Risk Factors for Postcesarean Maternal Infection in a Trial of Extended-Spectrum Antibiotic Prophylaxis

To identify maternal clinical risk factors for postcesarean maternal infection in a randomized clinical trial of preincision extended-spectrum antibiotic prophylaxis

A Randomized Clinical Trial Testing the Anti-Inflammatory Effects of Preemptive Inhaled Nitric Oxide in Human Liver Transplantation

<div><p>Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were $1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:<a href="http://clinicaltrials.gov/show/NCT00582010" target="_blank">http://clinicaltrials.gov/show/NCT00582010</a>.</p></div

Patient and Surgery Demographics for Center A Cohort.

<p>Values show median (range). P-values calculated from unpaired t-test for placebo vs. iNO. N = 20 except An = 19. Bn = 18.</p

Effects of iNO on liver nitrite levels pre- (LB1) and post-reperfusion (LB2).

<p>Nitrite was measured in paired liver biopsies and data normalized to protein. No significant differences in nitrite levels were observed pre- vs. post-reperfusion or between placebo and iNO treatments.</p

Effects of iNO on reperfusion induced injury and PMN accumulation.

<p>Liver biopsy samples were collected pre- (LB1, □) and 1 hr post dual reperfusion (LB2, ▪) and assessed for injury by histopathologic evaluation (Panel A, B) and infiltration of PMN (panel C, D). Data from both UAB and UW cohorts are combined (n = 38). P-values indicated on graph are by paired t-test for panels A and C or by * unpaired t-test (panels B and D).</p

Patient and Surgery Demographics for Center B Cohort.

<p>Values show median (range). P-values calculated from unpaired t-test for placebo vs. iNO.</p

iNO effects on plasma ceruloplasmin activity.

<p>Plasma ceruloplasmin activity was measured in venous samples collected during surgery from patients administered placebo (□) or iNO (•). Data show mean ± SEM (n = 19–20).</p

Patient demographic differences between study sites.

<p>Panels A–E show respectively patient weight, MELD scores, surgery, warm ischemic times and donor risk index (DRI). Each data point represents individual patient (n = 37–40 for Center A, and n = 40 for Center B). Indicated P-values are from unpaired t-test (panel A and E) or Mann-Whitney U test (panels B–D).</p

Changes in metHb and nitrogen dioxide (NO₂) as a function of blood draw (BD) in placebo (○) or iNO (▪) groups.

<p>Data are mean ± SEM (n = 20 for each group, except UAB placebo where n = 19 and UW iNO where n = 17–20. *P<0.0001 by 2-way ANOVA with Bonferroni multiple comparisons post-test.</p

Individual responses to iNO on TUNEL staining pre- and post-reperfusion.

<p>Panel A and B show changes in TUNEL positive nuclei in hepatic central vein area and panels C and D in the hepatic triad area for Center A (panel A and B) and Center B (panel C and D) cohorts. Indicated P-values determined by Wilcoxon rank-sum (n = 18–20).</p