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Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all by 14 days postvaccination, but VZV DNA, which can be managed with antivirals, was detected in 1 child in the CLD group at 21 days and 1 control at 28 days postvaccination. Humoral or cell-mediated vaccine response was 100% to measles virus and 94% to VZV in the CLD group postvaccination, whereas it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14 days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine-preventable infections in vulnerable children with CLD.
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BACKGROUND: The COVID-19 pandemic has affected all aspects of the US healthcare system, including liver transplantation. The objective of this study was to understand national changes to pediatric liver transplantation during COVID-19. METHODS: Using SRTR data, we compared waitlist additions, removals, and liver transplantations for pre-COVID-19 (March-November 2016-2019), early COVID-19 (March-May 2020), and late COVID-19 (June-November 2020). RESULTS: Waitlist additions decreased by 25% during early COVID-19 (41.3/month vs. 55.4/month, p < .001) with black candidates most affected (p = .04). Children spent longer on the waitlist during early COVID-19 compared to pre-COVID-19 (140 vs. 96 days, p < .001). There was a 38% decrease in liver transplantations during early COVID-19 (IRR 0.62, 95% CI 0.49-0.78), recovering to pre-pandemic rates during late COVID-19 (IRR 1.03, NS), and no change in percentage of living and deceased donors. White children had a 30% decrease in overall liver transplantation but no change in living donor liver transplantation (IRR 0.7, 95% CI 0.50-0.95; IRR 0.96, NS), while non-white children had a 44% decrease in overall liver transplantation (IRR 0.56, 95% CI 0.40-0.77) and 81% decrease in living donor liver transplantation (IRR 0.19, 95% CI 0.02-0.76). CONCLUSIONS: The COVID-19 pandemic decreased access to pediatric liver transplantation, particularly in its early stage. There were no regional differences in liver transplantation during COVID-19 despite the increased national sharing of organs. While pediatric liver transplantation has resumed pre-pandemic levels, ongoing racial disparities must be addressed.
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COVID-19 , Accesibilidad a los Servicios de Salud/tendencias , Disparidades en Atención de Salud/tendencias , Trasplante de Hígado/tendencias , Listas de Espera/mortalidad , Adolescente , Niño , Preescolar , Femenino , Disparidades en Atención de Salud/etnología , Humanos , Lactante , Recién Nacido , Donadores Vivos/estadística & datos numéricos , Masculino , Sistema de Registros , Estudios Retrospectivos , Estados UnidosRESUMEN
OBJECTIVES: The COVID-19 pandemic has significantly affected graduate medical education with redistribution of trainees, altered clinical care, and decreased research. For graduating trainees, there remains concern that financial stability of health systems will affect the availability of new positions and hiring practices. This survey aims to evaluate the pandemic's impact from pediatric gastroenterology fellows' perspectives. METHODS: An anonymous survey was distributed by e-mail from June 11 to July 1, 2020 to all North American pediatric gastroenterology and advanced training fellows. The survey was tailored for the fellows' year of training including questions on education, clinical experience, research, and job outlook. RESULTS: Of the 434 pediatric gastroenterology fellows, 145 completed the survey. Of all respondents, negative impact was reported in 52% on clinical training, 46% research projects, and 41% procedural confidence. A majority (93%) of third-year respondents had a job contract signed at the time of the survey; however, 18% of those contracts were subsequently altered with 5 respondents having job contracts rescinded due to hiring freezes. Fifty-four percent of first- and second-year fellow respondents reported concern regarding finding a job with the majority being second-year fellows (78%). CONCLUSIONS: The COVID-19 pandemic continues to affect the medical system and healthcare professionals. This survey identified significant impact on job acquisition for graduating pediatric gastroenterology fellows and other critical components of training, which are likely applicable to other pediatric trainees. The survey results raise questions about potential strategies to improve medical education and job search success for graduating trainees.
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COVID-19 , Educación de Postgrado en Medicina , Empleo , Becas , Gastroenterología/educación , Pandemias , Niño , Contratos , Humanos , Pediatría , Investigación , SARS-CoV-2 , Autoimagen , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Hepatitis-associated aplastic anemia (HAAA) is a potentially life-threatening diagnosis without clear treatment guidelines. The goal of the study was to characterize the presentation, evaluation, histopathology, and outcomes of therapy in children with HAAA to guide future research and to develop standardized care guidelines for this rare disease. METHODS: Retrospective chart review of 4 patients with HAAA who presented to Children's Hospital Colorado between 2016 and 2019 was conducted. Patient presentation, evaluation, bone marrow and liver pathology, interventions, and clinical course were collected. Immunohistochemistry of liver biopsies was performed. RESULTS: We treated 4 patients with HAAA without liver failure. All had evidence of systemic hyperinflammation and CD8+ T cell predominant liver tissue infiltration. One had a genetic mutation predisposing him to immune-mediated disease, but all other genetic testing was negative. In 3 of the 4 patients, hepatitis was poorly responsive to standard therapy with steroids, azathioprine, or tacrolimus; however, sustained biochemical remission of hepatitis was induced after more aggressive immunosuppressive therapies including Anti-Thymocyte Globulin (ATG) at standard immunosuppressive therapy (IST) dosing for severe Aplastic Anemia (sAA). Two patients underwent hematopoietic stem cell transplant (HSCT); 1 as first line therapy and 1 for refractory sAA. CONCLUSIONS: We found that ATG-based IST induced remission of hepatitis in patients with steroid-refractory HAAA. This is also an appropriate initial treatment for severe Aplastic Anemia, though may not prevent the need for HSCT. We propose that equine ATG based IST at standard dosing regimen for sAA is a therapy that in select cases can be considered early on in the treatment course and could lead to a sustained remission of both hepatitis and sAA. This should be considered in collaboration with a pediatric hematologist.
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Anemia Aplásica , Hepatitis , Anemia Aplásica/complicaciones , Anemia Aplásica/terapia , Animales , Niño , Colorado , Hepatitis/complicaciones , Hepatitis/diagnóstico , Caballos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Estudios Retrospectivos , Tacrolimus , Resultado del TratamientoRESUMEN
BACKGROUND: Historically, the IDSA and the AST have recommended that live vaccines not be administered post-transplant due to concern for induction of vaccine-strain disease in immunocompromised hosts. However, recent prospective studies and revised AST guidelines published in April 2019 suggest that in the current era of immunosuppression minimization, live vaccines may be safely administered to select transplant recipients with resulting immunoprotection. The goal of this study was to assess current post-transplant live vaccine practices at individual pediatric liver transplant centers following the updated AST guidelines. METHODS: A six-item email survey detailing center-specific post-transplant live vaccine practices followed by up to three response-specific questions were distributed between July 2019 and May 2020 to a representative from each center participating in the SPLIT consortium. RESULTS: The overall survey response rate was 93% (41/44 centers). Only 29% (12/41) of centers offer live vaccines post-transplant; each of these 12 centers uses different eligibility criteria for live vaccines. There was no difference between large (ten or more transplants per year) and small (less than ten transplants per year) centers in likelihood to offer live vaccines post-transplant. The main reasons for a center not offering post-transplant live vaccines were safety concerns and inability to reach group consensus. CONCLUSIONS: The majority of pediatric liver transplant centers are reluctant to offer live vaccines post-transplant despite the updated AST guidelines. Prospective multicenter studies are needed to confirm safety and immunogenicity of live vaccines post-transplant.
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Trasplante de Hígado , Cuidados Posoperatorios/métodos , Disfunción Primaria del Injerto/prevención & control , Sociedades Médicas , Receptores de Trasplantes , Vacunación/estadística & datos numéricos , Vacunas Atenuadas/administración & dosificación , Niño , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: Biliary atresia (BA) is likely caused by a common phenotypic response to various triggers; one proposed trigger, cytomegalovirus (CMV), may lead to worse outcomes. The aim of this study was to determine the severity of disease and pretransplant outcomes of infants with BA, who have evidence of CMV (CMV+) at diagnosis compared with CMV-negative (CMV-) infants. METHODS: The study used data and biospecimens from the Childhood Liver Disease Research Network PROBE study of cholestatic infants. Plasma obtained at the time of hepatic portoenterostomy (HPE) of 249 infants with BA was tested for CMV by DNA-PCR and CMV-IgM. Comparisons between CMV+ and CMV- infants were made using Wilcoxon rank sum, Student t test, chi-square, or Fisher exact test. Native liver survival (NLS) outcomes were analyzed using Kaplan-Meier and Cox regression adjusting for age at HPE; pretransplant patient survival outcomes were analyzed using a competing risk model and adjusting for age at HPE. RESULTS: CMV+ infants (n = 29, 12%) underwent HPE later (67.8±13.6 d vs. 55.1±18.5 d, p = 0.0005) and had higher baseline alkaline phosphatase and aminotransferases. There was no difference between groups in jaundice clearance or NLS. The subdistribution HR of pretransplant death for CMV+ infants adjusted for age at HPE was 3.8 (p = 0.034). CONCLUSIONS: CMV infection at the time of HPE in infants with BA is not associated with worse NLS despite the association with worse liver injury, older age at HPE, and increased risk of pretransplant death adjusted for age at HPE. Continued evaluation of the consequences of CMV infection and the effects of antiviral treatment should be explored.
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Atresia Biliar , Infecciones por Citomegalovirus , Lactante , Humanos , Niño , Atresia Biliar/cirugía , Citomegalovirus , Hígado/cirugía , Portoenterostomía Hepática , Infecciones por Citomegalovirus/complicacionesRESUMEN
Background: Pyloric botulinum toxin injection has improved symptoms in children with delayed gastric emptying. We aimed to determine the clinical response to combined endoscopic intra-pyloric botulinum toxin injection and pyloric balloon dilation (IPBT-BD) in patients with dyspepsia. Methods: Electronic medical records were reviewed to gather demographic data, symptoms, and follow-up on patients with dyspepsia. Cases were defined as those who underwent IPBT-BD in addition to their ongoing management. Controls received pharmacotherapy, behavioral intervention, or dietary management alone. Clinical response was defined as no change, partial, or complete improvement in symptoms within 12 months. Propensity score matching based on age, gender, and symptom duration was used to pair cases and controls. Results: In total, 79 cases and 83 controls were identified. After propensity matching, 63 patients were included in each group. The mean age for cases was 14.5 ± 3.9y; 62% were females and 98% were Caucasian. Further, 83% of 46 cases and 94% of 49 controls who had scintigraphy scans showed delayed gastric emptying. After matching, 76% of cases showed partial or complete improvement compared with 49% controls within 12 months (P = 0.004). Younger children tended to respond more favorably to the procedure (P = 0.08). Conclusions: In our propensity-matched analysis, combined IPBT-BD in addition to pharmacotherapy, behavioral, or dietary management clearly showed a benefit over these modalities alone. This favorable response lasted up to 12 months.
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Toxinas Botulínicas , Dispepsia , Gastroparesia , Adolescente , Toxinas Botulínicas/uso terapéutico , Niño , Dilatación , Dispepsia/tratamiento farmacológico , Femenino , Vaciamiento Gástrico , Gastroparesia/tratamiento farmacológico , Humanos , Masculino , Factores de TiempoRESUMEN
In chronic hepatitis, a broad differential diagnosis should be considered to accurately identify the cause(s) of liver injury. Autoimmune liver diseases (autoimmune hepatitis, primary sclerosing cholangitis, overlap syndrome) can occur in the setting of limited symptoms; therefore, a high index of suspicion and appropriate diagnostic workup should be performed. Most children with autoimmune hepatitis achieve sustained remission with medical therapy; however, there are no equivalent therapies for primary sclerosing cholangitis that impact the progression of disease. Research should include biomarker studies to predict histologic remission in autoimmune hepatitis and mechanistic studies to define future treatment targets for primary sclerosing cholangitis.
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Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/terapia , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/terapia , Adolescente , Enfermedades Asintomáticas , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Azatioprina/uso terapéutico , Biomarcadores/análisis , Niño , Colangitis Esclerosante/epidemiología , Femenino , Glucocorticoides/uso terapéutico , Hepatitis Autoinmune/epidemiología , Humanos , Hígado/patología , Hepatopatías/diagnóstico , Hepatopatías/terapia , Trasplante de Hígado/métodos , Masculino , Síndrome , Transaminasas/análisis , Adulto JovenRESUMEN
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