Palliative care needs among outpatient adults with cystic fibrosis: Baseline data from the Improving Life with CF trial.

BACKGROUND: Little is known about the burden of illness experienced by people with cystic fibrosis (pwCF) since the advent of CF transmembrane conductance regulator (CFTR) modulator therapies. Studies that characterize the nature of illness burden are needed to inform the development and implementation of palliative care programs that can serve this population and address quality of life concerns. METHODS: Adults with CF treated at five U.S. CF centers were surveyed to obtain baseline data for the Improving Life with CF primary palliative care implementation trial. Consenting patients completed the Integrated Palliative Care Outcome Scale (IPOS), a multidimensional measure of unmet needs for palliative care. Sociodemographic and clinical information was also obtained. The associations among these variables were examined through bivariate and multivariable analyses. RESULTS: Among 256 adults, the most distressing symptoms included not feeling "at peace", communication difficulties with family/friends, anxiety over illness or its treatment, and a lack of energy. In the multivariable analyses, CFTR modulator use was associated with lower IPOS total and physical symptoms scores; female sex and increased hospitalizations were associated with higher scores. Increased age and history of distal intestinal obstructive syndrome were associated with higher IPOS physical symptoms scores. CONCLUSIONS: These findings illuminate the nature of illness burden for pwCF in the era of CFTR modulator therapies. Although illness burden is positively affected by modulator therapy, there is a continuing need for palliative care to address physical, emotional, and spiritual distress, and the communication and practical needs experienced by adults with CF.

Intestinal SIRT1 Deficiency Protects Mice from Ethanol-Induced Liver Injury by Mitigating Ferroptosis.

Aberrant liver sirtuin 1 (SIRT1), a mammalian NAD+-dependent protein deacetylase, is implicated in the pathogenesis of alcoholic liver disease (ALD). However, the role of intestinal SIRT1 in ALD is presently unknown. This study investigated the involvement of intestine-specific SIRT1 in ethanol-induced liver dysfunction in mice. Ethanol feeding studies were performed on knockout mice with intestinal-specific SIRT1 deletion [SIRT1i knockout (KO)] and flox control [wild-type (WT)] mice with a chronic-plus-binge ethanol feeding protocol. After ethanol administration, hepatic inflammation and liver injury were substantially attenuated in the SIRT1iKO mice compared with the WT mice, suggesting that intestinal SIRT1 played a detrimental role in the ethanol-induced liver injury. Mechanistically, the hepatic protective effect of intestinal SIRT1 deficiency was attributable to ameliorated dysfunctional iron metabolism, increased hepatic glutathione contents, and attenuated lipid peroxidation, along with inhibition of a panel of genes implicated in the ferroptosis process in the livers of ethanol-fed mice. This study demonstrates that ablation of intestinal SIRT1 protected mice from the ethanol-induced inflammation and liver damage. The protective effects of intestinal SIRT1 deficiency are mediated, at least partially, by mitigating hepatic ferroptosis. Targeting intestinal SIRT1 or dampening hepatic ferroptosis signaling may have therapeutic potential for ALD in humans.