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Background: Enhanced B-cell presentation of donor alloantigen relative to presentation of HLA-mismatched reference alloantigen is associated with acute cellular rejection (ACR), when expressed as a ratio called the antigen presenting index (API) in an exploratory cohort of liver and intestine transplant (LT and IT) recipients. Methods: To test clinical performance, we measured the API using the previously described 6-h assay in 84 LT and 54 IT recipients with median age 3.3 y (0.05-23.96). Recipients experiencing ACR within 60 d after testing were termed rejectors. Results: We first confirmed that B-cell uptake and presentation of alloantigen induced and thus reflected the alloresponse of T-helper cells, which were incubated without and with cytochalasin and primaquine to inhibit antigen uptake and presentation, respectively. Transplant recipients included 76 males and 62 females. Rejectors were tested at median 3.6 d before diagnosis. The API was higher among rejectors compared with nonrejectors (2.2 ±â€…0.2 versus 0.6 ±â€…0.04, P value = 1.7E-09). In logistic regression and receiver-operating-characteristic analysis, API ≥1.1 achieved sensitivity, specificity, and positive and negative predictive values for predicting ACR in 99 training set samples. Corresponding metrics ranged from 80% to 88% in 32 independent posttransplant samples, and 73% to 100% in 20 independent pretransplant samples. In time-to-event analysis, API ≥1.1 predicted higher incidence of late donor-specific anti-HLA antibodies after API measurements in LT recipients (P = 0.011) and graft loss in IT recipients (P = 0.008), compared with recipients with API <1.1, respectively. Conclusions: Enhanced donor antigen presentation by circulating B cells predicts rejection after liver or intestine transplantation as well as higher incidence of DSA and graft loss late after transplantation.

RESUMO

OBJECTIVE: To evaluate associations between neighborhood income and burden of hospitalizations for children with short bowel syndrome (SBS). STUDY DESIGN: We used the Pediatric Health Information System (PHIS) database to evaluate associations between neighborhood income and hospital readmissions, readmissions for central line-associated bloodstream infections (CLABSI), and hospital length of stay (LOS) for patients <18 years with SBS hospitalized between January 1, 2006, and October 1, 2015. We analyzed readmissions with recurrent event analysis and analyzed LOS with linear mixed effects modeling. We used a conceptual model to guide our multivariable analyses, adjusting for race, ethnicity, and insurance status. RESULTS: We included 4289 children with 16 347 hospitalizations from 43 institutions. Fifty-seven percent of the children were male, 21% were Black, 19% were Hispanic, and 67% had public insurance. In univariable analysis, children from low-income neighborhoods had a 38% increased risk for all-cause hospitalizations (rate ratio [RR] 1.38, 95% CI 1.10-1.72, P = .01), an 83% increased risk for CLABSI hospitalizations (RR 1.83, 95% CI 1.37-2.44, P < .001), and increased hospital LOS (ß 0.15, 95% CI 0.01-0.29, P = .04). In multivariable analysis, the association between low-income neighborhoods and elevated risk for CLABSI hospitalizations persisted (RR 1.70, 95% CI 1.23-2.35, P < .01, respectively). CONCLUSIONS: Children with SBS from low-income neighborhoods are at increased risk for hospitalizations due to CLABSI. Examination of specific household- and neighborhood-level factors contributing to this disparity may inform equity-based interventions.

Assuntos

Síndrome do Intestino Curto , Criança , Humanos , Masculino , Feminino , Síndrome do Intestino Curto/epidemiologia , Síndrome do Intestino Curto/terapia , Renda , Hospitalização , Tempo de Internação , Atenção à Saúde

RESUMO

BACKGROUND: Caregivers of children with intestinal failure (IF) face difficult decisions without a clear best alternative. Providers assist in decision-making but often lack knowledge of caregiver perspectives. Using decision-making around anemia treatment as a focal point, we explored how caregivers of children with IF prefer to make decisions. Our goal was to offer insight to guide providers as they assist in decision-making. METHODS: We conducted 12 half-hour semistructured interviews with parents of children with IF. Interview questions addressed general decision-making and specifics of iron supplementation, including key factors and stakeholders in decision-making. Interviews were transcribed verbatim. Two investigators coded the transcripts and inductively derived themes. RESULTS: Four themes were identified regarding decision-making. They involved the search for reliable, accurate, and positive information; the role of caretakers on the medical team; the relationships between caretakers and the medical team; and effective communication. Themes around anemia treatment included: identification of anemia by bloodwork; proactive supplementation; individualized regimens; prioritizing safety and convenience. CONCLUSIONS: Understanding caregiver perspectives regarding anemia treatment in pediatric IF identifies opportunities for systematic quality improvement.

Assuntos

Anemia Ferropriva , Cuidadores , Anemia Ferropriva/tratamento farmacológico , Criança , Tomada de Decisões , Humanos , Pais , Pesquisa Qualitativa

RESUMO

BACKGROUND: Teduglutide use in pediatric patients with short bowel syndrome can aid in the achievement of enteral autonomy, but with a price of >$400,000 per y. OBJECTIVE: The current study evaluated the cost-effectiveness of using teduglutide in conjunction with offering intestinal transplantation in US pediatric patients with short bowel syndrome. DESIGN: A Markov model was used to evaluate the costs (in US dollars) and effectiveness [in quality-adjusted life years (QALYs)] of using teduglutide compared with offering intestinal transplantation. Parameters were estimated from published data where available. The primary effect modeled was the probability of weaning from parenteral nutrition while on teduglutide. Sensitivity analyses were performed on all model parameters. RESULTS: Compared with offering only intestinal transplantation, adding teduglutide cost ${\$}$124,353/QALY gained. Reducing the cost of the medication by 16% allowed the cost to reach the typical benchmark of ${\$}$100,000/QALY gained. Probabilistic sensitivity analysis favored transplantation without offering teduglutide in 68% of iterations at a ${\$}$100,000/QALY threshold. Never using teduglutide created an opportunity cost of over ${\$}$100,000 per patient. CONCLUSIONS: At its current price, teduglutide does not provide a cost-effective addition to transplantation in the treatment of pediatric short bowel syndrome. Further work should look to identify cost-reducing strategies, including alternative dosing regimens.