Antiretroviral therapy at the end of life: the experience of an academic HIV clinic.

INTRODUCTION: There are no guidelines regarding the discontinuation of antiretroviral therapy at the end of life. METHODS: We retrospectively reviewed our databases and identified patients with HIV/AIDS who died over the last 12 months in our HIV clinic. RESULTS: A total of 41 patients from our HIV clinic died in a period of 12 months. Seventy-three percent of the patients were on antiretroviral therapy during the last clinic visit. During the last 3 months of life, 32% (13 of 41) were off antiretroviral therapy, with 77% (10 of 13) of them having intermittent therapy due to noncompliance. The remaining 23% (3 of 13) decided to stop antiretroviral therapy after discussion among families, patients, and providers. CONCLUSION: Discussions among providers, patients, and families are encouraged to establish goals of care and role of antiretrovirals during the last months of life.

Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV-associated primary effusion lymphoma.

Sphingosine kinase (SPHK) is overexpressed by a variety of cancers, and its phosphorylation of sphingosine results in accumulation of sphingosine-1-phosphate (S1P) and activation of antiapoptotic signal transduction. Existing data indicate a role for S1P in viral pathogenesis, but roles for SPHK and S1P in virus-associated cancer progression have not been defined. Rare pathologic variants of diffuse large B-cell lymphoma arise preferentially in the setting of HIV infection, including primary effusion lymphoma (PEL), a highly mortal tumor etiologically linked to the Kaposi's sarcoma-associated herpesvirus (KSHV). We have found that ABC294640, a novel clinical-grade small molecule selectively targeting SPHK (SPHK2 >> SPHK1), induces dose-dependent caspase cleavage and apoptosis for KSHV(+) patient-derived PEL cells, in part through inhibition of constitutive signal transduction associated with PEL cell proliferation and survival. These results were validated with induction of PEL cell apoptosis using SPHK2-specific siRNA, as well as confirmation of drug-induced SPHK inhibition in PEL cells with dose-dependent accumulation of proapoptotic ceramides and reduction of intracellular S1P. Furthermore, we demonstrate that systemic administration of ABC294640 induces tumor regression in an established human PEL xenograft model. Complimentary ex vivo analyses revealed suppression of signal transduction and increased KSHV lytic gene expression within drug-treated tumors, with the latter validated in vitro through demonstration of dose-dependent viral lytic gene expression within PEL cells exposed to ABC294640. Collectively, these results implicate interrelated mechanisms and SPHK2 inhibition in the induction of PEL cell death by ABC294640 and rationalize evaluation of ABC294640 in clinical trials for the treatment of KSHV-associated lymphoma.

Falls in HIV-infected patients: a geriatric syndrome in a susceptible population.

BACKGROUND: Falls is a common geriatric syndrome that has not been well characterized in HIV-infected populations. METHODS: We retrospectively reviewed our database and identified patients who fell over the last 12 months. RESULTS: Thirty-two patients were identified (incidence rate of 16 × 1000 patients per year). Twenty-five percent were female and 75% male. Sixty-seven percent were African American with 33% Caucasians. Average age was 48.19, number of years with HIV infection on average was 9.38 years, mean CD4 count 347.2 cell/mm(3), mean HIV viral load was 31 379 copies/mL. The average number of medications was 8.7 with a mean of 3.48 comorbidities. The mean vitamin D level was 27.20. Sixty-two percent of patients were compliant with antiretroviral therapy. Univariate and multivariate analysis showed that number of medications (< .005 medications; P < .005), more than 3 comorbidities (P < .005), and noncompliance (P < .001) were related to falls in this population. CONCLUSION: Falls is a common geriatric syndrome. Associated risk factors in our cohort included number of medications, more than 3 comorbidities, and noncompliance. Larger studies are needed to properly characterize this geriatric syndrome in HIV-infected patients. As HIV-infected populations age, a shift into a more comprehensive geriatrics care including fall risk evaluation may be needed.

Non-AIDS-defining cancers in New Orleans.

BACKGROUND: Non-AIDS-defining cancers in HIV-infected patients in the highly active antiretroviral therapy era have increased. To our knowledge a comprehensive review of non-AIDS-related malignancies in New Orleans has not yet been conducted. METHODS: Databases from main institutions in New Orleans were queried retrospectively for the years 2001 to 2011. The International Classification of Diseases, Ninth Revision codes were used to search for HIV infection and cancer comorbidity. RESULTS: A total of 16 patients were diagnosed with lung cancer (mean age 50 years) with 81% of the patients presenting with advanced stages. In all, 20 (mean age 47 years) were diagnosed with anal cancer, and 35% presented in late stages. In all, 14 patients (mean age 42 years) were diagnosed with Hodgkin Lymphoma, and 64% were diagnosed at late stage. A total of 5 women (mean age 44 years) were diagnosed with breast cancer with 40% of them presenting at late stage. CONCLUSION: Malignancies were diagnosed at late stages in the majority of the cases, presented with worse outcomes, and had higher recurrence rates. The role of HIV and other viruses (Epstein Barr virus, human papillomavirus) and the potential mechanisms or pathways of oncogene activation also need to be clarified.

Differences in outcomes between elderly and nonelderly breast cancer patients in Louisiana.

INTRODUCTION: Elderly breast cancer patients are diagnosed with a higher stage of disease. They are also found to undergo less surgery, receive more frequently hormonal treatment and have decreased relative survival. The interest of this study was to examine the differences in treatment and survival between elderly versus young (>65 versus <65) patients in Louisiana. METHODS: The SEER database was searched, and all cases of female breast cancer in the state of Louisiana between 2000 and 2008 were analyzed. Data were stratified by age group and year of occurrence. The SEER definitions for breast cancer, surgery, chemotherapy, elderly populations, young populations, radiation therapy and breast conservative surgery were applied. RESULTS: The state prevalence of localized breast cancer is lower compared with the national rate (128.5 versus 144, P < 0.001). The rate of regional breast disease is much higher in Louisiana patients than national average rate (69.7 versus 57.9, P < 0.001). There is no difference in disseminated disease. The elderly group was offered less surgery compared with the young group (11.39% versus 6.68%, P < 0.005). The elderly group received more general radiation interventions than the young group (65.97% versus 53.86%, P < 0.005). Mortality rates for the elderly group were higher in Louisiana compared with the national average. This difference was more remarkable in the >85 age group (127.8 versus 118.5, P < 0.001). CONCLUSIONS: Differences between young and elderly breast cancer patients were observed. Mortality is higher among elderly breast cancer patients in Louisiana compared with the national average. Further studies are needed to review these differences.

Management of elderly and frail elderly cancer patients: the importance of comprehensive geriatrics assessment and the need for guidelines.

OBJECTIVES: Management of elderly and frail patients with cancer is complex and requires a multidisciplinary approach. This article reviews and discusses the current literature that evaluates the relevance of comprehensive geriatrics assessment (CGA) and other evaluation tools in the detection of this vulnerable patient population. METHODS: A literature search of articles in English, Spanish and Portuguese was conducted in PubMed through September 2011. RESULTS: There is lack of detailed information concerning the efficacy, tolerability and toxicity of cancer therapies in senior adults, although the literature indicates that there is a trend toward including elderly patients and their outcome. Recent guidelines advocate a careful patient selection through a CGA. For vulnerable (pre-frail) and frail elderly cancer patients, there is no consensus in relation to selection and type of treatments. CGA has been advocated as the gold standard for evaluation of elderly patients, but thorough evaluation of vulnerable and frail patients has not been undertaken. A tool to evaluate vulnerable elderly patients to predict treatment outcomes is also needed. DISCUSSION: The adoption of the CGA in oncology practice has been slow because of the difficulties with practicality and objectivity. A shorter reliable tool for rapid and complete assessment is needed. Inclusion of frail elderly patients in treatment trials is recommended. New treatment approaches for frail elderly cancer patients need to be further investigated. Some studies that used serum markers of frailty found that even in the absence of clinical signs, some elderly patients might be already vulnerable. A potential cancer frailty index also needs further investigation.

Frailty syndrome in geriatric medicine.

Frailty syndrome is frequently encountered in elderly populations. Frailty has been defined as a geriatric syndrome of increased vulnerability to environmental factors. Although knowledge of this syndrome continues to develop, there are still many areas of uncertainty. The pathophysiological pathways, role of biomarkers in the early identification of this syndrome and best management strategies are still under investigation. This study is a literature review of articles published on frailty syndrome in English, French and Spanish. Frailty and aging are similar processes with some differences. Multiple pathophysiological models of frailty have been studied. Factors associated with frailty include hormonal adjustments, sarcopenia and vitamin deficiencies among others. Biomarkers have been studied, but they are not specific. Phenotypes have been developed, but early recognition and prevention of this syndrome are still difficult. In conclusion, early recognition of this syndrome is of paramount importance. Preventative strategies need to be studied. The role of specific biomarkers in early detection of frailty needs to be defined. Clinical trials are needed to find better interventions for this syndrome.