Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial.

Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis. Design, Setting, and Participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. Main Outcomes and Measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. Conclusion and Relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

OBJECTIVES: The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). METHODS: In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. RESULTS: Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. CONCLUSIONS: Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

Pancreatic phospholipase A2 contributes to lung injury in experimental meconium aspiration.

To investigate the role of pancreatic (group I) secretory PLA2 (sPLA2-I) in the pathogenesis of meconium aspiration syndrome, human particulate meconium or its supernatant either before or after extraction of PLA2-I was insufflated into rat lungs. In addition, the pulmonary effects of intra-tracheal human and bovine PLA2-I were studied. Lungs with saline instillation served as controls. Intrapulmonary particulate meconium (both before and after PLA2-I extraction), unlike meconium supernatant, resulted in markedly elevated lung tissue PLA2 catalytic activity and human PLA2-I concentrations when compared with controls. On the other hand, tissue concentrations of the group II PLA2 remained unchanged in all meconium lungs. Pulmonary PLA2-I concentrations further correlated positively with lung injury scores. Instillation of meconium-derived human PLA2-I, at a concentration of one-third of that in particulate meconium, did not raise PLA2 activity or concentrations of PLA2-I or PLA2-II in the lung tissue from the control level, but still resulted in significantly elevated lung wet/dry ratio and injury score. In contrast, insufflation of bovine pancreatic PLA2 increased the lung tissue enzyme activity and wet/dry ratio from the control level, but had no effect on the type II PLA2 concentration or lung injury score. Our data thus indicate that human pancreatic PLA2, introduced in high amounts within aspirated meconium especially in particulate form, is a potent inducer of lung tissue inflammatory injury.