Objective-To test the safety, tolerability, and pharmacokinetics of the anti-TNF-α monoclonal antibody, infliximab, in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).Study design-We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever following initial treatment with IVIG. Primary outcome measures were infliximab safety, tolerability, and pharmacokinetics. Secondary outcome measures were duration of fever and changes in markers of inflammation.Results-Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were © 2008 Mosby, Inc. All rights reserved.Corresponding author: Jane C. Burns, M.D. Dept of Pediatrics 9500 Gilman Dr. La Jolla, CA 92093-0830 Tel. 619-543-5326 FAX 619-543-3546 jcburns@ucsd.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. NIH Public AccessConclusion-Both infliximab and a second IVIG infusion were safe and well-tolerated in subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined. KeywordsTNF-α; cytokine; monoclonal antibody; coronary artery aneurysm; infliximab; Kawasaki disease Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms in up to 25% of untreated children. Administration of high-dose intravenous immunoglobulin (IVIG) in combination with aspirin (ASA) results in dramatic clinical improvement and reduced incidence of coronary artery aneurysms in the majority of patients with KD (1). However, a subset of patients has persistence or recrudescence of fever following IVIG treatment (2). Common practice is to administer a second dose of IVIG (2 g/kg) to patients who fail to become afebrile within 24 to 48 hours after completion of the first infusion, even though the benefits of this approach have never been formally evaluated (3). Fever persists in approximately half of the patients treated with a second dose of IVIG (2 g/kg) (2). Because KD is a self-limited illness from which most children eventually recover with no specific therapy, it is unclear whether retreated patients become afebrile as a result of the addition...

In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.

Background— Galectin (Gal)-3 is a β-galactoside-binding lectin and currently intensely studied as a biomarker in heart failure. Gal-3 also exerts proinflammatory effects, at least in extracardiac tissues. Objective of this study was to characterize the relationship of plasma and myocardial Gal-3 levels with cardiac fibrosis and inflammation in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy (iCMP). Methods and Results— Endomyocardial biopsies and blood samples were obtained from patients with newly diagnosed cardiomyopathy and clinical suspicion of myocarditis. According to histopathologic findings, patients were classified as having dilated cardiomyopathy (n=40) or iCMP (n=75). Cardiac fibrosis was assessed histologically on endomyocardial biopsy sections. In patients with iCMP, myocardial Gal-3 expression significantly correlated with inflammatory cell count on endomyocardial biopsy ( r =0.56; P <0.05). In contrast, an inverse association was observed between myocardial Gal-3 expression and cardiac fibrosis in patients with iCMP ( r =−0.59; P <0.05). In patients with dilated cardiomyopathy, myocardial Gal-3 expression correlated with cardiac fibrosis on left ventricular biopsy ( P =0.63; P <0.01). Of note, in both groups, plasma Gal-3 levels did not correlate with myocardial Gal-3 levels or left ventricular fibrosis, whereas a positive correlation between plasma Gal-3 levels and inflammatory cell count on endomyocardial biopsy was observed in patients with iCMP. Conclusions— The present study suggests that myocardial Gal-3 can be considered as a possible marker for both cardiac inflammation and fibrosis, depending on the pathogenesis of heart failure. However, circulating concentrations of Gal-3 do not seem to reflect endomyocardial Gal-3 levels or cardiac fibrosis.

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The present study demonstrates that miR-133a levels correlate with macrophage infiltration, cardiac injury, improved LV function, and clinical outcome in patients with iCMP. miR-133a may serve as a potential novel biomarker and therapeutic target in human iCMP.

This prospective study was conducted to examine pain after endoscopic sinus surgery (ESS). The hypothesis was that a long-acting anesthetic agent would result in patients experiencing less pain in the 24-hour postoperative period and therefore needing fewer oral analgesics. We randomized 100 patients undergoing ESS to receive either lidocaine (1% or 2%) with epinephrine or bupivacaine (0.25% or 0.5%) with epinephrine as an anesthetic and for a sphenopalatine block. Postoperative pain was assessed with a standard numeric pain assessment scale at baseline and at 2, 6, and 24 hours after surgery. The use of analgesics during this period was also documented. We compared the results between patients receiving bupivacaine and those receiving lidocaine, as well as between patients who required nasal packing and those who did not. We discovered that in general, pain after ESS was less severe than expected. We further found that the type of anesthetic used did not significantly affect postoperative pain; pain score changes and use of analgesics were similar between the two anesthesia groups. Postoperative pain was also similar between the "packing" and "no packing" groups. Although patients receiving packing had consistently lower increases in pain (and in fact many patients in this group had decreases in pain from baseline), none of the differences between group means was statistically significant.

These findings prove the theoretical concept of ECV as an estimate for diffuse myocardial fibrosis, but only in the absence of significant myocardial inflammation. Assuming that various degrees of myocardial inflammation and fibrosis coexist in such a scenario, the measured ECV will reflect a sum of these different pathologies but will not inform solely on the extent of diffuse fibrosis.