recommendations. Caregivers completed questionnaires pre-HSCT and 30 days, 100 days, and one year post-HSCT. A subset provided a 24-h recall of food intake. Results showed generally high caregiver confidence and low difficulty supporting their child nutritionally. However, lower confidence was associated with higher caregiver depression, anxiety, and stress 30 days post-HSCT. Further, higher difficulty at various time points was correlated with lower income, higher depression and anxiety, stress, and miscarried helping (i.e., negative caregiver-child interactions surrounding eating), as well as child overweight status and failure to meet protein intake guidelines. Nutritional criteria for protein, fiber, added sugar, and saturated fat were met by 65%, 0%, 75%, and 75%, respectively. Caregiver attitudes and child behavior were the most frequently reported barriers to healthy eating. Results suggest that directing resources to caregivers struggling emotionally, economically, or transactionally could support pediatric patients undergoing HSCT in maintaining optimal nutritional status.

Cytomegalovirus Triplex vaccine in pediatric hematopoietic stem cell transplant patients at high risk for cytomegalovirus complications: evaluation of vaccine safety, immunogenicity and impact on viremia requiring antivirals.

Not available.

Impact of the operative technique on mid- and long-term results following paediatric heart transplantation.

The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long-term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation. All 134 patients (aged <18years) - (group-1) biatrial (n=84), versus (group-2) bicaval (n=50), who underwent heart transplantation between October 1988 and December 2021, were analysed. Freedom from events were estimated using the Kaplan-Meier method. Potential differences were analysed using the log rank test and Cox proportional hazard models. Mean±standard deviation: Bypass time (per minutes) was higher in the group 1 as compared with group 2 (P=0.050). Survival was not significantly different (P=0.604) in either groups. Eighteen patients required permanent pacemaker implantation in the group 1 and only one patient required it in the group 2 (P=0.001). Paediatric heart transplantation using bicaval technique results similar long-term survival compared with the biatrial technique. The incidence of atrial rhythm disorders was significantly higher in the biatrial group, requiring a higher frequency of pacemaker implantation in this group. As a results, the bicaval technique has replaced the biatrial technique in our centre.

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach.

Neurologic complications, both infectious and non-infectious, are frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. Up to 46% of HCT and 50% of SOT recipients experience a neurological complication, including cerebrovascular accidents, drug toxicities, as well as infections. Defects in innate, adaptive, and humoral immune function among transplant recipients predispose to opportunistic infections, including central nervous system (CNS) disease. CNS infections remain uncommon overall amongst HCT and SOT recipients, compromising approximately 1% of total cases among adult patients. Given the relatively lower number of pediatric transplant recipients, the incidence of CNS disease amongst in this population remains unknown. Although infections comprise a small percentage of the neurological complications that occur post-transplant, the associated morbidity and mortality in an immunosuppressed state makes it imperative to promptly evaluate and aggressively treat a pediatric transplant patient with suspicion for viral meningoencephalitis. This manuscript guides the reader through a broad infectious and non-infectious diagnostic differential in a transplant recipient presenting with altered mentation and fever and thereafter, elaborates on diagnostics and management of viral meningoencephalitis. Hypothetical SOT and HCT patient cases have also been constructed to illustrate the diagnostic and management process in select viral etiologies. Given the unique risk for various opportunistic viral infections resulting in CNS disease among transplant recipients, the manuscript will provide a contemporary review of the epidemiology, risk factors, diagnosis, and management of viral meningoencephalitis in these patients.

New Insights into Pediatric Kidney Transplant Rejection Biomarkers: Tissue, Plasma and Urine MicroRNAs Compared to Protocol Biopsy Histology.

The early identification of a subclinical rejection (SCR) can improve the long-term outcome of the transplanted kidney through intensified immunosuppression. However, the only approved diagnostic method is the protocol biopsy, which remains an invasive method and not without minor and/or major complications. The protocol biopsy is defined as the sampling of allograft tissue at pre-established times even in the absence of an impaired renal function; however, it does not avoid histological damage. Therefore, the discovery of new possible biomarkers useful in the prevention of SCR has gained great interest. Among all the possible candidates, there are microRNAs (miRNAs), which are short, noncoding RNA sequences, that are involved in mediating numerous post-transcriptional pathways. They can be found not only in tissues, but also in different biological fluids, both as free particles and contained in extracellular vesicles (EVs) released by different cell types. In this study, we firstly performed a retrospective miRNA screening analysis on biopsies and serum EV samples of 20 pediatric transplanted patients, followed by a second screening on another 10 pediatric transplanted patients' urine samples at one year post-transplant. In both cohorts, we divided the patients into two groups: patients with histological SCR and patients without histological SCR at one year post-transplantation. The isolated miRNAs were analyzed in an NGS platform to identify different expressions in the two allograft states. Although no statistical data were found in sera, in the tissue and urinary EVs, we highlighted signatures of miRNAs associated with the histological SCR state.

Defibrotide Prophylaxis after Second Hematopoietic Cell Transplant in Pediatric Patients at Very High Risk for Veno-Occlusive Disease

Defibrotide Prophylaxis after Second Hematopoietic Cell Transplant in Pediatric Patients at Very High Risk for Veno-Occlusive Disease