Faculty Bibliography

BACKGROUND:Despite decreasing rates of HIV among many populations, HIV-related health disparities among gay, bisexual and other men who have sex with men persist, with disproportional percentages of new HIV diagnoses among racial and ethnic minority men. Despite increasing awareness of HIV pre-exposure prophylaxis (PrEP), PrEP use remains low. In addition to exploring individual-level factors for this slow uptake, structural drivers of PrEP use must also be identified in order to maximize the effectiveness of biomedical HIV prevention strategies. METHOD/METHODS:Using cross-sectional data from an ongoing cohort study of young sexual minority men (N=492), we examine the extent to which structural-level barriers, including access to health care, medication logistics, counseling support, and stigma are related to PrEP use. RESULTS:While almost all participants indicated awareness of PrEP, only 14% had ever used PrEP. PrEP use was associated with lower concerns about health care access, particularly paying for PrEP. Those with greater concerns talking with their provider about their sexual behaviors were less likely to use PrEP. CONCLUSION/CONCLUSIONS:Paying for PrEP and talking to one's provider about sexual behaviors are concerns for young sexual minority men. In particular, stigma from healthcare providers poses a significant barrier to PrEP use in this population. Providers need not only to increase their own awareness of and advocacy for PrEP as an effective risk-management strategy for HIV prevention, but also must work to create open and non-judgmental spaces in which patients can discuss sexual behaviors without the fear of stigma.

OBJECTIVE:In the United States, hepatocellular carcinoma (HCC) is more common among communities with low socioeconomic status (SES), and these groups tend to be diagnosed with later-stage cancers. Sorafenib is the primary treatment for advanced HCC, however its substantial cost raises concern for access to treatment. METHODS:The newly developed Case-Background method was used to estimate odds ratios for the impacts of various sociodemographic factors on sorafenib access in clinically eligible patients. Socioeconomic status was defined as a factor of median income and education level based on ZIP code of residence. RESULTS:There was a strong association between sorafenib prescription and residence in an area of higher SES. While controlling for age, race/ethnicity, and insurance status, high SES residence doubled the odds of sorafenib prescription (OR=2.05, p<.01). CONCLUSIONS:Low socioeconomic status communities appear to have a reduced chance of receiving the only effective treatment for advanced HCC.

BACKGROUND:Hyaluronic acid (HA), an extracellular matrix component, is degraded in response to local tissue injury or stress. In various animal models of lung injury, HA has been shown to play a mechanistic role in modulating inflammation and injury. While HA is present in the lungs of patients with acute respiratory distress syndrome (ARDS), its relationship to patient outcomes is unknown. METHODS:We studied 86 patients with ARDS previously enrolled in the Phase II Randomized Trial of Fish Oil in Patients with Acute Lung Injury (NCT00351533) at five North American medical centers. We examined paired serum and bronchoalveolar lavage fluid (BALF) samples obtained within 48 hours of diagnosis of ARDS. We evaluated the association of HA levels in serum and BALF with local (lung injury score (LIS)) and systemic (sequential organ failure assessment score (SOFA)) measures of organ dysfunction with regression analysis adjusting for age, sex, race, treatment group, and risk factor for ARDS. RESULTS:We found that both day-0 circulating and alveolar levels of HA were associated with worsening LIS (p = 0.04 and p = 0.003, respectively), particularly via associations with degree of hypoxemia (p = 0.02 and p < 0.001, respectively) and set positive end-expiratory pressure (p = 0.01 and p = 0.02, respectively). Circulating HA was associated with SOFA score (p < 0.001), driven by associations with the respiratory (p = 0.02), coagulation (p < 0.001), liver (p = 0.006), and renal (p = 0.01) components. Notably, the alveolar HA levels were associated with the respiratory component of the SOFA score (p = 0.003) but not the composite SOFA score (p = 0.27). CONCLUSIONS:Elevated alveolar levels of HA are associated with LIS while circulating levels are associated with both lung injury and SOFA scores. These findings suggest that HA has a potential role in both local and systemic organ dysfunction in patients with ARDS.

The plasmid-encoded colistin resistance gene (mcr-1) has recently been reported in various Gram-negative species. However, the expression profile of mcr-1 remains unknown. Here, we investigated the expression of mcr-1 in various plasmids and bacteria. The mcr-1 expression levels in pMCR1_IncX4 varied from 1.81 × 10^-5 to 1.05 × 10^-4 (pmol per μg total RNA) in the two K. pneumoniae strains SZ03 and SZ04 (ST25) and the two E. coli strains SZ01 and CDA6 (ST2448 and ST167, respectively). The mcr-1 expression levels of pMCR1_IncI2 in E. coli SZ02 (ST2085) and E. coli BJ13 (ST457) were 5.27 × 10^-5 and 2.58 × 10^-5, respectively. In addition, the expression of chromosomal mcr-1 in ST156 E. coli BJ10 was 5.49×10^-5. Interestingly, after 4μg/ml colistin treatment, mcr-1 in pMCR1_IncX4 increased 2- and 4-fold at 20 and 120 mins, respectively, in all pMCR1_IncX4-harboring strains, except for ST2448 E. coli, which had a lower expression after 20 mins that restored to baseline levels after 120 mins. In contrast, mcr-1 expression of pMCR1_IncI2 in the two E. coli strains (SZ02, BJ13) and the chromosomal mcr-1 in E. coli (BJ10) remained at baseline levels after 20 and 120 mins. In the same genetic background host strain E. coli E600, mcr-1 expression of pMCR1_IncX4 and pMCR1_IncI2 were similar and were decreased after colistin treatment for 20 min. However, mcr-1 in pMCR1_IncX4 was up-regulated after colistin treatment for 120 min, while mcr-1 in pMCR1_IncI2 was down-regulated compared to the untreated control. Our results suggested that mcr-1 has distinct expression profiles on different plasmids, bacterial hosts, and after antibiotic treatment.