Safety of Percutaneous Dilatational Tracheostomy in Critically Ill Patients with Liver Cirrhosis.

INTRODUCTION: Percutaneous dilatational tracheostomy (PDT) is a safe and cost-effective alternative to surgical tracheostomy. Cirrhotic patients often require ICU admission and prolonged mechanical ventilation. Patients with liver cirrhosis (LC) are known to have coagulopathy and relatively safe and simple procedures such as tracheostomy may be associated with high complication rates, specifically high bleeding rates. Current guidelines are unable to make a specific recommendation on the safety of PDT among cirrhotic patients. We aimed to evaluate the safety of PDT in critically ill patients with LC. METHODS: A retrospective chart review identified critically ill patients who underwent PDT between January 2012 and March 2023. The study group was defined as all patients with a diagnosis of LC. The primary outcome was early (7-day) bleeding, categorized as minor or major. Secondary outcomes were PDT-related and 30-day all-cause mortality. Propensity score matching was performed to adjust the imbalances between the groups. RESULTS: A total of 1,628 were included in the analysis. Thirty-three of them (2.0%) had LC. In the LC group, only 1 patient (3.0%, 95% CI: 0.0-15.8%) developed early bleeding. Intra-operative, early, late bleeding, and PDT-related mortality rates did not differ significantly between those with LC and those without. CONCLUSION: This retrospective cohort study indicates that PDT can be safely performed in critically ill cirrhotic patients, without significantly increasing the risk of bleeding complications.

The retinal toxicity profile towards assemblies of Amyloid-ß indicate the predominant pathophysiological activity of oligomeric species.

Amyloid-ß (Aß), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aß species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aß. Fibrillar (Aß40, Aß42) and oligomeric (Aß42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aß assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aß species. Oligomeric Aß42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aß42, whereas no retinal compromise was recorded in response to Aß40 fibrils. The toxic effect of Aß42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aß42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aß species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aß aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders.