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1.
J Surg Res ; 277: 84-91, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35472725

RESUMO

INTRODUCTION: Clinical and radiographic findings often lead to diagnostic laparoscopy for presumed adnexal torsion (AT). To better understand the preoperative factors leading to AT, we evaluated the clinical course of patients with ultrasound findings concerning for AT to assess intraoperative AT rates and predictive factors for AT. METHODS: An institutional review board-approved retrospective review in two hospital centers over a period of 5 y was performed for females (4-18 y) with ultrasound (US) findings concerning for AT (n = 225). Preoperative clinical, radiographic, and intraoperative findings were assessed for patients with intraoperative AT versus for those without. RESULTS: The median age of patients was 14 y. Of those who went to the operating room (OR) (n = 113), AT was found in 57%. There was no difference between patients taken to the OR with or without AT regarding demographics or presentation. The presence of nausea/vomiting, tenderness, leukocytosis, lack of blood flow, or a mass/cyst >5 cm were found to be more likely in patients with AT than in those without. An ovarian volume ratio >15 was noted to be predictive of AT. Six patients initially discharged from the emergency department returned and went to the OR, two of which had AT, both with ovarian salvage. CONCLUSIONS: Limited data are available when counseling patients with presumed AT. We found the larger mean ovarian volume and an ovarian volume ratio >15 were predictive of AT. Despite this, 43% of patients taken to the OR did not have AT. This relatively high rate of not finding AT intraoperatively may be justified given the sequelae of missing AT.


Assuntos
Doenças dos Anexos , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/cirurgia , Adolescente , Criança , Feminino , Humanos , Náusea/complicações , Torção Ovariana , Estudos Retrospectivos , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/cirurgia , Vômito/complicações
2.
Clin Chem Lab Med ; 58(5): 787-797, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-31639099

RESUMO

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.


Assuntos
Ácidos e Sais Biliares/sangue , Cromatografia Líquida de Alta Pressão/métodos , Enteropatias/diagnóstico , Fígado/metabolismo , Espectrometria de Massas em Tandem/métodos , Atresia Biliar/diagnóstico , Biomarcadores/sangue , Criança , Citrulinemia/diagnóstico , Enterocolite Necrosante/diagnóstico , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Estudos de Validação como Assunto
3.
Pediatr Surg Int ; 36(6): 687-696, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32377785

RESUMO

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.


Assuntos
Tubos Torácicos , Esofagoplastia/métodos , Complicações Pós-Operatórias/prevenção & controle , Fístula Traqueoesofágica/cirurgia , Feminino , Humanos , Recém-Nascido , Tempo de Internação , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
4.
J Surg Res ; 241: 57-62, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31009886

RESUMO

INTRODUCTION: Nonmedical opioid use is a major public health problem. There is little standardization in opioid-prescribing practices for pediatric ambulatory surgery, which can result in patients being prescribed large quantities of opioids. We have evaluated the variability in postoperative pain medication given to pediatric patients following routine ambulatory pediatric surgical procedures. METHODS: Following IRB approval, pediatric patients undergoing umbilical hernia repair, inguinal hernia repair, hydrocelectomy, and orchiopexy from 2/1/2017 to 2/1/2018 at our tertiary care children's hospital were retrospectively reviewed. Data collected include operation, surgeon, resident or fellow involvement, utilization of preoperative analgesia, opioid prescription on discharge, and patient follow-up. RESULTS: Of 329 patients identified, opioids were prescribed on discharge to 37.4% of patients (66.3% of umbilical hernia repairs, 20.6% of laparoscopic inguinal hernia repairs, and 33.3% of open inguinal hernia repairs [including hydrocelectomies and orchiopexies]). For each procedure, there was large intrasurgeon and intersurgeon variability in the number of opioid doses prescribed. Opioid prescription ranged from 0 to 33 doses for umbilical hernia repairs, 0 to 24 doses for laparoscopic inguinal repairs, and 0 to 20 doses prescribed for open inguinal repairs, hydrocelectomies, and orchiopexies. Pediatric surgical fellows were less likely to discharge a patient with an opioid prescription than surgical resident prescribers (P < 0.01). In addition, surgical residents were more likely to prescribe more than twelve doses of opioids than pediatric surgical fellows (P < 0.01). Increasing patient age was associated with an increased likelihood of opioid prescription (P < 0.01). There were two phone calls and two clinic visits for pain control issues with equal numbers for those with and without opioid prescriptions. CONCLUSIONS: There is significant variation in opioid-prescribing practices after pediatric surgical procedures; increased awareness may help minimize this variability and reduce overprescribing. Training level has an impact on the frequency and quantity of opioids prescribed.


Assuntos
Analgésicos Opioides/uso terapêutico , Ambulatório Hospitalar/estatística & dados numéricos , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Criança , Pré-Escolar , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Herniorrafia/efeitos adversos , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Masculino , Epidemia de Opioides/etiologia , Epidemia de Opioides/prevenção & controle , Orquidopexia/efeitos adversos , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricos , Hidrocele Testicular/cirurgia , Estados Unidos/epidemiologia
5.
Am J Physiol Gastrointest Liver Physiol ; 315(2): G259-G271, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672156

RESUMO

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.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Enterócitos , Receptores ErbB/metabolismo , Enteropatias , Sepse , Ácido Ursodesoxicólico , Animais , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/farmacologia , Movimento Celular/fisiologia , Colagogos e Coleréticos/metabolismo , Colagogos e Coleréticos/farmacologia , Modelos Animais de Doenças , Enterócitos/efeitos dos fármacos , Enterócitos/fisiologia , Enteropatias/complicações , Enteropatias/metabolismo , Camundongos , Fatores de Proteção , Sepse/etiologia , Sepse/prevenção & controle , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/farmacologia
6.
J Surg Res ; 228: 228-237, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907216

RESUMO

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.


Assuntos
Ácidos e Sais Biliares/análise , Atresia Biliar/diagnóstico , Colestase/diagnóstico , Hiperbilirrubinemia/sangue , Espectrometria de Massas/métodos , Adolescente , Animais , Atresia Biliar/sangue , Atresia Biliar/complicações , Atresia Biliar/urina , Criança , Pré-Escolar , Colestase/sangue , Colestase/etiologia , Colestase/urina , Cromatografia Líquida de Alta Pressão/métodos , Diagnóstico Diferencial , Modelos Animais de Doenças , Fezes/química , Feminino , Humanos , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/urina , Lactente , Recém-Nascido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos
7.
Pediatr Surg Int ; 33(2): 125-131, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27837262

RESUMO

PURPOSE: Extracorporeal life support (ECLS) is applied to refractory pulmonary hypertension in congenital diaphragmatic hernia (CDH). We evaluate the single-center outcomes of infants with CDH to determine the utility of late repair on ECLS versus repair post-decannulation. METHODS: Records of infants with CDH (2004-2014) were retrospectively reviewed. RESULTS: CDH was diagnosed in 177 infants. Sixty six (37%) underwent ECLS, of which, 11 died prior to repair, 33 were repaired post-decannulation, and 22 were repaired on ECLS. Repair was delayed in patients on ECLS (19 versus 10 days, p < 0.001). Patients repaired on ECLS had longer ECLS runs (22 versus 12 days, p < 0.001) and higher rates of bleeding and mortality than those repaired post-decannulation. Survival was 54% in infants undergoing ECLS, 65% in those who underwent repair, 36% in those repaired during ECLS, and 85% in those who were decannulated prior to repair. Eighteen percent (N = 4) of deaths after repair on ECLS were attributable to surgical bleeding. The remainder was due to pulmonary hypertension or sepsis. CONCLUSION: Infants who underwent CDH repair post-decannulation had excellent outcomes and no mortalities attributable to repair. Neonates who underwent repair on ECLS late on bypass had the lowest survival rate with only 18% of mortality in this cohort attributable to surgical bleeding.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hérnias Diafragmáticas Congênitas/cirurgia , Cuidados para Prolongar a Vida/métodos , Perda Sanguínea Cirúrgica , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
8.
Pediatr Surg Int ; 33(7): 771-775, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28289880

RESUMO

INTRODUCTION: The Morgagni hernia (MH) accounts for 3-4% of congenital diaphragmatic hernias. There is a paucity of data regarding this rare defect. The purpose of this study is to describe the characteristics of children with MH, surgical approaches for repair, and patient outcomes. METHODS: Pediatric patients (ages 0-18) with a MH from 2002 to 2014 at a single, freestanding pediatric hospital were retrospectively reviewed. Patient presentation, demographics, operative methods and findings, and outcomes were evaluated. RESULTS: Twenty-six infants and children with a congenital MH were treated. There were 20 males (77%) and six females (23%) with a median age at diagnosis of 14.75 months (range 1 week to 13 years). Half were symptomatic. Sixteen hernias were repaired laparoscopically, nine by an open approach, and one laparoscopic converted to open. Colon was the most commonly herniated organ (N = 14). Hernia sacs were found in 22 patients of which, 20 were resected. Two patients underwent treatment with ECLS. There was one mortality in a patient who underwent repair on ECLS in the setting of an omphalocele and SVC obstruction. There were no recurrences in our sample. CONCLUSION: In this series, congenital MH appears to have a male predominance, frequently presents with pulmonary symptoms, and has excellent outcomes regardless of operative approach.


Assuntos
Hérnias Diafragmáticas Congênitas/diagnóstico , Hérnias Diafragmáticas Congênitas/cirurgia , Dor Abdominal/etiologia , Adolescente , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Lactente , Recém-Nascido , Laparoscopia , Masculino , Complicações Pós-Operatórias , Recidiva , Transtornos Respiratórios/etiologia , Estudos Retrospectivos
9.
Pediatr Surg Int ; 33(11): 1221-1230, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28965232

RESUMO

PURPOSE: To evaluate whether simultaneous abdominal surgery or wound contamination at the time of ventriculoperitoneal (VP) shunt placement are associated with increased shunt complications. METHODS: Pediatric patients who underwent VP shunt placement were identified using the National Surgical Quality Improvement Program Pediatric database. VP shunt complication rates were compared between patients who underwent simultaneous abdominal surgeries at the time of VP shunt placement vs those who did not and between those with clean/clean-contaminated and contaminated/dirty wound classifications. Adjusted analysis was performed using 1:5 case-control matching. RESULTS: Among 2715 patients who underwent VP shunt placement, 21 had simultaneous abdominal procedures and were matched with 105 control patients. No significant difference was found in overall (34.3 vs 14.3%, p = 0.07), infectious (8.6 vs 4.8%, p = 1.000), or non-infectious (25.7 vs 9.5%, p = 0.156) shunt complications in the simultaneous vs non-simultaneous group, respectively. In a separate analysis of wound classification, 12 patients with contaminated/dirty wounds were matched with 60 patients with clean/clean-contaminated wounds. The rates of shunt infections for clean/clean-contaminated and contaminated/dirty cases were 10.0 and 16.7%, respectively (p = 0.613). CONCLUSION: In our matched case-control study, neither simultaneous abdominal surgery nor wound contamination at the time of VP shunt placement demonstrated significant increased risk of 30-day post-operative complication.


Assuntos
Abdome/cirurgia , Complicações Pós-Operatórias/classificação , Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/classificação
10.
Pediatr Surg Int ; 33(3): 311-316, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27878593

RESUMO

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.


Assuntos
Traumatismos Abdominais/sangue , Traumatismos Abdominais/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X/métodos , Transaminases/sangue , Ferimentos não Penetrantes/sangue , Ferimentos não Penetrantes/diagnóstico por imagem , Abdome/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco
11.
Am J Physiol Gastrointest Liver Physiol ; 310(2): G81-92, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26608185

RESUMO

Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation.


Assuntos
Ácidos e Sais Biliares/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Intestino Delgado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Ácido Cólico/farmacologia , Ácido Desoxicólico/farmacologia , Intestino Delgado/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos
12.
Pediatr Surg Int ; 31(6): 509-18, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25854935

RESUMO

Although necrotizing enterocolitis (NEC) is the most lethal gastrointestinal disease in the neonatal population, its pathogenesis is poorly understood. Risk factors include prematurity, bacterial colonization, and formula feeding. This review examines how mucosal injury permits opportunistic pathogens to breach the gut barrier and incite an inflammatory response that leads to sustained overproduction of mediators such as nitric oxide and its potent adduct, peroxynitrite. These mediators not only exacerbate the initial mucosal injury, but they also suppress the intestinal repair mechanisms, which further compromises the gut barrier and culminates in bacterial translocation, sepsis, and full-blown NEC.


Assuntos
Enterocolite Necrosante/patologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Mucosa Intestinal/patologia , Intestinos/patologia
13.
Shock ; 54(3): 394-401, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31490357

RESUMO

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.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Enterocolite Necrosante/metabolismo , Inflamação/metabolismo , Peritonite/metabolismo , Animais , Linhagem Celular , Dinoprostona/farmacologia , Dinoprostona/uso terapêutico , Enterocolite Necrosante/tratamento farmacológico , Immunoblotting , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Peritonite/tratamento farmacológico , Ratos , Reação em Cadeia da Polimerase em Tempo Real
14.
J Neurosci ; 28(10): 2313-9, 2008 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-18322078

RESUMO

The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear learning in both animals and humans. The anxiolytic effects of delta(9)-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are believed to be mediated through direct and selective agonism of CB(1) receptors localized within the basolateral amygdala, a critical brain region for threat perception. However, little is known about the effects of THC on amygdala reactivity in humans. We used functional magnetic resonance imaging and a well validated task to probe amygdala responses to threat signals in 16 healthy, recreational cannabis users after a double-blind crossover administration of THC or placebo. We found that THC significantly reduced amygdala reactivity to social signals of threat but did not affect activity in primary visual and motor cortex. The current findings fit well with the notion that THC and other cannabinoids may have an anxiolytic role in central mechanisms of fear behaviors and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid system for disorders of anxiety and social fear.


Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Canabinoides/farmacologia , Medo/efeitos dos fármacos , Comportamento Social , Adolescente , Adulto , Tonsila do Cerebelo/fisiologia , Método Duplo-Cego , Dronabinol/farmacologia , Medo/fisiologia , Medo/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia
15.
J Pediatr Surg ; 54(9): 1861-1865, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31101425

RESUMO

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.


Assuntos
Traumatismo Cerebrovascular/diagnóstico por imagem , Ferimentos não Penetrantes/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Angiografia por Tomografia Computadorizada , Humanos , Lactente , Recém-Nascido , Classificação Internacional de Doenças , Estudos Retrospectivos
16.
J Pediatr Surg ; 54(1): 60-64, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30482541

RESUMO

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.


Assuntos
Gastrosquise/classificação , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Seguimentos , Gastrosquise/mortalidade , Gastrosquise/cirurgia , Humanos , Recém-Nascido , Atresia Intestinal/etiologia , Intestinos/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
17.
J Pediatr Surg ; 54(9): 1736-1739, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31103272

RESUMO

PURPOSE: The risks of laparotomy during extracorporeal life support (ECLS) are poorly defined. We examined risk factors associated with bleeding and mortality after laparotomy on ECLS. METHODS: The Extracorporeal Life Support Organization (ELSO) database was queried for all pediatric patients [0-17 years] with a procedure code for laparotomy. Outcome data were analyzed to define factors contributing to laparotomy complications and mortality while on ECLS. Univariate and multivariate analyses were applied to determine independent risk factors. RESULTS: 196 patients who met inclusion criteria were identified. The mortality rate in the entire cohort was 67.3%. In both univariate and multivariate analyses, surgical site bleeding did not significantly increase the risk of mortality (OR 0.8; 95% CI 0.4-1.7). Logistic regression analysis revealed that lower gestational age, infectious complications and nonsurgical site hemorrhagic complications were independently increased mortality risk (all p < 0.05). CONCLUSION: Mortality following laparotomy on ECLS is not independently associated with surgical site bleeding, but is associated with lower gestational age, infectious and nonsurgical site hemorrhagic complications. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.


Assuntos
Perda Sanguínea Cirúrgica , Oxigenação por Membrana Extracorpórea , Laparotomia , Adolescente , Perda Sanguínea Cirúrgica/mortalidade , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Laparotomia/efeitos adversos , Laparotomia/mortalidade , Laparotomia/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
18.
J Pediatr Surg ; 53(8): 1499-1503, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29249456

RESUMO

INTRODUCTION: Children with kidney failure requiring PD catheter placement often require additional intraabdominal surgery. However, the risk of complication related to simultaneous abdominal surgery at time of catheter placement is unknown. METHODS: Patients (0-18years) who underwent PD catheter placement (2012-2015) in the NSQIP-P database were reviewed. Complication rates between patients who underwent additional abdominal surgery at the time of PD catheter placement and those that did not were evaluated. One to one case control matching was performed for additional adjusted analysis. RESULTS: Of 563 patients who met inclusion criteria, 82 underwent simultaneous abdominal surgery at time of PD catheter placement. Patients in the simultaneous group had a higher rate of wound contamination but there was no difference in rates of SSI, 30-day PD catheter complication, or 30-day mortality compared with the nonsimultaneous group. There was no difference when overall simultaneous abdominal surgery or gastrointestinal surgery was evaluated. In our 1:1 adjusted analysis, there was a higher rate of PD catheter complication (11.3% vs. 2.8%, p=0.049) and SSI (31.0% vs. 4.2%, p<0.001) in the nonsimultaneous group. CONCLUSIONS: Thirty-day PD catheter complication and SSI in patients who underwent simultaneous abdominal surgery at time of catheter placement were noninferior to outcomes in the nonsimultaneous. LEVEL OF EVIDENCE: Level III, Treatment study, Retrospective comparative study.


Assuntos
Abdome/cirurgia , Cateterismo/efeitos adversos , Nefropatias/terapia , Diálise Peritoneal/efeitos adversos , Infecção da Ferida Cirúrgica/terapia , Adolescente , Cateterismo/estatística & dados numéricos , Cateteres de Demora/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Nefropatias/complicações , Masculino , Diálise Peritoneal/estatística & dados numéricos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/complicações
19.
PLoS One ; 13(6): e0196710, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29933378

RESUMO

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.


Assuntos
Enterocolite Necrosante/prevenção & controle , Microbioma Gastrointestinal , Intestinos/microbiologia , Lactobacillus , Probióticos , Animais , Animais Recém-Nascidos , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/patologia , Intestinos/patologia , Ratos , Ratos Sprague-Dawley
20.
Am J Surg ; 213(4): 640-644, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28057296

RESUMO

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.


Assuntos
Atresia Esofágica/cirurgia , Esôfago/diagnóstico por imagem , Cuidados Pós-Operatórios , Fístula Traqueoesofágica/cirurgia , Fístula Anastomótica/diagnóstico por imagem , Tubos Torácicos/estatística & dados numéricos , Dilatação/estatística & dados numéricos , Estenose Esofágica/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Procedimentos Desnecessários
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