30 research outputs found

    Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

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    The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

    Primary Appendiceal Mucinous Adenocarcinoma

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    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory

    'Pragmatic randomized controlled trial of individually prescribed exercise versus usual care in a heterogeneous cancer survivor population': A feasibility study PEACH Trial: Prescribed exercise after chemotherapy

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    <p>Abstract</p> <p>Background</p> <p>Many cancer survivors suffer a range of physical and psychological symptoms which may persist for months or years after cessation of treatment. Despite the known benefits of exercise and its potential to address many of the adverse effects of treatment, the role of exercise as well as optimum duration, frequency, and intensity in this population has yet to be fully elucidated. Many cancer rehabilitation programmes presented in the literature are very long and have tight eligibility criteria which make them non-applicable to the majority of cancer survivors. This paper presents the protocol of a novel 8-week intervention which aims to increase fitness, and address other physical symptoms in a heterogeneous cancer survivor population.</p> <p>Methods/design</p> <p>The aim is to recruit 64 cancer survivors 2-6 months after completion of chemotherapy, usually adjuvant, with curative intent. Subjects will be recruited through oncology clinics in a single institution and randomised to usual care or an exercise intervention. The exercise intervention consists of two specifically tailored supervised moderate intensity aerobic exercise sessions weekly over 8-weeks. All participants will be assessed at baseline (0 weeks), at the end of the intervention (8 weeks), and at 3-month follow-up. The primary outcome measure is fitness, and secondary patient-related outcome measures include fatigue, quality of life, and morphological outcomes. A further secondary outcome is process evaluation including adherence to and compliance with the exercise program.</p> <p>Discussion</p> <p>This study will provide valuable information about the physical outcomes of this 8-week supervised aerobic programme. Additionally, process information and economic evaluation will inform the feasibility of implementing this program in a heterogeneous population post cessation of chemotherapy.</p> <p>Trial Registration</p> <p>NCT01030887</p
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