James W. Eubanks

Early vs interval appendectomy for children with perforated appendicitis.

OBJECTIVE To compare the effectiveness and adverse event rates of early vs interval appendectomy in children with perforated appendicitis. DESIGN Nonblinded randomized trial. SETTING A tertiary-referral urban childrens hospital. PATIENTS A total of 131 patients younger than 18 years with a preoperative diagnosis of perforated appendicitis. INTERVENTIONS Early appendectomy (within 24 hours of admission) vs interval appendectomy (6-8 weeks after diagnosis). MAIN OUTCOME MEASURES Time away from normal activities (days). Secondary outcomes included the overall adverse event rates and the rate of predefined specific adverse events (eg, intra-abdominal abscess, surgical site infection, unplanned readmission). RESULTS Early appendectomy, compared with interval appendectomy, significantly reduced the time away from normal activities (mean, 13.8 vs 19.4 days; P < .001). The overall adverse event rate was 30% for early appendectomy vs 55% for interval appendectomy (relative risk with interval appendectomy, 1.86; 95% confidence interval, 1.21-2.87; P = .003). Of the patients randomized to interval appendectomy, 23 (34%) had an appendectomy earlier than planned owing to failure to improve (n = 17), recurrent appendicitis (n = 5), or other reasons (n = 1). CONCLUSIONS Early appendectomy significantly reduced the time away from normal activities. The overall adverse event rate after early appendectomy was significantly lower compared with interval appendectomy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00435032.

Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo.

Acute pancreatitis (AP) is characterized by release of proteolytic enzymes from the pancreas and a powerful inflammatory cytokine cascade that mediates the systemic manifestations and contributes to the mortality of the disease. The purpose of this study was to examine a potential link between pancreatic proteolytic enzymes, which are increased in AP, and cytokine production. To evaluate this, we incubated rat peritoneal macrophages (PMØ) with increasing concentrations of trypsin and measured cytokine production. Supernatants from the cell cultures were assayed for TNF-&agr; and IL-1&bgr;, and the PMØ were collected for the evaluation of cytokine mRNA by polymerase chain reaction (PCR). Further to evaluate the role of pancreatic proteases in triggering the cytokine cascade in AP, trypsin was injected into the peritoneal cavity of Sprague–Dawley rats, and the production of cytokines was measured in the peritoneal fluid. Controls included injection of inactivated trypsin. Incubation of PMØ with trypsin in vitro resulted in a dose-dependent increase in TNF-&agr; production with maximal response (2,660.5 ± 748.8 pg/mL) at 10 &mgr;g/mL protease. Peak TNF-&agr; and IL-1&bgr; release was noted 16 h after stimulation of the PMØ (2,759.5 ± 698.0 pg/mL and 160,596 ± 4,065 cpm, respectively). Trypsin-induced TNF-&agr; production was not due to release of cell-associated cytokine, inasmuch as activation of PMØ with this protease causing an increase in TNF-&agr; mRNA by 30 minutes, reaching a 14-fold increase at 4 h. Trypsin-injected animals produced TNF-&agr;–containing ascitic fluid in a dose-dependent manner with peak TNF-&agr; at 2 h (371.3 ± 180 pg/mL) versus control (53.8 ± 11.2 pg/mL;p < 0.022). No TNF-&agr; was found in ascites of rats injected with heat-inactivated trypsin. Histologic examination of trypsin-injected animals revealed evidence of pulmonary inflammation at 2 and 4 hours. We conclude that the proteolytic enzyme trypsin stimulates cytokine production from macrophages in vitro and in vivo. This model demonstrates for the first time that trypsin is a potential mediator of the cytokine response seen during AP.

Diagnosing ruptured appendicitis preoperatively in pediatric patients.

BACKGROUND Over the past decade, pediatric patients with ruptured appendicitis (RA) have been successfully treated with IV antibiotics and an interval appendectomy. Because the treatment of acute appendicitis (AA) and RA in children is now diverging, distinguishing between these two conditions preoperatively is critical. STUDY DESIGN A prospective cohort study was conducted. Clinical data were collected, and the attending surgeons preoperative diagnosis was recorded. Accuracy of the pediatric surgeons diagnosis was determined. Univariable and multivariable logistic regression were then used to determine independent clinical predictors of RA. Using the relative beta coefficients of these predictors, a scoring system was constructed to aid in the diagnosis of RA. RESULTS Two hundred forty-seven patients were evaluated: 98 AA (40%), 53 RA (21%), and 97 not appendicitis (39%). Median age was 10 years old. The overall accuracy of the pediatric surgeons preoperative diagnosis was 92%. Sensitivity and specificity for the diagnosis of RA were 96% and 83%, respectively. Multivariable regression analysis identified generalized tenderness on examination, duration of symptoms longer than 48 hours, WBC>19,400 cells/microL, abscess, and fecalith on CT scan as independent predictors for RA. A novel scoring system was developed with these variables, and, when applied to the study population, the specificity for the diagnosis of RA improved to 98%. CONCLUSIONS Pediatric surgeons differentiate AA from RA and not appendicitis preoperatively with high accuracy and sensitivity, but the specificity for diagnosing ruptured appendicitis is lower. The scoring system improved the specificity of the preoperative diagnosis. The validity and utility of this scoring system should be examined in future studies in larger patient populations.

Nonoperative management of blunt liver and spleen injury in children: Evaluation of the ATOMAC guideline using GRADE.

BACKGROUND Nonoperative management of liver and spleen injury should be achievable for more than 95% of children. Large national studies continue to show that some regions fail to meet these benchmarks. Simultaneously, current guidelines recommend hospitalization for injury grade + 2 (in days). A new treatment algorithm, the ATOMAC guideline, is in clinical use at many centers but has not been prospectively validated. METHODS A literature review conducted through MEDLINE identified publications after the American Pediatric Surgery Association guidelines using the search terms blunt liver trauma pediatric, blunt spleen trauma pediatric, and blunt abdominal trauma pediatric. Decision points in the new algorithm generated clinical questions, and GRADE [Grading of Recommendations, Assessment, Development, and Evaluations] methodology was used to assess the evidence supporting the guideline. RESULTS The algorithm generated 27 clinical questions. The algorithm was supported by six 1A recommendations, two 1B recommendations, one 2B recommendation, eight 2C recommendations, and ten 2D recommendations. The 1A recommendations included management based on hemodynamic status rather than grade of injury, support for an abbreviated period of bed rest, transfusion thresholds of 7.0 g/dL, exclusion of peritonitis from a guideline, accounting for local resources and concurrent injuries in the management of children failing to stabilize, as well as the use of a guideline in patients with multiple injuries. The use of more than 40 mL/kg or 4 U of blood to define end points for the guideline, and discharging stable patients before 24 hours received 1B recommendations. CONCLUSION The original American Pediatric Surgery Association guideline for pediatric blunt solid organ injury was instrumental in improving care, but sufficient evidence now exists for an updated management guideline. LEVEL OF EVIDENCE Expert opinion, guideline, grades I to IV.

Hospital cost analysis of a prospective, randomized trial of early vs interval appendectomy for perforated appendicitis in children

BACKGROUND The methods of surgical care for children with perforated appendicitis are controversial. Some surgeons prefer early appendectomy; others prefer initial nonoperative management followed by interval appendectomy. Determining which of these two therapies is most cost-effective was the goal of this study. STUDY DESIGN We conducted a prospective, randomized trial in children with a preoperative diagnosis of perforated appendicitis. Patients were randomized to early or interval appendectomy. Overall hospital costs were extracted from the hospitals internal cost accounting system and the two treatment groups were compared using an intention-to-treat analysis. Nonparametric data were reported as median ± standard deviation (or range) and compared using a Wilcoxon rank sum test. RESULTS One hundred thirty-one patients were randomized to either early (n = 64) or interval (n = 67) appendectomy. Hospital charges and costs were significantly lower in patients randomized to early appendectomy. Total median hospital costs were

Acute pancreatitis induces cytokine production in endotoxin-resistant mice.

17,450 (range

Blunt cerebrovascular injury in children: Underreported or underrecognized?: A multicenter atomac study

7,020 to

Omental infarction: preoperative diagnosis and laparoscopic management in children.

55,993) for patients treated with early appendectomy vs

Full Work Analysis of Resident Work Hours

22,518 (range

Prospective validation of the shock index pediatric-adjusted (SIPA) in blunt liver and spleen trauma: An ATOMAC + study☆

4,722 to