The Lantern Vol. 14, No. 2, February 1946

• Dog Daze • Locomotion • The Battle • Thoughts at Midnight • We Have a Race to Run • A Parable • Darkness at Dawn • Room for Error • Elegy Americana • Will This Happen Here • Last Mission • Free Trade • Love Letterhttps://digitalcommons.ursinus.edu/lantern/1038/thumbnail.jp

Supplementary material: Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma

These are peer-reviewed supplementary materials for the article 'Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma' published in the Journal of Comparative Effectiveness Research.1. Feasibility assessment1.1 Heterogeneity assessment1.1.1 Items assessed for heterogeneity between trials1.1.2 Overview of relevant baseline characteristics across trials1.2 Assessment of the proportional hazards (PH) assumption1.2.1 Criteria applied1.2.2 Results1.3 Network of evidence2. Non-proportional hazards NMA outcomes2.1 Model fitting2.2 Model selection algorithm: face validity check of first- and second-order models2.2.1 Time-varying HR plots versus trial hazards second order polynomial for OS2.3 Model selection algorithm: Predictive accuracy against trial data2.3.1 PFS2.3.2 OSAim: Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for nonproportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models. Methods: The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study. Overall survival (OS) and progression free survival (PFS) data were reconstructed from the literature, 46 models were fitted. The algorithm entailed a-priori face validity criteria for survival and hazards, based on clinical expert input, and predictive accuracy against trial data. Selected models were compared with statistically best-fitting models. Results: Three valid PFS and two OS models were identified. All models overestimated PFS, the OS model featured crossing ICI + TKI versus TKI curves as per expert opinion. Conventionally selected models showed implausible survival. Conclusion: The selection algorithm considering face validity, predictive accuracy, and expert opinion improved the clinical plausibility of first-line RCC survival models.</p

Applicators for Magnetic Resonance–Guided Ultrasonic Ablation of Benign Prostatic Hyperplasia

ObjectivesThe aims of this study were to evaluate in a canine model applicators designed for ablation of human benign prostatic hyperplasia (BPH) in vivo under magnetic resonance imaging (MRI) guidance, including magnetic resonance thermal imaging (MRTI), determine the ability of MRI techniques to visualize ablative changes in prostate, and evaluate the acute and longer term histologic appearances of prostate tissue ablated during these studies.Materials and methodsAn MRI-compatible transurethral device incorporating a tubular transducer array with dual 120° sectors was used to ablate canine prostate tissue in vivo, in zones similar to regions of human BPH (enlarged transition zones). Magnetic resonance thermal imaging was used for monitoring of ablation in a 3-T environment, and postablation MRIs were performed to determine the visibility of ablated regions. Three canine prostates were ablated in acute studies, and 2 animals were rescanned before killing at 31 days postablation. Acute and chronic appearances of ablated prostate tissue were evaluated histologically and were correlated with the MRTI and postablation MRI scans.ResultsIt was possible to ablate regions similar in size to enlarged transition zone in human BPH in 6 to 18 minutes. Regions of acute ablation showed a central "heat-fixed" region surrounded by a region of more obvious necrosis with complete disruption of tissue architecture. After 31 days, ablated regions demonstrated complete apparent resorption of ablated tissue with formation of cystic regions containing fluid. The inherent cooling of the urethra using the technique resulted in complete urethral preservation in all cases.ConclusionsProstatic ablation of zones of size and shape corresponding to human BPH is possible using appropriate transurethral applicators using MRTI, and ablated tissue may be depicted clearly in contrast-enhanced magnetic resonance images. The ability accurately to monitor prostate tissue heating, the apparent resorption of ablated regions over 1 month, and the inherent urethral preservation suggest that the magnetic resonance-guided techniques described are highly promising for the in vivo ablation of symptomatic human BPH