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  • Dong C
  • Song Z
  • Sun C
  • Wang K
  • Zhang W
  • et al.
BACKGROUND:

Optimizing the immunosuppressive regimen is essential to improve the long-term outcomes of pediatric liver transplant recipients.

METHODS:

We conducted a prospective, randomized, open-label study to compare the safety and efficacy of 2 treatment approaches during pediatric liver transplantation: tacrolimus monotherapy following basiliximab induction (the study group) and a dual regimen of tacrolimus plus steroids (the control group). A total of 150 patients were enrolled, with 75 patients allocated to each group.

RESULTS:

In both groups, recipients achieved graft and recipient overall survival rates exceeding 93%, with no statistically significant differences between them. However, the study group exhibited a significantly lower incidence of acute cellular rejection (ACR), delayed occurrence of ACR, and an improved ACR-free survival rate at 2 y compared with the control group. Notably, the study group also showed a significant reduction in the incidence of de novo donor-specific antibodies at 3-mo and 2-y posttransplant. Furthermore, 6 mo after the transplant, the study group demonstrated significant improvements in weight-for-age Z score and height-for-age Z score. No notable differences were observed in postoperative complications or the incidence of liver fibrosis between the 2 groups.

CONCLUSIONS:

Basiliximab induction combine with tacrolimus (TAC) monotherapy is a safe and effective immunosuppressive regimen to reduce the episodes of ACR without influencing the development of liver fibrosis and graft and recipient survival rate after pediatric liver transplantation.

  • Sayegh C
  • Im D
  • Moss IK
  • Urquiza R
  • Patel S
  • et al.
Pediatr Transplant. 2022 Nov;26(7):e14361 doi: 10.1111/petr.14361.
CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This is an interesting study that paves the way for larger studies, with some adaptations. Young adult and adolescent liver transplant recipients were randomised to standard care, or to receive “praise text messages” when their immune suppression drug levels were in range. The study focussed on self-reported levels of confidence in taking medications, and self-reported adherence, which was already very high in the standard care group. There was also a high recognition of the importance of medication adherence. In multivariate analysis, participants in the intervention arm were significantly more likely to report taking their medications on time and as directed. The study was too small to see any endpoints in treatment outcome and there was no significant difference in measures of drug level variation. The intervention was cheap to install in terms of staff time and cost, it was also feasible and acceptable to patients. However, no difference in actual drug levels could be shown in this study, nor clinical outcomes and the self-reported confidence can certainly be confounded. With refinement of the protocol and personalisation of text messages, this could be taken forward to a larger study population.
Aims: The aim of this study was to investigate the feasibility, acceptability and impact of a brief mobile health (mHealth) intervention on medication adherence among adolescent and young adult (AYA) liver transplant recipients.
Interventions: Participants were randomised to receive either praise text messages or to usual care.
Participants: 35 adolescent and young adult liver transplant recipients (13–21 years old).
Outcomes: Self-reported motivation and adherence, and medication level variability index (MLVI).
Follow Up: 1 year
BACKGROUND:

AYA who have undergone liver transplantations often struggle to adhere to their post-transplant immunosuppressant medications, which can lead to serious health complications. The objective of this pilot study is to examine the acceptability and feasibility of a brief mobile health (mHealth) intervention and its impact on medication adherence among AYA liver transplant recipients.

METHODS:

Thirty-five AYAs (13-21 years old) were randomized to either (1) receive praise text messages whenever laboratory results indicated immunosuppressant medications within the expected range or (2) usual care. Motivation for adherence and adherence were assessed via self-report, and a MLVI was calculated based on values abstracted from the electronic health record.

RESULTS:

Multilevel, multivariate models showed significant associations between group assignment and some self-reported motivation and adherence outcomes but not MLVI. Specifically, AYA receiving the praise text messages were significantly more likely to report taking their prescribed doses (OR = 2.49, p = .03), taking their medicine according to the directions (OR = 2.39, p = .04), and being highly confident in taking their medication (OR = 2.46, p = .04), compared with the usual services group. Qualitative responses indicated praise texts were mostly helpful but could be improved.

CONCLUSIONS:

The results suggest texting patients about positive health indicators was acceptable and, with refinement, might promote AYA illness self-management.

  • Lerret SM
  • Flynn E
  • White-Traut R
  • Alonso E
  • Mavis AM
  • et al.
JMIR Nurs. 2022 Jul 15;5(1):e39263 doi: 10.2196/39263.
BACKGROUND:

Around 1800 pediatric transplantations were performed in 2021, which is approximately 5% of the annual rate of solid organ transplantations carried out in the United States. Effective family self-management in the transition from hospital to home-based recovery promotes successful outcomes of transplantation. The use of mHealth to deliver self-management interventions is a strategy that can be used to support family self-management for transplantation recipients and their families.

OBJECTIVE:

The study aims to evaluate the acceptability of an mHealth intervention (myFAMI) that combined use of a smartphone app with triggered nurse communication with family members of pediatric transplantation recipients.

METHODS:

This is a secondary analysis of qualitative data from family members who received the myFAMI intervention within a larger randomized controlled trial. Eligible participants used the app in the 30-day time frame after discharge and participated in a 30-day postdischarge telephone interview. Content analysis was used to generate themes.

RESULTS:

A total of 4 key themes were identified: (1) general acceptance, (2) positive interactions, (3) home management after hospital discharge, and (4) opportunities for improvement.

CONCLUSIONS:

Acceptability of the intervention was high. Family members rated the smartphone application as easy to use. myFAMI allowed the opportunity for families to feel connected to and engage with the medical team while in their home environment. Family members valued and appreciated ongoing support and education specifically in this first 30 days after their child's hospital discharge and many felt it contributed positively to the management of their child's medical needs at home. Family members provided recommendations for future refinement of the app and some suggested that a longer follow-up period would be beneficial. The development and refinement of mHealth care delivery strategies hold potential for improving outcomes for solid organ transplantation patients and their families and as a model to consider in other chronic illness populations.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT03533049; https://clinicaltrials.gov/ct2/show/NCT03533049.

  • Grabinski ZG
  • Boscamp NS
  • Zuckerman WA
  • Zviti R
  • O'Brien A
  • et al.
Pediatr Emerg Care. 2022 Feb 1;38(2):e811-e815 doi: 10.1097/PEC.0000000000002458.
OBJECTIVE:

Distraction can reduce pain and distress associated with painful procedures but has never been studied in children with solid organ transplants. We aimed to determine whether there is a difference in pain and distress associated with venipuncture in pediatric posttransplant patients who receive distraction compared with those who do not.

METHODS:

Randomized controlled trial of children aged 4 to 17 years with solid organ transplants undergoing venipuncture in the outpatient setting. Patients were randomized to receive distraction or no distraction. The primary outcome was the Faces Pain Scale-Revised. Secondary outcomes were the Observational Scale of Behavioral Distress-Revised; Faces, Leg, Activity, Cry, Consolability; and Children's Hospital of Eastern Ontario Pain Scale. Exploratory outcomes included the number of venipuncture attempts, time to successful venipuncture, and satisfaction of phlebotomists and parents.

RESULTS:

Median age of the 40 children enrolled was 11.5 years. Type of transplants included the heart (67.5%), kidney (22.5%), liver (7.5%), and more than 1 organ (2.5%). There was no difference between the Faces Pain Scale-Revised scores in distraction and no distraction groups (1.4; 95% confidence interval, 0.9-1.9; and 1.3, 95% confidence interval, 0.5-2.1, respectively). There was also no difference in the Observational Scale of Behavioral Distress-Revised; Faces, Leg, Activity, Cry, Consolability; and Children's Hospital of Eastern Ontario Pain Scale scores, number of venipuncture attempts, or time to successful venipuncture. Phlebotomists were more satisfied with the venipuncture when distraction was implemented.

CONCLUSIONS:

In children with solid organ transplants, there was no difference in pain and distress associated with venipuncture between those who did and did not receive distraction. There was also no difference in other procedure-related outcomes except for greater phlebotomist satisfaction when distraction was implemented.

  • Sintusek P
  • Buranapraditkun S
  • Wanawongsawad P
  • Posuwan N
  • Thantiworasit P
  • et al.
Vaccines (Basel). 2022 Jan 8;10(1) doi: 10.3390/vaccines10010092.
CET Conclusion
Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: The randomised controlled trial evaluated the safety and immunogenicity of a standard 3-dose (10 µg) versus a double 3-dose (20 µg) hepatitis B (HepB) vaccine in paediatric liver transplant recipients with immunologic loss who had previously received HepB immunisation. Sample size calculation showed that 68 participants needed to be recruited to allow for 10% dropouts. The trial enrolled 68 participants and 61 participants completed the study. The authors did not describe how the randomisation order was generated or whether allocation to groups was concealed. Humoral response was not significantly different between groups at any time point over 12 months. Cellular response was assessed in 42 participants and showed no statistically significant differences between groups. Safety outcomes were also similar between groups. Participants were categorised as hyporesponders, responders or nonresponders and their baseline characteristics were compared to identify factors associated with immunologic response to vaccination. Early revaccination, lower anti-HBs levels at baseline, and higher tacrolimus trough levels were associated with no seroprotective antibody levels after vaccination.
Aims: The aim of this study was to compare the safety and immunogenicity of standard three-dose versus double three-dose hepatitis B (HepB) vaccine regimens in paediatric patients following liver transplantation.
Interventions: Participants were randomly assigned to receive either a standard 3-dose or double 3-dose HepB vaccine.
Participants: Paediatric liver transplant recipients (aged 1-18 years).
Outcomes: Safety outcomes included incidence of adverse events. Immunogenicity outcomes included assessment of humoral response and cellular response.
Follow Up: 12 months

A high prevalence of hepatitis B (HepB) antibody loss after liver transplantation (LT) and de novo HepB infection (DNH) was documented, hence revaccination to prevent DNH is crucial. This study aimed to compare the safety and immunogenicity of two HepB vaccine regimens in liver-transplanted children. Liver-transplanted children who were previously immunised but showed HepB surface antibodies (anti-HBs) ≤ 100 mIU/mL were randomised to receive a standard three-dose (SD) and double three-dose (DD) vaccine intramuscularly in months 0-1-6. Anti-HBs and T-cell-specific response to the HepB antigen were assessed. A total of 61 children (54.1% male, aged 1.32 ± 1.02 years) completed the study without any serious adverse reaction. The seroprotective rate was 69.6% vs. 60% (p = 0.368) and 91.3% vs. 85% (p = 0.431) in SD and DD after the first and third 3-dose vaccinations, respectively. The geometric mean titre (95% confidence interval) of anti-HBs in SD and DD were 443.33 (200.75-979.07) vs. 446.17 (155.58-1279.50) mIU/mL, respectively, at completion. Numbers of interferon-γ-secreting cells were higher in hyporesponders/responders than in nonresponders (p = 0.003). The significant factors for the immunologic response to HepB vaccination were anti-HB levels prevaccination, tacrolimus trough levels, and time from LT to revaccination. SD and DD had comparative immunogenicity and were safe for liver-transplanted children who were previously immunised.

  • Lloyd C
  • Arshad A
  • Jara P
  • Burdelski M
  • Gridelli B
  • et al.
Transplant Direct. 2021 Sep 20;7(10):e765 doi: 10.1097/TXD.0000000000001221.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This manuscript reports long-term outcomes from a randomized controlled trial of tacrolimus versus cyclosporine microemulsion in paediatric liver transplantation. The original study recruited 156 recipients between 1997 and 2000. 81% patients randomized to tacrolimus remained on protocol treatment at study end, compared to just 31% of patients on CsA. Due to the large number of crossovers, the authors sensibly present narrative data. There were numerically fewer deaths from chronic rejection/liver failure, and less cosmetic side effects with tacrolimus. Clearly, the strength of conclusions are limited by the large crossover which precluded statistical analysis. Nonetheless, it appears that CsA is poorly tolerated in this population, supporting the adoption of tacrolimus as first-line immunosuppression seen in most centres.
Aims: The aim of this study was to report the long-term outcomes of a randomised controlled trial comparing tacrolimus (Tac) and cyclosporine immunosuppression in paediatric liver transplant recipients.
Interventions: Patients in the original trial were randomised to either a dual Tac regimen (tacrolimus and corticosteroids) or to cyclosporine A microemulsion (CyA-ME) therapy (CyA-ME, corticosteroids and azathioprine).
Participants: 156 paediatric liver transplant recipients.
Outcomes: The outcomes of interest included time to first rejection episode (acute or chronic), renal function, graft survival, patient survival, posttransplant lymphoproliferative disease (PTLD) incidence, Epstein-Barr virus (EBV) infection, and adverse events.
Follow Up: 14 years
UNLABELLED:

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.

  • Liu JQ
  • Chen WJ
  • Zhou MJ
  • Li WF
  • Tang J
Int J Gen Med. 2021 Apr 30;14:1599-1609 doi: 10.2147/IJGM.S305827.
BACKGROUND:

Ischemic-type biliary lesions (ITBL) are accepted as the most incomprehensible biliary complications after living-donor liver transplantation (LDLT). Early predicting the development of ITBL in pediatric patients permits more preventive strategies. However, few studies have focused on the early prediction of ITBL.

OBJECTIVE:

This study aimed to establish a nomogram including ultrasound-based multimodal imaging to predict ITBL in children with biliary atresia (BA) within 2 years after receiving LDLT.

METHODS:

The records of 94 BA children with at least one year of follow-up after LDLT were reviewed retrospectively. They were randomly divided into a training cohort for constructing a nomogram (n=64) and a validation cohort (n=30). In the training cohort, patients diagnosed as ITBL were included in the ITBL group and those without any vascular and biliary complication were included in the non-ITBL group. Multivariate Cox regression was used for the establishment of the nomogram in predicting the risk of ITBL within 2 years post-LDLT. The discrimination and calibration of the nomogram were internally and externally validated. The performances of the nomogram and the individual components were compared by the area under the curve (AUC) of receiver operating characteristic (ROC) curve.

RESULTS:

In the training cohort, 18 BA children were included in the ITBL group and 46 were in the non-ITBL group. Last pediatric end-stage liver disease (PELD) score, gamma-glutamyl transpeptidase (GGT), resistive index (RI), and liver stiffness measurement (LSM) were the independent predictors for the development of ITBL within 2 years post-LDLT. The nomogram incorporating these independent predictors showed good discrimination and calibration by the internal and external validation. Its performance was better than any individual component in predicting the prognosis (P < 0.05).

CONCLUSION:

The established nomogram may be used to predict the risk of ITBL within 2 years post-LDLT in BA children.

  • Qi B
  • Wang XQ
  • Pan ST
  • Li PY
  • Chen LK
  • et al.
World J Gastroenterol. 2021 Jan 28;27(4):345-357 doi: 10.3748/wjg.v27.i4.345.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This study investigates the use of donor, recipient, or both donor and recipient ischemic preconditioning prior to living donor liver transplant in paediatric recipients. In this population, with the preconditioning regimen used, there was no difference in early biochemical graft function or graft outcomes. The study is well reported and reasonably well designed, with randomization into 4 groups using sealed envelopes. It is not entirely clear what the primary endpoint is – the sample size calculation uses peak ALT, but this endpoint is only reported for subgroup analyses and not the population as a whole. There are no biomarkers of ischaemia reperfusion injury reported, only clinical outcomes, and it is unclear whether the protocol used created a significant enough ischemic insult to have a clinical effect.
Aims: The aim of this study was to evaluate the protective effects of remote ischemic preconditioning (RIPC) on living liver donors and paediatric liver transplant recipients posttransplantation.
Interventions: Patients were randomised into four groups: the S-RIPC group, where no intervention was received by donors and recipients; the D-RIPC group, where donors received RIPC; the R-RIPC group, in which only the recipients received RIPC; and the DR-RIPC group, where both donors and recipients received RIPC.
Participants: 220 paediatric living-donor liver transplant recipients with biliary atresia and family liver donors.
Outcomes: The primary endpoints were maximum postoperative alanine transaminase (ALTmax) and maximum aspartate aminotransferase (ASTmax). Secondary endpoints included early allograft dysfunction (EAD), primary nonfunction (PNF), postoperative complications and overall recipient survival.
Follow Up: N/A
BACKGROUND:

Studies suggested that remote ischemic preconditioning (RIPC) may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery.

AIM:

To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation.

METHODS:

From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, 208 donors were recruited and randomly assigned to four groups: S-RIPC group (no intervention; n = 55), D-RIPC group (donors received RIPC; n = 51), R-RIPC group (recipients received RIPC, n = 51) and DR-RIPC group (both donors and recipients received RIPC; n = 51). We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction, primary nonfunction and postoperative complications among recipients.

RESULTS:

RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction, primary nonfunction, and postoperative complications among recipients. Limited protective effects were observed, including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0 (P < 0.05). However, no significant improvements were found in donors who received RIPC. Furthermore, RIPC had no effects on the overall survival of recipients.

CONCLUSION:

The protective effects of RIPC were limited for recipients who received living liver transplantation, and no significant improvement of the prognosis was observed in recipients.

  • Steenaart E
  • Crutzen R
  • de Vries NK
BMC Public Health. 2020 May 20;20(1):739 doi: 10.1186/s12889-020-08900-5.
BACKGROUND:

As organ donation registration rates remain low, especially among lower-educated people, it is important to support this group in making their registration decision. To prepare lower-educated students in the Netherlands for making a well-informed decision, an interactive educational program was developed. We aim to understand both the (quality of) implementation as well as to contextualize the effects of this program in a lower-educated school setting.

METHODS:

The process evaluation was part of a Cluster Randomized Controlled Trial, in which 11 schools for Intermediate Vocational Education throughout the Netherlands participated. Teachers who taught a course on Citizenship delivered three intervention elements (i.e. video fragments and discussion, quizzes with tailored feedback and an exercise filling out a registration form) to their students. Implementation was assessed by interviews with teachers, questionnaires from students, logbooks from teachers and user data from Google Analytics.

RESULTS:

The program was well received and implemented, but on-the-spot adaptations were made by teachers to fit their students better. Within the lower-educated target group, differences between students are high in terms of active participation, reading abilities, knowledge and attention span. The program fit well within their regular teaching activities, but the topic of organ donation is not always prioritized by teachers.

CONCLUSIONS:

We see opportunities to disseminate the program on a larger scale and reach a group that has been neglected in organ donation education before. Within the program, there are possibilities to increase the effectiveness of the program, such as alternative delivery methods for the elements with a lot of text, the addition of booster sessions and guidelines for teachers to adapt the program to students of different levels within Intermediate Vocational Education. Moreover, in order to have an impact on a national level, strategies need to be employed to reach high numbers of students and, therefore, support on a higher level is needed (both within schools and at policy level).

TRIAL REGISTRATION:

Dutch Trial Register, NTR6771. Prospectively registered on 24 October 2017.

  • Weng Y
  • Yuan S
  • Li H
  • Yu W
Ann Transplant. 2020 May 12;25:e923398 doi: 10.12659/AOT.923398.

BACKGROUND Our study compared the myocardiac protective effect of propofol vs. sevoflurane in pediatric patients receiving living donor liver transplantation (LDLT) surgery. MATERIAL AND METHODS We randomly and equally divided 120 children who underwent LDLT into a sevoflurane group and a propofol group. Preoperative, intraoperative, and postoperative data were collected and compared between the 2 groups. The concentrations of cTnI, CK-MB, IL-6, TNF-alpha, and HMGB1 at 5 min after induction (T0), 30 min in the anhepatic period (T1), and 3 h after reperfusion (T2), and at the end of surgery (T3) were measured. RESULTS There was no statistically significant difference in the characteristics of children in the 2 groups. Compared with T0, the levels of IL-6 and TNF-alpha at T1, T2, and T3 were higher, while the HMGB1 at T2 and T3 were higher (P<0.05). A similar trend for IL-6, TNF-alpha, and HMGB1 at different time points in the 2 groups was observed. Compared with T0, the cTnI and CK-MB at T2 and T3 were significantly higher (P<0.05), but there was no significant difference at different time points in the 2 groups. For the adverse events, there was no significant difference between the 2 groups. CONCLUSIONS Our study shows that the cardioprotective effect in pediatric patients undergoing living donor liver transplantation is similar with propofol and sevoflurane anesthesia.