Aim
Colorectal anastomotic leakage (AL) is a serious complication. Studies on the impact of AL on health‐related quality of life (HRQoL) are scarce. We aimed to investigate the association between AL ...and HRQoL in colorectal cancer patients up to 2 years after diagnosis, and to evaluate whether AL is associated with a clinically relevant decrease in HRQoL over time.
Methods
Patients diagnosed with Stage I–III colorectal cancer undergoing elective surgical resection with primary anastomosis between 2010 and 2017 were included. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, represented by the summary score, and analysed at diagnosis and at 6 months and 2 years post‐diagnosis. Multivariable linear regression was performed to assess the association between AL and HRQoL, while multivariable logistic regression was used to investigate the association between AL and a clinically relevant HRQoL decrease (≥10 points) during follow‐up compared to the time of diagnosis.
Results
In total, 1197 patients were included of whom 63 (5%) developed AL. AL was not associated with HRQoL at 6 months post‐diagnosis nor at 2 years post‐diagnosis. However, having AL was associated with an increased risk of a clinically relevant decrease in HRQoL at 6 months post‐diagnosis (OR 3.65, 95% CI 1.62–8.21) but not at 2 years after diagnosis (OR 1.91, 95% CI 0.62–5.93).
Conclusion
Although AL was not associated with HRQoL at 6 months or 2 years post‐diagnosis, AL was a determinant of a clinically relevant decrease in HRQoL at 6 months after diagnosis. Future work should identify feasible and effective strategies to prevent declines in QoL in this patient population.
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that impair the function of CFTR, an epithelial chloride channel required for proper function of ...the lung, pancreas, and other organs. Most patients with CF carry the F508del CFTR mutation, which causes defective CFTR protein folding and processing in the endoplasmic reticulum, resulting in minimal amounts of CFTR at the cell surface. One strategy to treat these patients is to correct the processing of F508del-CFTR with small molecules. Here we describe the in vitro pharmacology of VX-809, a CFTR corrector that was advanced into clinical development for the treatment of CF. In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, VX-809 improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50, 81 ± 19 nM), a level associated with mild CF in patients with less disruptive CFTR mutations. F508del-CFTR corrected by VX-809 exhibited biochemical and functional characteristics similar to normal CFTR, including biochemical susceptibility to proteolysis, residence time in the plasma membrane, and single-channel open probability. VX-809 was more efficacious and selective for CFTR than previously reported CFTR correctors. VX-809 represents a class of CFTR corrector that specifically addresses the underlying processing defect in F508del-CFTR.
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