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Katherine B Snyder,1,2 Chase L Calkins,3 Alena Golubkova,1,2 Tyler Leiva,1,2 Camille Schlegel,1 Catherine J Hunter1,2 1Division of Pediatric Surgery, Oklahoma City, OK, 73104, USA; 2Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; 3College of Medicine, The University of Oklahoma College of Medicine, Oklahoma City, OK, 73104, USACorrespondence: Catherine J Hunter, Department of Pediatric Surgery, Oklahoma Children’s Hospital, 1200 Everett Drive, ET NP 2320, Oklahoma City, OK, 73104, USA, Email catherine-hunter@ouhsc.eduBackground: Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death of premature neonates. NEC is associated with prematurity, a hyperinflammatory response, and dysregulation of intestinal barrier function. We hypothesize that patients with NEC will have, and continue to have after recovery, an increased hyperinflammatory intestinal response compared to those patients without NEC.Methods: Neonates with NEC, those that have recovered from NEC, and those without NEC undergoing intestinal resections had specimens collected and snap frozen or generated into enteroids. The enteroids were treated with 100ug/mL lipopolysaccharide (LPS) and subjected to 24 hr of hypoxia together, then compared with untreated controls. Expression of Tumor Necrosis Factor (TNF-α) and interleukin 8 (IL-8) were evaluated via RT-qPCR and ELISA to measure inflammatory response. ANOVA determined statistical significance (p< 0.05).Results: There was no difference in inflammatory markers in recovered NEC tissue compared to non-NEC tissue on RTqPCR (p=0.701 TNF-α and 0.861 IL-8). However, recovered NEC enteroids demonstrate elevated levels of inflammatory markers after treatment compared to non-NEC enteroids after treatment on RTqPCR (p=0.0485 TNF-α, p=0.0057 IL-8) and ELISA (p=0.0354 TNF-α, p=0.0011 IL-8). Recovered NEC enteroids that underwent treatment demonstrated increased inflammatory markers compared to recovered NEC enteroids without treatment on RTqPCR (p=0.0045 TNF-α, p=0.0002 IL-8) and ELISA (p=0.034 TNF-α, p=0.0002 IL-8) suggesting a heightened inflammatory response to a second hit.Conclusion: Intestinal tissue resected from neonates with NEC has an elevated hyperinflammatory response compared to neonates recovered from NEC and neonates without NEC. Enteroids generated from patients that have recovered from NEC have a heightened inflammatory response in response to NEC inducing stimuli compared to controls. This tendency towards an increased hyperinflammatory state may be correlated with an infant’s proclivity to develop NEC and demonstrates the significance of a second hit on this tissue creating a heightened inflammatory response. This could be correlated with the impact and trajectory of an illness post recovery from NEC.Keywords: necrotizing enterocolitis, recovery, hyperinflammatory, enteroids

AbstractThe field of surgery has relied on innovation and creativity to improve patient care and propel the field forward. Historically, regulatory oversight of innovative approaches to surgery has been largely inconsistent, rendering surgeons relatively unrestricted creative latitude in the operating room; whether this has proven to be more beneficial or harmful is subject to debate. While innovation plays a crucial role in the advancement of surgical techniques, the potential drawbacks of unregulated innovation must be seriously considered, especially when treating vulnerable populations such as infants and children. This article provides an overview of the ethical aspects surrounding innovation in pediatric surgery, including discussion of relevant considerations, controversies, and pitfalls. The following includes a review of the current and past literature surrounding the topic. The purpose of this review is to heighten awareness of the ethical challenges that surgeons face when considering novel operative techniques on pediatric patients.

Introduction: Literature shows failure of the outpatient clinic (OC) pathway after emergency department (ED) ultrasound diagnosis of symptomatic cholelithiasis (SC). We hypothesized SC to be more prevalent on final surgical pathology (FSP) in patients who successfully completed OC pathway., Methods: This retrospective single-institution chart review compared OC and ED patients with right upper quadrant (RUQ) pain and cholelithiasis whom underwent cholecystectomy. Clinical evaluation was considered positive if RUQ pain >4 h, or + Murphy's sign. Ultrasound was positive if two of these three were present: sonographic Murphy's, wall thickness > 4 mm, or pericholecystic fluid. Results were compared with FSP., Results: Six hundred-seven patients underwent cholecystectomy, 299 OC and 308 ED. OC was more likely to SC (23% versus 4.6%) (P < 0.0001) and ED acute cholecystitis (39.3% versus 4.7%). Chronic cholecystitis was the most common FSP in both OC (72%) and ED (56%) populations, of these, 73% of OC denied pain >4 h versus only 10% of ED (P < 0.001). Median time from evaluation to cholecystectomy was 14 d versus 14 h in the OC and ED respectively (P < 0.0001)., Conclusions: While chronic cholecystitis was the most common FSP in both OC and ED, the majority of OC reported RUQ pain <4 h delineating these presentations. Duration of pain should be utilized as algorithm triage. We recommend patients with pain episode <4 h should complete OC algorithm with expedited cholecystectomy within 14 d., (Published by Elsevier Inc.)

Introduction: Peri-intubation hypotension is associated with increased hospital length of stay and morbidity. Propofol is associated with alterations in hemodynamics. We hypothesize that using propofol for induction leads to peri-intubation hypotension in trauma critical care patients., Methods: Patients that underwent unplanned intubation in the trauma intensive care unit (TICU) were prospectively enrolled. Peri-intubation vitals and medications were recorded to assess hypotension within 10 ​min of intubation. Patients were divided into propofol (PROP) or other medication (OTR) groups., Results: Data was complete for 69 patients; 31 PROP and 38 OTR. In OTR there was an 8.8-point (-21.1, 3.6) SBP decrease (p ​= ​0.159) and in PROP there was a 30.8-point (-45.6, -16.0) SBP decrease (p ​= ​0.0002) with significant increases in heart rate (HR) and shock index (SI) (HR p ​= ​0.001, SI p ​< ​0.0001)., Conclusion: In patients without hypotension prior to intubation, we observed a statistically significant drop in the patients' SBP with use of propofol. In trauma critical care unit patients, we recommend considering an induction medication for unplanned intubation other than propofol., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose. During preparation of this manuscript no generative AI technology was utilized., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although appendicitis has been described for more than 300 years, its optimal management remains a topic of active investigation. Acute appendicitis is the most common cause of peritonitis in children, and rates of perforated appendicitis are much higher in children than in adults. Increased risk for perforated appendicitis in children is related to a delay in diagnosis due to age, size, access to care, and more. Surgical options include immediate appendectomy versus nonoperative management with intravenous antibiotics ± a drainage procedure, with a subsequent interval appendectomy. Microbiota of perforated appendicitis in children most often includes Escherichia coli, Bacteroides fragilis, Streptococcus, and more. Even though the most common organisms are known, there is a large variety of practice when it comes to postoperative antibiotic management in these patients. Studies discuss the benefits of mono- versus dual or triple therapy without a particular consensus regarding what to use. This is reflected across differing practices at various institutions. In this review, we aim to explore the implications of perforated appendicitis in pediatrics, common organisms seen, antibiotic regimen coverage, and the implications of variations of practice. Resistance to commonly used broad-spectrum antibiotics is evolving, therefore minimization of care variability is needed for improved patient outcomes and proper antibiotic stewardship., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The majority of final surgical pathology (FSP) from both emergency department (ED) and outpatient clinic (OC) patients is chronic cholecystitis. We aimed to differentiate these presentations and identify disparities associated with ED utilization and OC failure., Methods: Retrospective chart review of single institution ED and OC cholecystectomies for cholelithiasis. Clinical presentation, FSP, demographics, and zip code poverty (ZCP) levels were evaluated. Data analysis by summary statistics, bivariate comparisons, and logistic regression., Results: Of 299 OC and 308 ED patients, OC was more likely to be Caucasian (78% vs 46%, p < 0.0001) and insured (89% vs. 32%, p < 0.0001). 71.8% of OC with ZCP <10% had insurance versus only 32.5% in ZCP >20%. Uninsured ED OR was 13.1 (95% CI 8.7-22.9)., Conclusion: Uninsured ED patients are vulnerable to fail the outpatient algorithm, especially when misdiagnosed by US. Clinical diagnosis of cholecystitis in this population should warrant offering of urgent cholecystectomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Emergency department (ED) wait times and ED length of stay (LOS) have a significant impact on patient morbidity and mortality and patient satisfaction. Consultation-to-decision time can contribute to increased wait times and LOS in the ED. Up to 40% of patients presenting to the ED require consultation from subspecialty services. We hypothesize that in surgical patients, completion of workup prior to consultation will decrease consultation-to-decision time, ED wait times, and LOS in the ED., Methods: A retrospective review was conducted at a single site including all overnight general surgery consultations from the ED over 2-months. Data collected included wait times, LOS, and workup completed prior to consultation. Summary statistics were calculated and bivariate tests were performed using t-tests for continuous variables., Results: Time to final surgical plan and LOS in ED were evaluated for 137 patients comparing "complete" and "incomplete" workups at time of consultation. It was considered a "complete" workup if labs and imaging were resulted prior to time of consult. If any baseline tests were not ordered prior to time of consult, it was considered an "incomplete" workup. Analysis demonstrated an average time of 4.9 and 2.5 hours for consultation-to-decision time for "incomplete" and "complete" workups respectively (p < 0.0001). For LOS in ED, there was an average of 11.4 and 7.9 hours for "incomplete" and "complete" workups respectively (p < 0.0001)., Conclusions: There is a significant difference in consultation-to-decision time and LOS in the ED when consultation is performed following a complete versus incomplete workup for surgical patients independent of inherent wait times for testing to result and the need for additional testing requested from consulting services. Developing strategies to optimize workups from the ED prior to surgical consultation, including the development of care pathways, could significantly decrease patient wait times and LOS in the ED., (Published by Elsevier Inc.)

Background: Necrotizing enterocolitis (NEC) is a devastating disease of premature neonates with substantial morbidity and mortality. Necrotizing enterocolitis is associated with prematurity, a hyperinflammatory response, and dysregulation of intestinal barrier function. We hypothesize that patients with NEC will have an increased hyperinflammatory intestinal response compared with those without NEC. Patients and Methods: Enteroids were generated from intestinal tissue from neonates undergoing resection. They were treated with 100 mcg/mL lipopolysaccharide (LPS), subjected to 24 hours of hypoxia inducing experimental NEC, then compared with untreated controls. Expression of tumor necrosis factor (TNF-α) and interleukin 8 (IL-8) were evaluated via reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) to measure inflammatory response. Analysis of variance (ANOVA) determined statistical significance (p < 0.05). Results: Treated NEC-derived enteroids expressed significantly higher levels of IL-8 (RT-qPCR, p = 0.003; ELISA, p = 0.0002) compared with untreated NEC-derived enteroids with an increase in inflammatory marker concentration in those with a greater degree of prematurity (ELISA, p = 0.0015). A higher level of IL-8 was seen in NEC-derived enteroids compared with control after treatment (RT-qPCR, p = 0.024). Tumor necrosis factor-α levels were elevated in treated NEC-derived enteroids compared with untreated NEC-derived enteroids (RT-qPCR, p = 0.006; ELISA, p = 0.002) and compared with treated non-NEC-derived enteroids (RT-qPCR, p = 0.025; ELISA, p < 0.0001). Conclusions: Enteroids generated from neonates with NEC have an elevated hyperinflammatory response in response to NEC-inducing stimuli compared with controls. Enteroids generated from neonates with NEC with a greater degree of prematurity have a larger increase in inflammatory markers. This tendency toward a hyperinflammatory state may be correlated with an infant's proclivity to develop NEC and further demonstrates the hyperinflammatory state of prematurity.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease that affects premature neonates. It frequently results in significant morbidity and mortality for those affected. Years of research into the pathophysiology of NEC have revealed it to be a variable and multifactorial disease. However, there are risk factors associated with NEC including low birth weight, prematurity, intestinal immaturity, alterations in microbial colonization, and history of rapid or formula based enteral feeds (Fig. 1). 1-3 An accepted generalization of the pathogenesis of NEC includes a hyperresponsive immune reaction to insults such as ischemia, starting formula feeds, or alterations in the microbiome with pathologic bacterial colonization and translocation. This reaction causes a hyperinflammatory response disrupting the normal intestinal barrier, allowing abnormal bacterial translocation and ultimately sepsis. 1 , 2 , 4 This review will focus specifically on the interactions with the microbiome and intestinal barrier function in NEC., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. We are funded by the Oklahoma Center for Adult Stem Cell Research (CH); however, we have no conflicts of interest with this funding., (Copyright © 2023. Published by Elsevier Inc.)

Background: Historically, youth violence prevention strategies used deterrence-based programming with limited success. We developed a youth violence prevention program, Dusk to Dawn (D2D), intended to improve youths' recognition of high-risk situations and teach new skills in conflict resolution. The aim of this study was to evaluate the effect of D2D on youths' perceptions of personal risk factors and high-risk situations., Methods: Youth ages 12 years to 18 years were referred to D2D by community-based organizations, probation, or youth detention center. The youth completed a self-report survey before and after participating in D2D., Results: One hundred eight youth participated in D2D. Pretest and posttest results for self-reported personal risk factors and high-risk situations for violence are presented. For personal risk factors, a statistically significant increase in the perception that family (p < 0.01) and other issues (p < 0.05), and a decrease in the perception that school problems (<0.05) were seen as important personal risk factors. For high-risk situations, increases in the perception that peer violence and substance use as high-risk situations were seen as significant at the trend level (p < 0.10). Of the 60% of participants who answered questions regarding satisfaction with D2D, 83.3% agreed or strongly agreed that D2D helped them to better understand violence and 83.3% would recommend D2D to others., Conclusion: Youth violence prevention programming including an explicit discussion of how violence is learned and the role of family, friends, school, and a community in shaping youths' attitudes toward violence can effectively raise awareness of one's own risk factors. Risk factors for youth violence are often preventable or modifiable, making awareness of one's own risk factors a realistic target for youth violence prevention programs., Level of Evidence: Therapeutic/Care Management, Level III.

From May 1986 through May 1989, the annual number of patients evaluated for dog-bite injuries in the Los Angeles County Hospital jail ward more than doubled. During this period, the number of annual extremity angiograms increased from two to 42. Forty-six of the 48 angiograms were done to evaluate injuries sustained from police dog bites. Only two angiograms, both negative, were performed to evaluate injuries sustained from nonpolice dog bites. Ten of 48 angiograms (24%) demonstrated significant arterial vascular injuries. A similar incidence has been reported with more common causes of penetrating and blunt trauma (eg, knives, gun shots, and motor vehicle accidents). The majority of injuries (seven of ten) were in the right upper extremity. An absent or decreased pulse was observed in five patients. Three patients had proximity-only injuries. The most common injury was occlusion (six of ten). Three patients required surgical repair. From this study, the first on extremity arterial injuries secondary to dog bites, we conclude that bites can result in significant injury. A careful physical examination and an awareness of the possibility of significant arterial damage in proximity-only trauma will help to eliminate missed arterial injuries.

We have investigated the effects of taxol on steady-state tubulin flux and on the apparent molecular rate constants for tubulin addition and loss at the two ends of bovine brain microtubules in vitro. These microtubules, which consist of a mixture of 70% tubulin and 30% microtubule-associated proteins (MAPs), undergo a net addition of tubulin at one end of each microtubule (A end) and a precisely balanced net loss of tubulin at the opposite end (D end) at steady state in vitro. They do not exhibit to a detectable extent the "dynamic instability" behavior described recently for MAP-free microtubules, which would be evident as an increase in the mean microtubule length and a decrease in the number of microtubules in the suspensions [Mitchison, T., & Kirschner, M. (1984) Nature (London) 312, 237-242]. We used a double-label procedure in which microtubules were labeled with tritium and carbon-14 at A ends and carbon-14 at D ends to distinguish the two ends, combined with a microtubule collection procedure that permitted rapid and accurate analysis of retention of the two labels in the microtubules. We found that taxol slowed the flux of tubulin in a concentration-dependent manner, with 50% inhibition occurring between 5 and 7 microM drug. The effects of taxol on the apparent molecular rate constants for tubulin addition and loss at the two microtubule ends were determined by dilution analysis at an intermediate taxol concentration. The results indicated that taxol decreased the magnitudes of the dissociation rate constants at the two ends to similar extents, while exerting little effect on the association rate constants.(ABSTRACT TRUNCATED AT 250 WORDS)