Lipodystrophy in HIV patients: its challenges and management approaches

HIV-associated lipodystrophy is a term used to describe a constellation of body composition (lipoatrophy and lipohypertrophy) and metabolic (dyslipidemia and insulin resistance) alterations that accompany highly active antiretroviral therapy. These changes, which resemble metabolic syndrome, have been associated with a variety of adverse outcomes including accelerated cardiovascular disease. The body composition and metabolic changes appear to cluster in HIV infection, although they are distinct alterations and do not necessarily coexist. Epidemiological studies have demonstrated multiple pathogenic influences associated with host, disease, and treatment-related factors. The adverse treatment effects were more prominent in early regimens; continued drug development has led to the application of metabolically safer regimens with equal or greater potency than the regimens being replaced. Disease-related factors include HIV infection as well as inflammation, immune activation, and immune depletion. The body composition changes promote anxiety and depression in patients and may affect treatment adherence. Treatment of dyslipidemia and alterations in glucose metabolism is the same as in non-HIV-infected individuals. Lipoatrophy is managed by strategic choice of antivirals or by antiviral switching, and in some cases by plastic/reconstructive surgery. Lipohypertrophy has been managed mainly by lifestyle modification, ie, a hypocaloric diet and increased exercise. A growth hormone releasing factor, which reduces central fat, has recently become available for clinical use

Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C- reactive protein) in male patients (n=40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r=0.390, p lt 0.05), extent of reported weight loss (r=-0.492, p lt 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r=0.686, p lt 0.001), and logo C-reactive protein concentrations (r=-0.545, p lt 0.001). On multiple regression analysis, the percent predicted total body potassium and log(10) C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r(2) = 0.626, p lt 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer

The relationship between the insulin-like growth factor-1 axis, weight loss, an inflammation-based score and survival in patients with inoperable non-small cell lung cancer

<b>Background & aims:</b> The involvement of a systemic inflammatory response, as evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss and poor outcome in patients with non-small cell lung cancer. There is good evidence that nutritional and functional decline in patients with advanced malignant disease is associated with catabolic changes in metabolism. However, defects in anabolism may also contribute towards nutritional decline in patients with cancer. The aim of the present study was to examine the relationship between IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with inoperable NSCLC. <b>Methods:</b> 56 patients with inoperable NSCLC were studied. The plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and RIA. <b>Results:</b> The patients were predominantly male (61%), over 60 years old (80%), with advanced (stage III or IV) disease (98%), with a BMI≥20 (84%), an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the reference range. On follow-up 43 patients died of their cancer. On univariate analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05), white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3, IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS was not associated with either IGF-1(p>0.20), or leptin (p>0.20). <b>Conclusions:</b> In summary, the results of this study suggest that anabolism (IGF-1 axis) does not play a significant role in the relationship between nutritional and functional decline, systemic inflammation and poor survival in patients with inoperable NSCLC

Alcohol-Attributable Fraction in Liver Disease: Does GDP Per Capita Matter?

Background: The alcohol-attributable fraction (AAF) quantifies alcohol's disease burden. Alcoholic liver disease (ALD) is influenced by alcohol consumption per capita, duration, gender, ethnicity, and other comorbidities. In this study, we investigated the association between AAF/alcohol-related liver mortality and alcohol consumption per capita, while stratifying to per-capita gross domestic product (GDP). Methods: Data obtained from the World Health Organization and World Bank for both genders on AAF on liver disease, per-capita alcohol consumption (L/y), and per-capita GDP (USD/y) were used to conduct a cross-sectional study. Countries were classified as “high-income” and “very low income” if their respective per-capita GDP was greater than $30,000 or less than$1,000. Differences in total alcohol consumption per capita and AAF were calculated using a 2-sample 't' test. Scatterplots were generated to supplement the Pearson correlation coefficients, and F test was conducted to assess for differences in variance of ALD between high-income and very low income countries. Findings: Twenty-six and 27 countries met the criteria for high-income and very low income countries, respectively. Alcohol consumption per capita was higher in high-income countries. AAF and alcohol consumption per capita for both genders in high-income and very low income countries had a positive correlation. The F test yielded an F value of 1.44 with 'P' = .357. No statistically significant correlation was found among alcohol types and AAF. Significantly higher mortality from ALD was found in very low income countries relative to high-income countries. Discussion: Previous studies had noted a decreased AAF in low-income countries as compared to higher-income countries. However, the non-statistically significant difference between AAF variances of low-income and high-income countries was found by this study. A possible explanation is that both high-income and low-income populations will consume sufficient amount of alcohol, irrespective of its type, enough to weigh into equivalent AAF. Conclusions: No significant difference of AAF variance was found between high-income and very low income countries relating to sex-specific alcohol consumption per capita. Alcohol consumption per capita was greater in high-income countries. Type of preferred alcohol did not correlate with AAF. ALD related mortality was less in high-income countries as a result of better developed healthcare systems. ALD remains a significant burden globally, requiring prevention from socioeconomic, medical, and political realms

Association of Serum Albumin with Markers of Nutritional Status among HIV-Infected and Uninfected Rwandan Women

The objectives of this study are to address if and how albumin can be used as an indication of malnutrition in HIV infected and uninfected Africans.In 2005, 710 HIV-infected and 226 HIV-uninfected women enrolled in a cohort study. Clinical/demographic parameters, CD4 count, albumin, liver transaminases; anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were performed. Malnutrition outcomes were defined as body mass index (BMI), Fat-free mass index (FFMI) and Fat mass index (FMI). Separate linear predictive models including albumin were fit to these outcomes in HIV negative and HIV positive women by CD4 strata (CD4>350,200-350 and <200 cells/µl).In unadjusted models for each outcome in HIV-negative and HIV positive women with CD4>350 cells/µl, serum albumin was not significantly associated with BMI, FFMI or FMI. Albumin was significantly associated with all three outcomes (p<0.05) in HIV+ women with CD4 200-350 cells/µl, and highly significant in HIV+ women with CD4<200 cells/µl (P<0.001). In multivariable linear regression, albumin remained associated with FFMI in women with CD4 count<200 cells/µl (p<0.01) but not in HIV+ women with CD4>200.While serum albumin is widely used to indicate nutritional status it did not consistently predict malnutrition outcomes in HIV- women or HIV+ women with higher CD4. This result suggests that albumin may measure end stage disease as well as malnutrition and should not be used as a proxy for nutritional status without further study of its association with validated measures

Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV- Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

Background: Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Methodology/Principal Findings: Randomized, double-blind, placebo-controlled, multicenter trial using a 262 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2- hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (217.5% in rhGH/rosiglitazone and 222.7% in rhGH) but not in the rosiglitazone alone (22.5%) or control arms (21.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. Conclusions/Significance: The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT

Destination images, holistic images and personal normative beliefs: Predictors of intention to revisit a destination

This research examines the complex relationship between components of images of destinations and behavioral intentions, incorporating two pivotal constructs that have not been explored in the related literature, namely holistic image and personal normative beliefs (PNBs). Previous studies incorporating destination images as predictors of intention to revisit have mostly investigated their direct effect. This research integrates holistic image as a mediator and PNBs as a moderating variable. The findings verify the mediating role of holistic image for predicting tourists’ intentions to revisit a destination, supporting a model that incorporates a partial effect and two indirect mediations. Interestingly, only affective and conative images contribute to the prediction of tourists’ intentions to revisit a destination through the holistic image towards this destination. Moreover, PNBs moderate the effect that conative destination images have on tourists’ holistic images. Practically, the research sheds light to factors that affect tourists' tendency to select a tourism destination, which can serve as a basis for tailoring the effective positioning of destinations