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OBJECTIVE: To examine the association between prolonged in-hospital time to appendectomy (TTA) and the risk of complicated appendicitis. SUMMARY BACKGROUND DATA: Historically, acute appendicitis was treated with emergency appendectomy. More recently, practice patterns have shifted to urgent appendectomy, with acceptable in-hospital delays of up to 24âhours. However, the consequences of prolonged TTA remain poorly understood. Herein, we present the largest individual analysis to date of outcomes associated with prolonged in-hospital delay before appendectomy in children. METHODS: Data from patients who underwent appendectomy within 24âhours of hospital presentation were obtained from the American College of Surgeons Pediatric National Surgical Quality Improvement Program Procedure Targeted Appendectomy database from 2016 to 2018. Appendectomy within 16âhours of presentation was considered early, whereas those between 16 to 24âhours were defined as late. The primary outcome was operative findings of complicated appendicitis. Secondary outcomes included 30-day complications and resource utilization. RESULTS: This study consisted of 18,927 patients, with 20.6% undergoing late appendectomy. The rate of complicated appendicitis was significantly higher in the late group (Early: 26.3%, Late: 30.3%, P < 0.05). Additionally, the late group had longer operative times, increased need for postoperative percutaneous drainage, antibiotics at discharge, parenteral nutrition, and an extended hospital length of stay (P < 0.05). On multivariate analysis, late appendectomy remained a predictor of complicated disease (odds ratio 1.17 [95% confidence interval, 1.08-1.27]). CONCLUSIONS: A significant proportion of pediatric patients with acute appendicitis experience prolonged in-hospital delays before appendectomy, which are associated with modestly increased rates of complicated appendicitis. Although this does not indicate appendectomy needs to be done emergently, prolonged in-hospital TTA should be avoided whenever possible.
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Apendicitis , Laparoscopía , Enfermedad Aguda , Apendicectomía/efectos adversos , Apendicectomía/métodos , Apendicitis/complicaciones , Apendicitis/cirugía , Niño , Drenaje/métodos , Hospitales , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Necrotising enterocolitis (NEC) is a devastating gastrointestinal disease of prematurity that typically develops after the administration of infant formula, suggesting a link between nutritional components and disease development. One of the most significant complications that develops in patients with NEC is severe lung injury. We have previously shown that the administration of a nutritional formula that is enriched in pre-digested Triacylglyceride that do not require lipase action can significantly reduce the severity of NEC in a mouse model. We now hypothesise that this 'pre-digested fat (PDF) system' may reduce NEC-associated lung injury. In support of this hypothesis, we now show that rearing newborn mice on a nutritional formula based on the 'PDF system' promotes lung development, as evidenced by increased tight junctions and surfactant protein expression. Mice that were administered this 'PDF system' were significantly less vulnerable to the development of NEC-induced lung inflammation, and the administration of the 'PDF system' conferred lung protection. In seeking to define the mechanisms involved, the administration of the 'PDF system' significantly enhanced lung maturation and reduced the production of reactive oxygen species (ROS). These findings suggest that the PDF system protects the development of NEC-induced lung injury through effects on lung maturation and reduced ROS in the lung and also increases lung maturation in non-NEC mice.
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Enterocolitis Necrotizante , Lesión Pulmonar , Animales , Ratones , Enterocolitis Necrotizante/etiología , Animales Recién Nacidos , Especies Reactivas de Oxígeno , Lesión Pulmonar/complicaciones , Lesión Pulmonar/metabolismo , Alimentos Formulados , Modelos Animales de EnfermedadRESUMEN
Angiotensin-converting enzyme 2 (ACE2) is a potent negative regulator capable of restraining overactivation of the renin-angiotensin system, which contributes to exuberant inflammation after bacterial infection. However, the mechanism through which ACE2 modulates this inflammatory response is not well understood. Accumulating evidence indicates that infectious insults perturb ACE2 activity, allowing for uncontrolled inflammation. In the current study, we demonstrate that pulmonary ACE2 levels are dynamically varied during bacterial lung infection, and the fluctuation is critical in determining the severity of bacterial pneumonia. Specifically, we found that a pre-existing and persistent deficiency of active ACE2 led to excessive neutrophil accumulation in mouse lungs subjected to bacterial infection, resulting in a hyperinflammatory response and lung damage. In contrast, pre-existing and persistent increased ACE2 activity reduces neutrophil infiltration and compromises host defense, leading to overwhelming bacterial infection. Further, we found that the interruption of pulmonary ACE2 restitution in the model of bacterial lung infection delays the recovery process from neutrophilic lung inflammation. We observed the beneficial effects of recombinant ACE2 when administered to bacterially infected mouse lungs following an initial inflammatory response. In seeking to elucidate the mechanisms involved, we discovered that ACE2 inhibits neutrophil infiltration and lung inflammation by limiting IL-17 signaling by reducing the activity of the STAT3 pathway. The results suggest that the alteration of active ACE2 is not only a consequence of bacterial lung infection but also a critical component of host defense through modulation of the innate immune response to bacterial lung infection by regulating neutrophil influx.
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Inflamación/inmunología , Neutrófilos/inmunología , Peptidil-Dipeptidasa A/inmunología , Infecciones por Pseudomonas/inmunología , Pseudomonas aeruginosa/inmunología , Enzima Convertidora de Angiotensina 2 , Animales , Modelos Animales de Enfermedad , Femenino , Imidazoles/administración & dosificación , Imidazoles/farmacología , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Inflamación/tratamiento farmacológico , Inflamación/patología , Leucina/administración & dosificación , Leucina/análogos & derivados , Leucina/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Pruebas de Sensibilidad Microbiana , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Peptidil-Dipeptidasa A/deficiencia , Peptidil-Dipeptidasa A/genética , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/patología , Pseudomonas aeruginosa/efectos de los fármacosRESUMEN
BACKGROUND: Revascularization after lower extremity bypass failure poses many challenges. Despite nearly 7 decades of experience with lower extremity revascularization, there is little data on the success of redo bypass particularly when autogenous conduit is utilized. The purpose of this study is to review outcomes of redo infrainguinal bypass constructed solely of autogenous vein. METHODS: All patients who underwent redo infrainguinal bypass at a single institution by a single surgeon were retrospectively reviewed. Bypasses were categorized into 3 groups: femoral-popliteal, femoral-distal, and popliteal-distal bypasses. Since the repeat bypasses were all done for limb salvage, freedom from above or below knee amputation (FFA) was primary outcome, which was defined as the number of days from redo bypass to subsequent amputation or the most recent follow-up. RESULTS: From 2006 to 2016, 100 limbs underwent redo bypass. Fifty-nine (59.0%) limbs had undergone one previous bypass while 41 (41.0%) had undergone 2 or more. The redo configurations consisted of 23 (23.0%) femoral-popliteal, 70 (70.0%) femoral-distal, and 7 (7.0%) popliteal-distal bypasses. Ninety-seven (97.0%) underwent redo using autologous vein grafts including 41 (95.5%) of those who had 2 or more previous bypasses. The 3 patients who ultimately underwent prosthetic bypass had bilateral great and small saphenous veins and bilateral basilic and cephalic veins previously harvested. Nine (9.0%) limbs were subsequently amputated: 2 (2.0%) above knee and 7 (7.0%) below knee amputations. Of these, all had had 2 or more previous bypasses and 2 of the 3 patients who ultimately received prosthetic bypasses were in this group. In patients with one previous bypass, FFA was 775 days (IQR: 213-1,626 days). In patients with 2 or more previous bypasses, FFA was 263 days (IQR: 106-1,148 days). No patients with femoral-popliteal bypasses suffered amputation while 7 (10.0%) of the femoral-distal and 2 (28.6%) of the popliteal-distal bypasses suffered subsequent amputations (P = 0.067). CONCLUSIONS: Redo infrainguinal bypass is effective in salvaging threatened lower extremities. Furthermore, once a patient is deemed a bypass candidate, revascularization with autologous vein can be achieved. A significant FFA rate is achieved with redo bypass, although patients with more distal disease are harder to salvage.
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Implantación de Prótesis Vascular , Oclusión de Injerto Vascular/cirugía , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/cirugía , Venas/trasplante , Anciano , Amputación Quirúrgica , Baltimore , Implantación de Prótesis Vascular/efectos adversos , Femenino , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/fisiopatología , Humanos , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: There is an increasing national trend toward initial venovenous (VV) extracorporeal membrane oxygenation (ECMO) for infants and children with respiratory disease; however, some proportion of patients initiated on VV ECMO will ultimately require conversion to venoarterial (VA) support for circulatory augmentation. The purpose of this work is to describe patients who required conversion from VV to VA ECMO and to highlight the increased mortality in this population. MATERIALS AND METHODS: Demographic and disease-specific data on children who underwent VV-to-VA ECMO conversion were extracted from the Extracorporeal Life Support Organization registry. Survival comparisons to age-matched patients undergoing unconverted ECMO runs were made using the 2016 Extracorporeal Life Support Organization International Summary report. The relative risk (RR) of death associated with VV-to-VA conversion was calculated, and statistical analysis of survival was performed using a chi-squared test with P < 0.05 for significance. RESULTS: This study cohort consisted of 1382 patients who required VV-to-VA conversion. The overall hospital survival rate for neonates requiring conversion was 60%, compared with 83% for unconverted VV runs and 64% for unconverted VA runs (RR 1.23; 95% confidence interval, 1.14-1.34). Similarly, the survival of older children requiring conversion was 46% compared with 66% and 51%, respectively (RR 1.16; 95% confidence interval, 1.06-1.27). CONCLUSIONS: VV-to-VA conversion does occur and is associated with increased mortality. The need for conversion from VV to VA ECMO may represent an early failure to recognize physiologic parameters or disease severity that would be better managed with initial VA support. Further research is needed to pinpoint the cause of increased mortality and to identify predictors of VV failure to optimize initial mode selection.
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Oxigenación por Membrana Extracorpórea/mortalidad , Oxigenación por Membrana Extracorpórea/métodos , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , MasculinoAsunto(s)
Apendicitis , Laparoscopía , Apendicectomía/efectos adversos , Apendicitis/cirugía , Niño , Hospitales , Humanos , Tiempo de InternaciónRESUMEN
OBJECTIVES: Varying team size based on anticipated injury acuity is a common method for limiting personnel during trauma resuscitation. While missing personnel may delay treatment, large teams may worsen care through role confusion and interference. This study investigates factors associated with varying team size and task completion during trauma resuscitation. METHODS: Video-recorded resuscitations of pediatric trauma patients (n = 201) were reviewed for team size (bedside and total) and completion of 24 resuscitation tasks. Additional patient characteristics were abstracted from our trauma registry. Linear regression was used to assess which characteristics were associated with varying team size and task completion. Task completion was then analyzed in relation to team size using best-fit curves. RESULTS: The average bedside team ranged from 2.7 to 10.0 members (mean, 6.5 [SD, 1.7]), with 4.3 to 17.7 (mean, 11.0 [SD, 2.8]) people total. More people were present during high-acuity activations (+4.9, P < 0.001) and for patients with a penetrating injury (+2.3, P = 0.002). Fewer people were present during activations without prearrival notification (-4.77, P < 0.001) and at night (-1.25, P = 0.002). Task completion in the first 2 minutes ranged from 4 to 19 (mean, 11.7 [SD, 3.8]). The maximum number of tasks was performed at our hospital by teams with 7 people at the bedside (13 total). CONCLUSIONS: Resuscitation task completion varies by team size, with a nonlinear association between number of team members and completed tasks. Management of team size during high-acuity activations, those without prior notification, and those in which the patient has a penetrating injury may help optimize performance.
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Grupo de Atención al Paciente/organización & administración , Pediatría , Resucitación/métodos , Análisis y Desempeño de Tareas , Centros Traumatológicos , Traumatología , Niño , District of Columbia , Femenino , Humanos , Masculino , Pediatría/organización & administración , Análisis de Regresión , Resucitación/estadística & datos numéricos , Centros Traumatológicos/organización & administración , Recursos HumanosRESUMEN
BACKGROUND AND OBJECTIVES: The Covid-19 pandemic has forced mass closures of childcare facilities and schools. While these measures are necessary to slow virus transmission, little is known regarding the secondary health consequences of social distancing. The purpose of this study is to assess the proportion of injuries secondary to physical child abuse (PCA) at a level I pediatric trauma center during the Covid-19 pandemic. METHODS: A retrospective review of patients at our center was conducted to identify injuries caused by PCA in the month following the statewide closure of childcare facilities in Maryland. The proportion of PCA patients treated during the Covid-19 era were compared to the corresponding period in the preceding two years by Fisher's exact test. Demographics, injury profiles, and outcomes were described for each period. RESULTS: Eight patients with PCA injuries were treated during the Covid-19 period (13 % of total trauma patients), compared to four in 2019 (4 %, p < 0.05) and three in 2018 (3 %, p < 0.05). The median age of patients in the Covid-19 period was 11.5 months (IQR 6.8-24.5). Most patients were black (75 %) with public health insurance (75 %). All injuries were caused by blunt trauma, resulting in scalp/face contusions (63 %), skull fractures (50 %), intracranial hemorrhage (38 %), and long bone fractures (25 %). CONCLUSIONS: There was an increase in the proportion of traumatic injuries caused by physical child abuse at our center during the Covid-19 pandemic. Strategies to mitigate this secondary effect of social distancing should be thoughtfully implemented.
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COVID-19 , Maltrato a los Niños/estadística & datos numéricos , Abuso Físico/estadística & datos numéricos , Centros Traumatológicos , COVID-19/psicología , Preescolar , Traumatismos Craneocerebrales/etiología , Femenino , Humanos , Lactante , Masculino , Pandemias , Distanciamiento Físico , Estudios Retrospectivos , SARS-CoV-2 , Fracturas Craneales/etiologíaRESUMEN
Necrotizing enterocolitis (NEC) is a devastating disease of premature infants, whose pathogenesis remains incompletely understood, although activation of the Gram-negative bacterial receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium plays a critical role. Patients with NEC typically display gastrointestinal dysmotility before systemic disease is manifest, suggesting that dysmotility could drive NEC development. Both intestinal motility and inflammation are governed by the enteric nervous system, a network of enteric neurons and glia. We hypothesized here that enteric glia loss in the premature intestine could lead to dysmotility, exaggerated TLR4 signaling, and NEC development. We found that intestinal motility is reduced early in NEC in mice, preceding the onset of intestinal inflammation, whereas pharmacologic restoration of intestinal motility reduced NEC severity. Ileal samples from mouse, piglet, and human NEC revealed enteric glia depletion, and glia-deficient mice (Plp1ΔDTR, Sox10ΔDTR, and BdnfΔDTR) showed increased NEC severity compared with wild-type mice. Mice lacking TLR4 on enteric glia (Sox10-Tlr4ko) did not show NEC-induced enteric glia depletion and were protected from NEC. Mechanistically, brain-derived neurotrophic factor (BDNF) from enteric glia restrained TLR4 signaling on the intestine to prevent NEC. BDNF was reduced in mouse and human NEC, and BDNF administration reduced both TLR4 signaling and NEC severity in enteric gliadeficient mice. Last, we identified an agent (J11) that enhanced enteric glial BDNF release, inhibited intestinal TLR4, restored motility, and prevented NEC in mice. Thus, enteric glia loss might contribute to NEC through intestinal dysmotility and increased TLR4 activation, suggesting enteric glia therapies for this disorder.
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Enterocolitis Necrotizante , Receptor Toll-Like 4 , Humanos , Recién Nacido , Neuroglía , Receptor Toll-Like 4/genética , Animales , RatonesRESUMEN
Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand ("A18") that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Enterocolitis Necrotizante/genética , Indoles/administración & dosificación , Leche Humana/fisiología , Receptores de Hidrocarburo de Aril/genética , Receptor Toll-Like 4/genética , Animales , Animales Recién Nacidos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/agonistas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/inmunología , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/inmunología , Dieta/métodos , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/inmunología , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/prevención & control , Femenino , Regulación de la Expresión Génica , Humanos , Recién Nacido , Recien Nacido Prematuro , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Ligandos , Exposición Materna , Ratones , Embarazo , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/inmunología , Transducción de Señal , Porcinos , Receptor Toll-Like 4/inmunologíaRESUMEN
BACKGROUND: The COVID-19 pandemic has had far-reaching effects on healthcare systems and society with resultant impact on trauma systems worldwide. This study evaluates the impact the pandemic has had in the Washington, DC Metropolitan Region as compared with similar months in 2019. DESIGN: A retrospective multicenter study of all adult trauma centers in the Washington, DC region was conducted using trauma registry data between January 1, 2019 and May 31, 2020. March 1, 2020 through May 31, 2020 was defined as COVID-19, and January 1, 2019 through February 28, 2020 was defined as pre-COVID-19. Variables examined include number of trauma contacts, trauma admissions, mechanism of injury, Injury Severity Score, trauma center location (urban vs. suburban), and patient demographics. RESULTS: There was a 22.4% decrease in the overall incidence of trauma during COVID-19 compared with a 3.4% increase in trauma during pre-COVID-19. Blunt mechanism of injury decreased significantly during COVID-19 (77.4% vs. 84.9%, p<0.001). There was no change in the specific mechanisms of fall from standing, blunt assault, and motor vehicle crash. The proportion of trauma evaluations for penetrating trauma increased significantly during COVID-19 (22.6% vs. 15.1%, p<0.001). Firearm-related and stabbing injury mechanisms both increased significantly during COVID-19 (11.8% vs. 6.8%, p<0.001; 9.2%, 6.9%, p=0.002, respectively). CONCLUSIONS AND RELEVANCE: The overall incidence of trauma has decreased since the arrival of COVID-19. However, there has been a significant rise in penetrating trauma. Preparation for future pandemic response should include planning for an increase in trauma center resource utilization from penetrating trauma. LEVEL OF EVIDENCE: Epidemiological, level III.
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Here we describe a case of a 15-year-old child with Rett syndrome who presented with extreme gastric distension and fatal perforation in the setting of long-standing aerophagia and pathologic colonization with Sarcina ventriculi, a rare bacteria implicated in gastric perforation. This is the first report of gastric perforation associated with colonization by Sarcina in a patient with pathologic aerophagia. Gastric colonization with Sarcina should be considered in intellectually disabled children with pathologic air swallowing who present with severe gastric dilation and/or perforation.
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Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and remains stubbornly difficult to treat in many cases. Much of our understanding of NEC pathogenesis has been gained through the study of highly translational animal models. However, most models of NEC are limited by their overall complexity and by the fact that they do not incorporate human tissue. To address these limitations, investigators have recently developed precision-based ex vivo models of NEC, also termed 'NEC-in-a-dish' models, which provide the opportunity to increase our understanding of this disease and for drug discovery. These approaches involve exposing intestinal cells from either humans or animals with or without NEC to a combination of environmental and microbial factors associated with NEC pathogenesis. This Review highlights the current progress in the field of NEC model development, introduces NEC-in-a-dish models as a means to understand NEC pathogenesis and examines the fundamental questions that remain unanswered in NEC research. By answering these questions, and through a renewed focus on precision model development, the research community may finally achieve enduring success in improving the outcome of patients with this devastating disease.
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Enterocolitis Necrotizante , Intestino Delgado , Animales , Técnicas de Cultivo de Célula , Células Cultivadas , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/patología , Humanos , Intestino Delgado/metabolismo , Intestino Delgado/microbiología , Intestino Delgado/patología , Organoides , Transducción de Señal , Receptor Toll-Like 4/metabolismoRESUMEN
PROBLEM: Although early environmental influences are thought to influence the development of inflammatory bowel disease (IBD), little is known about the role of the in utero environment on subsequent IBD risk. We hypothesized that prenatal exposure to bacterial lipopolysaccharide (LPS) could modify the subsequent development of dextran sulfate sodium (DSS)-induced ulcerative colitis in adulthood by influencing the associated cellular and immune response. METHOD OF STUDY: To test this hypothesis, we exposed developing mice in utero to LPS or saline (PBS) at E17.5, and then induced colitis at 5 weeks. We then assessed colitis severity and effects on the microbiome. In order to define the developmental impact of any potential LPS effect, we also exposed 1-week-old mice to either LPS or saline before inducing colitis at 5 weeks. RESULTS: Mice that had been exposed to LPS but not saline in utero were protected from subsequent colitis development, and their intestinal barrier integrity and tight junction expression distribution were similar to that of control mice that were not exposed to DSS. By contrast, mice exposed to either LPS or saline at day 7 of life all developed severe colitis upon subsequent DSS exposure. CONCLUSION: These results identify an informative time window during fetal development during which exposure to an otherwise pro-inflammatory agent like LPS protects against an inflammatory disease in adulthood.
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Colitis Ulcerosa/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Lipopolisacáridos/metabolismo , Útero/metabolismo , Animales , Sulfato de Dextran , Modelos Animales de Enfermedad , Resistencia a la Enfermedad , Femenino , Microbioma Gastrointestinal , Humanos , Inmunidad Celular , Ratones , Ratones Endogámicos C57BL , Embarazo , Efectos Tardíos de la Exposición PrenatalRESUMEN
BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by Toll-like receptor 4 (TLR4)-dependent intestinal inflammation and enterocyte death. Given that necroptosis is a proinflammatory cell death process that is linked to bacterial signaling, we investigated its potential role in NEC, and the mechanisms involved. METHODS: Human and mouse NEC intestine were analyzed for necroptosis gene expression (ie, RIPK1, RIPK3, and MLKL), and protein activation (phosphorylated RIPK3). To evaluate a potential role for necroptosis in NEC, the effects of genetic (ie, Ripk3 knockout or Mlkl knockout) or pharmacologic (ie, Nec1s) inhibition of intestinal inflammation were assessed in a mouse NEC model, and a possible upstream role of TLR4 was assessed in Tlr4-deficient mice. The NEC-protective effects of human breast milk and its constituent milk oligosaccharides on necroptosis were assessed in a NEC-in-a-dish model, in which mouse intestinal organoids were cultured as either undifferentiated or differentiated epithelium in the presence of NEC bacteria and hypoxia. RESULTS: Necroptosis was activated in the intestines of human and mouse NEC in a TLR4-dependent manner, and was up-regulated specifically in differentiated epithelium of the immature ileum. Inhibition of necroptosis genetically and pharmacologically reduced intestinal-epithelial cell death and mucosal inflammation in experimental NEC, and ex vivo in the NEC-in-a-dish system. Strikingly, the addition of human breast milk, or the human milk oligosaccharide 2 fucosyllactose in the ex vivo system, reduced necroptosis and inflammation. CONCLUSIONS: Necroptosis is activated in the intestinal epithelium upon TLR4 signaling and is required for NEC development, and explains in part the protective effects of breast milk.
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Enterocolitis Necrotizante/patología , Enterocitos/patología , Mucosa Intestinal/patología , Leche Humana/química , Necroptosis/inmunología , Animales , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/genética , Enterocolitis Necrotizante/inmunología , Enterocitos/efectos de los fármacos , Enterocitos/inmunología , Femenino , Humanos , Recién Nacido , Mucosa Intestinal/efectos de los fármacos , Ratones , Ratones Noqueados , Necroptosis/efectos de los fármacos , Proteínas Quinasas/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Trisacáridos/farmacología , Trisacáridos/uso terapéutico , Regulación hacia ArribaRESUMEN
Acute appendicitis is one of the most common causes of abdominal pain in children but remains a diagnostic challenge, and insight into the aetiology of the condition is lacking. A case of simultaneous acute appendicitis in monozygotic twin boys is reported here. Familial aggregation in acute appendicitis has been described, but the underlying causes for this are not well understood. The patients reported here were both genetically identical and lived a mostly identical lifestyle. Their simultaneous presentation would be exceedingly rare if explained entirely by chance, suggesting a role for both genetic and environmental influences. Increased knowledge of this occurrence may assist in prompt diagnosis and reporting on the incidence and timing of appendicitis in monozygotic twins could better elucidate the genetic and environmental factors that predispose to this disease.
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Apendicitis/etiología , Gemelos Monocigóticos , Apendicectomía , Apendicitis/diagnóstico por imagen , Apendicitis/genética , Apendicitis/cirugía , Niño , Diagnóstico Diferencial , Interacción Gen-Ambiente , Humanos , Estilo de Vida , Masculino , Factores de Tiempo , UltrasonografíaRESUMEN
Congenital diaphragmatic hernia (CDH) is a condition that results from incomplete diaphragm formation during embryogenesis. The diaphragmatic defect allows for herniation of abdominal viscera into the chest, and the resulting pulmonary hypoplasia and pulmonary hypertension can lead to cardiorespiratory failure in the neonatal period. There is a wide spectrum of disease severity in CDH, and while advances in neonatal care and the introduction of extracorporeal membrane oxygenation have improved outcomes in many cases, the most severe defects are still associated with high morbidity and mortality. Improvements in prenatal diagnostic and prognostic capabilities have created an opportunity to select high risk patients for fetal intervention. Three decades of refinements in the fetal surgical therapy for CDH have led to the current technique of Fetoscopic Endoluminal Tracheal Occlusion (FETO). Herein, we review the current considerations for selecting patients for fetal intervention, and the contemporary fetal surgical operation for CDH, FETO, with a focus on early outcomes and ongoing studies.
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Fetoscopía , Feto/cirugía , Hernias Diafragmáticas Congénitas/cirugía , Ensayos Clínicos como Asunto , Femenino , Feto/diagnóstico por imagen , Hernia/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hígado/diagnóstico por imagen , Mediciones del Volumen Pulmonar , Imagen por Resonancia Magnética , Embarazo , Pronóstico , Índice de Severidad de la Enfermedad , Ultrasonografía PrenatalRESUMEN
Intestinal failure is defined as the inability to maintain fluid, nutrition, energy, and micronutrient balance that leads to the inability to gain or maintain weight, resulting in malnutrition and dehydration. Causes of intestinal failure include short bowel syndrome (ie, the physical loss of intestinal surface area and severe intestinal dysmotility). For patients with intestinal failure who fail to achieve enteral autonomy through intestinal rehabilitation programs, the current treatment options are expensive and associated with severe complications. Therefore, the need persists for next-generation therapies, including cell-based therapy, to increase intestinal regeneration, and development of the tissue-engineered small intestine.
Asunto(s)
Órganos Artificiales , Intestino Delgado , Síndrome del Intestino Corto/cirugía , Ingeniería de Tejidos/métodos , Proteínas Morfogenéticas Óseas/metabolismo , Sistema Nervioso Entérico/citología , Factor de Crecimiento Epidérmico/fisiología , Motilidad Gastrointestinal/fisiología , Humanos , Mucosa Intestinal/fisiología , Organoides/fisiología , Células de Paneth/fisiología , Receptores Notch/fisiología , Regeneración , Transducción de Señal/fisiología , Trasplante de Células Madre , Andamios del Tejido , Vía de Señalización Wnt/fisiologíaRESUMEN
Introduction: Solid pseudopapillary neoplasm (SPN) is the most commonly encountered pancreatic tumor in adolescents. Owing to its malignant potential, the current recommendation for management is complete surgical resection; however, there is no broad consensus on the operation of choice to accomplish this. Herein, we describe three consecutive laparoscopic spleen-preserving distal pancreatectomies for SPN in adolescents. Materials and Methods: Our cohort included all patients <18 years of age treated at our institution from 2015 to 2018 who underwent surgical resection of an SPN. Results: Three patients (age 13-16) were identified. Two of the patients were male. All patients underwent laparoscopic distal pancreatectomy with preservation of the main splenic artery and vein. No patients suffered from postoperative pancreatic fistula. Median length of stay was 5 days. Final histology revealed SPN in all 3 cases, with tumor size ranging from 2 to 10 cm in greatest dimension. All margins were negative for tumor. All 3 patients have been followed (mean: 6 months) with surveillance ultrasound demonstrating a normal remnant pancreas and normal splenic perfusion. Conclusions: Laparoscopic spleen-preserving distal pancreatectomy is a safe and effective treatment for SPNs of the body and tail of the pancreas in adolescents. This approach achieves the margin negative resection that is appropriate for the disease without subjecting children to the risk of postsplenectomy sepsis or the need for antibiotic prophylaxis, and may be associated with a reduction in perioperative morbidity. Therefore, laparoscopic distal pancreatectomy with splenic preservation is our preferred operation in adolescents presenting with SPN.
Asunto(s)
Carcinoma Papilar/cirugía , Laparoscopía/métodos , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Bazo/cirugía , Adolescente , Femenino , Humanos , Masculino , Arteria Esplénica/cirugía , Resultado del TratamientoRESUMEN
Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) is a treatment strategy for pediatric patients with cardiopulmonary failure. Femoral cannulation is a commonly used technique for obtaining central access in children and adolescents despite high rates of vascular complications. Ischemic limb complications remain one of the most common problems facing survivors of femoral VA ECMO. Our aim is to review the literature on femoral cannulation in children and to present a review of techniques for femoral cannula placement, decannulation, and arterial repair to help minimize and ameliorate complications related to cannulation. We performed a literature review for pediatric ECMO cannulation, complications, and femoral artery repair in pediatric patients. We focused on the management of arterial and ischemia-related complications during and after ECMO support via femoral cannulation. Vascular complications are not infrequent for patients requiring ECMO support via femoral cannulation. As such, judicious distal perfusion monitoring as well as augmentation of distal flow are important strategies during mechanical support. The use of distal perfusion catheters can be used to minimize the risk of limb ischemia. As femoral cannulation grows more popular in pediatric patients, strategies for arterial repair are essential to ensure extremity perfusion upon decannulation.