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Introduction: Cystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del is the most frequent mutation (70% of alleles in Italy), while other mutations have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% in Italy) emerges as a mutation characterized by a severe CFTR folding and trafficking defect. Methods: To investigate the pharmacological responsiveness of the G85E-CFTR variant, we performed a functional and biochemical characterization in heterologous expression systems and ex vivo models based on patient-derived human nasal epithelial cells (HNEC). Results: Our study demonstrated that treatment of primary airway cells with elexacaftor and tezacaftor causes a significant (although modest) rescue of CFTR function, that reaches 15%–25% of the activity measured in non-CF epithelia. A detrimental effect of chronic treatment with ivacaftor, further limiting G85E rescue, was also observed. A higher rescue of CFTR function, up to 25%–35% of the normal CFTR activity, with no evidence of negative effects upon chronic potentiator treatment, can be achieved by combining elexacaftor with ARN23765, a novel type 1 corrector endowed with very high potency. Importantly, dose-response relationships suggest that G85E might alter the binding of type 1 correctors, possibly affecting their affinity for the target. Discussion: In conclusion, our studies suggest that novel combinations of modulators, endowed with higher efficacy leading to increased rescue of G85E-CFTR, are needed to improve the clinical benefit in patients for this variant. [ABSTRACT FROM AUTHOR]

The aim of this article is to identify and illustrate the most used psychological techniques in the field of cystic fibrosis (CF) and to help clinicians choose the most appropriate strategy among various possibilities. The disease and its medical treatments can be difficult to tolerate and can cause anxiety about health status or feelings of hopelessness and stress. The prevalence of depression and anxiety is 2.3 times higher in adults with CF than in community samples. A strong correlation has been identified between elevated psychological distress and unfavorable health outcomes, including, among others, impaired lung function, reduced BMI, an increased incidence of pulmonary exacerbations, and an elevated risk of transplantation. The use of psychological interventions is useful in addressing these common distresses in CF patients. Aware of the necessity of identifying efficacious interventions for all levels of depression and anxiety in CF patients, this study presents an overview of the research on psychological interventions for patients with CF, in order to complement the treatments suggested by the international guidelines on mental health in CF cases. In fact, the aim of this study is to conduct a review and quantitative synthesis of the psychological intervention techniques that are currently available for individuals with CF. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Gallstones, microlithiasis, gallbladder sludge, and micro‐gallbladder are frequently reported in cystic fibrosis patients, and modulators could modify gallbladder disease, probably reducing biliary secretions viscosity. [ABSTRACT FROM AUTHOR]

A recent study published in Clinical Otolaryngology evaluated the association between triple combination therapy and the need for endoscopic sinus surgery (ESS) in adult patients with cystic fibrosis (CF) and chronic rhinosinusitis. The study included 128 patients, with 51 receiving triple combination therapy and the remaining patients serving as a control group. The results showed that the group receiving triple combination therapy had a statistically significant reduction in the number of ESS procedures performed compared to the control group. Additionally, the therapy was associated with improvements in sinus CT scores and sinonasal quality of life. However, the study has limitations, and further research is needed to confirm these findings. [Extracted from the article]