Chronic Alcohol Exposure Among People Living with HIV Is Associated with Innate Immune Activation and Alterations in Monocyte Phenotype and Plasma Cytokine Profile.

Despite advances in antiretroviral therapy, chronic immune activation continues to be observed among individuals with well-controlled HIV viral loads, and is associated with non-AIDS defining morbidities among people living with HIV. Alcohol use disorder impacts a significant proportion of individuals living with HIV, and alcohol exposure is known to damage the intestinal epithelium which may increase translocation of pathogens and their molecular products, driving systemic immune activation and dysregulation. The aim of this study was to determine if adults living with HIV with well-controlled viral loads, who also suffer from alcohol use disorder with and without hepatitis C virus co-infection (n=23), exhibit evidence of advanced systemic immune activation, intestinal damage, and microbial translocation, as compared to adults living with HIV who are not exposed to chronic alcohol or other substances of abuse (n=29). The impact of a 1-month intervention to treat alcohol-use disorder was also examined. Alcohol-use disorder was associated with evidence of advanced innate immune activation, alterations in monocyte phenotype including increased expression of Toll-like receptor 4, increased burden of stimulatory ligands for Toll-like receptor 4, and alterations in plasma cytokine signature, most notably elevations in soluble CD40 ligand and transforming growth factor beta. Alcohol-associated immune activation was more pronounced among individuals with hepatitis C virus co-infection. Although the 1-month intervention to treat alcohol use disorder did not result in significant reductions in the interrogated indicators of immune activation, our findings suggest that chronic alcohol exposure is a major modifiable risk factor for chronic immune activation and dysregulation among people-living with HIV.

Altered monocyte phenotype and dysregulated innate cytokine responses among people living with HIV and opioid-use disorder.

BACKGROUND: Opioid-use disorders (OUD) and hepatitis C or B co-infection (HEP) are common among people living with HIV (PLHIV). The impact of OUD on innate and adaptive immunity among PLHIV with and without HEP is unknown. OBJECTIVES: To investigate the impact of OUD on monocyte and T-cell phenotypes, cytokine responses to lipopolysaccharide (LPS) and phytohemagglutinin (PHA), and plasma inflammatory markers, among PLHIV with and without HEP. METHODS: Cross-sectional study enrolling PLHIV receiving ART, with and without OUD. Flow cytometry determined monocyte and T-cell phenotypes; LPS and PHA-induced cytokine production was assessed following LPS and PHA stimulation by multiplex cytokine array; plasma IL-6, soluble CD163, and soluble CD14 were measured by ELISA. RESULTS: Twenty-two PLHIV with OUD and 37 PLHIV without OUD were included. PLHIV with OUD exhibited higher frequencies of intermediate (CD14CD16) and nonclassical (CD14CD16) monocytes when compared with PLHIV without OUD (P = 0.0025; P = 0.0001, respectively), regardless of HEP co-infection. Soluble CD163 and monocyte cell surface CD163 expression was increased among PLHIV with OUD and HEP, specifically. Regardless of HEP co-infection, PLHIV with OUD exhibited reduced production of IL-10, IL-8, IL-6, IL-1alpha, and TNF-alpha in response to LPS when compared with PLHIV without OUD; PHA-induced production of IL-10, IL-1alpha, IL-1beta, IL-6, and TNF-alpha were also reduced among individuals with OUD. CONCLUSION: OUD among PLHIV are associated with altered monocyte phenotypes and a dysregulated innate cytokine response. Defining underlying mechanisms of opioid-associated innate immune dysregulation among PLHIV should be prioritized to identify optimal OUD treatment strategies.

Gd-EOB-DTPA based magnetic resonance imaging for predicting liver response to portal vein embolization.

AIM: To evaluate the correlation between degree of kinetic growth (kGR) of the liver following portal vein embolization (PVE) liver and the enhancement of the during the hepatobiliary phase of contrast administration and to evaluate if the enhancement can be used to predict response to PVE prior to the procedure. METHODS: Seventeen patients were consented for the prospective study. All patients had an MR of the abdomen with Gd-EOB-DTPA. Fourteen patients underwent PVE. The correlation between the kGR of the liver and the degree of enhancement was evaluated with linear regression (strong assumptions) and Spearman's correlation test (rank based, no assumptions). The correlation was examined for the whole liver, segments I, VIII, VII, VI, V, IV, right liver and left liver. RESULTS: There was no correlation between the degree of enhancement during the hepatobiliary phase and kGR for any segment, lobe of the liver or whole liver (P = 0.19 to 0.91 by Spearman's correlation test). CONCLUSION: The relative enhancement of the liver during the hepatobiliary phase with Gd-EOB-DTPA cannot be used to predict the liver response to PVE.

Technical challenges in 3 T magnetic resonance spectroscopic imaging of the prostate-A single-institution experience.

The magnetic resonance spectroscopic imaging (MRSI) is the only technique that is currently available in the clinical practice to provide the metabolic status of prostate tissue at the cellular level with a great potential to improve the clinical patient care. Increasing the field strength from 1.5 to 3 T can theoretically provide proportionately higher signal-to-noise ratio (SNR) and improve spectral separation between prostatic metabolite peaks. The technique, however, has been limited to a few academic institutions that are equipped with a team of experts primarily due to due to serious technical challenges in optimizing the spectral quality. High quality shimming is key to the successful MRSI acquisition. Without optimization of the increased field inhomogeneity and radiofrequency (RF) dielectric effect at 3 T, the spectral peak broadening and residual signal from the periprostatic fat tissue may render the overall spectra non-diagnostic. The purpose of this technical note is to present the practical steps of successful acquisition of 3 T MRSI and to address several important technical challenges in minimizing the effect of the increased magnetic field and RF field inhomogeneity in order to obtain highest possible spectral quality based on our initial experience in using 3 T MRSI prototype software.