Real-World Results of Cabozantinib Given as Alternative Schedule in Metastatic Renal Cell Carcinoma.

BACKGROUND: The multikinase-inhibitor Cabozantinib is a widely used treatment strategy in metastatic renal cell carcinoma (mRCC), either in combination with the programmed cell death protein-1 (PD-1) inhibitor nivolumab or as monotherapy. Cabozantinib is given continuously at a dose of 60 mg once daily when used as a single agent and at 40 mg when combined with nivolumab. Treatment-related adverse events (TRAE's) were shown to occur frequently. OBJECTIVE: We aimed to assess the safety and efficacy of cabozantinib in patients with mRCC. Patients were treated in various lines. Furthermore, we analyzed the impact of an alternative treatment schedule in patients not able to maintain continuous dosing. PATIENTS: This is a single center retrospective study from the Medical University of Vienna. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall response rates (ORR), progression free survival (PFS) and overall survival (OS) were evaluated for the entire cohort, by treatment line and by treatment schedule. RESULTS: Between January 2014 until April 2021, 71 patients received cabozantinib. Sixty-seven patients were eligible for full evaluation. By IMDC criteria, 32.4%, 59.2%, and 8.5% were classified as favorable, intermediate and poor risk respectively. Cabozantinib was offered as a 2nd-line or 3rd-line treatment in 38.0% and 32.4% of patients, respectively. An alternative treatment schedule was offered in 39.1% of patients. Objective responses were found in 43.3% (CR 6%) of patients and the median PFS was 10.8 months (95% CI: 5.5-16.2). When compared to continuous dosing, an alternative treatment schedule was associated with longer PFS (12.2 months (95% CI: 0-25.5) vs. 6.1 months (95% CI: 0.37-11.8) (P = .014, HR 0.46 (95% CI: 0.24-0.86), respectively) and a lower frequency and severity of TRAE's. CONCLUSIONS: Safety and efficacy of cabozantinib in real world is comparable to what has been observed in the pivotal trials, irrespective of the treatment line. An alternative schedule may further improve efficacy and safety.

Quantum-enhanced sensing on optical transitions through finite-range interactions.

The control over quantum states in atomic systems has led to the most precise optical atomic clocks so far1-3. Their sensitivity is bounded at present by the standard quantum limit, a fundamental floor set by quantum mechanics for uncorrelated particles, which can-nevertheless-be overcome when operated with entangled particles. Yet demonstrating a quantum advantage in real-world sensors is extremely challenging. Here we illustrate a pathway for harnessing large-scale entanglement in an optical transition using 1D chains of up to 51 ions with interactions that decay as a power-law function of the ion separation. We show that our sensor can emulate many features of the one-axis-twisting (OAT) model, an iconic, fully connected model known to generate scalable squeezing4 and Greenberger-Horne-Zeilinger-like states5-8. The collective nature of the state manifests itself in the preservation of the total transverse magnetization, the reduced growth of the structure factor, that is, spin-wave excitations (SWE), at finite momenta, the generation of spin squeezing comparable with OAT (a Wineland parameter9,10 of -3.9 ± 0.3 dB for only N = 12 ions) and the development of non-Gaussian states in the form of multi-headed cat states in the Q-distribution. We demonstrate the metrological utility of the states in a Ramsey-type interferometer, in which we reduce the measurement uncertainty by -3.2 ± 0.5 dB below the standard quantum limit for N = 51 ions.

Final-year medical students' knowledge of cardiac arrest and CPR: We must do more!

BACKGROUND: Students are an important part of the community response to an out-of-hospital cardiac arrest (OHCA). If even schoolchildren now know cardio-pulmonary resuscitation (CPR), even more the reason a young doctor should know how to treat an OHCA. The aim of our study was to assess medical students' knowledge of CPR and OHCA throughout Europe. METHODS: An online survey was given to final-year students by the Medical Student Associations of different countries. RESULTS: 1012 medical students from 99 different universities and 14 different countries completed the questionnaire. A total of 82.2% attended a BLS or BLS/AED course, provided by the University in only 69.7% of cases. In 84.3% it was a mandatory part of their degree. A total of 78.6% felt able to rescue a person in OHCA. Only 49.3% knew that 'unresponsiveness' and 'absence of normal breathing' are sufficient for lay people to identify an OHCA, and less than half of those interviewed knew the incidence of OHCA in Europe and the decrease in chance of survival if CPR is not performed. The correct compression:ventilation ratio was known by 90.2%, the correct compression depth by 69.7%, whilst only 57.8% knew the right compression rate. In total, 69.7% knew that an AED must be used immediately when available, and only 57.2% recognized the AED symbol. CONCLUSIONS: Medical students' knowledge of cardiac arrest and CPR needs to be improved throughout Europe and we believe that BLS/AED training should be mandatory in all European Universities.

Effects of recent climate trends on the distribution of potential natural vegetation in Central Germany.

Introducing climate quotients for the growing season (Q(gs)) provides a way to quantify effects of climate trends with respect to Potential Natural Vegetation (PNV), especially beech forests (Fagus sylvatica L.) in Central Germany. What is crucial in this regard is the great influence of the dominant decrease in the amount of precipitation (up to 40% in the last 50 years) during the growing season versus the dormant season. However, precipitation during the dormant season (which is predominantly increasing: up to 40% in the last 50 years) is also important for replenishing the soil water supply. The Q(gs) values of the Climatic Normal period of 1971-2000 are generally higher (up to 12% in lowland areas) compared with the Climatic Normal period of 1961-1990, the extent of the difference being in general inversely proportional to elevation above sea level. What this means for the area under investigation is that humidity conditions, which generally improve as the elevation above sea level increases, have a positive effect on the site potential. However, a comparison of the climatologically important period of 1991-2003 with the period of 1961-1990 (area-wide increase between 12% and 16%) could not identify this positive effect of elevation on precipitation for the area under investigation. With regard to the recent climate-based trends of PNV, we have shown that all natural spatial units in Central Germany are affected by progressing continentality (i.e., dryness) during the growing season and the resulting deterioration of the site potential. The area of potential beech forest at lower elevation has decreased in favour of oak forest as PNV, while less change is observed in the montane area.