Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Fetal Diagn Ther ; 51(3): 235-242, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38402872

RESUMO

INTRODUCTION: Congenital dermal sinus (CDS) is an open neural tube defect (NTD) that occurs in 1 in 2,500 births a year and often goes undetected until patients present with complications like infection and neurological deficits. Early diagnosis and repair of CDS may prevent formation of these complications. In utero diagnosis of these lesions may improve long-term outcomes by enabling referral to specialty services and planned postnatal repair; however, only 2 such cases have been reported in the literature. We present a third case of in utero diagnosis of CDS with a description and discussion of findings from surgical exploration and pathology. CASE PRESENTATION: Routine prenatal ultrasound scan detected a tethered cystic structure arising from the back of the fetus at 20 weeks of gestation. Dedicated fetal ultrasound confirmed the presence of a cystic lesion protruding through a lamina defect, while fetal magnetic resonance imaging showed an intact spinal cord and meninges, suggesting a diagnosis of CDS. Neurosurgery followed along closely and took the child for surgical exploration on day 2 of life. A fibrous stalk with an intradural component and associated cord tethering was excised. Histology showed fibrous tissue without an epithelial-lined lumen. CONCLUSION: CDS is a form of NTD that occurs from nondisjunction of the cutaneous ectoderm and neuroectoderm during formation of the neural tube. Slight differences in how this error occurs can explain variations seen in this spectrum of disease, including CDS without an epithelial-lined lumen as seen in this case. Newborns with CDS can go undiagnosed for years and present with long-term complications. Fetal imaging can assist in early recognition and surgical excision of CDS in newborns.


Assuntos
Espinha Bífida Oculta , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Espinha Bífida Oculta/diagnóstico por imagem , Espinha Bífida Oculta/cirurgia , Adulto , Recém-Nascido , Imageamento por Ressonância Magnética
2.
J Surg Res ; 295: 168-174, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38016270

RESUMO

INTRODUCTION: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement. METHODS: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. RESULTS: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. CONCLUSIONS: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Estomia , Lactente , Recém-Nascido , Humanos , Gastrostomia/efeitos adversos , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/cirurgia , Estudos Retrospectivos , Morbidade
3.
J Pediatr Surg ; 59(5): 962-968, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38160185

RESUMO

INTRODUCTION: Prosthetic patches (patch) and muscle flaps (flap) are techniques used for repair of congenital diaphragmatic hernia (CDH) with a large defect unamenable to primary closure. We hypothesized that the flap technique for CDH repair while on extra-corporeal membrane oxygenation (on-ECMO) would have decreased bleeding complications compared to patch due to the hemostatic advantage of native tissue. METHODS: A single-center retrospective comparative study of patients who underwent on-ECMO CDH repair between 2008 and 2022 was performed. RESULTS: Fifty-two patients met inclusion criteria: 18 patch (34.6%) and 34 flap (65.4%). There was no difference in CDH severity between groups. On univariate analysis, reoperation for surgical bleeding was lower following flap repair compared to patch (23.5% vs 55.6%, respectively; p = 0.045), 48-h postoperative blood product transfusion was lower after flap repair (132 mL/kg vs 273.5 mL/kg patch; p = 0.006), and two-year survival was increased in the flap repair group compared to patch (53.1% vs 17.7%, respectively; p = 0.036). On multivariate analysis adjusting for CDH side, day on ECMO repaired, and day of life CDH repaired, flap repair was significantly associated with lower five-day postoperative packed red blood cell transfusion amount, improved survival to hospital discharge, and improved two-year survival. CONCLUSIONS: Our experience suggests that the muscle flap technique for on-ECMO CDH repair is associated with reduced bleeding complications compared to prosthetic patch repair, which may in part be responsible for the improved survival seen in the flap repair group. These results support the flap repair technique as a favored method for on-ECMO CDH repair. LEVEL OF EVIDENCE: Level III.


Assuntos
Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Humanos , Hérnias Diafragmáticas Congênitas/cirurgia , Estudos Retrospectivos , Diafragma , Retalhos Cirúrgicos
4.
Prenat Diagn ; 43(12): 1514-1519, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37807606

RESUMO

OBJECTIVE: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. METHOD: A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36 weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. RESULTS: 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36 weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35 mL: one died of respiratory failure, and the other two required tracheostomy. CONCLUSIONS: Fetal MRI TLV measured between 32 and 36 weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.


Assuntos
Hérnia Umbilical , Hérnias Diafragmáticas Congênitas , Lactente , Feminino , Gravidez , Humanos , Hérnia Umbilical/complicações , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Feto , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Morbidade
5.
Biochem Pharmacol ; 216: 115764, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37634595

RESUMO

Development of specific therapies that target and accelerate diabetic wound repair is an urgent need to alleviate pain and suffering and the huge socioeconomic burden of this debilitating disease. C-X-C Motif Chemokine Ligand 12 (CXCL12) also know an stromal cell-derived factor 1α (SDF-1α) is a chemokine that binds the CXC chemokine receptor type 4 (CXCR4) and activates downstream signaling resulting in recruitment of hematopoietic cells to locations of tissue injury and promotes tissue repair. In diabetes, low expression of CXCL12 correlates with impaired wound healing. Activation of CXCR4 receptor signaling with agonists or positive allosteric modulators (PAMs) provides a potential for small molecule therapeutic discovery and development. We recently reported high throughput screening and identification of the CXCR4 partial agonist UCUF-728, characterization of in vitro activity and reduced wound closure time in diabetic mice at 100 µM as a proof-of-concept study. We report here, the discovery of a second chemical scaffold demonstrating increased agonist potency and represented by thiadiazine derivative, UCUF-965. UCUF-965 is a potent partial agonist of ß-arrestin recruitment in CXCR4 receptor overexpressing cell line. Furthermore, UCUF-965 potentiates the CXCL12 maximal response in cAMP signaling pathway, activates CXCL12 stimulated migration in lymphoblast cells and modulates the levels of specific microRNA involved in the complex wound repair process, specifically in mouse fibroblasts. Our results indicate that UCUF-965 acts as a PAM agonist of the CXCR4 receptor. Furthermore, UCUF-965 enhanced angiogenesis markers and reduced wound healing time by 36% at 10.0 µM in diabetic mice models compared to untreated control.


Assuntos
Diabetes Mellitus Experimental , Receptores CXCR4 , Cicatrização , Animais , Camundongos , Movimento Celular/fisiologia , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/imunologia , Células-Tronco Hematopoéticas , Receptores CXCR4/agonistas , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Transdução de Sinais , Cicatrização/efeitos dos fármacos , Cicatrização/genética , Cicatrização/fisiologia
6.
J Pediatr Surg ; 58(1): 20-26, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36289034

RESUMO

PURPOSE: Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP. METHODS: A single-center retrospective study of patients who underwent fetal MMC or myeloschisis repair between March 2013 and February 2022 was performed. Outcomes were evaluated (n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests (p < 0.05 significant). RESULTS: Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p < 0.0001). Myofascial closure was also associated with an increased rate of HBH improvement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group (n = 21), however this did not reach statistical significance (23.8% vs 41.9%, p = 0.19). CONCLUSIONS: We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herniation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.


Assuntos
Hidrocefalia , Meningomielocele , Gravidez , Feminino , Humanos , Meningomielocele/cirurgia , Estudos Retrospectivos , Feto/cirurgia , Cuidado Pré-Natal , Hidrocefalia/cirurgia
7.
Int J Mol Sci ; 23(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35216311

RESUMO

Diabetes produces a chronic inflammatory state that contributes to the development of vascular disease and impaired wound healing. Despite the known individual and societal impacts of diabetic ulcers, there are limited therapies effective at improving healing. Stromal cell-derived factor 1α (SDF-1α) is a CXC chemokine that functions via activation of the CXC chemokine receptor type 4 (CXCR4) receptor to recruit hematopoietic cells to locations of tissue injury and promote tissue repair. The expression of SDF-1α is reduced in diabetic wounds, suggesting a potential contribution to wound healing impairment and presenting the CXCR4 receptor as a target for therapeutic investigations. We developed a high-throughput ß-arrestin recruitment assay and conducted structure-activity relationship (SAR) studies to screen compounds for utility as CXCR4 agonists. We identified CXCR4 agonist UCUF-728 from our studies and further validated its activity in vitro in diabetic fibroblasts. UCUF-728 reduced overexpression of miRNA-15b and miRNA-29a, negative regulators of angiogenesis and type I collagen production, respectively, in diabetic fibroblasts. In vivo, UCUF-728 reduced the wound closure time by 36% and increased the evidence of angiogenesis in diabetic mice. Together, this work demonstrates the clinical potential of small molecule CXCR4 agonists as novel therapies for pathologic wound healing in diabetes.


Assuntos
Diabetes Mellitus Experimental , Receptores CXCR4 , Cicatrização , Animais , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , MicroRNAs , Neovascularização Fisiológica , Receptores CXCR4/agonistas , Receptores CXCR4/metabolismo
8.
Nanomedicine ; 40: 102498, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34838994

RESUMO

Acute respiratory distress syndrome (ARDS) is a highly morbid pulmonary disease characterized by hypoxic respiratory failure. Its pathogenesis is characterized by unrestrained oxidative stress and inflammation, with long-term sequelae of pulmonary fibrosis and diminished lung function. Unfortunately, prior therapeutic ARDS trials have failed and therapy is limited to supportive measures. Free radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA-146a (miR146a), termed CNP-miR146a, have been shown to prevent acute lung injury in a pre-clinical model. In this study, we evaluated the potential of delayed treatment with CNP-miR146a at three or seven days after injury to rescue the lung from acute injury. We found that intratracheal CNP-miR146a administered three days after injury lowers pulmonary leukocyte infiltration, reduce inflammation and oxidative stress, lower pro-fibrotic gene expression and collagen deposition in the lung, and ultimately improve pulmonary function.


Assuntos
Lesão Pulmonar Aguda , Lesão Pulmonar , Nanopartículas , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Cério , Humanos , Pulmão/patologia , Lesão Pulmonar/patologia , Tempo para o Tratamento
10.
Pediatr Surg Int ; 37(11): 1499-1504, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34505169

RESUMO

PURPOSE: In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. METHODS: We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right-left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. RESULTS: Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. CONCLUSION: O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. LEVEL OF EVIDENCE: Level III, retrospective comparative study.


Assuntos
Hérnias Diafragmáticas Congênitas , Feminino , Idade Gestacional , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Gravidez , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Ultrassonografia Pré-Natal
11.
Transl Res ; 236: 109-116, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34089902

RESUMO

Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the pathogenesis of diabetic wounds and novel therapeutics. A relatively new area of interest has been macrophage polarization and its role in diabetic wound healing. Diabetic wounds show dysregulated and persistent M1 (pro-inflammatory) macrophage polarization whereas normal wounds will display a transition to M2 (pro-healing) macrophages around day three after wounding. We reviewed factors known to affect macrophage polarization, mostly focused on those that contribute to M2 macrophage polarization, and potential treatments that at least in part target macrophage polarization in the diabetic wound bed. Much of the work has been aimed at reducing hyperglycemia and encouraging pro-inflammatory cytokine neutralization or decreased expression given this has a significant role in producing M1 macrophages. Treatment of diabetic wounds will likely require a multi-modal approach including management of underlying diabetes and control of hyperglycemia, topical therapeutics, and prevention of secondary infection and inflammation.


Assuntos
Polaridade Celular , Diabetes Mellitus/patologia , Macrófagos/patologia , Cicatrização , Animais , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Humanos , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cicatrização/genética
12.
Am J Obstet Gynecol MFM ; 3(2): 100296, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33485023

RESUMO

BACKGROUND: For pregnancies complicated by fetal myelomeningocele who meet the established criteria, prenatal closure is a viable management option. Prenatal closure is an open procedure, with some techniques requiring greater dissection of maternal tissue than cesarean delivery; pain control is an important postoperative goal. Given the rising rates of opioid dependence and concerns regarding the fetal and neonatal effects of opioid use, our practice has turned to nonopioid pain management techniques. OBJECTIVE: This study aimed to compare postoperative opioid use and pain scores in women undergoing open fetal myelomeningocele repair with and without continuous local bupivacaine wound infusion. STUDY DESIGN: This was a retrospective, single-center chart review of all consecutive patients who underwent open myelomeningocele repair from March 2013 to December 2019. Women were enrolled at the time of referral and locally followed for 2 weeks postoperatively. The control group received patient-controlled epidural analgesia for 48 hours with acetaminophen and oral and intravenous opioids as needed. The treatment group received patient-controlled epidural analgesia for 24 hours with acetaminophen, oral and intravenous opioids, and continuous local bupivacaine infusion. Pain scores, medication use, and postoperative milestones and complications through discharge were abstracted from the chart and compared. RESULTS: Of 72 subjects, 51 were in the control group and 21 in the treatment group. Total opioid use, including intravenous doses (165 vs 52.5 mg; P=.001) and daily average oral opioid use (30 vs 10.5 mg; P=.002) were lower in the treatment group. In addition, 24% of women in the treatment group used no opioid postoperatively, compared with 4% in the control group. There was no difference in postoperative day 1 to 4 pain scores, antiemetic use, or bowel function; the treatment group was discharged significantly earlier. CONCLUSION: Postoperative opioid use was reduced in women who received continuous local wound infusion of bupivacaine for incisional pain control after prenatal myelomeningocele repair. Pain control is paramount following open myelomeningocele repair; local bupivacaine wound infusion is an important adjunct to reduce opioid use postoperatively.


Assuntos
Meningomielocele , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Anestésicos Locais , Bupivacaína , Feminino , Humanos , Recém-Nascido , Meningomielocele/cirurgia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Estudos Retrospectivos
13.
Pediatr Surg Int ; 36(9): 1027-1033, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32607833

RESUMO

PURPOSE: Congenital diaphragmatic hernia (CDH) can cause severe hemodynamic deterioration requiring support with extracorporeal membrane oxygenation (ECMO). ECMO is associated with hemorrhagic and thromboembolic complications. In 2015, we standardized anti-coagulation management on ECMO, incorporating thromboelastography (TEG) as an adjunct to manage hemostasis of CDH patients. The purpose of this study is to evaluate our blood product utilization, choice of blood product use in response to abnormal TEG parameters, and the associated effect on bleeding and thrombotic complications. METHODS: We retrospectively reviewed all CDH neonates supported by ECMO between 2008 and 2018. Blood product administration, TEG data, and hemorrhagic and thrombotic complications data were collected. We divided subjects into two groups pre-2015 and post-2015. RESULTS: After 2015, platelet transfusion was administered for a low maximum amplitude (MA) more frequently (77% compared to 65%, p = 0.0007). Cryoprecipitate was administered less frequently for a low alpha-angle (28% compared to 41%, p = 0.0016). There was no difference in fresh frozen plasma use over time. After standardizing the use of TEG, we observed a significant reduction in hemothoraces (18% compared to 54%, p = 0.026). CONCLUSION: Institutional standardization of anti-coagulation management of CDH neonates on ECMO, including the use of goal-directed TEG monitoring may lead to improved blood product utilization and a decrease in bleeding complications in neonates with CDH supported by ECMO. LEVEL OF EVIDENCE/TYPE OF STUDY: Level III, Retrospective comparative study.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Oxigenação por Membrana Extracorpórea/métodos , Hérnias Diafragmáticas Congênitas/cirurgia , Herniorrafia/métodos , Terapia Assistida por Computador/métodos , Tromboelastografia/métodos , Transtornos da Coagulação Sanguínea/complicações , Feminino , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/diagnóstico , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
14.
Int J Mol Sci ; 21(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397166

RESUMO

A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages in diabetic wounds. Persistence of the M1 macrophage phenotype and failure to transition to the regenerative or pro-remodeling (M2) macrophage phenotype plays an indispensable role in diabetic wound impairment; however, the mechanism underlying this relationship remains unclear. Recently, microRNAs have been shown to provide an additional layer of regulation of gene expression. In particular, microRNA-21 (miR-21) is essential for an inflammatory immune response. We hypothesize that miR-21 plays a role in regulating inflammation by promoting M1 macrophage polarization and the production of reactive oxygen species (ROS). To test our hypothesis, we employed an in vivo mouse skin wound model in conjunction with an in vitro mouse model to assess miR-21 expression and macrophage polarization. First, we found that miR-21 exhibits a distinct expression pattern in each phase of healing in diabetic wounds. MiR-21 abundance was higher during early and late phases of wound repair in diabetic wounds, while it was significantly lower in the middle phase of wounding (at days 3 and 7 following wounding). In macrophage cells, M1 polarized macrophages exhibited an upregulation of miR-21, as well as the M1 and pro-inflammatory markers IL-1b, TNFa, iNos, IL-6, and IL-8. Overexpression of miR-21 in macrophage cells resulted in an upregulation of miR-21 and also increased expression of the M1 markers IL-1b, TNFa, iNos, and IL-6. Furthermore, hyperglycemia induced NOX2 expression and ROS production through the HG/miR-21/PI3K/NOX2/ROS signaling cascade. These findings provide evidence that miR-21 is involved in the regulation of inflammation. Dysregulation of miR-21 may explain the abnormal inflammation and persistent M1 macrophage polarization seen in diabetic wounds.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais/genética , Cicatrização/genética , Animais , Diabetes Mellitus Experimental/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Hiperglicemia/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Pessoa de Meia-Idade , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
15.
J Pediatr Surg ; 55(6): 1002-1005, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32173119

RESUMO

AIM OF STUDY: Gastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado. METHODS: A case-control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into <21, 21-30, and >30 years of age. Descriptive analysis, bivariate analysis, and logistic regression was performed. RESULTS: There were 236 cases of gastroschisis compared to 944 controls. Maternal age did vary significantly between groups (23.4 ±â€¯5 years (cases) vs. 28.7 ±â€¯5.9 years (controls); p < 0.0001). Unadjusted analysis demonstrated that those with young maternal age (<21 years of age) had a 14.14 (95% CI 8.44-23.67) higher odds of gastroschisis compared to those >30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36-14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03). CONCLUSIONS: Young maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.


Assuntos
Gastrosquise/epidemiologia , Exposição Materna/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Fumar Cigarros , Colorado/epidemiologia , Feminino , Humanos , Recém-Nascido , Idade Materna , Sistema de Registros , Fatores de Risco , Adulto Jovem
16.
J Invest Dermatol ; 140(8): 1629-1638, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32004569

RESUMO

A central feature of diabetic (Db) wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of proinflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that long noncoding RNA GAS5 is dysregulated in Db wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is increased significantly in Db wounds and in cells isolated from Db wounds. Hyperglycemia induced GAS5 expression in macrophages in vitro. Overexpression of GAS5 in vitro promoted macrophage polarization toward an M1 phenotype by upregulating signal transducer and activator of transcription 1. Of most significance in our judgment, GAS5 loss-of-function enhanced Db wound healing. These data indicate that the relative level of long noncoding RNA GAS5 in wounds plays a key role in the wound healing response. Reductions in the levels of GAS5 in wounds appeared to enhance healing by promoting transition of M1 macrophages to M2 macrophages. Thus, our results suggest that targeting long noncoding RNA GAS5 may provide a therapeutic intervention for correcting impaired Db wound healing.


Assuntos
Pé Diabético/imunologia , Ativação de Macrófagos/genética , RNA Longo não Codificante/metabolismo , Pele/imunologia , Cicatrização/imunologia , Animais , Pé Diabético/genética , Pé Diabético/patologia , Modelos Animais de Doenças , Feminino , Fibroblastos , Humanos , Camundongos , Células RAW 264.7 , Receptores para Leptina/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pele/patologia , Cicatrização/genética
17.
Clin Case Rep ; 8(1): 18-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31998479

RESUMO

A foregut duplication cyst occurring together with both a congenital cystic pulmonary airway malformation and extralobar pulmonary sequestration is an unusual combination. Prenatal ultrasound, MRI, and postnatal CT are helpful for operative planning. Surgical resection is the definitive management for all three anomalies.

18.
J Surg Res ; 246: 1-5, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31541708

RESUMO

BACKGROUND: Intestinal atresia is a congenital defect resulting in intestinal discontinuity and can be associated with significant morbidity related to intestinal failure. The bowel proximal to the atresia is often significantly dilated and dysfunctional. The treatment approaches of this dilated bowel include resection with primary anastomosis versus tapering enteroplasty with preservation of bowel length. The purpose of this study was to compare these two approaches in regard to bowel function as characterized by the time to full enteral feeding. METHODS: A retrospective review was performed of intestinal atresia repair performed at a tertiary referral pediatric hospital from 2007 to 2017. Length of stay, time to full enteral feeds, and complications were assessed in patients who underwent repair with tapering enteroplasty (n = 8) and compared with those who underwent resection and anastomosis (n = 39). RESULTS: The median age at surgery, gender distribution, weeks gestational age (WGA), location of the atresia, and comorbidities were similar between the two groups. Overall, there was no statistically significant difference in length of stay and time to full enteral feeds between groups. Three of eight (38%) patients in the tapered group and five of 39 patients (13%; P = 0.12) in the nontapered group underwent further surgical exploration because of bowel dysmotility. Factors associated with longer length of hospital stay were abdominal reoperation and WGA, and factors associated with longer time to full enteral feeds were WGA, abdominal reoperation, and gastroschisis. CONCLUSIONS: Tapering enteroplasty at initial operation for intestinal atresias preserves bowel length and has statistically equivalent outcomes to resection and anastomosis in regard to the length of stay and time to full enteral feeds.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Nutrição Enteral/estatística & dados numéricos , Atresia Intestinal/cirurgia , Intestino Delgado/anormalidades , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Dilatação Patológica/etiologia , Dilatação Patológica/cirurgia , Feminino , Motilidade Gastrointestinal , Humanos , Lactente , Recém-Nascido , Atresia Intestinal/complicações , Intestino Delgado/cirurgia , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Reoperação/métodos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
J Pediatr Surg ; 55(1): 39-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31679772

RESUMO

INTRODUCTION: Accurate, real-time technology is needed to predict which newborns with congenital diaphragmatic hernia (CDH) will require ECMO. The Compensatory Reserve Index (CRI) is a noninvasive monitoring technology that continuously trends an individual's capacity to compensate from normovolemia (CRI = 1) to decompensation (CRI = 0). We hypothesized that postnatal CRI values would be lower in CDH newborns that required ECMO than those who did not require ECMO. METHODS: Newborns with a CDH were prospectively monitored with a CipherOx® CRI M1 device. We compared CRI values from delivery to ECMO (ECMO group) versus delivery to clinical stabilization (non-ECMO group). RESULTS: Postnatal CRI values were available from 26 newborns. Eight underwent ECMO within 33 h of delivery, and median CRI prior to ECMO was 0.068 (IQR: 0.057, 0.078). Eighteen did not require ECMO. Median CRI from birth to 48 h was 0.112 (IQR: 0.082, 0.15). CRI values were significantly lower in newborns that required ECMO versus those who did not (p = 0.0035). Postnatal CRI had the highest AUC (0.85) compared to other prenatal prognostic measures. CONCLUSION: Humans from newborns to adults share elemental features of the pulsatile waveform that are associated with progression to decompensation. CRI may be helpful when deciding when to initiate ECMO. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Diagnostic test.


Assuntos
Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Monitorização Fisiológica , Hérnias Diafragmáticas Congênitas/fisiopatologia , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Recém-Nascido , Estudos Prospectivos
20.
J Pediatr Surg ; 54(12): 2487-2491, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31515112

RESUMO

BACKGROUND: Congenital diaphragmatic hernia (CDH) repair is technically challenging with different approaches for repair. The aim of this study was to compare outcomes between patch and flap repair. METHODS: CDH repairs performed at a quaternary care children's hospital between 2008 and 2018 were reviewed. Seventy CDH repairs were analyzed after primary repairs were excluded (n = 52). Analysis included proportions or median with interquartile range and chi-square or Wilcoxon rank-sum test. RESULTS: Comparing patch and flap repairs, demographic characteristics and hernia parameters were similar. Examining outcomes, length of stay, 30-day mortality, and 1-year mortality were all similar between groups, but total/symptomatic recurrence was higher in the patch group (10%/7% vs. 3%/0%), and the median time to recurrence was 3 months. A sub-analysis comparing those who recurred to those who did not demonstrated no significant difference between the two groups. CONCLUSION: Patients who undergo flap repair have a lower risk of recurrence compared to those who undergo patch repair, and this may be due to the ability of the flap to grow over time with the child. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: III.


Assuntos
Hérnias Diafragmáticas Congênitas/cirurgia , Herniorrafia/métodos , Retalhos Cirúrgicos , Feminino , Hérnias Diafragmáticas Congênitas/mortalidade , Humanos , Recém-Nascido , Tempo de Internação , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA