Vaccination practices in pediatric transplantation: A survey among member centers of the European reference network TransplantChild.

BACKGROUND: There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN-TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence-based protocols. METHODS: A cross-sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN-TransplantChild. RESULTS: A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on-site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%-100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2-4 weeks) for live-attenuated vaccines (LAVs). Almost all sites recommended immunization in the post-transplant period, with a time window of 4-8 months for the inactivated vaccines and 16-24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases. CONCLUSIONS: The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence-based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies.

Socioeconomic and clinical factors associated with prolonged hospital length of stay after traumatic brain injury.

BACKGROUND: Hospital length of stay (HLOS) after traumatic brain injury (TBI) is a metric of injury severity, resource utilization, and access to services. This study aimed to evaluate socioeconomic and clinical factors associated with prolonged HLOS after TBI. METHODS: Retrospective data from adult hospitalized patients diagnosed with acute TBI at a US Level 1 trauma center between August 1, 2019 - April 1, 2022 were extracted from the electronic health record. HLOS was stratified by Tier (1: 1-74th percentile; 2: 75-84th; 3: 85-94th; 4: 95-99th). Demographic, socioeconomic, injury severity, and level-of-care factors were compared by HLOS. Multivariable logistic regressions evaluated associations between socioeconomic and clinical variables and prolonged HLOS, using multivariable odds ratios (mOR) and [95% confidence intervals]. Estimated daily charges were calculated for a subset of medically-stable inpatients awaiting placement. Statistical significance was assessed at p < 0.05. RESULTS: In 1443 patients, median HLOS was 4 days (interquartile range 2-8; range 0-145). HLOS Tiers were 0-7, 8-13, 14-27, and ≥28 days (Tiers 1-4, respectively). Patients with Tier 4 HLOS differed significantly from others, with increased Medicaid insurance (53.4% vs. 30.3-33.1%, p = 0.003), severe TBI (Glasgow Coma Scale 3-8: 38.4% vs. 8.7-18.2%, p < 0.001), younger age (mean 52.3-years vs. 61.1-63.7-years, p = 0.003), low socioeconomic status (53.4% vs. 32.0-33.9%, p = 0.003), and need for post-acute care (60.3% vs. 11.2-39.7%, p < 0.001). Independent factors associated with prolonged (Tier 4) HLOS were Medicaid (mOR = 1.99 [1.08-3.68], vs. Medicare/commercial), moderate and severe TBI (mOR = 3.48 [1.61-7.56]; mOR = 4.43 [2.18-8.99], respectively, vs. mild TBI), and need for post-acute placement (mOR = 10.68 [5.74-19.89], while age was protective (per-year mOR = 0.98 [0.97-0.99]). Estimated daily charges for a medically-stable inpatient was $17126. CONCLUSIONS: Medicaid insurance, moderate/severe TBI, and need for post-acute care were independently associated with prolonged HLOS ≥28 days. Medically-stable inpatients awaiting placement accrue immense daily healthcare costs. At-risk patients should be identified early, receive care transitions resources, and be prioritized for discharge coordination pathways.

Predictors of Extreme Hospital Length of Stay After Traumatic Brain Injury.

BACKGROUND: Hospital length of stay (HLOS) after traumatic brain injury (TBI) is an important metric of injury severity, resource utilization, and access to post-acute care services. Risk factors for protracted HLOS after TBI require further characterization. METHODS: Data regarding adult inpatients admitted to a single U.S. level 1 trauma center with a diagnosis of acute TBI between August 1, 2019, and April 1, 2022, were extracted from the electronic health record. Patients with extreme HLOS (XHLOS, >99th percentile of institutional TBI HLOS) were compared with those without XHLOS. Socioeconomic status (SES), clinical/injury factors, and discharge disposition were analyzed. RESULTS: In 1638 patients, the median HLOS was 3 days (interquartile range [IQR]: 2-8 days). XHLOS threshold was >70 days (N = 18; range: 72-146 days). XHLOS was associated with younger age (XHLOS/non-XHLOS: 50.4/59.6 years; P = 0.042) and greater proportions with severe TBI (55.6%/11.4%; P < 0.001), low SES (72.2%/31.4%; P < 0.001), and Medicaid insurance (77.8%/30.1%; P < 0.001). XHLOS patients were more likely to die in hospital (22.2%/8.1%) and discharge to post-acute facility (77.8%/16.3%; P < 0.001). No XHLOS patients were discharged to home. In XHLOS patients alive at discharge, medical stability was documented at median 39 days (IQR: 28-58 days) and were hospitalized for another 56 days (IQR: 26.5-78.5 days). CONCLUSIONS: XHLOS patients were more likely to have severe injuries, low SES, and Medicaid. XHLOS is associated with in-hospital mortality and need for post-acute placement. XHLOS patients often demonstrated medical stability long before placement, underscoring complex relationships between SES, health insurance, and outcome. These findings have important implications for quality improvement and resource utilization at acute care hospitals and await validation from larger trials.

Prognosis of Children Undergoing Liver Transplantation: A 30-Year European Study.

OBJECTIVES: The European Liver Transplant Registry has been collecting data on virtually all pediatric liver transplant (PLT) procedures in Europe since 1968. We analyzed patient outcome over time and identified parameters associated with long-term patient outcome. METHODS: Participating centers and European organ-sharing organizations provided retrospective data to the European Liver Transplant Registry. To identify trends, data were grouped into consecutive time spans: era A: before 2000, era B: 2000 to 2009, and the current era, era C: since 2010. RESULTS: From June 1968 until December 2017, 16 641 PLT were performed on 14 515 children by 133 centers. The children <7 years of age represented 58% in era A, and 66% in the current era (P <.01). The main indications for PLT were congenital biliary diseases (44%) and metabolic diseases (18%). Patient survival at 5 years is currently 86% overall and 97% in children who survive the first year after PLT. The survival rate has improved from 74% in era A to 83% in era B and 85% in era C (P <.0001). Low-volume centers (<5 PLT/year) represented 75% of centers but performed only 19% of PLT and were associated with a decreased survival rate. In the current era, however, survival rates has become irrespective of volume. Infection is the leading cause of death (4.1%), followed by primary nonfunction of the graft (1.4%). CONCLUSIONS: PLT has become a highly successful medical treatment that should be considered for all children with end-stage liver disease. The main challenge for further improving the prognosis remains the early postoperative period.

Social Resources for Transplanted Children and Families in European Union Hospitals of ERN TransplantChild.

Social well-being is an intrinsic part of the current concept of health. In the context of chronic disease, there are many challenges we face in order to provide social well-being to patients and their families, even more if we talk about rare diseases. TransplantChild, a European Reference Network (ERN) in paediatric transplantation, works to improve the quality of life of transplanted children. It is not possible to improve the quality of life if the human and material resources are not available. With this study, we want to identify the economic aids, facilities, services, and financed products that are offered to families in different European centres. We also want to find out who provides these resources and the accessibility to them. We designed an ad hoc survey using the EU Survey software tool. The survey was sent to representatives of the 26 ERN members. In this article we present the results obtained in relation to two of the aspects analysed: long-term financial assistance and drugs, pharmaceuticals and medical devices. Some resources are equally available in all participating centres but there are significant differences in others, such as education aids or parapharmacy product financing. A local analysis of these differences is necessary to find feasible solutions for equal opportunities for all transplanted children in Europe. The experience of centres that already provide certain solutions successfully may facilitate the implementation of these solutions in other hospitals.

ABO Incompatible Liver Transplantation in Children: A 20 Year Experience from Centres in the TransplantChild European Reference Network.

An increasing number of AB0-incompatible (AB0i) liver transplantations (LT) are being undertaken internationally in recent years due to organ shortages and the need for urgent transplantation. The aim of our study was establish the value of ABOi LT from available retrospective results of AB0i pediatric liver transplantations performed in European reference centers now belonging to the TransplantChild, European Reference Network (ERN). Data from medical records were analyzed, including demographic data, diagnosis, urgency of transplantation, time on the waiting list, PELD/MELD score, desensitization procedures, immunosuppression, selected post-transplant complications, and patient and graft survival. A total of 142 patients (pts) with transplants between 1986 and 2018 in 8 European transplant centers were included in the study. The indications for liver transplantation were: cholestatic diseases in 62 pts, acute liver failure in 42 pts, and other conditions in the remaining 38 pts. Sixty-six patients received grafts from living donors, and seventy-six received grafts from deceased donors. Both patient and graft survival were significantly affected by deceased donor type, urgent transplantation, and the development of vascular complications. In the multivariate analysis, vascular complications had a negative impact on patient and graft survival, while a longer time from the first AB0i LT in the study showed better results, suggesting an international learning experience. In conclusion, we believe that AB0i LT in children is now a safe procedure that may be adopted more readily in children.

Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers' approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012-2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

Hemocromatosis neonatal: tratamiento con inmunoglobulinas en la gestación / Neonatal haemochromatosis: treatment with immunoglobulins in pregnancy

La hemocromatosis neonatal (HN) es una enfermedad hepática grave neonatal con alta tasa demortalidad y recurrencia. Se postulaun origen a lo inmunitario, resultado de la presencia de un anticuerpo materno aún por determinar que interfiera con el metabolismo férrico fetal. En esta teoría se basa el tratamiento materno con inmunoglobulinas por vía intravenosa en gestaciones sucesivas. Describimos el caso de una paciente con un hijo anterior diagnosticado y fallecido por HN, que tratamos en la siguiente gestación con inmunoglobulinas por vía intravenosa. Es el primer caso descrito en España y demuestra el éxito de la terapia, tal como describe la literatura científica (AU)

Neonatal hemochromatosis is a severe neonatal liver disease with a high mortality and recurrence rate. In theory, it is a gestational alloimmune disease due to there being maternal antibodies against fetal hepatic metabolism. On the basis of this hypothesis, the administration of intravenous immunoglobulin has been reported as a succesful treatment during subsequent pregnancies. Here, we describe the first case of this treatment in Spain which confirms the data available in the literature (AU)

[Wilson's disease: forms of presentation in childhood]. / La enfermedad de Wilson: formas de presentación en la infancia.

Wilson's disease can manifest with symptoms of liver disease or neuropsychiatric disorders in children and adults. This autosomal recessive disorder is caused by a copper metabolism disorder due to a mutation in the ATP7B transporter. Excessive amounts of copper accumulate in the body due to inhibition of the release of copper into bile. Because effective treatment is available, recognizing this disease in presymptomatic or early stages, when it can be reversed, is highly important. Diagnosis is often easy but the available tests (measurement of ceruloplasmin, and blood, urinary and liver copper levels) can be misleading. There is no single test with 100% sensitivity in screening nor do any of the tests, when used alone, provide 100% specificity. Diagnosis is currently based on the combination of clinical findings and the results of laboratory tests. Genetic study, with a finding of mutations in the two alleles of the ATP7B gene, is still not a rapid and easily available alternative and the absence of these mutations does not rule out the possible presence of other mutations not yet described.

La enfermedad de Wilson: formas de presentación en la infancia / Wilson’s disease: forms of presentation in childhood

La enfermedad de Wilson puede manifestarse por síntomas de hepatopatía o trastornos neuropsiquiátricos, en niños y adultos. La causa es un trastorno en el metabolismo del cobre, por mutación en el transportador ATP7B, de herencia recesiva. Se produce una acumulación de cobre por la imposibilidad de eliminar el exceso mediante su excreción en la bilis. Hay un tratamiento eficaz, por lo que es de gran importancia reconocer la enfermedad preferiblemente en estadios tempranos de lesión o presintomáticos, susceptibles de ser completamente reversibles. El diagnóstico es fácil en muchos pacientes, pero las pruebas disponibles (ceruloplasmina, cobre en sangre, cupruria, cobre en tejido hepático) no siempre son inequívocas. No hay ninguna prueba que de forma aislada sea totalmente sensible para el cribado, y ninguna prueba es totalmente específica. La combinación de los hallazgos clínicos y las pruebas analíticas son actualmente la base para el diagnóstico. El estudio genético, con la demostración de mutaciones en los 2 alelos del gen ATP7B, todavía no es una alternativa accesible con rapidez, y la ausencia de las mutaciones ya identificadas no excluye la posibilidad de que el paciente tenga otras no descritas

Wilson's disease can manifest with symptoms of liver disease or neuropsychiatric disorders in children and adults. This autosomal recessive disorder is caused by a copper metabolism disorder due to a mutation in the ATP7B transporter. Excessive amounts of copper accumulate in the body due to inhibition of the release of copper into bile. Because effective treatment is available, recognizing this disease in presymptomatic or early stages, when it can be reversed, is highly important. Diagnosis is often easy but the available tests (measurement of ceruloplasmin, and blood, urinary and liver copper levels) can be misleading. There is no single test with 100% sensitivity in screening nor do any of the tests, when used alone, provide 100% specificity. Diagnosis is currently based on the combination of clinical findings and the results of laboratory tests. Genetic study, with a finding of mutations in the two alleles of the ATP7B gene, is still not a rapid and easily available alternative and the absence of these mutations does not rule out the possible presence of other mutations not yet described