PurposeThe present study aims to assess whether CT-derived muscle mass, muscle density, and visceral fat mass are associated with in-hospital complications and clinical outcome in level-1 trauma... Show morePurposeThe present study aims to assess whether CT-derived muscle mass, muscle density, and visceral fat mass are associated with in-hospital complications and clinical outcome in level-1 trauma patients.MethodsA retrospective cohort study was conducted on adult patients admitted to the University Medical Center Utrecht following a trauma between January 1 and December 31, 2017. Trauma patients aged 16 years or older without severe neurological injuries, who underwent a CT that included the abdomen within 7 days of admission, were included. An artificial intelligence (AI) algorithm was used to retrieve muscle areas to calculate the psoas muscle index and to retrieve psoas muscle radiation attenuation and visceral fat (VF) area from axial CT images. Multivariable logistic and linear regression analyses were performed to assess associations between body composition parameters and outcomes.ResultsA total of 404 patients were included for analysis. The median age was 49 years (interquartile range [IQR] 30-64), and 66.6% were male. Severe comorbidities (ASA 3-4) were seen in 10.9%, and the median ISS was 9 (IQR 5-14). Psoas muscle index was not independently associated with complications, but it was associated with ICU admission (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.65-0.95), and an unfavorable Glasgow Outcome Scale (GOS) score at discharge (OR 0.62, 95% CI 0.45-0.85). Psoas muscle radiation attenuation was independently associated with the development of any complication (OR 0.60, 95% CI 0.42-0.85), pneumonia (OR 0.63, 95% CI 0.41-0.96), and delirium (OR 0.49, 95% CI 0.28-0.87). VF was associated with developing a delirium (OR 1.95, 95% CI 1.12-3.41).ConclusionIn level-1 trauma patients without severe neurological injuries, automatically derived body composition parameters are able to independently predict an increased risk of specific complications and other poor outcomes. Show less
Boosman, R.J.; Jebbink, M.; Veldhuis, W.B.; Groenland, S.L.; Veggel, B.A.M.H. van; Moeskops, P.; ... ; Steeghs, N. 2022
Background: Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung cancer (NSCLC).... Show moreBackground: Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung cancer (NSCLC). Clinical trials with osimertinib could not demonstrate an exposure-efficacy relationship, while a relationship between exposure and toxicity has been found. In this study, we report the exposure-response relationships of osimertinib in a real-life setting. Methods: A retrospective observational cohort study was performed, including patients receiving 40 - 80 mg osimertinib as >= 2 line therapy and from whom pharmacokinetic samples were collected during routine care. Trough plasma concentrations (C-min,C-pred) were estimated and used as a measure of osimertinib exposure. A previously defined exploratory pharmacokinetic threshold of 166 mu g/L was taken to explore the exposure-efficacy relationship. Results: A total of 145 patients and 513 osimertinib plasma concentration samples were included. Median progression free survival (PFS) was 13.3 (95% confidence interval (CI):10.3 - 19.1) months and 9.3 (95% CI: 7.2 - 11.1) months for patients with C-min,C-pred < 166 mu g/L and C-min,C-pred >= 166 mu g/L, respectively (p = 0.03). In the multivariate analysis, a C-min,C-pred < 166 mu g/L resulted in a non-statistically significant hazard ratio of 1.10 (95% CI: 0.60 - 2.01; p = 77). Presence of a EGFR driver-mutation other than the exon 19 del or L858R mutations, led to a shorter PFS with a hazard ratio of 2.89 (95% CI: 1.18 - 7.08; p = 0.02). No relationship between exposure and toxicity was observed (p = 0.91). Conclusion: In our real-life cohort, no exposure-response relationship was observed for osimertinib in the current dosing scheme. The feasibility of a standard lower fixed dosing of osimertinib in clinical practice should be studied prospectively. Show less
