RESUMO
OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.
Assuntos
Enterocolite Necrosante/diagnóstico , Biomarcadores/urina , Estudos de Casos e Controles , Cromatografia Líquida , Cistatina C/urina , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Proteínas do Olho/urina , Feminino , Fibrinogênio/urina , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico , Receptores de Lipopolissacarídeos/urina , Masculino , Espectrometria de Massas , Fatores de Crescimento Neural/urina , Fragmentos de Peptídeos/urina , Prognóstico , Estudos Prospectivos , Proteínas Plasmáticas de Ligação ao Retinol/urina , Sensibilidade e Especificidade , Sepse/diagnóstico , Serpinas/urina , Regulação para Cima , alfa-Macroglobulinas/urinaRESUMO
OBJECTIVE: To determine whether pulmonary function decreases as a function of severity of pectus excavatum, and whether reduced function is restrictive or obstructive in nature in a large multicenter study. STUDY DESIGN: We evaluated preoperative spirometry data in 310 patients and lung volumes in 218 patients aged 6 to 21 years at 11 North American centers. We modeled the impact of the severity of deformity (based on the Haller index) on pulmonary function. RESULTS: The percentages of patients with abnormal forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow from 25% exhalation to 75% exhalation, and total lung capacity findings increased with increasing Haller index score. Less than 2% of patients demonstrated an obstructive pattern (FEV(1)/FVC <67%), and 14.5% demonstrated a restrictive pattern (FVC and FEV(1) <80% predicted; FEV(1)/FVC >80%). Patients with a Haller index of 7 are >4 times more likely to have an FVC of ≤80% than those with a Haller index of 4, and are also 4 times more likely to exhibit a restrictive pulmonary pattern. CONCLUSIONS: Among patients presenting for surgical repair of pectus excavatum, those with more severe deformities have a much higher likelihood of decreased pulmonary function with a restrictive pulmonary pattern.
Assuntos
Fluxo Expiratório Forçado/fisiologia , Tórax em Funil/diagnóstico , Insuficiência Respiratória/etiologia , Capacidade Vital/fisiologia , Adolescente , Criança , Progressão da Doença , Feminino , Seguimentos , Tórax em Funil/complicações , Tórax em Funil/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Radiografia Torácica , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença , Espirometria , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN: Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS: Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION: The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.