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OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22âmonths corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22âmonths corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.
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Drenagem , Enterocolite Necrosante/cirurgia , Doenças do Prematuro/cirurgia , Perfuração Intestinal/cirurgia , Laparotomia , Transtornos do Neurodesenvolvimento/epidemiologia , Enterocolite Necrosante/mortalidade , Enterocolite Necrosante/psicologia , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/psicologia , Perfuração Intestinal/mortalidade , Perfuração Intestinal/psicologia , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: The purpose of this study is to characterize the cytokine response of preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) before surgical treatment and to relate these finding to intestinal disease (NEC vs. SIP). STUDY DESIGN: The study was a 14-month prospective, cohort study of neonates undergoing surgery or drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex cytokine detection technology was used to analyze six inflammatory markers: interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 ß (IL-1ß), interferon-gamma, and tumor necrosis factor-α (TNF-α). RESULTS: Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381 pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p < 0.001), IL-8 (NEC: 18,438 pg/mL; SIP: 2,473 pg/mL; PDA: 1,110 pg/mL, p = 0.001), TNF-α (NEC: 161 pg/mL; SIP: 77 pg/mL; PDA: 71 pg/mL, p < 0.001), and IL-1ß (NEC: 85 pg/mL; SIP: 31 pg/mL; PDA: 24 pg/mL, p = 0.001). Patients with NEC totalis (NEC-totalis had the highest levels of IL-8 and were significantly different from infants with limited NEC (28,141 vs. 11,429 pg/mL, p = 0.03). CONCLUSION: Surgical NEC is a profoundly more proinflammatory disease than SIP. The cytokine profiles of patients with SIP are closer to those of a nonseptic surgical neonate.
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Citocinas/sangue , Enterocolite Necrosante/sangue , Perfuração Intestinal/sangue , Nascimento Prematuro/sangue , Biomarcadores/sangue , Permeabilidade do Canal Arterial/sangue , Permeabilidade do Canal Arterial/cirurgia , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/cirurgia , Feminino , Humanos , Recém-Nascido , Interferon gama/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/cirurgia , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The aim was to evaluate short- and long-term outcomes for thoracoscopic repair of EA/TEF and compare with open repair. METHODS: Patients who underwent EA/TEF repair during 2000-2020 were evaluated retrospectively. Patients with delayed repair were excluded. Demographic, operative, outcome data was collected. Outcomes were compared using Wilcoxon-rank sum tests for continuous, Chi-squared/Fisher's exact tests for categorical data. RESULTS: There were 104 patients with primary repair, 49 (47.1%) underwent thoracoscopic repair per surgeon's choice. Type C accounted for 101 (97.1%) of the cases. Gestational age and birth weight were higher in the thoracoscopy group (p = 0.001). The rate of ≥3 VACTERL anomalies was higher in the OR group (p = 0.016). Operative time, rate of anastomotic leak, time to first oral feeding were similar (p > 0.05). Thoracoscopy group had decreased length of ventilation (p = 0.026) and length of stay (p = 0.029). The incidence of anastomotic stricture was higher in the thoracoscopy group (p = 0.012). Recurrent TEF was one case in each group. Rates of tube feeding at discharge and in first year were similar (p > 0.05), rate in third year was decreased (p = 0.032) in the thoracoscopy group. Rates of anti-reflux medication in first and third years, and fundoplication rate were similar (p > 0.05). CONCLUSIONS: Many of the short- and long-term outcomes are comparable between thoracoscopic and open repair of EA/TEF. Length of ventilation, length of stay are decreased in the thoracoscopy group. Anastomotic stricture is higher, the need for long-term tube feeding is lower after thoracoscopic repair. Although these results could be affected by selection bias, they are still promising for advancing thoracoscopic repair of EA/TEF safely and efficiently. LEVEL OF EVIDENCE: Level III.
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PURPOSE: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are severe gastrointestinal complications of prematurity. The clinical presentation and treatment of NEC and SIP (peritoneal drain vs laparotomy) can overlap; however, the pathogenesis is distinct. Therefore, a patient initially treated for SIP can subsequently develop NEC. This phenomenon has only been described in case reports, and no risk factor evaluation exists. We evaluate clinical characteristics, risk factors, and outcomes of patients treated for a distinct episode of NEC after SIP. METHODS: We performed a retrospective review of very low birth weight (<1500 g) neonates who presented with pneumoperitoneum between 07/2004 and 09/2022. Data was obtained from two separate neonatal intensive care units that were part of the same institution. Patients with an initial preoperative, intraoperative, or pathological diagnosis of NEC were excluded. Patients with an intraoperative diagnosis of SIP or preoperative diagnosis of SIP successfully treated with a peritoneal drain (PD) were evaluated. Patients subsequently treated (medically or surgically) for NEC after SIP were then compared to SIP-alone patients. Clinical characteristics included demographics, gestational age (GA), birth weight (BW), perinatal risk factors (chorioamnionitis, steroids, indomethacin), postoperative feeding regimen, and length of stay (LOS) were compared. RESULTS: Of the 278 patients included, 31 (11.2%) patients had NEC after SIP. There was no difference in GA (25 weeks vs 25 weeks, p = 0.933) or BW (760 g vs 735 g, p = 0.370) between NEC after SIP vs SIP alone cohorts, respectively. Twenty (64%) of NEC after-SIP patients were previously treated with LP. NEC after SIP occurred with a median onset of 56 days. Pneumatosis was the most frequent (81%) presenting symptom and 12 (39%) patients had hematochezia. Four (12.9%) patients required LP for NEC and all had NEC intraoperatively and on pathology. A majority (77.4%) of patients were on breast milk (BM) at time of NEC diagnosis. NEC after SIP patients had lower maternal age at delivery (29.0 vs 25.0, p = 0.055) and the incidence of NEC after LP (primary or failed drain) was higher than PD alone (16.7% vs 6.2%, p = 0.007). NEC after SIP patients had longer LOS (135 vs 81, p < 0.001). CONCLUSION: We report an 11.2% incidence of NEC at a median of 56 days following successful treatment of SIP, resulting in increased LOS. SIP patients are a high-risk cohort and protocols to prevent this phenomenon should be investigated.
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Background: In the United States, 33% of households with children contain firearms, however only one-third reportedly store firearms securely. It's estimated that 31% of unintentional firearm injury deaths can be prevented with safety devices. Our objective was to distribute safe storage devices, provide safe storage education, evaluate receptivity, and assess impact of intervention at follow-up. Method: At five independent, community safety events, parents received a safe storage device after completing a survey that assessed firearms storage methods and parental comfort with discussions regarding firearm safety. Follow-up surveys collected 4 weeks later. Data were evaluated using descriptive analysis. Result: 320 participants completed the surveys, and 288 participants were gunowners living with children. Most participants were comfortable discussing safe storage with healthcare providers and were willing to talk with friends about firearm safety. 54% reported inquiring about firearm storage in homes their children visit, 39% stored all their firearms locked-up and unloaded, 32% stored firearms/ammunition separately. 121 (37%0.8) of participants completed the follow-up survey, 84% reported using the distributed safety device and 23% had purchased additional locks for other firearms. Conclusion: Participants were receptive to firearm safe storage education by a healthcare provider and distribution of a safe storage device. Our follow up survey results showed that pairing firearm safety education with device distribution increased overall use of safe storage devices which in turn has the potential to reduce the incidence of unintentional and intentional self-inflicted firearm injuries. Providing messaging to promote utilization of safe storage will impact a firearm safety culture change.
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Armas de Fogo , Ferimentos por Arma de Fogo , Criança , Humanos , Estados Unidos , Ferimentos por Arma de Fogo/prevenção & controle , Ferimentos por Arma de Fogo/epidemiologia , Equipamentos de Proteção , Pais , Gestão da SegurançaRESUMO
PURPOSE: Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are distinct disease processes associated with significant morbidity and mortality. Initial treatment, laparotomy (LP) versus peritoneal drainage (PD), is disease specific however it can be difficult to distinguish these diagnoses preoperatively. We investigated clinical characteristics associated with each diagnosis and constructed a scoring algorithm for accurate preoperative diagnosis. METHODS: A cohort of extreme and very low birth weight (<1500 g) neonates surgically treated for SIP or NEC between 07/2004-09/2022 were reviewed. Clinical characteristics included gestational age (GA), birth weight (BW), feeding history, physical exam, and laboratory/radiological findings. Intraoperative diagnosis was used to determine SIP vs NEC. Pre-drain diagnosis was used for patients treated with PD only. RESULTS: 338 neonates were managed for SIP (n = 269, 79.6%) vs NEC (n = 69, 20.4%). PD was definitive treatment in 146 (43.2%) patients and 75 (22.2%) patients were treated with upfront LP. Characteristics associated with SIP included younger GA, younger age at initial laparotomy or drainage (ALD), and history of trophic or no feeds. Multivariate logistic regression determined pneumatosis, abdominal wall erythema, higher ALD and history of feeds to be highly predictive of NEC. A 0-8-point scale was designed based on these characteristics with the area under the receiver operating characteristic curve of 0.819 (95% CI 0.756-0.882) for the diagnosis of NEC. A threshold score of 1.5 had a 95.2% specificity for NEC. CONCLUSION: Utilizing clinical characteristics associated with SIP & NEC we developed a scoring system designed to assist surgeons accurately distinguish SIP vs NEC in neonates. TYPE OF STUDY: Retrospective Chart Review. LEVEL OF EVIDENCE: Level III.
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Drenagem , Enterocolite Necrosante , Recém-Nascido de muito Baixo Peso , Perfuração Intestinal , Humanos , Recém-Nascido , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/cirurgia , Perfuração Intestinal/etiologia , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Diagnóstico Diferencial , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/cirurgia , Algoritmos , Laparotomia , Idade Gestacional , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Perfuração Espontânea/diagnósticoRESUMO
OBJECTIVE: To investigate the accuracy of preoperative and intraoperative diagnosis via comparison to pathologic diagnosis in spontaneous intestinal perforation (SIP) vs. necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective review of neonates <1500 g treated for pneumoperitoneum between 07/2004-09/2022 was conducted. Patients treated for NEC medically prior to diagnosis and those treated with drain only were excluded. Fleiss' Kappa analysis assessed agreement between all three diagnoses: preoperative, intraoperative, and pathologic. RESULT: Overall, 125 patients were included with mean birthweight 834.2 g (SD:259.2) and mean gestational age 25.8 weeks (SD:2.2). Preoperative and intraoperative diagnoses agreed in 90.3%, intraoperative and pathologic agreed in 71.1%, and preoperative and pathologic agreed in 75.2% of patients. Fleiss' Kappa was 0.55 (95% CI:0.43,0.68), indicating moderate agreement between the three diagnoses. CONCLUSION: Our study shows moderate agreement between preoperative, intraoperative, and pathologic diagnoses. Further studies investigating the clinical characteristics of SIP and NEC are needed to improve diagnostic accuracy and management.
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Enterocolite Necrosante , Doenças Fetais , Doenças do Recém-Nascido , Perfuração Intestinal , Cirurgiões , Feminino , Recém-Nascido , Humanos , Lactente , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/cirurgia , Enterocolite Necrosante/patologia , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Nonoperative management (NOM) is the standard of care for the management of blunt liver and spleen injuries (BLSI) in the stable pediatric patient. Angiography with embolization (AE) is used as an adjunctive therapy in the management of adult BLSI patients, but it is rarely used in the pediatric population. In this planned secondary analysis, we describe the current utilization patterns of AE in the management of pediatric BLSI. METHODS: After obtaining IRB approval at each center, cohort data was collected prospectively for children admitted with BLSI confirmed on CT at 10 Level I pediatric trauma centers (PTCs) throughout the United States from April 2013 to January 2016. All patients who underwent angiography with or without embolization for a BLSI were included in this analysis. Data collected included patient demographics, injury details, organ injured and grade of injury, CT finding specifics such as contrast blush, complications, failure of NOM, time to angiography and techniques for embolization. RESULTS: Data were collected for 1004 pediatric patients treated for BLSI over the study period, 30 (3.0%) of which underwent angiography with or without embolization for BLSI. Ten of the patients who underwent angiography for BLSI failed NOM. For patients with embolized splenic injuries, splenic salvage was 100%. Four of the nine patients undergoing embolization of the liver ultimately required an operative intervention, but only one patient required hepatorrhaphy and no patient required hepatectomy after AE. Few angiography studies were obtained early during hospitalization for BLSI, with only one patient undergoing angiography within 1 hour of arrival at the PTC, and 7 within 3 hours. CONCLUSION: Angioembolization is rarely used in the management of BLSI in pediatric trauma patients with blunt abdominal trauma and is generally used in a delayed fashion. However, when implemented, angioembolization is associated with 100% splenic salvage for splenic injuries. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.
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Embolização Terapêutica , Fígado , Baço , Ferimentos não Penetrantes , Humanos , Embolização Terapêutica/métodos , Ferimentos não Penetrantes/terapia , Ferimentos não Penetrantes/diagnóstico por imagem , Baço/lesões , Baço/irrigação sanguínea , Baço/diagnóstico por imagem , Criança , Masculino , Feminino , Fígado/lesões , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Adolescente , Angiografia , Pré-Escolar , Tomografia Computadorizada por Raios X , Centros de Traumatologia , Escala de Gravidade do Ferimento , Traumatismos Abdominais/terapia , Traumatismos Abdominais/diagnóstico por imagem , Resultado do Tratamento , Estados Unidos , Estudos ProspectivosRESUMO
PURPOSE: The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy. METHODS: We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy. RESULTS: We identified 171 patients treated for SIP (drain nâ¯=â¯110 vs. laparotomy nâ¯=â¯61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48â¯h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2â¯weeks, pâ¯<â¯0.001) and had lower median birth weight (710â¯g vs. 896â¯g, pâ¯<â¯0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, pâ¯=â¯0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed. CONCLUSIONS: SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma. THE LEVEL OF EVIDENCE: III.
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Drenagem , Perfuração Intestinal/cirurgia , Laparotomia , Drenagem/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Perfuração Intestinal/etiologia , Masculino , Peritônio/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: After NOM for BLSI, APSA guidelines recommend activity restriction for grade of injury +2 in weeks. This study evaluates activity restriction adherence and 60â¯day outcomes. METHODS: Non-parametric tests and logistic regression were utilized to assess difference between adherent and non-adherent patients from a 3-year prospective study of NOM for BLSI (≤18â¯years). RESULTS: Of 1007 children with BLSI, 366 patients (44.1%) met the inclusion criteria of a completed 60â¯day follow-up; 170 (46.4%) had liver injury, 159 (43.4%) had spleen injury and 37 (10.1%) had both. Adherence to recommended activity restriction was claimed by 279 (76.3%) patients; 49 (13.4%) reported non-adherence and 38 (10.4%) patients had unknown adherence. For 279 patients who adhered to activity restrictions, unplanned return to the emergency department (ED) was noted for 35 (12.5%) with 16 (5.7%) readmitted; 202 (72.4%) returned to normal activity by 60â¯days. No patient bled after discharge. There was no statistical difference between adherent patients (nâ¯=â¯279) and non-adherent (nâ¯=â¯49) for return to ED (χ2â¯=â¯0.8 [pâ¯<â¯0.4]) or readmission (χ2â¯=â¯3.0 [pâ¯<â¯0.09]); for 216 high injury grade patients, there was no difference between adherent (nâ¯=â¯164) and non-adherent (nâ¯=â¯30) patients for return to ED (χ2â¯=â¯0.6 [pâ¯<â¯0.4]) or readmission (χ2â¯=â¯1.7 [pâ¯<â¯0.2]). CONCLUSION: For children with BLSI, there was no difference in frequencies of bleeding or ED re-evaluation between patients adherent or non-adherent to the APSA activity restriction guideline. LEVEL OF EVIDENCE: Level II, Prognosis.
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Guias como Assunto , Fígado/lesões , Cooperação do Paciente/estatística & dados numéricos , Baço/lesões , Ferimentos não Penetrantes/terapia , Adolescente , Criança , Serviço Hospitalar de Emergência/estatística & dados numéricos , Exercício Físico , Feminino , Seguimentos , Humanos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Long-term dysphagia occurs in up to 50% of repaired esophageal atresia and tracheoesophageal fistula (EA/TEF) patients. The underlying factors are unclear and may include stricture, esophageal dysmotility, or associated anomalies. Our purpose was to determine whether structural airway abnormalities (SAA) are associated with dysphagia in EA/TEF. METHODS: We conducted a retrospective chart review of children who underwent EA/TEF repair in our hospital system from 2007 to 2016. Children with identified SAA (oropharyngeal abnormalities, laryngeal clefts, laryngomalacia, vocal cord paralysis, and tracheomalacia) were compared to those without airway abnormalities. Dysphagia outcomes were determined by the need for tube feeding and the modified pediatric Functional Oral Intake Scale (FOIS) at 1 year. RESULTS: SAA was diagnosed in 55/145 (37.9%) patients with EA/TEF. Oropharyngeal aspiration was more common in children with SAA (58.3% vs. 36.4%, p=0.028). Children with SAA were more likely to require tube feeding both at discharge (79.6% vs. 48.3%, p<0.001) and at 1 year (52.7% vs. 13.6%, p<0.001) and had lower mean FOIS (4.18 vs. 6.21, p<0.001). In the logistic regression model adjusting for gestational age, long gap EA, and esophageal stricture, the presence of SAA remained a significant risk factor for dysphagia (OR 4.17 (95% CI 1.58-11.03)). CONCLUSION: SAA are common in children with EA/TEF and are associated with dysphagia, even after accounting for gestational age, esophageal gap and stricture. This study highlights the need for a multidisciplinary approach, including early laryngoscopy and bronchoscopy, in the evaluation of the EA/TEF child with dysphagia. LEVEL OF EVIDENCE: Level II retrospective prognostic study.
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Anormalidades Múltiplas , Transtornos de Deglutição/etiologia , Atresia Esofágica/complicações , Anormalidades do Sistema Respiratório/complicações , Fístula Traqueoesofágica/complicações , Anormalidades Múltiplas/cirurgia , Criança , Pré-Escolar , Transtornos de Deglutição/diagnóstico , Atresia Esofágica/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Prognóstico , Anormalidades do Sistema Respiratório/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fístula Traqueoesofágica/cirurgiaRESUMO
Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC.
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Imunidade Adaptativa , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/fisiopatologia , Imunidade Inata , Doenças do Prematuro/imunologia , Doenças do Prematuro/fisiopatologia , Enterocolite Necrosante/microbiologia , Medicina Baseada em Evidências , Humanos , Recém-Nascido Prematuro , Doenças do Prematuro/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Intestinos/irrigação sanguínea , Intestinos/imunologia , Intestinos/fisiopatologia , Leite Humano/imunologiaRESUMO
BACKGROUND: The pathogenesis of esophageal atresia and tracheoesophageal fistula (EA/TEF) remains unknown. We have found previously that an initial esophageal atresia, followed by an abnormal (absent) branching pattern of the middle branch of a trifurcation of the lung/tracheal bud, leads to the neonatal finding of TEF. Mice null mutant for hedgehog signaling can experience the development of EA/TEF, but the mechanism for this development is also unknown. Given that EA/TEF in humans appears not to be due to genetic defects, a hedgehog mutation cause seems very unlikely. However, defective hedgehog signaling that is caused by environmental effects in the human embryo likely could be implicated. We studied a teratogen-induced model of EA/TEF to determine the mechanism by which defective hedgehog signaling may lead to EA/TEF. METHODS: We injected Adriamycin into pregnant rats to induce EA/TEF in rat embryos. We first quantified sonic hedgehog (Shh) signaling pathway molecule expression using real-time, semiquantitative reverse-transcriptase polymerase chain reaction for Shh, Shh receptors (patched and smoothened), and downstream intracellular targets of those receptors (Gli family members). On the basis of these findings, we then developed an in vitro culture system for the day-12 embryonic TEF and manipulated Shh signaling using either exogenous Shh or Shh inhibitors. RESULTS: By reverse transcriptase-polymerase chain reaction, a unique difference between the fistula tract and control tissues was that Gli-2 (downstream signaling molecule of Shh) messenger RNA levels were much lower in the fistula tract than in the adjacent esophagus (P =.002). Surprisingly, in the culture experiments, the fistula tract was induced to branch by exogenous Shh. Such branching of the fistula was unexpected and further supports the presumed respiratory origin of the fistula tract because the normal lung, but not normal esophagus, branched in response to Shh. The Shh inhibitor had no effect, which indicated that defective signaling, rather than hyperfunctioning Shh, is critical to the nonbranching phenotype of the fistula tract in TEF. CONCLUSIONS: The recapitulation of respiratory developmental morphogenesis by the fistula tract of TEF in the presence of exogenous Shh, together with the quantitative reduction in normal, endogenous levels of Gli-2, strongly suggests that 1 mechanism for the formation of the fistula tract is the lack of proper Shh signaling because of Gli-2 deficiency, with subsequent straight, nonbranching caudal growth of the fistula tract. This deficiency can be rescued by excess exogenous Shh, thus reestablishing respiratory morphogenesis.
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Atresia Esofágica/embriologia , Atresia Esofágica/etiologia , Transdução de Sinais , Fístula Traqueoesofágica/embriologia , Fístula Traqueoesofágica/etiologia , Transativadores/metabolismo , Animais , Doxorrubicina , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Atresia Esofágica/induzido quimicamente , Feminino , Proteínas Hedgehog , Fatores de Transcrição Kruppel-Like , Técnicas de Cultura de Órgãos , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fístula Traqueoesofágica/induzido quimicamente , Transativadores/farmacologia , Fatores de Transcrição/genética , Proteína Gli2 com Dedos de ZincoRESUMO
BACKGROUND/PURPOSE: The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS. DESIGN/METHODS: We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS. RESULTS: Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p<0.001). This association persisted in the multivariable equation (ß=1.35, 95% CI: 1.21, 1.52, p<0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections. CONCLUSIONS: In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair.
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Parede Abdominal/cirurgia , Gastrosquise/cirurgia , Recém-Nascido de Baixo Peso , Doenças do Prematuro/cirurgia , Procedimentos Cirúrgicos Operatórios/métodos , Cicatrização , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Tempo de Internação/tendências , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Hirschsprung's disease (HD), congenital absence of ganglion cells, is considered uncommon in preterm infants. The aim was to describe the frequency, presentation, and surgical outcomes of preterm infants with HD. A retrospective cohort study was conducted of all patients diagnosed with HD from 2002 to 2012 at a single children's hospital. Clinical presentation and surgical outcomes were obtained for term (37 weeks of gestation or greater) and preterm infants. One hundred twenty-nine subjects with HD were identified, 24 (19%) preterm and 105 (81%) term. Preterm infants were more likely to be diagnosed after 30 days of life (66.7 vs 37.1%, P < 0.01; median age 2.9 vs 0.3 months, P < 0.05) and to have associated major congenital anomalies (45.8 vs 20.0%, P < 0.01). Fewer preterm infants had primary pull-through operations (45.8 vs 76.2%, P < 0.005). Preterm infants were more likely to have an episode of Hirschsprung's-associated enterocolitis (45.8 vs 24.0%, P < 0.05) but were not more likely to die from any cause (8.3 vs 5.8%, P = 0.64). HD may be more common in preterm infants than previously recognized, and increased comorbidities in these patients may lead to delayed diagnosis and increased morbidity. HD should be considered in the preterm infant presenting with a bowel obstruction, especially when accompanied by associated anomalies.
Assuntos
Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/cirurgia , Recém-Nascido Prematuro , Anormalidades Múltiplas/epidemiologia , Distribuição de Qui-Quadrado , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Doença de Hirschsprung/epidemiologia , Hospitais Pediátricos , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Unlike other sharp objects, pens and pencils are readily available to children both at home and school. Although case reports are published, no series of pen or pencil injuries have been reported in the recent literature. We therefore reviewed the incidence and injury profiles of writing instruments as compared with other sources of penetrating trauma. The trauma registry from a large urban pediatric hospital system was queried for nonmissile, nonbite penetrating injuries from 2005 through 2009. Retrospective data was collected on demographics, injuries, operations, admissions, and mortalities. Additionally, data regarding pen and pencil injuries from 2009 to 2010 were collected prospectively, and one case from 2003 was included retrospectively. Fourteen injuries from writing instruments were seen and involved the head and neck (9), chest (1), bladder/perineum (2), and extremities (2). Eleven children were admitted and eight required surgical intervention. One child died from a transhemispheric brain injury after intraorbital penetration by a pencil. Penetrating trauma from writing instruments is not an uncommon source of injury and often requires surgical intervention to remove the object. Injuries from pens and pencils can be severe or even fatal. Appropriate parent and teacher education regarding the potential risks may help to prevent such injuries.
Assuntos
Acidentes Domésticos/estatística & dados numéricos , Ferimentos Penetrantes/epidemiologia , Adolescente , Distribuição por Idade , Causalidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Hospitais Pediátricos , Humanos , Incidência , Lactente , Escala de Gravidade do Ferimento , Masculino , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Taxa de Sobrevida , Resultado do Tratamento , Ferimentos Penetrantes/cirurgiaRESUMO
Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion consisting of mammary stromal proliferation with anastomosing slits mimicking vascular spaces. Grossly, it most often resembles fibroadenoma, but may commonly be confused with angiosarcoma and other types of benign vascular proliferations. While PASH has been described in female and male adults since the mid-1980s, there have been only a few accounts in the pediatric population. We present a series of 12 pediatric patients with PASH, including a 3-year-old male, who we believe to be the youngest patient to present with this entity. In our study, PASH was found in 12% of tumors diagnosed preoperatively as fibroadenomas and in 12% of cases diagnosed preoperatively as gynecomastia. Our series documents that PASH is not uncommon in pediatric breast pathology and delineates important differences between adult and pediatric presentations of this entity.
Assuntos
Doenças Mamárias/patologia , Células Estromais/patologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Fibroadenoma/patologia , Ginecomastia/patologia , Humanos , Hiperplasia/patologia , MasculinoRESUMO
PURPOSE: Contralateral inguinal hernia exploration in cases of unilateral inguinal hernia remains a controversial topic. The authors have been using the in-line laparoscopic technique of contralateral evaluation for unilateral inguinal hernia in children less than 2 years of age. Because of the case of the procedure and lack of morbidity, we decided to expand the use of this procedure up to age 8 years in January 2000. The purpose of this study is to evaluate if the incidence of contralateral hernia in children greater than 2 years justifies the procedure. METHODS: This is a retrospective study of all children who underwent contralateral exploration for unilateral inguinal exploration over a 20-month period. The procedure was offered routinely to all patients up to age 8 years. During the repair, the contralateral inguinal ring was examined laparoscopically using the in-line technique for the presence of a contralateral hernia. The incidence of contralateral hernia was determined, and the results were stratified by age. Patients who underwent unilateral inguinal hernia repair without laparoscopic contralateral exploration or bilateral inguinal hernia repair without laparoscopic contralateral explorations were excluded from the study. RESULTS: A total of 284 laparoscopic explorations were performed. Positive explorations were seen in 65 of 171 (38%) of children less than 2 years of age, 19 of 101 (20%) of children 2 to 8 years of age, and 1 of 12 children greater than 8 years of age (8%). There were no operative complications. CONCLUSIONS: Laparoscopic contralateral exploration is safe and effective. Because of the low morbidity, the risk to benefit ratio warrants its use in children up to 8 years of age. This sample size is too small to make any meaningful statement in children older than 8 years.
Assuntos
Hérnia Inguinal/diagnóstico , Canal Inguinal/anormalidades , Laparoscopia , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
BACKGROUND & AIMS: The early embryonic pancreas gives rise to exocrine (ducts and acini) and endocrine lineages. Control of exocrine differentiation is poorly understood, but may be a critical avenue through which to manipulate pancreatic ductal carcinoma. Retinoids have been shown to change the character of pancreatic ductal cancer cells to a less malignant phenotype. We have shown that 9-cis retinoic acid (9cRA) inhibits acinar differentiation in the developing pancreas, in favor of ducts, and we wanted to determine the role of retinoids in duct versus acinar differentiation. METHODS: We used multiple culture systems for the 11-day embryonic mouse pancreas. RESULTS: Retinoic acid receptor (RAR)-selective agonists mimicked the acinar suppressive effect of 9cRA, suggesting that RAR-RXR heterodimers were critical to ductal differentiation. RARalpha was only expressed in mesenchyme, whereas RXRalpha was expressed in epithelium and mesenchyme. Retinaldehyde dehydrogenase 2, a critical enzyme in retinoid synthesis, was expressed only in pancreatic epithelium. 9cRA did not induce ductal differentiation in the absence of mesenchyme, implicating a requirement for mesenchyme in 9cRA effects. Mesenchymal laminin is necessary for duct differentiation, and retinoids are known to enhance laminin expression. In 9cRA-treated pancreas, immunohistochemistry for laminin showed a strong band of staining around ducts, and blockage of laminin signaling blocked all 9cRA effects. Western blot and RT-PCR of pancreatic mesenchyme showed laminin-beta1 protein and mRNA induction by 9cRA. CONCLUSIONS: Retinoids regulate exocrine lineage selection through epithelial-mesenchymal interactions, mediated through up-regulation of mesenchymal laminin-1.