Pediatric Transplantation最新文献

Outcomes in pediatric thoracic transplantation have significantly improved, yet stark inequities persist. Disparities arise from biases in the healthcare system toward racial, ethnic, or religious groups as well as LGBTQ+ patients and families. Furthermore, geographic and socioeconomic factors and other social determinants of health also play an important role in outcomes. While the impact of these disparities on pediatric transplant recipients has been previously reported, a comprehensive approach to address these root causes is lacking. This article reviews the existing literature on the origins and manifestations of healthcare disparities in pediatric thoracic transplantation. Building upon this analysis, we then propose a blueprint for change, outlining actionable strategies to address the identified causes of inequity and, ultimately, improve outcomes for all pediatric thoracic transplant patients.

Background: Liver transplantation (LT) is a life-saving treatment for pediatric patients suffering end-stage liver disease, with the potential to yield positive long-term outcomes. Recently, remarkable progress has been achieved in mainland China. The purpose of this research is to describe the status in our center.

Method: 116 recipients from July 2019 to July 2023 were included in our study. The characteristics of recipients and donors, preoperative assessments, intraoperative details and posttransplant complications were described. The Kaplan-Meier method was applied to analyze the overall survival curves and was examined with the log-rank test.

Result: A total of 116 pediatric LTs were performed, including 57 (49.1%) living donor liver transplantation (LDLT), 57 (49.1%) split liver transplantation (SLT) and 2 (1.8%) whole liver transplantation (WLT). The 1- and 3-year overall survival rates were 93.1% and 92.2%. The survival of DDLT was comparable to that of LDLT in our center (89.4% vs. 96.3% for 3-year survival rate). After LT, 7 (6.03%) vascular complications and 3 (2.59%) biliary complications were observed. The primary causes of mortality were drug-resistant bacteria infection and post-transplant lymphoproliferative disorder (PTLD).

Conclusion: Pediatric LT has achieved tremendous progress in mainland China. The survival rate of our center was comparable to the published results worldwide. The survival rate of SLT from DBD donors was comparable to LDLT. Further research on the postoperative management and attempts of ISW will be required to improve survival.

Background: Children's Hospital 2 in Ho Chi Minh City is the only public pediatric center performing pediatric liver transplantation (PLT) in Southern Vietnam. Before the COVID-19 pandemic, our PLT program was implemented and operated in collaboration with Belgian surgical teams who supported both graft procurement and implantation. The program enabled capacity-building and protocol development.

Methods: Travel restrictions necessitated a transition to a hybrid local model. Building on the Pre-COVID groundwork, the team successfully performed 12 living-donor PLTs between 10/2021 and 9/2022. Standardized protocols- developed through earlier international collaboration- were consistently applied. Procurement surgery was carried out by an experienced adult hepatobiliary surgeon from a local hospital, while the implantation was conducted by the pediatric surgical team.

Results: Donors had a mean age of 32 ± 6.1 years. Procurement surgery lasted 422 ± 78.1 min. Mean blood loss was 237.5 ± 122.7 mL, and two donors required transfusion. All donor complications were Clavien-Dindo grade I. Recipients had a median age of 28 months and a weight of 10.4 kg. Biliary atresia accounted for 91.7% of indications. Grafts included seven left lateral segments and five full-left lobes. Recipient surgeries lasted 650 ± 91.5 min; mean transfusion volume was 231.2 ± 164.3 mL; cold ischemia time was 83.2 ± 24.9 min. Complications included chylous ascites (n = 2), portal vein stenosis (n = 1), and acute rejection (n = 2). One patient died from a hospital-acquired infection.

Conclusion: This crisis-driven transition to local autonomization demonstrated that prior supportive preparation and implementation enabled safe and effective PLT during a global health emergency.

Background: Human adenovirus in immunocompromised patients can be life-threatening. We describe the prevalence, clinical presentation, and treatment of adenovirus after pediatric liver transplantation at a large transplant center.

Methods: We performed a retrospective cohort study of adenovirus infection in children from 2013 to 2022. We compared incidence, clinical characteristics, and outcomes of post-transplant children by adenovirus treatment status.

Results: Adenovirus disease developed in 26% (84/320) children after liver transplant. Median age at liver transplant was 17.5 months, 48% were female; 50% had biliary atresia. Fever (53%), gastrointestinal symptoms (48%), and hepatitis (41%) were the most common clinical presentations at diagnosis. Median time to adenovirus diagnosis was 80 days (IQR 19-260) with 40% (n = 31/84) identified within 30 days post-transplant. Disseminated adenovirus (≥ 2 organ involvement) occurred in 24% (20/84). Fourteen patients (17%) received cidofovir, and most (13/14, 93%) had DNAemia, compared to 57% untreated patients with DNAemia (p = 0.013). Median peak adenovirus load was 491 805 copies/mL (IQR 24 800-1 900 000) in treated vs. 1000 copies/mL (IQR 595-794 794) in untreated patients (p < 0.001). Overall mortality was 8% (7/84).

Conclusion: The incidence of symptomatic and disseminated adenovirus disease was high in our pediatric liver transplant patients, particularly within 30 days post-transplant. Patients who received cidofovir treatment presented with high viral load and had the highest mortality. There is a critical need for evidence-based guidance for early antiviral management of adenovirus disease after pediatric liver transplant.

Background: Children undergoing hematopoietic stem cell transplantation are at increased risk of developing invasive fungal infection. Micafungin is an echinocandin with broad-spectrum antifungal properties. Recent trials have reported on the efficacy of intermittent daily dosing of micafungin for fungal prophylaxis in pediatric patients undergoing transplantation, with success rates of 76%-99%, success defined as absence of proven, probable, or possible invasive fungal infection. We implemented a twice-weekly micafungin regimen as antifungal prophylaxis in our unit.

Patients and methods: One hundred consecutive transplants performed between May 2018 and February 2024 were analyzed. Micafungin prophylaxis was dosed at 3-5 mg/kg daily given twice weekly from Day 0 till stable neutrophil engraftment, after which oral fluconazole was prescribed till Day +100. Fungal infection status was evaluated by radiological procedures and cultures from blood or sterile body sites as clinically indicated. The primary endpoint of the study was the evaluation of efficacy; secondary endpoints were safety and tolerability.

Results: Ninety three patients who underwent 95 transplants fulfilled the inclusion criteria. Underlying diagnoses were: leukemia (47), inborn errors of immunity (11), other malignancies (11), hemoglobinopathy (8), and others (16). There were no proven or probable fungal infections. Seventeen patients (18%) required change from prophylaxis to empirical antifungal treatment for persistent fever (n = 5) and possible fungal infections, mainly oesophagitis (n = 8). All patients who failed micafungin prophylaxis received allogeneic transplants, and HLA-haploidentical was the majority (14/17). None of the patients had to discontinue micafungin due to safety or tolerability concerns.

Conclusions: Twice-weekly IV micafungin is a safe and effective option as antifungal prophylaxis for children undergoing HSCT.

Background: Pediatric solid organ transplant (SOT) recipients are at increased risk of vaccine preventable diseases (VPD) due to both under-vaccination and ineffective responses to vaccines while immunosuppressed. Current guidelines recommend timely post-transplant immunization with non-live vaccines and surveillance of vaccine-specific titers to assess vaccine responses; however, institutional adherence to these recommendations may be variable.

Methods: This single-center retrospective study of 199 pediatric SOT recipients (59 heart, 10 intestinal/multi-visceral, 34 kidney, and 96 liver) evaluated guideline adherence to post-vaccine serologic monitoring and identified sociodemographic and clinical factors associated with delayed and incomplete schedules for routine childhood non-live vaccines after transplant.

Results: Serologic monitoring was utilized after only 8% of recommended vaccines, while participants' age at transplant (odds ratio [OR], 95% confidence interval [CI]: 0.86, 0.81-0.91), receipt of a heart transplant (OR, 95% CI: 0.32, 0.17-0.60), and coverage with private insurance (OR, 95% CI: 0.46, 0.25-0.85) were factors negatively associated with timely initiation or completion of non-live vaccines after transplant.

Conclusions: The associations between age at transplant, heart transplantation, and type of insurance with under-immunization warrant further investigation to address modifiable gaps in vaccine coverage and ensure pediatric SOT recipients are optimally protected from VPD.

Over the past six decades, liver transplantation (LT) in Japan has evolved from an experimental surgery to a globally recognized model of ethical and technical excellence. Following the world's first LT in 1963, Japan's early progress was impeded by the 1968 "Wada heart transplant" controversy, which suspended brain-dead donation for more than 30 years. This personal viewpoint reviews the historical development of LT in Japan, focusing on the emergence of living donor liver transplantation (LDLT), key technical innovations, legislative changes, and international contributions-particularly in pediatric transplantation. During this period, Japanese surgeons-many of whom were trained in Western centers-pioneered living donor liver transplantation (LDLT), introducing microsurgical techniques for hepatic artery anastomosis and innovative size-reduction procedures that enabled successful grafting even in infants weighing under 5 kg. Pediatric LDLT became the foundation for adult applications, achieving outstanding long-term outcomes. The Organ Transplant Law (1997) and its 2010 revision gradually permitted brain-dead and pediatric donation, but LDLT remains predominant. Japan's achievements, supported by advancements in tacrolimus immunosuppression, ABO-incompatible LT, and laparoscopic donor hepatectomy, have produced national survival rates comparable to leading Western programs. To date, over 4000 pediatric liver transplants have been performed, establishing Japan as a global leader in pediatric LDLT. Through sustained educational missions, National Center for Child Health and Development and its partner institutions have supported program development in over 20 countries, particularly in Southeast Asia and the Middle East. Despite limited experience with pediatric deceased-donor transplantation, Japan's balanced pursuit of donor safety, ethical integrity, and innovation continues to shape the international landscape. This personal viewpoint reflects on Japan's 60-year journey-progress born from limitation-and its ongoing commitment to advancing pediatric transplantation worldwide under the vision of the International Pediatric Transplant Association.

Background: Congenital portosystemic shunts (CPSS) are rare vascular malformations in which portal venous blood bypasses the liver and drains directly into systemic circulation. Type I Abernethy malformations, characterized by absent intrahepatic portal veins, rarely close spontaneously and often require liver transplantation. Small-for-size syndrome (SFSS), typically described in adult living donor liver transplantation, is increasingly recognized in pediatric recipients, particularly with graft-to-recipient weight ratio (GRWR) < 1.5%.

Methods: We report the case of a 5-year-old female with Type I Abernethy malformation who underwent deceased donor whole graft liver transplantation. Intraoperative findings demonstrated marked size discrepancy between the donor portal vein and the patient's large portosystemic shunt. Postoperatively, she developed acute liver dysfunction concerning for relative hyperperfusion and SFSS physiology.

Results: Despite a GRWR of 1.78%, the patient exhibited rapid elevations in transaminases, INR, and bilirubin postoperatively, raising concern for SFSS physiology. Octreotide therapy resulted in partial biochemical improvement. The subsequent initiation of terlipressin resulted in a marked and sustained decline in liver enzymes and normalization of coagulation parameters. At 18 months post-transplant, the patient remains clinically well without hepatic dysfunction.

Conclusions: This is the first reported pediatric case of successful use of terlipressin, bridged by octreotide, for management of suspected SFSS physiology following liver transplantation. Terlipressin may represent a safe and effective therapeutic option to modulate portal pressures in pediatric patients with graft hyperperfusion.

Background: Portal vein (PV) reconstruction is a crucial step in pediatric liver transplantation (LT). Pediatric recipients with a hypoplastic or sclerotic PV often require an interposition vein graft. Allogeneic grafts from donors are generally preferred. However, if they are not available, the use of autologous vessels is necessary.

Case presentation: An 8-month-old girl with biliary atresia (BA) underwent living donor LT with a left lateral segment graft. During the operation, portal vein thrombosis (PVT) developed after direct anastomosis between the recipient PV and graft left PV. We used several techniques to resolve this problem, including ligation of collateral circulation and use of interposition grafts from the left internal jugular vein (IJV) and left renal vein (LRV). On postoperative day 1, PVT reoccurred. Emergency exploratory laparotomy was performed for thrombectomy, using the retrohepatic inferior vena cava (IVC) as an additional vascular graft. The final reconstruction successfully utilized a combination of LRV and IVC grafts between the superior mesenteric vein and graft left PV. Postoperatively, the patient received thrombolytic therapy followed by anticoagulants for thrombus prevention, along with immunosuppressive drugs. The patient's postoperative clinical course was uneventful.

Conclusion: Although the IJV and LRV are established options for PV reconstruction in pediatric LT, we propose retrohepatic IVC as a feasible and effective alternative option. This approach maximizes the availability of autologous vessels; however, selection must be individualized based on graft availability and the patient condition.

Background: Peripheral blood stem cell (PBSC) collection from healthy pediatric sibling donors is increasingly preferred for allogeneic hematopoietic stem cell transplantation (HSCT) because of higher yields and faster engraftment. However, challenges such as small circulating blood volumes, difficult venous access, and the need for sedation pose safety concerns, particularly in low-weight donors. Data from developing countries remain scarce.

Study design and methods: We retrospectively analyzed 35 healthy pediatric sibling donors who underwent PBSC mobilization and collection at a single center in South India between June 2019 and April 2024. All donors received granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day for 5 days. Plerixafor (0.24 mg/kg) was administered on day 4 in donors with a donor-recipient weight ratio (DRWR) < 0.75. Apheresis was performed on day 5 using the Spectra Optia continuous mononuclear cell collection protocol. Donor demographics, procedural characteristics, collection efficiency, and adverse events were recorded.

Results: 135 allogeneic pediatric PBSCTs were performed, of which 35 were pediatric sibling donors, predominantly for haemoglobinopathies (n = 22). Higher donor weight was associated with greater blood volume processed, anticoagulant use, and higher product leukocyte and platelet counts (p < 0.05), without differences in CD34⁺ yield or collection efficiency. Plerixafor use resulted in higher peripheral blood CD34⁺ counts and final CD34⁺ yield compared with G-CSF alone (p < 0.01). All procedures were well tolerated, with only mild, transient adverse events in 15.7% of collections and no serious adverse events.

Conclusions: PBSC collection in healthy pediatric sibling donors, including those with low DRWR, is safe and effective when supported by individualized priming strategies and multidisciplinary care.