Improved outcomes following gastrointestinal surgery among people living with HIV in the HAART-era: A scoping review.

BACKGROUND: This study aimed to review the varied 1-4 gastrointestinal (GI) system surgical outcomes among people living with Human Immunodeficiency Virus (PLWH) in the HAART-era. METHODS: MEDLINE and EMBASE were searched for primary publications on GI surgery outcomes exclusively in HAART-treated HIV patients. NSQIP-reported complications (NRCs), all-cause complications (ACC) and HIV disease parameters were extracted. RESULTS: 12 studies met study inclusion criteria, examining bowel (4), bariatric (5), cholecystectomy (1), appendectomy (1), and other general abdominal operations (1). The NRC rate was 0%, ≥44.4% and 13.3% in bariatric, bowel and appendix surgeries, respectively. Over half of NRCs were infectious. HAART-treated patients had lower ACC, LOS, and sepsis versus untreated-HIV, and higher ACC, LOS and reoperation rates versus HIV-negative patients. CONCLUSION: HAART use is associated with markedly improved NRC outcomes post GI surgery among PLWH; however, these remained inferior to those documented among HIV uninfected individuals.

Assessing attitudes to ED-based HIV testing: Development of a short-structured survey instrument.

INTRODUCTION: Emergency Department (ED)-based HIV counseling and testing (HCT) has had a significant impact on improving rates of HIV diagnosis and linkage to care. Unfortunately, expansion of this strategy to low- and middle-income countries has been limited. Successful implementation of ED-based HCT is dependent on patient and provider acceptance of the intervention, and their attitudes and pre-existing biases towards the disease. This study sought to develop validated survey instruments to assess attitudes towards ED-based HCT. METHODS: This cross-sectional study surveyed patients and providers in three EDs in the Eastern Cape province, South Africa. A convenience sample of patients and providers in the ED were surveyed. Exploratory factor analysis was conducted using questions on attitudes to HIV testing to develop validated survey instruments. An ANOVA test assessed variance in attitudes towards HCT based on demographic variables collected. RESULTS: A total of 104 patient and 132 provider surveys were completed. Exploratory factor analysis resulted in a 17- and 7-question attitudes survey for patients and providers, respectively. Overall, 92.3% of patients and 70.7% of providers supported ED-based HCT, however, both groups displayed only mildly positive attitudes. Questions representing 'confidentiality' and 'stigma around HIV testing' had the least positive influence on patients' overall attitudes. Questions representing 'comfort with HIV testing' had the least positive influence on providers' overall attitudes. CONCLUSION: Our study demonstrated ED patients and providers are generally supportive of ED-based HCT. A validated survey instrument was able to provide a standardized approach to identify barriers to HCT implementation in an ED setting, across contexts. For successful implementation, behavioral interventions must focus on strengthening patient beliefs around confidentiality and the consent process, and providers' comfort levels with providing HIV testing services in the ED.

Cleavage and Sub-Cellular Redistribution of Nuclear Pore Protein 98 by Coxsackievirus B3 Protease 2A Impairs Cardioprotection.

Myocarditis, inflammation of the heart muscle, affects all demographics and is a major cause of sudden and unexpected death in young people. It is most commonly caused by viral infections of the heart, with coxsackievirus B3 (CVB3) being among the most prevalent pathogens. To understand the molecular pathogenesis of CVB3 infection and provide strategies for developing treatments, we examined the role of a key nuclear pore protein 98 (NUP98) in the setting of viral myocarditis. NUP98 was cleaved as early as 2 h post-CVB3 infection. This cleavage was further verified through both the ectopic expression of viral proteases and in vitro using purified recombinant CVB3 proteases (2A and 3C), which demonstrated that CVB3 2A but not 3C is responsible for this cleavage. By immunostaining and confocal imaging, we observed that cleavage resulted in the redistribution of NUP98 to punctate structures in the cytoplasm. Targeted siRNA knockdown of NUP98 during infection further increased viral protein expression and viral titer, and reduced cell viability, suggesting a potential antiviral role of NUP98. Moreover, we discovered that expression levels of neuregulin-1 (NRG1), a cardioprotective gene, and presenilin-1 (PSEN1), a cellular protease processing the tyrosine kinase receptor ERBB4 of NRG1, were reliant upon NUP98 and were downregulated during CVB3 infection. In addition, expression of these NUP98 target genes in myocardium tissue not only occurred at an earlier phase of infection, but also appeared in areas away from the initial inflammatory regions. Collectively, CVB3-induced cleavage of NUP98 and subsequent impairment of the cardioprotective NRG1-ERBB4/PSEN1 signaling cascade may contribute to increased myocardial damage in the context of CVB3-induced myocarditis. To our knowledge, this is the first study to demonstrate the link between NUP98 and the NRG1 signaling pathway in viral myocarditis.