Early Elevation of Matrix Metalloproteinase-8 and -9 in Pediatric ARDS Is Associated with an Increased Risk of Prolonged Mechanical Ventilation

BACKGROUND: Matrix metalloproteinases (MMP) -8 and -9 may play key roles in the modulation of neutrophilic lung inflammation seen in pediatric Acute Respiratory Distress Syndrome (ARDS). We aimed to perform a comprehensive analysis of MMP-8 and MMP-9 activity in tracheal aspirates of pediatric ARDS patients compared with non-ARDS controls, testing whether increased MMP-8 and -9 activities were associated with clinical outcomes. METHODS: Tracheal aspirates were collected from 33 pediatric ARDS patients and 21 non-ARDS controls at 48 hours of intubation, and serially for those who remained intubated greater than five days. MMPs, tissue inhibitor of metalloproteinases (TIMPs), human neutrophil elastase (HNE) and myeloperoxidase (MPO) activity were measured by ELISA, and correlated with clinical indicators of disease severity such as PRISM (Pediatric Risk of Mortality) scores, oxygen index (OI), multi-organ system failure (MOSF) and clinical outcome measures including length of intubation, ventilator-free days (VFDs) and mortality in the Pediatric Intensive Care Unit (PICU). RESULTS: Active MMP-9 was elevated early in pediatric ARDS subjects compared to non-ARDS controls. Higher MMP-8 and active MMP-9 levels at 48 hours correlated with a longer course of mechanical ventilation (r = 0.41, p = 0.018 and r = 0.75, p<0.001; respectively) and fewer number of VFDs (r = -0.43, p = 0.013 and r = -0.76, p<0.001; respectively), independent of age, gender and severity of illness. Patients with the highest number of ventilator days had the highest levels of active MMP-9. MMP-9 and to a lesser extent MMP-8 activities in tracheal aspirates from ARDS subjects were sensitive to blockade by small molecule inhibitors. CONCLUSIONS: Higher MMP-8 and active MMP-9 levels at 48 hours of disease onset are associated with a longer duration of mechanical ventilation and fewer ventilator-free days among pediatric patients with ARDS. Together, these results identify early biomarkers predictive of disease course and potential therapeutic targets for this life threatening disease

Accuracy of ultrasonography in the diagnosis of acute appendicitis in adult patients: review of the literature

Background: Ultrasound is a widely used technique in the diagnosis of acute appendicitis; nevertheless, its utilization still remains controversial. Methods: The accuracy of the Ultrasound technique in the diagnosis of acute appendicitis in the adult patient, as shown in the literature, was searched for. Results: The gold standard for the diagnosis of appendicitis still remains pathologic confirmation after appendectomy. In the published literature, graded-compression Ultrasound has shown an extremely variable diagnostic accuracy in the diagnosis of acute appendicitis (sensitivity range from 44% to 100%; specificity range from 47% to 99% ). This is due to many reasons, including lack of operator skill, increased bowel gas content, obesity, anatomic variants, and limitations to explore patients with previuos laparotomies. Conclusions: Graded-compression Ultrasound still remains our first-line method in patients referred with clinically suspected acute appendicitis: nevertheless, due to variable diagnostic accuracy, individual skill is requested not only to perform a successful exam, but also in order to triage those equivocal cases that, subsequently, will have to undergo assessment by means of Computed Tomography