Clinical thermography at extreme temperatures.

Every day, emergency departments and acute medical units all over the world receive and assess thousands of patients. Most are stable, but a few require immediate stabilization. To identify these, all patients are routinely triaged and have vital signs measured. Our group has shown that thermographic images of the face can be an alternative method for identifying patients at increased risk of 30-day mortality. In our previous studies, the thermographic images were taken after the patients had been inside for at least 30 minutes. However, to identify patients at risk, the images have to be available as quickly as triage, i.e. at the door when the patient arrives. Therefore, we have performed a small study, with the aim of illustrating the effect of such heat-gradients on thermal images of the face.

Identification of a novel mutation in the factor VIII gene causing severe haemophilia A.

BACKGROUND: Deficiency in coagulation factor VIII encoded by F8 results in the X-linked recessive bleeding disorder haemophilia A (HEMA). Here we describe the identification of a novel variant in the factor VIII gene, F8, in an adult male patient with severe haemophilia A. CASE PRESENTATION: The patient was diagnosed in early childhood and subsequently co-infected with Hepatitis C and HIV acquired during early blood transfusion for haemophilia in the 1980ies. The identified F8 deletion, c.5411_5413delTCT, p.F1804del lies within a conserved part of the molecule, is predicted by bioinformatic software to be deleterious by the loss of Phenylalanine, and has not been previously described in any database. CONCLUSION: This novel F8 deletion as a cause of haemophilia A did not result in generation of inhibitory antibodies to Factor VIII treatment and may have impact on (prenatal) diagnosis, genetic counselling, and treatment decisions in the affected family as well as in other families diagnosed with this F8 mutation. Finally, this novel mutation should be included in the panel of known genetic variants in F8 when searching for the genetic etiology in patients suspected of HEMA.

Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs.

OBJECTIVES: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir. METHODS: This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm3 on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 µg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m2). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIVGag and viral inhibition. RESULTS: The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIVGag by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08). CONCLUSIONS: In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.

Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates with chronic immune activation.

The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive individuals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4(+) central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.