Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer:study protocol of the INDIBLADE trial

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).</p

Simple linear viscoelastic models of dilute solutions of polymer molecules and emulsions droplets.

The complex viscosity of microemulsions shows relaxation processes of which the largest relaxation time is about 10−5 s or less. This time can be attributed to relaxation of stresses in the surface of emulsion droplets pertaining to interfacial tension. Superimposed on a spherical droplet surface shape fluctuations can occur due to thermal energies. Our aim is to show the influence of thermal shape fluctuations on the complex viscosity of emulsions. The method used in the derivation has also been applied to inflexible rods to demonstrate its feasibility by showing the formal rheological equivalence of in length thermally fluctuating rods and Rouse's simple model of polymers. The emulsion results have been applied to a dilution series of a non-ionic microemulsion

Interobserver variability in the treatment of little finger metacarpal neck fractures

Item does not contain fulltextPURPOSE: To address the null hypothesis that surgeons shown radiographs of little finger metacarpal neck fractures with measured fracture angulation would recommend surgery as often as surgeons shown unmarked radiographs. METHODS: Members of the Science of Variation Group, an international collaboration of fully trained orthopedic and trauma surgeons, were asked to review 20 little finger metacarpal neck fracture cases, which included a vignette and 3 high-quality radiographs. Members were then randomized to review radiographs with or without measured fracture angulation on the lateral view and select operative or nonoperative management. RESULTS: Surgeons shown radiographs with measured angulation were more likely to recommend surgery, and there was less variability among these surgeons, particularly for fractures with less angular deformity. CONCLUSIONS: Measured fracture angulation has a small but significant influence on treatment recommendations for little finger metacarpal neck fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III

Numerical and physical modeling of diffraction, seismic diffraction (chapter 3)

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