Presentation 1: Psychological and health-related quality of life outcomes in ventilated and non-ventilated intensive care survivors: a multicentre, prospective observational cohort study

Presenter:  Sumeet Rai is an Intensive Care Specialist at Canberra Hospital and PhD candidate (School of Medicine and Psychology) researching the “Healthcare burden of intensive care survivors”

Abstract: Objective: To compare long-term psychological and Health Related QOL (HRQOL) outcomes in intubated and non-intubated intensive care survivors.

Design, setting and participants: Prospective, multicentre observational cohort study across four mixed general intensive care units (ICU) in Australia. Intubated and non-intubated survivors who received organ support in the ICU, were longitudinally followed over 12 months.

Main outcome measures: Primary: to compare the severity of psychological symptoms between intubated vs. non-intubated ICU survivors at 3- and 12-month follow-up using validated screening tools (Post-Traumatic Stress Disorder: PTSS-14; Depression, Anxiety, Stress: DASS 21). Secondary: to compare HRQOL (EQ-5D-5L) between these two groups.

Results: Overall, 133 patients were included. Over one-third of the survivors had at least one clinically significant psychological impairment during follow-up. At 3 and 12-month, respectively, clinically significant symptoms of PTSD were seen in 10% and 10%; depression in 21% and 20%; anxiety in 22% and 15%; stress in 14% and 9% of survivors respectively. The psychological outcomes for the intubated and non-intubated groups were similar. Survivors in the both groups described numerous problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression at 3 and 12-months. HRQOL outcomes were similar between intubated vs. non-intubated ICU survivors.

Conclusions: Intubated vs. non-intubated ICU survivors, at both 3 and 12 month follow-up, had similar prevalence of PTSD, depression, anxiety, stress symptoms with similar HRQOL scores. A subset of critically ill ICU survivors had ongoing psychological symptoms, and physical and mental impairments with their HRQOL on follow-up. The long-term psychological outcomes and impairment in HRQOL were similar between the intubated and non-intubated group of ICU survivors.

Presentation 2: Harnessing the Power of siRNAs to Combat Retinal Inflammation and Degeneration

Presenter: Adrian Cioanca completed his undergraduate degree in Advanced Vision Science at UNSW then pursued a Ph.D. from the Australian National University (ANU) with Riccardo Natoli in retinal degeneration. Following completion of his PhD, Adrian learned bioinformatics and computer programming and is currently a postdoctoral researcher at the Clear Vision Research lab with Riccardo Natoli. Adrian leads a research theme focused on transcription factor therapeutics for the treatment of retinal degeneration

Abstract: Retinal degeneration, a common culprit of vision loss, is often exacerbated by inflammation. Current treatments aimed at attenuating inflammation are not always effective, highlighting the need for alternative therapeutic targets to improve patient outcomes.

In this study, we employed RNA sequencing to uncover transcription factors involved in the inflammatory response, revealing that CCAAT enhancer binding proteins (CEBPs) play a central role in retinal degeneration-associated inflammation. Using siRNAs packaged in Invivofectamine and delivered intravitreally, we effectively inhibited CEBPs, leading to a substantial reduction in the inflammatory response, less loss of photoreceptor cells, and decreased levels of proinflammatory cytokines (Ccl2, Il6, Cxcl10) in the retina.

Moreover, employing single-cell RNA sequencing and RNAscope in situ hybridisation, we confirmed that CEBPs are predominantly expressed in glial cells and stressed photoreceptors. In vitro experiments also demonstrated that CEBPs translocate to the nucleus in response to proinflammatory stimuli.

In addition, our study demonstrated using animal models that inhibitors of CEBPs effectively prevented retinal degeneration. These findings provide compelling evidence for CEBPs as ideal therapeutic targets in treating retinal degeneration.