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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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Apendicite , Laparoscopia , Doença Aguda , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Apendicite/complicações , Apendicite/cirurgia , Criança , Drenagem/métodos , Hospitais , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Necrotizing enterocolitis (NEC) is the most prevalent gastrointestinal emergency in premature infants and is characterized by a dysfunctional gut microcirculation. Therefore, there is a dire need for in vivo methods to characterize NEC-induced changes in the structure and function of the gut microcirculation, that is, its vascular phenotype. Since in vivo gut imaging methods are often slow and employ a single-contrast mechanism, we developed a rapid multicontrast imaging technique and a novel analyses pipeline for phenotyping the gut microcirculation. METHODS: Using an experimental NEC model, we acquired in vivo images of the gut microvasculature and blood flow over a 5000 × 7000 µm2 field of view at 5 µm resolution via the following two endogenous contrast mechanisms: intrinsic optical signals and laser speckles. Next, we transformed intestinal images into rectilinear "flat maps," and delineated 1A/V gut microvessels and their perfusion territories as "intestinal vascular units" (IVUs). Employing IVUs, we quantified and visualized NEC-induced changes to the gut vascular phenotype. RESULTS: In vivo imaging required 60-100 s per animal. Relative to the healthy gut, NEC intestines showed a significant overall decrease (i.e. 64-72%) in perfusion, accompanied by vasoconstriction (i.e. 9-12%) and a reduction in perfusion entropy (19%)within sections of the vascular bed. CONCLUSIONS: Multicontrast imaging coupled with IVU-based in vivo vascular phenotyping is a powerful new tool for elucidating NEC pathogenesis.
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Enterocolite Necrosante , Humanos , Recém-Nascido , Animais , Enterocolite Necrosante/diagnóstico por imagem , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/patologia , Microvasos , Microcirculação/fisiologia , Recém-Nascido Prematuro , Imagem Óptica/efeitos adversosRESUMO
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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Enterocolite Necrosante , Lesão Pulmonar , Animais , Camundongos , Enterocolite Necrosante/etiologia , Animais Recém-Nascidos , Espécies Reativas de Oxigênio , Lesão Pulmonar/complicações , Lesão Pulmonar/metabolismo , Alimentos Formulados , Modelos Animais de DoençasRESUMO
BACKGROUND: Necrotizing enterocolitis (NEC) develops through exaggerated toll-like receptor 4 (TLR4) signaling in the intestinal epithelium. Breast milk is rich in non-digestible oligosaccharides and prevents NEC through unclear mechanisms. We now hypothesize that the human milk oligosaccharides 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) can reduce NEC through inhibition of TLR4 signaling. METHODS: NEC was induced in newborn mice and premature piglets and infant formula was supplemented with 2'-FL, 6'-SL, or lactose. Intestinal tissue was obtained at surgical resection. HMO inhibition of TLR4 was assessed in IEC-6 enterocytes, mice, and human tissue explants and via in silico modeling. RESULTS: Supplementation of infant formula with either 2'-FL and/or 6'-SL, but not the parent sugar lactose, reduced NEC in mice and piglets via reduced apoptosis, inflammation, weight loss, and histological appearance. Mechanistically, both 2'-FL and 6'-SL, but not lactose, reduced TLR4-mediated nuclear factor kappa light-chain enhancer of activated B cells (NF-kB) inflammatory signaling in the mouse and human intestine. Strikingly, in silico modeling revealed 2'-FL and 6'-SL, but not lactose, to dock into the binding pocket of the TLR4-MD2 complex, explaining their ability to inhibit TLR4 signaling. CONCLUSIONS: 2'-FL and 6'-SL, but not lactose, prevent NEC in mice and piglet models and attenuate NEC inflammation in the human ileum, in part through TLR4 inhibition. IMPACT: Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants that occurs in the setting of bacterial colonization of the gut and administration of formula feeds and activation by the innate immune receptor toll-like receptor 4 (TLR4). Breast milk prevents NEC through unclear mechanisms. We now show that breast milk-enriched human milk oligosaccharides (HMOs) that are derived from lactose prevent NEC through inhibition of TLR4. The human milk oligosaccharides 2'-FL and 6'-SL, but not the backbone sugar lactose, prevent NEC in mice and piglets. 2'-FL and 6'-SL but not lactose inhibited TLR4 signaling in cultured enterocytes, in enteroids derived from mouse intestine, and in human intestinal explants obtained at the time of surgical resection for patients with NEC. In seeking the mechanisms involved, 2'-FL and 6'-SL but not lactose were found to directly bind to TLR4, explaining the inhibition and protection against NEC. These findings may impact clinical practice by suggesting that administration of HMOs could serve as a preventive strategy for premature infants at risk for NEC development.
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Enterocolite Necrosante/prevenção & controle , Íleo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Lactose/análogos & derivados , Leite Humano/química , Receptor 4 Toll-Like/antagonistas & inibidores , Trissacarídeos/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Humanos , Íleo/imunologia , Íleo/metabolismo , Íleo/patologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lactose/isolamento & purificação , Lactose/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Transdução de Sinais , Sus scrofa , Receptor 4 Toll-Like/metabolismo , Trissacarídeos/isolamento & purificação , Redução de Peso/efeitos dos fármacosRESUMO
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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Inflamação/imunologia , Neutrófilos/imunologia , Peptidil Dipeptidase A/imunologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Enzima de Conversão de Angiotensina 2 , Animais , Modelos Animais de Doenças , Feminino , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Leucina/administração & dosagem , Leucina/análogos & derivados , Leucina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Testes de Sensibilidade Microbiana , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Peptidil Dipeptidase A/deficiência , Peptidil Dipeptidase A/genética , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
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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Implante de Prótese Vascular , Oclusão de Enxerto Vascular/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Veias/transplante , Idoso , Amputação Cirúrgica , Baltimore , Implante de Prótese Vascular/efeitos adversos , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
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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Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/métodos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoAssuntos
Apendicite , Laparoscopia , Apendicectomia/efeitos adversos , Apendicite/cirurgia , Criança , Hospitais , Humanos , Tempo de InternaçãoRESUMO
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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Equipe de Assistência ao Paciente/organização & administração , Pediatria , Ressuscitação/métodos , Análise e Desempenho de Tarefas , Centros de Traumatologia , Traumatologia , Criança , District of Columbia , Feminino , Humanos , Masculino , Pediatria/organização & administração , Análise de Regressão , Ressuscitação/estatística & dados numéricos , Centros de Traumatologia/organização & administração , Recursos HumanosRESUMO
BACKGROUND: The nitrofen model of congenital diaphragmatic hernia (CDH) is widely used in translational research. However, the molecular pathways associated with pulmonary hypoplasia in this model compared to the human CDH phenotype have not been well described. The aim of this study was to investigate differentially expressed genes (DEG) and signaling pathways in early stage fetal lungs in mouse and human CDH. METHODS: CDH lung tissue was obtained from human fetuses (21-23 weeks gestation) and nitrofen mouse pups (E15.5). NovaSeq Flowcell RNA-seq was performed to evaluate differentially expressed transcriptional and molecular pathways (DEGs) in fetal mice with CDH, compared with age-matched normal mouse lungs and human CDH samples. RESULTS: There were thirteen overlapping DEGs in human and mouse CDH lung samples compared to controls. These genes were involved in extracellular matrix, myogenesis, cilia, and immune modulation pathways. Human CDH was associated with an upregulation of collagen formation and extracellular matrix reorganization whereas mouse CDH was associated with an increase in muscular contraction. The most common cell types upregulated in human and mouse CDH samples were ciliated airway cells. CONCLUSIONS: This study highlights the unique gene transcriptional patterns in early fetal mouse and human lungs with CDH. These data have implications when determining the translational potential of novel therapies in CDH using nitrofen-based animal models. LEVEL OF EVIDENCE: Level IV. STUDY TYPE: Basic science/case series.
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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 , Maus-Tratos Infantis/estatística & dados numéricos , Abuso Físico/estatística & dados numéricos , Centros de Traumatologia , COVID-19/psicologia , Pré-Escolar , Traumatismos Craniocerebrais/etiologia , Feminino , Humanos , Lactente , Masculino , Pandemias , Distanciamento Físico , Estudos Retrospectivos , SARS-CoV-2 , Fraturas Cranianas/etiologiaRESUMO
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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Enterocolite Necrosante , Receptor 4 Toll-Like , Humanos , Recém-Nascido , Neuroglia , Receptor 4 Toll-Like/genética , Animais , CamundongosRESUMO
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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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Enterocolite Necrosante/genética , Indóis/administração & dosagem , Leite Humano/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Receptor 4 Toll-Like/genética , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/imunologia , Dieta/métodos , Modelos Animais de Doenças , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/prevenção & controle , Feminino , Regulação da Expressão Gênica , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Ligantes , Exposição Materna , Camundongos , Gravidez , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/imunologia , Transdução de Sinais , Suínos , Receptor 4 Toll-Like/imunologiaRESUMO
BACKGROUND: Despite the frequency of acute appendicitis in children, there is no evidence-based consensus surrounding the urgency of the operation if a diagnosis is made after regular business hours. Although a modest delay in time to operation does not increase disease severity, postponing cases to the next calendar day may be associated with higher resource utilization. We aimed to evaluate the trend of delaying appendectomies to the next calendar day and its associated outcomes. METHODS: We queried the Pediatric Health Information System to analyze appendectomy patients younger than 18 y of age from 2010 to 2018. Same-day appendectomy and next-day appendectomy cohorts were created using admission hour and operative day. Healthcare cost, length of stay, surgical complications, and 30-day readmission rates were collected. Bivariate analyses and multivariable regressions were used to evaluate groups stratified by time of presentation. RESULTS: During the study period, 113,662 appendectomies were performed, comprising 88,715 (78.1%) same-day appendectomies and 24,947 (21.9%) next-day appendectomies. A higher proportion of same-day appendectomies (80.5%) were performed during hours 12:00am to 5:00pm and 19.5% were performed during hours 6:00pm to 11:00pm. The trend of next-day appendectomies increased during the study period from 13.9% to 20.2%. This was primarily evident in the 6:00pm to 11:00pm period. The 5:00pm cutoff was most predictive of a next-day appendectomy. Next-day appendectomies had similar rates of surgical complications; however, they were associated with higher costs, longer lengths of stay, and higher readmission rates. CONCLUSION: As the understanding of appendicitis urgency has changed, a more tempered approach of delivering surgical care has trended. Although short delays appear safe, postponement to the next calendar day is associated with higher resource utilization.
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Apendicite/cirurgia , Tempo para o Tratamento , Adolescente , Criança , Pré-Escolar , Feminino , Custos de Cuidados de Saúde , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Admissão do Paciente , Readmissão do Paciente/estatística & dados numéricos , Análise de Regressão , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/tendências , Estados UnidosRESUMO
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.
Assuntos
Enterocolite Necrosante , Intestino Delgado , Animais , Técnicas de Cultura de Células , Células Cultivadas , Modelos Animais de Doenças , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/patologia , Humanos , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Intestino Delgado/patologia , Organoides , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
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.
Assuntos
Colite Ulcerativa/imunologia , Doenças Inflamatórias Intestinais/imunologia , Lipopolissacarídeos/metabolismo , Útero/metabolismo , Animais , Sulfato de Dextrana , Modelos Animais de Doenças , Resistência à Doença , Feminino , Microbioma Gastrointestinal , Humanos , Imunidade Celular , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-NatalRESUMO
BACKGROUND: The objective of this quality improvement initiative was to identify general surgery residents proficient in a non-English language and have each attempt the Clinician Cultural and Linguistic Assessment (CCLA) to become qualified bilingual staff speakers. METHODS: General surgery house staff were asked to self-identify as proficient in a language other than English. Fees for the certification examination were waived, and each resident was excused from clinical duties to complete the exam. McNemar's test was used for statistical analysis. RESULTS: All residents responded to the initial survey, with 18/65 reporting a non-English language proficiency. Of the 12 residents who sat for the CCLA exam, 9 (75.0%) passed, with 5 certifying in the most commonly spoken non-English languages at this institution. The number of certified residents increased from 1 to 10 (1.5 % to 15.4%, pâ¯=â¯0.004). CONCLUSION: Language barriers result in health care disparities for patients with limited English proficiency. This reproducible quality improvement initiative significantly increased the number of qualified bilingual speakers, while 25.0% of self-described proficient speakers did not demonstrate adequate language proficiency. These newly certified providers allow for increased language concordant care, which may be associated with improved outcomes.