Markers of neutrophil activation and extracellular trap formation predict appendicitis.

BACKGROUND: Although appendicitis is one of the most frequently occurring pediatric surgery emergencies, current biomarkers for diagnosis are unspecific and have low predictive values. Neutrophils are an essential component of the innate immune system involved during appendicitis. Thus, the current study aimed to evaluate neutrophils and their activation markers in a prospective cohort study. METHODS: The study population included all children with acute abdominal pain who presented to the pediatric surgery department of 2 large clinics between July 2018 and December 2019. All enrolled subjects underwent blood sample collection with an assessment of white blood cell count, C-reactive protein, cell-free DNA, neutrophil elastase, myeloperoxidase, and citrullinated histone H3. If an appendectomy was performed, the appendix was stained for myeloperoxidase, neutrophil elastase, and citrullinated histone H3 using immunofluorescence. RESULTS: In total, 198 subjects were included in the study, of whom 133 had histological verified appendicitis. In those with appendicitis, white blood cell count and C-reactive protein showed a moderate diagnostic value for (noncomplicated and complicated) appendicitis. However, cell-free DNA (area under the curve .87) and citrullinated histone H3 (area under the curve .88) demonstrated excellent predictive power for appendicitis. Most notably, citrullinated histone H3 was able to distinguish (1) noncomplicated from complicated appendicitis, and (2) predict patient outcome. Moreover, the examined biomarkers appear to reflect tissue expression and disease severity. CONCLUSION: Markers of neutrophil activation and extracellular trap formation are excellent biomarkers for appendicitis. In particular, citrullinated histone H3 may be used to identify children with an increased risk of developing complications after appendicitis.

The Spaced Learning Concept Significantly Improves Acquisition of Laparoscopic Suturing Skills in Students and Residents: A Randomized Control Trial.

INTRODUCTION: Spaced learning consists of blocks with highly condensed content that interrupted by breaks during which distractor activities, such as physical activity, are performed. The concept has been shown to be superior in complex motor skill acquisition like laparoscopic suturing and knot tying. Preliminary studies have solely been conducted with medical students. Therefore, it remained unanswered if the spaced learning concept would also work for pediatric surgery residents. MATERIALS AND METHODS: The study aimed to evaluate the effectiveness of spaced learning, students, and residents were asked to perform four surgeons' square knots on a bowel model within 30 minutes prior and post 3 hours of hands-on training. To examine the long-term skills, the same subjects were asked to perform a comparable, but more complex task 12 months later without receiving training in the meantime. Total time, knot stability, suture accuracy, knot quality, and laparoscopic performance were assessed. Additionally, motivation was accessed by using the questionnaire on current motivation. Differences were calculated using mixed analysis of variance, Mann-Whitney U test, and multivariate analysis of covariance. RESULTS: A total of 20 medical students and 14 residents participated in the study. After randomization, 18 were trained using the spaced learning concept and 16 via conventional methods. Both groups had comparable baseline characteristics and improved significantly after training in all assessed measures. The spaced learning concept improved procedure performance as well as knot quality and stability in both students and residents. However, residents that trained via spaced learning showed significantly better long-term results regarding knot quality and speed in comparison to students. Although anxiety was significantly reduced in both training groups over time, residents were significantly more interested regarding knot tying than students. CONCLUSION: This study dispels any remaining doubt that the spaced learning concept might only work for medical students. It appears that the spaced learning concept is very suitable for residents in acquiring complex motor skills. It is superior to conventional training, resulting in improved procedural performance as well as knot quality and speed. Hence, tailored training programs should not only be integrated early on in students' curricula but also in surgical training programs.

Markers of neutrophil activation and extracellular traps formation are predictive of appendicitis in mice and humans: a pilot study.

Appendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers for diagnosis are unspecific and have low predictive values. As neutrophils and extracellular traps (ETs) are an essential component of the immune defense against bacterial infections, and appendicitis is considered an inflammation reaction of the appendix, we hypothesized that neutrophil activation and NET formation play an essential role in appendicitis development and maintenance. Therefore, this pilot study aimed to establish a murine model of appendicitis and to evaluate ETs markers to diagnose appendicitis in mice and humans. The study used 20 (12 appendicitis- and 8 controls) 6-week old mice which underwent advanced appendicitis induction using a modified caecal ligation puncture procedure. During the study, cell-free DNA, neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated Histone H3 (H3cit) were assessed. Additionally, samples of 5 children with histologically confirmed appendicitis and 5 matched controls with catarrhal appendicitis, were examined for the same biomarkers. Moreover, NE, MPO, and H3cit were assessed histologically via immunofluorescence in mice and humans. All mice in the appendicitis group developed an advanced form of appendicitis with focal peritonitis. In mice and humans with appendicitis, markers of neutrophil activation and ETs formation (especially cfDNA, NE and H3cit) were significantly elevated in blood and tissue compared to controls. Ultimately, biomarkers correlated extremely well with tissue expression and thus disease severity. It appears that neutrophil activation and possibly NETs contribute to appendicitis development and biomarkers of neutrophil activation and ET formation reflect disease severity and thus could be used as biomarkers for appendicitis. However, large prospective clinical studies are needed to confirm our findings.