Infectious complications of intercostal nerve cryoablation mediated by perioperative hypothermia during pediatric Nuss procedure.

BACKGROUND: Intercostal nerve cryoablation (cryoanalgesia) is increasingly used for pain control in minimally invasive repair of pectus excavatum (MIRPE) by Nuss procedure. Cryoanalgesia may lower core body temperature and increase the risk of postoperative infectious complications. We investigated cryoanalgesia effects on infectious complications following MIRPE. METHOD: We performed a retrospective review of patients undergoing MIRPE at our institution. Patients treated via multimodal analgesia with cryoanalgesia (Cryo) were compared to patients treated via multimodal analgesia +/- elastomeric pain pumps (Non-cryo). Core body and intraoperative minimum/maximum temperatures were recorded. Primary outcomes were wound infection and pneumonia; secondary outcome was length of stay (LOS). Fisher's Exact and Mann-Whitney U tests compared proportions and medians respectively, p-value ≤ 0.05 being significant. RESULTS: 80 patients were included, 35(43.7%) Cryo and 45(56.3%) Non-cryo. There were no significant differences in median [IQR] for age(15[13.3,16.0];p =0.86), number of bars inserted (2[1,2];p = 0.57), or operative time(123.5[98.3, 148.8]; p = 0.11) between the two groups. We found no significant differences in median [IQR] minimum temperature (35.4°C [35.0,35.8];p = 0.76), median change in intraoperative temperature (-0.13°C [-0.44,0.00];p = 0.94) or median recovery temperature (-1.10°C [-1.56,-0.65]; p = 0.59) between Cryo and Non-cryo. PACU temperature was significantly lower in the Cryo group, 36.4°C [36.2,36.6] p = 0.04. There were no postoperative wound infections in either group and no significant difference in incidence of postoperative pneumonia (8.57% versus 2.22%,p =  0.31) or median[IQR] for LOS (4[3,4];p = 0.57), between Cryo and Non-cryo patients. CONCLUSION: Although cryoanalgesia for MIRPE resulted in lower core body temperature, there appears to be no significant difference between Cryo and Non-Cryo patients for LOS or infectious complications.

IMPPACT (Intravenous Monotherapy for Postoperative Perforated Appendicitis in Children Trial): Randomized Clinical Trial of Monotherapy Versus Multi-drug Antibiotic Therapy.

BACKGROUND: Perforated appendicitis is the most common cause of intraabdominal abscess (IAA) in children. The optimal postoperative antibiotic regimen to reduce IAA has evolved in the last decade from triple-drug to 2-drug therapy (CM). Recent retrospective studies show decreased infectious complications with monotherapy PT. To date prospective comparative data are lacking. Therefore, a prospective randomized trial comparing PT versus CM was conducted. METHODS: A multi-institutional prospective randomized trial was performed in children with perforated appendicitis comparing postoperative antibiotic regimens PT or CM. The primary outcome was 30-day postoperative IAA formation. Perforation was strictly defined as a hole in the appendix or fecalith in the abdomen, documented with intraoperative photographs. RESULTS: One hundred sixty-two patients were enrolled during the study period. No differences in age, weight, or duration of presenting symptoms were identified. In addition, length of stay, duration of intravenous antibiotic treatment, discharge oral antibiotic treatment, and antibiotic-related complications did not differ between groups. Compared to the CM group, the PT group had significantly lower IAA rate [6.1% vs 23.8%, odd ratio (OR) 4.80, P = 0.002], lower postoperative computed tomography imaging rate (13.9% vs 29.3%, OR 2.57, P = 0.030), and fewer emergency room visits (8.8% vs 26.4%, OR 3.73, P = 0.022). Multivariate logistic regression analysis found the use of CM versus PT (OR 9.21, P = 0.021) to be the most significant predictor for developing IAA. CONCLUSIONS: In children with perforated appendicitis, postoperative monotherapy with PT is superior to standard 2-drug therapy with CM and does not increase antibiotic-related complications or antibiotic exposure duration.

A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial.

BACKGROUND: West Nile virus (WNV) is a flavivirus that causes meningitis and encephalitis. There are no licensed vaccines to prevent WNV in humans. The safety and immunogenicity of a first-generation WNV DNA vaccine was demonstrated in a clinical trial and a similar DNA vaccine has been licensed for use in horses. METHODS: A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot. RESULTS: The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort. CONCLUSIONS: Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter. CLINICAL TRIALS REGISTRATION: NCT00300417.

Effects of immunomodulatory and organism-associated molecules on the permeability of an in vitro blood-brain barrier model to amphotericin B and fluconazole.

Amphotericin B (AMB) is used to treat fungal infections of the central nervous system (CNS). However, AMB shows poor penetration into the CNS and little is known about the factors affecting its permeation through the blood-brain barrier (BBB). Therefore, we studied immunomodulatory and organism-associated molecules affecting the permeability of an in vitro BBB model to AMB. We examined the effects of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan (ZYM), dexamethasone (DEX), cyclosporine, and tacrolimus on transendothelial electrical resistance (TEER); endothelial tight junctions; filamentous actin; and permeability to deoxycholate AMB (DAMB), liposomal AMB (LAMB), and fluconazole. Proinflammatory cytokines and organism-associated molecules significantly decreased the mean TEER by 40.7 to 100% (P < or = 0.004). DEX increased the mean TEER by 18.2 to 26.4% (P < or = 0.04). TNF-alpha and LPS increased the permeability to AMB by 8.2 to 14.5% compared to that for the controls (1.1 to 2.4%) (P < or = 0.04). None of the other molecules affected the model's permeability to AMB. By comparison, the BBB model's permeability to fluconazole was >78% under all conditions studied, without significant differences between the controls and the experimental groups. LPS and TNF-alpha decreased tight-junction protein zona occludens 1 (ZO-1) between endothelial cells. In conclusion, IL-1beta, ZYM, and LTA increased the permeability of the BBB to small ions but not to AMB, whereas TNF-alpha and LPS, which disrupted the endothelial layer integrity, increased the permeability to AMB.