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1.
Am J Physiol Gastrointest Liver Physiol ; 327(2): G175-G187, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38860296

RESUMEN

Accumulating literature suggests that the farnesoid-X receptor (FXR), a nuclear bile acid receptor best known for its role in bile acid homeostasis, is also a potent context-dependent regulator of inflammation. FXR may thus be relevant to several intestinal disease states including inflammatory bowel disease, necrotizing enterocolitis, and sepsis. In this study, we tested the effects of FXR deletion on acute murine intestinal inflammation. We found that FXR knockout (KO) mice were protected from intestinal injury and barrier dysfunction induced by lipopolysaccharide (LPS) injection, dithizone (DI)/Klebsiella, and cecal ligation/puncture models. In the LPS model, RNA sequencing and qPCR analysis showed that this protection correlated with substantial reduction in LPS-induced proinflammatory gene expression, including lower tissue levels of Il1a, Il1b, and Tnf. Examining functional effects on the epithelium, we found that LPS-induced tight junctional disruption as assessed by internalization of ZO-1 and occludin was ameliorated in FXR KO animals. Taken together, these data suggest a role for FXR in the intestinal barrier during inflammatory injury.NEW & NOTEWORTHY Intestinal barrier failure is a hallmark in gut-origin sepsis. We demonstrate that the intestinal barriers of farnesoid-X receptor (FXR) knockout (KO) animals are protected from inflammatory insult using multiple models of acute intestinal inflammation. This protection is due to decreased inflammatory cytokine production and maintenance of tight junctional architecture seen within the KO animals. This is the first report of FXR deletion being protective to the intestinal barrier.


Asunto(s)
Mucosa Intestinal , Lipopolisacáridos , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/deficiencia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Lipopolisacáridos/toxicidad , Ratones , Ratones Endogámicos C57BL , Masculino , Inflamación/metabolismo , Inflamación/genética , Uniones Estrechas/metabolismo , Uniones Estrechas/patología , Modelos Animales de Enfermedad
2.
J Surg Res ; 300: 54-62, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38795673

RESUMEN

INTRODUCTION: Pediatric surgical care is becoming increasingly regionalized, often resulting in limited access. Interfacility transfers pose a significant financial and emotional burden to when they are potentially avoidable. Of transferred patients, we sought to identify clinical factors associated with avoidable transfers in pediatric patients with suspected appendicitis. METHODS: We performed a single-center retrospective study at an academic tertiary referral children's hospital in an urban setting. We included children who underwent interfacility transfer to our center with a transfer diagnosis of appendicitis from July 1, 2021 to June 30, 2023. Encounters were designated as either an appropriate transfer (underwent appendectomy) or an avoidable transfer (did not undergo appendectomy). Encounters treated nonoperatively for complicated appendicitis were excluded. Bivariate analysis was performed using Mann-Whitney test and chi-square tests. RESULTS: A total of 444 patients were included: 71.2% were classified as appropriate transfers and 28.8% as avoidable transfers. Patients with avoidable transfer were younger compared to those in the appropriate transfer cohort (median age 9 y, interquartile range: 7-13 versus 11 y, interquartile range: 8-14; P < 0.001). Avoidable transfers less frequently presented with the typical symptoms of fever, migratory abdominal pain, anorexia, and nausea/emesis (P = 0.005). Avoidable transfers also reported shorter symptom duration (P = 0.040) with lower median white blood cell count (P < 0.001), neutrophil percentage (P < 0.001), and C-reactive protein levels (P < 0.003). Avoidable transfers more frequently underwent repeat imaging upon arrival (42.9% versus 12.7%, P < 0.001). CONCLUSIONS: These findings highlight the importance of clinical history in children with suspected appendicitis. Younger patients without typical symptoms of appendicitis, those with a shorter duration of symptoms, and lower serum inflammatory markers may benefit from close observation without transfer.


Asunto(s)
Apendicectomía , Apendicitis , Transferencia de Pacientes , Humanos , Apendicitis/cirugía , Apendicitis/diagnóstico , Niño , Transferencia de Pacientes/estadística & datos numéricos , Transferencia de Pacientes/organización & administración , Estudios Retrospectivos , Masculino , Femenino , Adolescente , Apendicectomía/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Hospitales Pediátricos/organización & administración , Preescolar
3.
Am Surg ; 90(10): 2534-2542, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38648035

RESUMEN

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.


Asunto(s)
Enterostomía , Complicaciones Posoperatorias , Humanos , Estudios Retrospectivos , Masculino , Femenino , Complicaciones Posoperatorias/epidemiología , Enterostomía/efectos adversos , Lactante , Recién Nacido , Resultado del Tratamiento , Peso Corporal , Recien Nacido Prematuro
4.
Am Surg ; 90(10): 2600-2608, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38684325

RESUMEN

BACKGROUND: Gastrostomy creation is a common pediatric surgical procedure, but the time to initiation of feeds and to goal feeding volumes postoperatively varies greatly. Delays in reaching goal feeding volumes promote malnutrition and may prolong hospital length of stay. We hypothesized that implementing an accelerated, standardized post-gastrostomy feeding protocol would allow patients to reach goal feeding volumes sooner, without increasing postoperative complications. METHODS: We conducted a retrospective cohort study of children who underwent gastrostomy tube placement between 1/1/2022 and 11/30/2023. The feeding protocol was implemented on 11/16/2022, with patients separated into pre- and post-protocol cohorts. Abstracted data included comorbidities, time to initiation of enteral feeds, time to goal feeding volume, and postoperative complications. RESULTS: 322 patients were included: 166 pre-protocol and 156 post-protocol. The post-protocol cohort had a greater proportion of patients with gastrointestinal and/or cardiac comorbidities (P < .001). Through the protocol, postoperative enteral feeds were initiated significantly faster (5.4 hrs [IQR 43-7.7] vs 7.0 hrs [IQR 5.6-14.3]; P < .001). The post-protocol cohort also achieved goal feeding volumes sooner (12.8 hrs [IQR 9.1-25.3] vs 26.3 hrs [IQR 21.6-38.9]; P < .001). Postoperative complication rates did not differ between cohorts. Sub-analysis of children with complex cardiac conditions also demonstrated faster time to goal nutrition without an associated increase in postoperative events. DISCUSSION: These findings demonstrate that our accelerated post-gastrostomy feeding protocol was effective in achieving goal enteral nutrition earlier without increasing postoperative adverse outcomes. This protocol may be used by other centers to safely expedite time to goal enteral feeds in children postoperatively.


Asunto(s)
Nutrición Enteral , Gastrostomía , Cuidados Posoperatorios , Complicaciones Posoperatorias , Humanos , Gastrostomía/métodos , Estudios Retrospectivos , Nutrición Enteral/métodos , Femenino , Masculino , Preescolar , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Niño , Lactante , Cuidados Posoperatorios/métodos , Factores de Tiempo , Protocolos Clínicos , Tiempo de Internación/estadística & datos numéricos
5.
Cells ; 10(11)2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34831429

RESUMEN

The Farnesoid-X Receptor, FXR, is a nuclear bile acid receptor. Its originally described function is in bile acid synthesis and regulation within the liver. More recently, however, FXR has been increasingly appreciated for its breadth of function and expression across multiple organ systems, including the intestine. While FXR's role within the liver continues to be investigated, increasing literature indicates that FXR has important roles in responding to inflammation, maintaining intestinal epithelial barrier function, and regulating immunity within the gastrointestinal (GI) tract. Given the complicated and multi-factorial nature of intestinal barrier dysfunction, it is not surprising that FXR's role appears equally complicated and not without conflicting data in different model systems. Recent work has suggested translational applications of FXR modulation in GI pathology; however, a better understanding of FXR physiology is necessary for these treatments to gain widespread use in human disease. This review aims to discuss current scientific work on the role of FXR within the GI tract, specifically in its role in intestinal inflammation, barrier function, and immune response, while also exploring areas of controversy.


Asunto(s)
Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/fisiopatología , Inmunidad Innata , Receptores Citoplasmáticos y Nucleares/metabolismo , Tracto Gastrointestinal/patología , Humanos , Inflamación/patología , Modelos Biológicos , Uniones Estrechas/metabolismo
6.
Pediatr Surg Int ; 36(6): 687-696, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32377785

RESUMEN

PURPOSE: Intraoperative chest tubes (IOCTs) can be placed during esophageal atresia/tracheoesophageal fistula (EA/TEF) repair to control pneumothoraces and detect esophageal leaks, potentially preventing the need for postoperative chest tubes (POCTs). However, data are lacking regarding IOCTs' effect. We hypothesized that IOCT placement would not reduce the risk of POCT placement and would increase hospital length of stay (LOS). METHODS: This was a single-center case-control study of type C EA/TEF patients repaired at a tertiary referral center between 2006 and 2017. Postoperative complications of patients who received IOCTs (n = 83) were compared to that of patients who did not receive IOCTs (n = 26). Patients were compared via propensity score matching. Additionally, sensitivity analyses excluding low birth weight (LBW) patients and patients undergoing delayed esophageal anastomosis were also performed. RESULTS: There was no significant difference in rates of pneumothoraces or esophageal leaks between the IOCT and no-IOCT groups, nor were either of these complications detected earlier in the IOCT group. Rates of POCT placement and mortality also did not differ between groups. IOCT patients were associated with increased hospital LOS (28 vs 15.5 days, p < 0.001) and esophageal strictures (30% vs 8%, p = 0.04) requiring a return to the operating room (RTOR). CONCLUSION: IOCTs did not improve outcomes in EA/TEF repair. IOCTs seem associated with increased LOS and ROTR for esophageal stricture, suggesting that IOCTs may not be beneficial after EA/TEF repair.


Asunto(s)
Tubos Torácicos , Esofagoplastia/métodos , Complicaciones Posoperatorias/prevención & control , Fístula Traqueoesofágica/cirugía , Femenino , Humanos , Recién Nacido , Tiempo de Internación , Masculino , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del Tratamiento
7.
Clin Chem Lab Med ; 58(5): 787-797, 2020 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-31639099

RESUMEN

Background A method for bile acid profiling measuring 21 primary and secondary bile acids in serum samples was developed and validated with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation included spiking with internal standards followed by protein precipitation, centrifugation, drying under nitrogen gas and reconstitution. Extracted samples were injected onto a Phenomenex Kinetex C18 column (150 × 4.60 mm, 2.6 µm). Methods Data was collected with LC-MS/MS operated in negative ion mode with multiple reaction monitoring (MRM) and single reaction monitoring (SRM). The analytical run time was 12 min. Results The method showed excellent linearity with high regression coefficients (>0.99) over a range of 0.05 and 25 µM for all analytes tested. The method also showed acceptable intra-day and inter-day accuracy and precision. As a proof of concept, the analytical method was applied to patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), biliary atresia (BA), and necrotizing enterocolitis (NEC), and distinct bile acids profiles were demonstrated. Conclusions The method could be poised to identify possible biomarkers for non-invasive early diagnosis of these disorders.


Asunto(s)
Ácidos y Sales Biliares/sangre , Cromatografía Líquida de Alta Presión/métodos , Enfermedades Intestinales/diagnóstico , Hígado/metabolismo , Espectrometría de Masas en Tándem/métodos , Atresia Biliar/diagnóstico , Biomarcadores/sangre , Niño , Citrulinemia/diagnóstico , Enterocolitis Necrotizante/diagnóstico , Humanos , Límite de Detección , Reproducibilidad de los Resultados , Estudios de Validación como Asunto
8.
Shock ; 54(3): 394-401, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31490357

RESUMEN

High levels of PGE2 have been implicated in the pathogenesis of intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) and peritonitis. However, PGE2 has a paradoxical effect: its low levels promote intestinal homeostasis, whereas high levels may contribute to pathology. These concentration-dependent effects are mediated by four receptors, EP1-EP4. In this study, we evaluate the effect of blockade of the low affinity pro-inflammatory receptors EP1 and EP2 on expression of COX-2, the rate-limiting enzyme in PGE2 biosynthesis, and on gut barrier permeability using cultured enterocytes and three different models of intestinal injury. PGE2 upregulated COX-2 in IEC-6 enterocytes, and this response was blocked by the EP2 antagonist PF-04418948, but not by the EP1 antagonist ONO-8711 or EP4 antagonist E7046. In the neonatal rat model of NEC, EP2 antagonist and low dose of COX-2 inhibitor Celecoxib, but not EP1 antagonist, reduced NEC pathology as well as COX-2 mRNA and protein expression. In the adult mouse endotoxemia and cecal ligation/puncture models, EP2, but not EP1 genetic deficiency decreased COX-2 expression in the intestine. Our results indicate that the EP2 receptor plays a critical role in the positive feedback regulation of intestinal COX-2 by its end-product PGE2 during inflammation and may be a novel therapeutic target in the treatment of NEC.


Asunto(s)
Ciclooxigenasa 2/metabolismo , Enterocolitis Necrotizante/metabolismo , Inflamación/metabolismo , Peritonitis/metabolismo , Animales , Línea Celular , Dinoprostona/farmacología , Dinoprostona/uso terapéutico , Enterocolitis Necrotizante/tratamiento farmacológico , Immunoblotting , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Fluorescente , Peritonitis/tratamiento farmacológico , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
PLoS One ; 14(11): e0216762, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31675374

RESUMEN

Enterococcus faecalis is a ubiquitous intestinal symbiont and common early colonizer of the neonatal gut. Although colonization with E. faecalis has been previously associated with decreased pathology of necrotizing enterocolitis (NEC), these bacteria have been also implicated as opportunistic pathogens. Here we characterized 21 strains of E. faecalis, naturally occurring in 4-day-old rats, for potentially pathogenic properties and ability to colonize the neonatal gut. The strains differed in hemolysis, gelatin liquefaction, antibiotic resistance, biofilm formation, and ability to activate the pro-inflammatory transcription factor NF-κB in cultured enterocytes. Only 3 strains, BB70, 224, and BB24 appreciably colonized the neonatal intestine on day 4 after artificial introduction with the first feeding. The best colonizer, strain BB70, effectively displaced E. faecalis of maternal origin. Whereas BB70 and BB24 significantly increased NEC pathology, strain 224 significantly protected from NEC. Our results show that different strains of E. faecalis may be pathogenic or protective in experimental NEC.


Asunto(s)
Enterococcus faecalis/patogenicidad , Enterocolitis Necrotizante/microbiología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Enterococcus faecalis/clasificación , Enterococcus faecalis/genética , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/prevención & control , Enterocitos/microbiología , Enterocitos/patología , Femenino , Variación Genética , Humanos , Recién Nacido , Intestinos/microbiología , Intestinos/patología , Fenotipo , Embarazo , Probióticos/uso terapéutico , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie , Virulencia
10.
J Pediatr Surg ; 54(9): 1861-1865, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31101425

RESUMEN

BACKGROUND: Adult imaging for blunt cerebrovascular injuries (BCVI) is based on the Denver and Memphis screening criteria where CT angiogram (CTA) is performed for any one of the criteria being positive. These guidelines have been extrapolated to the pediatric population. We hypothesize that the current adult criteria applied to pediatrics lead to unnecessary CTA in pediatric trauma patients. STUDY DESIGN: At our center, a 9-year retrospective study revealed that strict adherence to the Denver and Memphis criteria would have resulted in 332 unnecessary CTAs out of 2795 trauma patients with only 0.3% positive for BCVI. We also conducted a retrospective chart review of 776,355 pediatric trauma patients in the National Trauma Data Bank (NTDB) from 2007 to 2014. Data collection included children between ages 0 and 18, ICD-9 search for blunt cerebrovascular injury, and ICD-9 codes that applied to both Denver and Memphis criteria. RESULTS: Of 776,355 pediatric trauma activations, 81,294 pediatric patients in the NTDB fit the Denver/Memphis criteria for screening CTA neck or angiography based on ICD-9 codes, while only 2136 patients suffered BCVI. Strict utilization of the Denver/Memphis criteria would have led to a negative CTA in 79,158 (97.4%) patients. Multivariate regression analysis indicates that patients with skull base fracture, cervical spine fractures, cervical spine fracture with cervical cord injury, traumatic jugular venous injury, and cranial nerve injury should be considered part of the screening criteria for BCVI. CONCLUSION: Our study suggests the Denver and Memphis criteria are inadequate screening criteria for CTA looking for BCVI in the pediatric blunt trauma population. New criteria are needed to adequately indicate the need for CT angiography in the pediatric trauma population. LEVEL OF EVIDENCE: IV.


Asunto(s)
Traumatismos Cerebrovasculares/diagnóstico por imagen , Heridas no Penetrantes/diagnóstico por imagen , Adolescente , Niño , Preescolar , Angiografía por Tomografía Computarizada , Humanos , Lactante , Recién Nacido , Clasificación Internacional de Enfermedades , Estudios Retrospectivos
11.
JPEN J Parenter Enteral Nutr ; 43(7): 899-911, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30644566

RESUMEN

BACKGROUND: Dietary intake sharply impacts the structure and function of the gut microbiota, which is important for childhood health. However, little is known about the microbiota of children who cannot eat by mouth. Standard enteral formulas for supplemental nutrition are low in fiber and high in processed sugars and are commonly associated with gastrointestinal side effects. In this pilot study, we examined the effects of plant-based enteral nutrition (PBEN) upon the gut bacteria of chronically ill children. METHODS: Ten children (median age 3.5 years, age range 2-8 years) dependent upon conventional enteral formula were transitioned to PBEN for 2 months. Microbial diversity within fecal samples collected before and after PBEN was assessed by 16S ribosomal RNA gene sequence analysis and was compared with rectal swabs from healthy children. Fecal short-chain fatty acids and bile acids were measured in parallel. RESULTS: Relative to control samples, fecal samples from study subjects were depleted of commensals (eg, Faecalibacterium) and enriched with pathogens (eg, Enterococcus). Postintervention samples from study subjects were more similar to healthy controls. Most subjects experienced PBEN-induced alterations in the gut microbiota, but these changes varied significantly across individuals. Clinical diaries indicated that PBEN was well tolerated, with improvement in symptoms noted in several subjects. CONCLUSION: Results from this pilot study suggest that PBEN is well tolerated and could improve the health of the microbiota in chronically ill children. This trial provides a rationale for systematic evaluation of PBEN in clinical trials of children who require supplemental nutrition.


Asunto(s)
Enfermedad Crónica/terapia , Fibras de la Dieta/farmacología , Nutrición Enteral/métodos , Alimentos Formulados , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Plantas/química , Bacterias/genética , Bacterias/crecimiento & desarrollo , Bacterias/metabolismo , Niño , Preescolar , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Femenino , Tracto Gastrointestinal/microbiología , Humanos , Masculino , Proyectos Piloto , ARN Ribosómico 16S
12.
J Pediatr Surg ; 54(1): 60-64, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30482541

RESUMEN

PURPOSE: The diagnosis of "closing" or "closed gastroschisis" is made when bowel is incarcerated within a closed or nearly closed ring of fascia, usually with associated bowel atresia. It has been described as having a high morbidity and mortality. METHODS: A retrospective review of closing gastroschisis cases (n = 53) at six children's hospitals between 2000 and 2016 was completed after IRB approval. RESULTS: A new classification system for this disease was developed to represent the spectrum of the disease: Type A (15%): ischemic bowel that is constricted at the ring but without atresia; Type B (51%): intestinal atresia with a mass of ischemic, but viable, external bowel (owing to constriction at the ring); Type C (26%): closing ring with nonviable external bowel +/- atresia; and Type D (8%): completely closed defect with either a nubbin of exposed tissue or no external bowel. Overall, 87% of infants survived, and long-term data are provided for each type. CONCLUSIONS: This new classification system better captures the spectrum of disease and describes the expected long-term results for counseling. Unless the external bowel in a closing gastroschisis is clearly necrotic, it should be reduced and evaluated later. Survival was found to be much better than previously reported. TYPE OF STUDY: Retrospective case series with no comparison group. LEVEL OF EVIDENCE: Level IV.


Asunto(s)
Gastrosquisis/clasificación , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Estudios de Seguimiento , Gastrosquisis/mortalidad , Gastrosquisis/cirugía , Humanos , Recién Nacido , Atresia Intestinal/etiología , Intestinos/cirugía , Estudios Retrospectivos , Tasa de Supervivencia
13.
PLoS One ; 13(6): e0196710, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29933378

RESUMEN

The use of lactobacilli in prevention of necrotizing enterocolitis (NEC) is hampered by insufficient knowledge about optimal species/strains and effects on intestinal bacterial populations. We therefore sought to identify lactobacilli naturally occurring in postnatal rats and examine their ability to colonize the neonatal intestine and protect from NEC. L. murinus, L. acidophilus, and L. johnsonii were found in 42, 20, and 1 out of 51 4-day old rats, respectively. Higher proportion of L. murinus in microbiota correlated with lower NEC scores. Inoculation with each of the three species during first feeding significantly augmented intestinal populations of lactobacilli four days later, indicating successful colonization. L. murinus, but not L. acidophilus or L. johnsonii, significantly protected against NEC. Thus, lactobacilli protect rats from NEC in a species- or strain-specific manner. Our results may help rationalizing probiotic therapy in NEC.


Asunto(s)
Enterocolitis Necrotizante/prevención & control , Microbioma Gastrointestinal , Intestinos/microbiología , Lactobacillus , Probióticos , Animales , Animales Recién Nacidos , Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/patología , Intestinos/patología , Ratas , Ratas Sprague-Dawley
14.
J Surg Res ; 228: 228-237, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29907216

RESUMEN

BACKGROUND: Biliary atresia (BA) is difficult to distinguish from other causes of cholestasis. We evaluated the use of liquid chromatography-mass spectroscopy (LC-MS) and bile acid profiles in the rapid, noninvasive diagnosis of BA. MATERIALS AND METHODS: Following Institutional Animal Care and Use Committee and Institutional Review Board approval, we used LC-MS to measure 26 bile acids in serum and stool samples from experimental models of BA and in urine, stool, and serum samples from non-cholestatic and cholestatic human infants. RESULTS: We first evaluated the utility of LC-MS to distinguish bile acid profiles between sham, bile duct ligation, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of BA. Serum bile acids were significantly higher and stool bile acids were significantly lower in experimental BA. Next, we evaluated samples from non-cholestatic, cholestatic non-BA, and BA infants. There was no significant difference between cholestatic non-BA and BA stool and urine samples. However, primary bile acids were significantly higher in BA versus cholestatic non-BA samples (128.1 ± 14.2 versus 61.2 ± 20.5 µM). In addition, the primary, conjugated bile acids glycochenodeoxycholic acid and taurochenodeoxycholic acid were significantly elevated in BA compared with cholestatic non-BA serum samples. Using a receiver operating characteristic curve, we found that a serum glycochenodeoxycholic acid concentration of 30 µM had a sensitivity of 100%, specificity of 83.3%, positive predictive value of 88.9%, and negative predictive value of 100% in the diagnosis of BA. CONCLUSIONS: Our data indicate that bile acid patterns can be used to distinguish experimental and human BA from non-cholestatic and, more importantly, cholestatic disease. This suggests that LC-MS may be useful in the accurate, rapid, and non-invasive diagnosis of BA.


Asunto(s)
Ácidos y Sales Biliares/análisis , Atresia Biliar/diagnóstico , Colestasis/diagnóstico , Hiperbilirrubinemia/sangre , Espectrometría de Masas/métodos , Adolescente , Animales , Atresia Biliar/sangre , Atresia Biliar/complicaciones , Atresia Biliar/orina , Niño , Preescolar , Colestasis/sangre , Colestasis/etiología , Colestasis/orina , Cromatografía Líquida de Alta Presión/métodos , Diagnóstico Diferencial , Modelos Animales de Enfermedad , Heces/química , Femenino , Humanos , Hiperbilirrubinemia/etiología , Hiperbilirrubinemia/orina , Lactante , Recién Nacido , Masculino , Ratones , Ratones Endogámicos C57BL , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Estudios Retrospectivos
15.
Am J Physiol Gastrointest Liver Physiol ; 315(2): G259-G271, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29672156

RESUMEN

The intestinal barrier is often disrupted in disease states, and intestinal barrier failure leads to sepsis. Ursodeoxycholic acid (UDCA) is a bile acid that may protect the intestinal barrier. We hypothesized that UDCA would protect the intestinal epithelium in injury models. To test this hypothesis, we utilized an in vitro wound-healing assay and a mouse model of intestinal barrier injury. We found that UDCA stimulates intestinal epithelial cell migration in vitro, and this migration was blocked by inhibition of cyclooxygenase 2 (COX-2), epidermal growth factor receptor (EGFR), or ERK. Furthermore, UDCA stimulated both COX-2 induction and EGFR phosphorylation. In vivo UDCA protected the intestinal barrier from LPS-induced injury as measured by FITC dextran leakage into the serum. Using 5-bromo-2'-deoxyuridine and 5-ethynyl-2'-deoxyuridine injections, we found that UDCA stimulated intestinal epithelial cell migration in these animals. These effects were blocked with either administration of Rofecoxib, a COX-2 inhibitor, or in EGFR-dominant negative Velvet mice, wherein UDCA had no effect on LPS-induced injury. Finally, we found increased COX-2 and phosphorylated ERK levels in LPS animals also treated with UDCA. Taken together, these data suggest that UDCA can stimulate intestinal epithelial cell migration and protect against acute intestinal injury via an EGFR- and COX-2-dependent mechanism. UDCA may be an effective treatment to prevent the early onset of gut-origin sepsis. NEW & NOTEWORTHY In this study, we show that the secondary bile acid ursodeoxycholic acid stimulates intestinal epithelial cell migration after cellular injury and also protects the intestinal barrier in an acute rodent injury model, neither of which has been previously reported. These effects are dependent on epidermal growth factor receptor activation and downstream cyclooxygenase 2 upregulation in the small intestine. This provides a potential treatment for acute, gut-origin sepsis as seen in diseases such as necrotizing enterocolitis.


Asunto(s)
Ciclooxigenasa 2/metabolismo , Enterocitos , Receptores ErbB/metabolismo , Enfermedades Intestinales , Sepsis , Ácido Ursodesoxicólico , Animales , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Movimiento Celular/fisiología , Colagogos y Coleréticos/metabolismo , Colagogos y Coleréticos/farmacología , Modelos Animales de Enfermedad , Enterocitos/efectos de los fármacos , Enterocitos/fisiología , Enfermedades Intestinales/complicaciones , Enfermedades Intestinales/metabolismo , Ratones , Factores Protectores , Sepsis/etiología , Sepsis/prevención & control , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/farmacología
17.
Am J Surg ; 214(6): 1203-1207, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28969892

RESUMEN

PURPOSE: After radiologic reduction, patients with ileocolic intussusception are often admitted. We hypothesize that discharge of stable patients after 4 h of emergency department (ED) observation does not result in an increase of adverse outcomes. METHODS: We retrospectively reviewed pediatric patients with ileocolic intussusception between 2011 and 2016, managed with either 24-h inpatient or 4-h ED observation. Outcomes included length of stay, adverse outcomes, and total hospital charges. RESULTS: Fifty-one patients were managed with ED observation and 79 with inpatient observation. Recurrence rates, time to recurrence, and adverse outcomes were similar in both protocols. Total recurrence rates for ED observation was 15% versus 14% for inpatient observation. ED observation reduced time in the hospital by 26.8 h (4.9 versus 31.7 h). CONCLUSION: Discharging patients following uncomplicated hydrostatic reduction of ileocolic intussusception after a 4-h observation period does not result in an increase in adverse outcomes.


Asunto(s)
Hospitalización/estadística & datos numéricos , Intususcepción/diagnóstico por imagen , Intususcepción/cirugía , Servicio de Urgencia en Hospital , Femenino , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
18.
Lancet ; 390(10099): 1072-1082, 2017 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-28901937

RESUMEN

Recent developments in paediatric gastrointestinal surgery have focused on minimally invasive surgery, the accumulation of high-quality clinical evidence, and scientific research. The benefits of minimally invasive surgery for common disorders like appendicitis and hypertrophic pyloric stenosis are all supported by good clinical evidence. Although minimally invasive surgery has been extended to neonatal surgery, it is difficult to establish its role for neonatal disorders such as oesophageal atresia and biliary atresia through clinical trials because of the rarity of these disorders. Advances in treatments for biliary atresia and necrotising enterocolitis have been achieved through specialisation, multidisciplinary management, and multicentre collaboration in research; similarly robust clinical evidence for other rare gastrointestinal disorders is needed. As more neonates with gastrointestinal diseases survive into adulthood, their long-term sequelae will also need evidence-based multidisciplinary care. Identifying cures for long-term problems of a complex developmental anomaly such as Hirschsprung's disease will rely on unravelling its pathogenesis through genetics and the development of stem-cell therapy.


Asunto(s)
Gastroenterología/tendencias , Enfermedades Gastrointestinales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Apendicitis/cirugía , Atresia Biliar/cirugía , Niño , Enterocolitis Necrotizante/cirugía , Humanos , Recién Nacido , Diagnóstico Prenatal
19.
Am J Surg ; 213(4): 640-644, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28057296

RESUMEN

INTRODUCTION: Esophagrams are routinely performed following repair of esophageal atresia (EA) with or without tracheoesophageal fistula (TEF); however, its utility has not been validated. METHODS: EA/TEF repair performed from 2003 to 2014 at a single pediatric hospital and from 2004 to 2014 in the Pediatric Health Information System (PHIS) database were retrospectively reviewed to determine utility of esophagrams. RESULTS: Esophagram was performed in 99% of patients at our institution (N = 105). Clinical signs were seen prior to esophagram in patients whose leak changed clinical management. Esophagram on post-operative day ≤15 was performed in 66% of PHIS database patients (N = 3255). Esophagram did not change the incidence of chest tube placement, reoperation, or dilation. Patients who required a reoperation were less likely to have an esophagram than patients who did not require a reoperation (40.7% versus 65.7%, p < 0.001). CONCLUSION: Our data suggest that routine esophagram is not necessary in asymptomatic patients.


Asunto(s)
Atresia Esofágica/cirugía , Esófago/diagnóstico por imagen , Cuidados Posoperatorios , Fístula Traqueoesofágica/cirugía , Fuga Anastomótica/diagnóstico por imagen , Tubos Torácicos/estadística & datos numéricos , Dilatación/estadística & datos numéricos , Estenosis Esofágica/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Procedimientos Innecesarios
20.
Pediatr Surg Int ; 33(3): 311-316, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27878593

RESUMEN

PURPOSE: Current guidelines for computed tomography (CT) after blunt trauma were developed to capture all intra-abdominal injuries (IAI). We hypothesize that current AST/ALT guidelines are too low leading to unnecessary CT scans for children after blunt abdominal trauma (BAT). METHODS: Patients who received CT of the abdomen after blunt trauma at our Level I Pediatric Trauma Center were stratified into a high risk (HR) (liver/spleen/kidney grade ≥III, hollow viscous, or pancreatic injuries) and low risk (LR) (liver/kidney/spleen injuries grade ≤II, or no IAI) groups. RESULTS: 247 patients were included. Of the 18 patients in the HR group, two required surgery (splenectomy and sigmoidectomy). Transfusion was required in 30% of grade III and 50% of grade IV injuries. Eleven (5%) patients in LR group were transfused for indications other than IAI, and none were explored surgically. Both AST (r = 0.44, p < 0.001) and ALT (r = 0.43, p < 0.001) correlated with grade of liver injury. Using an increased threshold of AST/ALT, 400/200 had a negative predictive value of 96% in predicting the presence of HR liver injuries. CONCLUSION: The current cutoff of liver enzymes leads to over-identification of LR injuries. Consideration should be given to an approach that aims to utilize CT in pediatric BAT that identifies clinically HR injury.


Asunto(s)
Traumatismos Abdominales/sangre , Traumatismos Abdominales/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Tomografía Computarizada por Rayos X/métodos , Transaminasas/sangre , Heridas no Penetrantes/sangre , Heridas no Penetrantes/diagnóstico por imagen , Abdomen/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Medición de Riesgo
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