Recurrent Staphylococcal Scalded Skin Syndrome in an Extremely Low-Birth-Weight Neonate.

Staphylococcal scalded skin syndrome (SSSS) in premature infants is a rare condition. We present SSSS in an extremely low-birth-weight (ELBW) infant with recurrent and confirmed bacterial sepsis. We present it to emphasize the importance for clinicians to not only recognize the clinical manifestations of SSSS, but also the need to closely monitor infants, especially very low-birth-weight (VLBW) and ELBW infants with SSSS for recurrence and bacterial sepsis. SSSS in preterm infants is a potentially lethal condition and early recognition and appropriate supportive care could be life-saving.

A Comparative Phase I Study of Combination, Homologous Subtype-C DNA, MVA, and Env gp140 Protein/Adjuvant HIV Vaccines in Two Immunization Regimes.

There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140. They were randomised to receive them in combination at the same visit at 16 and 20 weeks (accelerated) or sequentially with MVA-C at 16, 20, and GLA-AF/gp140 at 24 and 28 weeks (standard). All vaccinations were intramuscular. Primary outcomes included ≥grade 3 safety events and the titer of CN54gp140-specific binding IgG. Other outcomes included neutralization, binding antibody specificity and T-cell responses. Two participants experienced asymptomatic ≥grade 3 transaminitis leading to discontinuation of vaccinations, and three had grade 3 solicited local or systemic reactions. A total of 100% made anti-CN54gp140 IgG and combining vaccines did not significantly alter the response; geometric mean titer 6424 (accelerated) and 6578 (standard); neutralization of MW965.2 Tier 1 pseudovirus was superior in the standard group (82 versus 45% responders, p = 0.04). T-cell ELISpot responses were CD4+ and Env-dominant; 85 and 82% responding in the accelerated and standard groups, respectively. Vaccine-induced IgG responses targeted multiple regions within gp120 with the V3 region most immunodominant and no differences between groups detected. Combining MVA and gp140 vaccines did not result in increased adverse events and did not significantly impact upon the titer of Env-specific binding antibodies, which were seen in 100% individuals. The approach did however affect other immune responses; neutralizing antibody responses, seen only to Tier 1 pseudoviruses, were poorer when the vaccines were combined and while T-cell responses were seen in >80% individuals in both groups and similarly CD4 and Env dominant, their breadth/polyfunctionality tended to be lower when the vaccines were combined, suggesting attenuation of immunogenicity and cautioning against this accelerated regimen.

Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition.

OBJECTIVES: The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers. DESIGN: Adenovirus serotype 5 (Ad5)-based regimens MRKAd5 and VRC DNA/Ad5, designed to elicit HIV-1-specific T cells, are immunogenic but failed to prevent infection or impact on viral loads in volunteers infected subsequently. Failure may be due in part to a lack of CD8 T cells with effective antiviral functions. METHODS: An in-vitro viral inhibition assay tested the ability of bispecific antibody expanded CD8 T cells from peripheral blood mononuclear cells to inhibit replication of a multiclade panel of HIV-1 isolates in autologous CD4 T cells. HIV-1 proteins recognized by CD8 T cells were assessed by IFNγ enzyme-linked immunospot assay. RESULTS: Ad5-based regimens elicited CD8 T cells that inhibited replication of HIV-1 IIIB isolate with more limited inhibition of other isolates. IIIB isolate Gag and Pol genes have high sequence identities (>96%) to vector HIV-1 gene inserts, and these were the predominant HIV-1 proteins recognized by CD8 T cells. Virus inhibition breadth was greater in antiretroviral naïve HIV-1-infected volunteers naturally controlling viremia (plasma viral load < 10 000/ml). HIV-1-inhibitory CD8 T cells were not elicited by the ALVAC/AIDSVAX regimen. CONCLUSION: The Ad5-based regimens, although immunogenic, elicited CD8 T cells with limited HIV-1-inhibition breadth. Effective T-cell-based vaccines should presumably elicit broader HIV-1-inhibition profiles. The viral inhibition assay can be used in vaccine design and to prioritize promising candidates with greater inhibition breadth for further clinical trials.

Operative treatment of acetabular fractures in the Medicare population.

The purpose of this study was to determine the incidence of and evaluate the risk for complications and mortality following open treatment of acetabular fractures in the Medicare population. Patients treated with open reduction and internal fixation (ORIF) for acetabular fractures were identified using current procedural terminology codes in a 5% national sample of Medicare records. Complications within 90 days and within 1 year were evaluated based on the presence of ICD-9-CM diagnosis codes and Current Procedural Terminology reoperation codes. A total of 1286 fractures were treated closed and 359 were treated with ORIF. Multivariate Cox regression was performed to compare complication rates and risk factors. The incidence of acetabular fractures in the Medicare population has increased by 29% since 1998. Complications in the ORIF group included cardiac complications, deep venous thrombosis, infection, pulmonary embolism, refixation, and conversion to total hip arthroplasty. Risk factors for complications with ORIF included advanced age and comorbidities. Mortality in the ORIF group was 14.4% at 1 year. The incidence of reoperation with conversion to total hip arthroplasty or revision fixation following ORIF is 10% and 15%, respectively. Further investigation is required to improve outcomes and decrease complications in this group of patients, especially cardiac, deep vein thrombosis, and infection.

Localised remobilization of metals in a marine sediment.

Trace metals and Fe and Mn were measured at vertical spatial resolutions of 2.5 and 5 mm in the top 35 cm of the profundal sediment of a Scottish sea-loch using DGT (diffusive gradients in thin films) technique. DGT probes lower adjacent metal concentrations in pore waters and induce a flux of metal from the solid phase to porewater. The concentrations of metals in porewaters at the interface of the probe were measured during its deployment in a box core. These measurements reflect porewater concentrations of metals and their rates of resupply from the local solid phase of a very small volume (25 microl) of sediment. There was pronounced horizontal and vertical structure in the interfacial concentrations. Horizontal variations were shown by results from adjacent DGT assemblies being markedly different in detail, while vertical structure was measured directly by the DGT-depth profiles. Iron and Mn varied systematically with depth, with both broad and detailed features of Co aligning with those of Mn. There was, however, evidence of additional localised sources of Co that were apparently unrelated to the redox behaviour that Mn typifies, but associated with the remobilization of Ni, possibly from mineral dissolution. Arsenic(III) was remobilized in well-defined zones. Detailed correspondence of As(II) with some Fe features suggest that its release is mechanistically-related to iron oxide dissolution, but the 3 orders of magnitude higher concentrations of Fe may sometimes obscure the association. These results demonstrate that, within sediments, metals may be released in discrete locations that are not measured by conventional porewater sampling techniques due to their horizontal averaging.

Elevated mucosal addressin cell adhesion molecule-1 expression in acquired immunodeficiency syndrome is maintained during antiretroviral therapy by intestinal pathogens and coincides with increased duodenal CD4 T cell densities.

Reduced intestinal CD4 T cell numbers and gastrointestinal disease are common features of acquired immunodeficiency syndrome (AIDS). Duodenal lymphocyte densities and mucosal addressin cell adhesion molecule (MAdCAM)-1 expression were analyzed in patients with AIDS after highly active antiretroviral therapy (HAART). Compared with human immunodeficiency virus (HIV)-seronegative individuals, HAART-naive patients with AIDS displayed reduced duodenal CD4 T cell densities. After HAART, AIDS patients with opportunistic intestinal pathogens displayed greater increases in duodenal lamina propria (LP) CD4 T cell densities than patients without such infections. Duodenal MAdCAM-1 expression was elevated in all HAART-naive patients with AIDS but remained elevated only in the intestinal pathogen group after HAART. The data suggest that, in HIV-1 infection, lymphocyte migration to the intestine may be promoted by increased MAdCAM-1 expression. After HAART, opportunistic intestinal pathogens maintain elevated MAdCAM-1 expression, which results in prominent increases in LP CD4 T cell densities in the absence of HIV-mediated CD4 T cell destruction.