Comparative Transcriptome Analysis of Human and Mouse Canalicular Lungs in Fetal Diaphragmatic Hernia.

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.

Prolonged In-hospital Time to Appendectomy is Associated With Increased Complicated Appendicitis in Children.

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 24 hours. 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 24 hours 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 16 hours of presentation was considered early, whereas those between 16 to 24 hours 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.

The administration of a pre-digested fat-enriched formula prevents necrotising enterocolitis-induced lung injury in mice.

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.

Impact of COVID-19 pandemic on injury prevalence and pattern in the Washington, DC Metropolitan Region: a multicenter study by the American College of Surgeons Committee on Trauma, Washington, DC.

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.

Case report of extreme gastric distention and perforation with pathologic Sarcina ventriculi colonization and Rett syndrome.

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.

Contemporary Outcomes following Redo Autogenous Infrainguinal Bypass.

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.

Generating an Artificial Intestine for the Treatment of Short Bowel Syndrome.

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.

Simultaneous acute appendicitis in identical twin boys.

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.

Fetal intervention for congenital diaphragmatic hernia.

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.

Laparoscopic Spleen-Preserving Distal Pancreatectomy for Solid Pseudopapillary Neoplasm in Adolescents.

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.