PRAME Expression in Mucosal Melanoma of the Head and Neck Region

PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy.</p> <p>Methods</p> <p>We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately.</p> <p>Results</p> <p>A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined.</p> <p>Conclusions</p> <p>Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.</p

Demographic and socio-economic predictors of physical activity among people living with HIV of low socio-economic status

Background: Physical activity (PA) is beneficial for the health of people living with HIV and AIDS (PLWHA). Aim: The aim of this study was to determine if age, body weight, height, gender, waist-to-hip ratio (WHR), educational attainment, employment status, CD4+ cell count and body mass index (BMI) can predict overall PA among PLWHA of low socio-economic status (SES). Setting: Participants in this study were HIV-infected patients on first-line antiretroviral therapy (ART) regimen offered by the South African National Department of Health, and those not on ART. Participants were conveniently sampled from a list at a community health care centre in Cape Town. Methods: This study sample consisted of 978 HIV-infected South Africans. Physical activity data were collected using the Global Physical Activity Questionnaire. Backward multiple linear regression modelling was used to determine the relative influence of variables (age, body weight, height, gender, WHR, educational attainment, employment status, CD4+ count and BMI) on total moderate-to-vigorous PA. Alpha level was set at 0.05. Results: The mean age of the participants was 38.2 (standard deviation [SD] = 8.76) years for men and 33.9 (SD = 8.53) years for women. Physical activity was significantly higher in men (480.2 [SD = 582.9] min/week) than among women (369.35 [SD = 222.53] min/week). The results of the multiple linear regression showed that educational attainment (β = 0.127; p = 0.00), employment (β = −0.087; p = 0.01) and gender (β = 0.235; p = 0.00) significantly predicted total moderate-to-vigorous PA. Gender had the greatest effect, followed by educational attainment and employment status. Conclusion: There is a need for PA programmes that are designed to (1) target women, (2) strengthen programmes for education and promotion of PA and (3) engage the unemployed into PA for PLWHA. Physical activity interventions for this particular group should be tailored for persons of low SES

HIV/HCV Co-infection: Pathogenesis, Clinical Complications, Treatment, and New Therapeutic Technologies

World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies

Homoanalogues des aldofuranosylnucleosides XI:3,6-anhydro-1-désoxy-1-(5-halogénouracil-1-yl)-D-mannitols

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Homoanalogues des adofuranosyl-nucléosides. IX 3,6-anhydro-1-désoxy-1-(pyrimidin-1-y1)-D-glucitols (bis-homonucléosides)

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