Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

This randomised phase III trial compared standard of care Everolimus with the anti-PD1 monoclonal antibody Nivolumab in previously treated patients with locally advanced inoperable or metastatic clear cell renal cancer. 810 patients were randomised to receive either Everolimus 10 mg orally daily or 3 mg/kg of Nivolumab intravenously every two weeks. Patients were treated until unacceptable toxicity or disease progression. Patients could be treated beyond progression if the investigator believed that the patient was gaining clinical benefit. The primary endpoint was overall survival. The median survival was 25 months for Nivolumab and 19.8 months for Everolimus (p=0.002). The objective response rate was higher for Nivolumab (25 versus 5%; p=<0.001).The median progression free survivals were 4.6 & 4.4 months (p=0.11). Grade 3 & 4 treatment related toxicities were observed in 19 & 37% of patients on Nivolumab or Everolimus respectively. In patients with previously treated renal cell carcinoma Nivolumab produced superior survival and more tolerable treatment than Everolimus

Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients

Cessation-related information, motivation, and behavioral skills in smokers living with HIV

There is a need for new, targeted smoking cessation interventions for smokers living with HIV. The Information-Motivation-Behavioral Skills (IMB) model has been applied effectively to HIV-related health behaviors and was used in this qualitative study to elicit factors that could lead to the development of innovative and successful cessation interventions for this population. Twenty individuals who smoked from two clinics providing care to people living with HIV participated in open-ended interviews, responding to questions covering the domains of the IMB model, as applied to smokers living with HIV. Participants were enrolled from a larger survey cohort to recruit into groups based on the impact of HIV diagnosis on smoking as well as attempting to enroll a mix of demographics characteristics. Interviews were recorded, transcribed, coded and thematically analyzed using a grounded theory qualitative approach. Interviews continued until thematic saturation was reached. Major themes included: Presence of knowledge deficits regarding HIV-specific health risks of smoking; use of smoking for emotional regulation, where many reported close contacts who smoke and concern with the effect of cessation on their social networks; Use of smoking cessation aids or a telephone-based wellness intervention were acceptable to most. Providing HIV-specific information in cessation advice is of the utmost importance for clinicians caring for smokers living with HIV, as this theme was noted consistently as a potential motivator to quit. Innovative and effective interventions must account for the social aspect of smoking and address other methods of emotional regulation in this population

Feasibility and patient satisfaction with smoking cessation interventions for prevention of healthcare-associated infections in inpatients

BackgroundSmoking increases hospitalization and healthcare-associated infection. Our primary aim of this pilot, randomized-controlled trial was to examine the feasibility and acceptability of a tobacco cessation intervention compared with usual care in inpatients. S. aureus carriage, healthcare-associated infections and infections post discharge were exploratory outcomes.MethodsCurrent inpatient smokers from a university hospital facility were randomized to usual care or a face to face tobacco cessation counseling session where patients' tobacco use and strategies for quitting were discussed. Patient engagement, satisfaction and withdrawal symptoms were measured at 1 week and 12 weeks post discharge. Nasal swabs were collected at enrollment and discharge and assessed for S. aureus colonization. P-values were calculated using Fisher's exact and t-tests were used to compare groups.ResultsFor the study's primary outcome, participants reported the intervention as being generally acceptable and reported high overall levels of satisfaction, with a Likert scale score of at least 4/5 for all measures of satisfaction. No subjects utilized free tobacco cessation services after discharge. 83 % of the intervention group and 93 % of the control group smoked at least one cigarette after discharge. Secondary outcomes with regard to infections showed that, at discharge, 12 % of the intervention group (n = 17) and 18 % of the control group (n = 22) tested positive for S. aureus. After 3 months, 9 % of the intervention group developed infection, 41 % visited an emergency room, and 24 % were readmitted within 3 months post-discharge, compared to 27, 32 and 36 % of the control group respectively.ConclusionsWith regards to the primary aim of this study, there were overall high levels of satisfaction with the intervention, indicating good feasibility and acceptance among patients. However, more intensive interventions in hospitalized patients and impact on healthcare-associated infections and post-discharge infections should be explored

''Oops! I forgot HIV'': Resident physician self-audits and universal HIV screening

Summary Background: Innovations are needed to increase universal HIV screening by primary care providers. One potential intervention is self-audit feedback, which describes the process of a clinician reviewing their own patient charts and reflecting on their performance. Methods: The effectiveness of self-audit feedback was investigated using a mixed methods approach. A total of 2111 patient charts were analyzed in a quantitative pre-post intervention study design, where the intervention was providing self-audit feedback to all internal medicine residents at one institution through an annual chart review. Qualitative data generated from the subsequent resident focus group discussions explored the motivation and mechanism for change using a knowledge-attitude-behavior framework

Young Incarcerated Men’s Perceptions of and Experiences With HIV Testing

We analyzed incarcerated men’s perceptions of and experiences with HIV testing. Interviews were conducted with 105 men, aged 18 to 29 years, in 4 states. Most men had received an HIV test while incarcerated because it was convenient or free or because they thought it was mandatory. At most sites, men believed they were HIV-negative because they never received test results. Some men did not know the diseases for which they had been tested. Some men avoided HIV testing outside prison because they lacked time, lacked resources, feared knowing the results, or perceived themselves to not be at risk

Infiltrating T cells increase IDO1 expression in glioblastoma and contribute to decreased patient survival

PURPOSE: Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression in human cancer, including the most common primary malignant brain tumor in adults, glioblastoma (GBM), is poorly understood. The major objective of this study is to address this gap in our understanding of how IDO1 expression contributes to the biology of GBM, and whether its level of expression is a determinant of GBM patient outcome. Experimental Design: Patient-resected GBM, the cancer genome atlas, human T cell:GBM co-cultures, as well as nu/nu, NOD-scid and humanized (NSG-SGM3-BLT) mice engrafted human GBM, form the basis of our investigation. Results: In situ hybridization for IDO1 revealed transcript expression throughout patient-resected GBM, whereas immunohistochemical IDO1 positivity was highly variable. Multivariate statistical analysis revealed that higher levels of IDO1 transcript predict a poor patient prognosis (P=0.0076). GBM IDO1 mRNA levels positively correlated with increased gene expression for markers of cytolytic and regulatory T cells, in addition to decreased patient survival. Humanized mice intracranially-engrafted human GBM revealed an IFNg-associated T cell-mediated increase of intratumoral IDO1 . Conclusions: Our data demonstrate that high intratumoral IDO1 mRNA levels correlate with a poor GBM patient prognosis. It also confirms the positive correlation between increased GBM IDO1 levels and human-infiltrating T cells. Collectively, this study suggests that future efforts aimed at increasing T cell-mediated effects against GBM, should consider combinatorial approaches that co-inhibit potential T cell-mediated IDO1 enhancement during therapy