A prospective randomized trial comparing image quality,study interpretability,and radiation dose of narrow acquisition window with widened acquisition window protocols in prospectively ECG-triggered coronary computed tomography angiography

BackgroundProspectively triggered coronary computed tomography angiography (CTA) is commonly performed with a widened acquisition window to provide flexibility in image reconstruction.ObjectiveWe conducted a randomized controlled trial to determine whether the use of a narrow acquisition window in prospectively triggered coronary CTA would allow lower radiation dose while preserving image quality and interpretability.MethodsProspective 2-center 2- platform randomized trial that evaluated 205 consecutive patients 96 with widened acquisition (WA) and 109 narrow acquisition (NA) referred for coronary CTA in sinus rhythm and heart rate <65 beats/min. Patients scanned with WA had phases reconstructed at 5% intervals, and each phase was assigned an individual study ID. Images were reviewed with individual phase reconstructions interpreted randomly by 2 level 3 readers with a third for consensus. Images were evaluated with a 5-point Likert scale on a per-vessel basis (best score on any phase). Scores were then dichotomized into diagnostic (score 3–5) compared with nondiagnostic (score 1–2). Readers also reported obstructive coronary artery disease on a per-patient basis. Agreement for the diagnosis of obstructive disease and per-artery interpretability was performed. Signal and noise measurements were also performed.ResultsNo difference in demographics between groups (P = NS). The signal-to-noise ratio was comparable 12.99 ± 3.4 NA and 12.53 ± 4.13 for the WA (P = 0.45). The median effective dose was 1.78 mSv for NA compared with 3.26 mSv for WA (P < 0.001). Image quality, diagnostic interpretability, interreader agreement, and downstream testing were not significantly different between the 2 groups (P= NS for all).ConclusionsCoronary CTA with NA resulted in a 47% lower radiation dose without significant difference in study interpretability or image quality or increased downstream resource use or testing.     

A phase i study of daily treatment with a ceramide-dominant triple lipid mixture commencing in neonates

Background

Defects in skin barrier function are associated with an increase risk of eczema and atopic sensitisation. Ceramide-dominant triple lipid mixture may improve and maintain the infant skin barrier function, and if shown to be safe and feasible, may therefore offer an effective approach to reduce the incidence of eczema and subsequent atopic sensitisation. We sort to assess the safety and compliance with daily application of a ceramide-dominant triple lipid formula (EpiCeram?) commencing in the neonatal period for the prevention of eczema.

Methods

Ten infants (0-4 weeks of age) with a family history of allergic disease were recruited into an open-label, phase one trial of daily application of EpiCeram? for six weeks. The primary outcomes were rate of compliance and adverse events. Data on development of eczema, and physiological properties of the skin (transepidermal water loss, hydration, and surface pH) were also measured.

Results

Eighty percent (8/10) of mothers applied the study cream on 80% or more of days during the six week intervention period. Though a number of adverse events unrelated to study product were reported, there were no adverse skin reactions to the study cream.

Conclusions

These preliminary results support the safety and parental compliance with daily applications of a ceramide-dominant formula for the prevention of eczema, providing the necessary ground work for a randomised clinical trial to evaluate EpiCeram? for the prevention of eczema.

Trial registration

The study was listed at the Australian/New Zealand Clinical Trial Registry (ANZCTR): reg. no. ACTRN12609000727246.     

beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones

Several myelin-associated factors that inhibit axon growth of mature neurons, including Nogo66, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), can associate with a common GPI-linked protein Nogo-66 receptor (NgR). Accumulating evidence suggests that myelin inhibitors also signal through unknown NgR-independent mechanisms. Here we show that MAG, a RGD tri-peptide containing protein, forms a complex with β1-integrin to mediate axonal growth cone turning responses of several neuronal types. Mutations that alter the RGD motif in MAG or inhibition of β1-integrin function, but not removal of NgRs, abolish these MAG-dependent events. In contrast, OMgp-induced repulsion is not affected by inhibition of b1-integrin function. We further show that MAG stimulates tyrosine phosphorylation of focal adhesion kinase (FAK), which in turn is required for MAG-induced growth cone turning. These studies identify β1-integrin as a specific mediator for MAG in growth cone turning responses, acting through FAK activation.     

The polymerase chain reaction in the diagnosis of vertically transmitted HIV infection

The presence of HIV-1 DNA sequences in DNA from peripheral blood mononuclear cells (PBMCs) was investigated in a two-stage polymerase chain reaction ('double' PCR) using four sets of nested primers. The PBMCs tested were obtained from 46 children born to HIV-seropositive mothers, seven 'control' children born to HIV-seronegative mothers and seropositive fathers, and 45 healthy adult blood donors who were HIV seronegative. Nine of the children had symptomatic HIV infection and other laboratory features characteristic of HIV infection: all nine were PCR-positive with each set of primers in each of their 22 blood samples tested. The remaining 44 children had no clinical or laboratory evidence of HIV infection, and each of their 50 samples was PCR-negative with each set of primers, as were all blood donor samples. PCR-positive samples were tested in more detail using two of the sets of primers, which spanned hypervariable regions in the env gene. Polyacrylamide gel electrophoresis of DNA amplified from these regions yielded patterns of amplified DNA length variation which were characteristic for each child, and which changed little with time (in serial samples obtained over periods of 3-7 months). This excluded contamination as a cause of PCR positivity. This is the first report of the use of a double PCR for the diagnosis of HIV infection. The results demonstrate the specificity of this PCR method in diagnosis, with failure to reveal in this cohort any cases of vertically transmitted HIV-1 infection in addition to those already confirmed by conventional laboratory techniques.     

Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV infection and after randomization to standard vs. intensified antiretroviral regimens

Introduction

HIV transmission risk is highest during acute HIV infection (AHI). We evaluated HIV RNA in the anogenital compartment in men who have sex with men (MSM) during AHI and compared time to undetectable HIV RNA after three-drug versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV transmission.

Methods

MSM with AHI (n=54) had blood, seminal plasma and anal lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and 24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody combo immunoassay [IA]–, third-generation IA–, n=15), 2 (fourth-generation IA+, third-generation IA–, n=9) and 3 (fourth-generation IA+, third-generation IA+, western blot–/indeterminate, n=30) by randomization to five-drug (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug (tenofovir+emtricitabine+efavirenz, n=18) regimens.

Results

Mean age was 29 years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA was 5.5 in blood, 3.9 in seminal plasma and 2.6 log₁₀ copies/ml in anal lavage (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was 60 days in blood, 15 days in seminal plasma and three days in anal lavage. Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal plasma (13 vs. 24 days, p=0.048).

Conclusions

Among MSM with AHI, HIV RNA was highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced HIV RNA in all compartments, with regimen intensified by raltegravir and maraviroc showing faster HIV RNA reductions in blood and seminal plasma.