RESUMO
In utero hematopoietic cell transplantation (IUHCT) is an experimental treatment for congenital hemoglobinopathies, including Sickle cell disease and thalassemias. One of the principal advantages of IUHCT is the predisposition of the developing fetus toward immunologic tolerance. This allows for engraftment across immune barriers without immunosuppression and, potentially, decreased susceptibility to graft-versus-host disease (GVHD). We demonstrate fetal resistance to GVHD following T cell-replete allogeneic hematopoietic cell transplantation compared with the neonate. We show that this resistance is associated with elevated fetal serum interleukin-10 conducive to the induction of regulatory T cells (Tregs). Finally, we demonstrate that the adoptive transfer of Tregs from IUHCT recipients to neonates uniformly prevents GVHD, recapitulating the predisposition to tolerance observed after fetal allotransplantation. These findings demonstrate fetal resistance to GVHD following hematopoietic cell transplantation and elucidate Tregs as important contributors.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Recém-Nascido , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Tolerância Imunológica , Feto , Linfócitos T ReguladoresRESUMO
BACKGROUND/PURPOSE: Blunt cerebrovascular injury (BCVI) is clinically challenging because these injuries are hard to detect and can have serious neurological consequences, and optimal screening criteria have not been established for children. This study aims to determine risk factors for BCVI in pediatric patients and to evaluate screening practices in a single institutional series. METHODS: A retrospective review of all pediatric blunt trauma patients evaluated over a 10-year period was performed. Demographic, clinical, and radiographic data were reviewed, including the presence of adult risk factors for BCVI. Logistic regression analyses were performed with statistical significance established at p<0.05. RESULTS: Of the 11,596 patients evaluated during the study period, 1018 (8.8%) had at least one adult risk factor for BCVI, but only 62 (6.1% of those with risk factors) underwent angiographic evaluation. Overall, 11 BCVIs were observed, resulting in an incidence of 0.095%. All 11 patients with BCVI had at least one risk factor. Multivariate logistic regression analysis identified cervical spine fracture (OR 36.88 [8.36, 169.95]), GCS score ≤ 8 (OR 16.42 [2.16, 102.33]), male gender (OR 10.52 [1.33, 363.30]), Le Fort II or III facial fracture (OR 63.71 [2.16, 1124.68]), and ISS (unit OR 1.10 [1.04, 1.17]) as independent risk factors for BCVI. CONCLUSION: Adult screening criteria for BCVI appear appropriate for pediatric patients, but most at-risk children are not being screened. LEVEL OF EVIDENCE: Level III (retrospective case-control study).
RESUMO
OBJECTIVES: The objective was to identify the correlates of willingness to pay for ambulance transports from a rural city to a regional hospital in Guatemala. METHODS: An innovative methodology that utilizes a novel randomization technique and satellite imagery was used to select a sample of homes in Santiago Atitlán, Guatemala. The respondents were surveyed at these homes about their willingness to pay for ambulance transport to a regional hospital. A price ladder was used to elicit respondents' willingness to pay for ambulance transport, depending on the level of severity of three types of emergencies: life-threatening emergencies, disability-causing emergencies, and simple emergencies. Simple and multiple linear regression modeling was used to identify the social and economic correlates of respondents' willingness to pay for ambulance transport and to predict demand for ambulance transport at a variety of price levels. Beta coefficients (ß) expressed as percentages with 95% confidence intervals (CIs) were estimated. RESULTS: The authors surveyed 134 respondents (response rate=3.3%). In the multivariable regression models, three variables correlated with willingness to pay: household income, location of residence (rural district vs. urban district), and respondents' education levels. Correlates for ambulance transport in life-threatening emergencies included greater household daily income (ß=1.32%, 95% CI=0.63% to 2.56%), rural location of residence (ß=-37.3%, 95% CI=-51.1% to -137.5%), and higher educational levels (ß=4.41%, 95% CI=1.00% to 6.36%). Correlates of willingness to pay in disability-causing emergencies included greater household daily income (ß=1.59%, 95% CI=0.81% to 3.19%) and rural location of residence (ß=-19.4%, 95% CI=-35.7% to -89.4%). Correlates of willingness to pay in simple emergencies included rural location of residence (ß=59.4%, 95% CI=37.9% to 133.7%) and higher educational levels (ß=7.96%, 95% CI=1.96% to 11.8%). At all price levels, more individuals were willing to pay for transport for a life-threatening emergency than a disability-causing emergency. Respondents' willingness to pay was more responsive to price changes for transport during disability-causing emergencies than for transport during life-threatening emergencies. CONCLUSIONS: The primary correlates of willingness to pay for ambulance transport in Santiago Atitlán, Guatemala, are household income, location of residence (rural district vs. urban district), and respondents' education levels. Furthermore, severity of emergency significantly appears to influence how much individuals are willing to pay for ambulance transport. Willingness-to-pay information may help public health planners in resource-poor settings develop price scales for health services and achieve economically efficient allocations of subsidies for referral ambulance transport.