Febrile urinary tract infection after ureteroneocystostomy: a contemporary assessment at a single institution.

PURPOSE: Febrile urinary tract infection represents significant morbidity in patients with vesicoureteral reflux, especially following open surgical or endoscopic treatment. The reported incidence of febrile urinary tract infection after ureteroneocystostomy varies from 10% to 24%. We investigated the incidence of febrile urinary tract infection following ureteroneocystostomy in a contemporary, single institution series. MATERIALS AND METHODS: We retrospectively reviewed medical records of 395 consecutive patients undergoing ureteroneocystostomy for primary vesicoureteral reflux at our institution between 2002 and 2007. We examined demographic, diagnostic and operative data, including presence of postoperative febrile urinary tract infection. A Cox proportional hazards model was performed to assess predictors of febrile urinary tract infection following ureteroneocystostomy. RESULTS: Ureteroneocystostomy was performed in 395 patients (673 ureters) at a mean age of 58 months. The most common reflux grade was III (41%). The incidence of postoperative febrile urinary tract infection was 4.6% at a mean followup of 15 months. Postoperative dysfunctional elimination syndrome was a significant predictor of febrile urinary tract infection (HR 3.8, 95% CI 1.2-12, p = 0.02), and was identified in 58 of 340 toilet trained children (15% overall). Age at diagnosis, initial presentation, age at surgery, indication for surgery, reflux grade, laterality, surgical technique and preoperative dysfunctional elimination syndrome were not predictive of postoperative febrile urinary tract infection. CONCLUSIONS: The incidence of febrile urinary tract infection following ureteroneocystostomy may be lower than previously reported. The presence of postoperative dysfunctional elimination syndrome is a significant predictor of postoperative febrile urinary tract infection.

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen required for optimal immunogenicity. We have evaluated activated alpha2-macroglobulin (alpha2M*) and a squalene-based stable emulsion containing monophosphoryl lipid A (MPL-SE) with granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvants to enhance the immunogencity of candidate HIV immunogens. Balb/c mice were subcutaneously immunized on days 0, 14 and 28 with 100-0.1 microg of HIV-1 envelope gp120 C4-V3 immunogens from either HIV IIIB (C4-V3(IIIB)) or SHIV 89.6P (C4-V3(89.6P)). Immunogens were tested covalently coupled to alpha2M*, formulated with MPL-SE/GM-CSF, or as a combination of both. Using CFA/IFA, only 50 and 100 microg, but not lower doses of C4-V3(IIIB) peptides, induced antibody responses. In contrast, peak antibody responses were detected in mice immunized with 10 microg of C4-V3 peptide coupled to alpha2M* (alpha2M*-peptide). Similar to CFA/IFA, MPL-SE/GM-CSF induced optimal antibody responses at 50 and 100 microg of C4-V3 immunogen. However, the combination of MPL-SE/GM-CSF with alpha2M*-C4-V3 peptide decreased the dose of C4-V3 required for optimal response to 5 microg for C4-V3(IIIB), and to 0.1 microg for C4-V3(89.6P). Taken together, HIV envelope gp120 C4-V3 peptides covalently complexed with alpha2M* and formulated with MPL-SE/GM-CSF resulted in a subunit HIV immunogen capable of inducing anti-HIV envelope antibody responses at doses up to 100-fold less than those needed with CFA/IFA or MPL-SE/GM-CSF alone.