Treatment Algorithm for Metastatic Renal Cell Carcinoma – Recommendations Based on Evidence and Clinical Practice

Until a few years ago, the treatment options for metastatic renal cell cancer (mRCC) were very limited. The growing understanding of the molecular pathomechanisms underlying RCC allowed the development of new treatment approaches. Meanwhile, several approved target-oriented substances from different drug classes are available for mRCC. The mechanism of action of vascular endothelial growth factor (VEGF) and VEGF receptor or mTOR inhibition is well documented by phase III trials and reflected in the current guidelines. However, no predictive biomarkers have been identified in mRCC so far to demonstrate a benefit by a specific compound in an individual patient. Meanwhile, the sequential use of ‘targeted therapies' in mRCC has been established as standard treatment. The optimal sequence of available agents is still unclear. A German RCC expert panel discussed and developed an algorithm for the choices of first- and second-line treatment in mRCC based on established clinical criteria

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Development of Scenarios for Modelling of Districts' Energy Supply and Analysis of Interdependencies between Energy and ICT

The increasing digital transformation in energy supply systems allows greater control and possibilities for performance optimization and efficiency. This is accompanied by increasing complexity of the system, and thus requires the evaluation of interactions between energy and information and communication technologies (ICT) involved. One of the goals of the project “Zukunftslabor Energie” (Future Laboratory “Digitalization Energy”) is to analyze these interactions in highly integrated digitalized systems for district energy supply. For this, simulation studies must be conducted to configure flexibilities. A first step is to define appropriate analysis scenarios. Requirements for these scenarios, the related models, and one of the considered scenarios are described in this paper. This allows to discuss the system, its boundaries, its components, and their interactions. Future research requires an analysis and discussion of requirement specifications, data collection and treatment, model construction, model implementation, and model validation

Development of Scenarios for Modelling of Districts' Energy Supply and Analysis of Interdependencies between Energy and ICT

The increasing digital transformation in energy supply systems allows greater control and possibilities for performance optimization and efficiency. This is accompanied by increasing complexity of the system, and thus requires the evaluation of interactions between energy and information and communication technologies (ICT) involved. One of the goals of the project “Zukunftslabor Energie” (Future Laboratory “Digitalization Energy”) is to analyze these interactions in highly integrated digitalized systems for district energy supply. For this, simulation studies must be conducted to configure flexibilities. A first step is to define appropriate analysis scenarios. Requirements for these scenarios, the related models, and one of the considered scenarios are described in this paper. This allows to discuss the system, its boundaries, its components, and their interactions. Future research requires an analysis and discussion of requirement specifications, data collection and treatment, model construction, model implementation, and model validation

Robot-assisted Radical Cystectomy with Orthotopic Neobladder Reconstruction: Techniques and Functional Outcomes in Males

Background: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. Objective: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. Design, setting, and participants: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. Surgical procedure: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. Measurements: The outcomes measured were UC and EF at 12 mo. Results and limitations: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58-70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88-7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55-11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91-0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25-0.89; p < 0.02) were inversely associated with EF. Conclusions: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. Patient summary: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery