Search

With a growing number of people in need of care and the shortage of skilled workers, caregivers express the desire for improved support to reduce physical strain and psychological stress. One task for burden relieve is documentation of nursing actions and treatment processes, as this can be done in parallel with the action. Hence tools capturing information in real time could improve information sharing. Also, contactless assessment of patients’ vital signs and emotions is desirable. Thus, the idea is to enhance an existing mobile platform, which can follow the nurse, includes a voice-controlled assistant, and be able for wireless (e.g., via Bluetooth) assessment of vital data from patients in its direct vicinity. Using the Temi telepresence robot as an open technical platform, we provide and discus requirements for this platform to potentially aid and relief to medical staff within caring and elderly homes, with respect to voice-control, Bluetooth-based vital data collection, interfaces to a digital patient manager and automated emotion recognition. The presented concept and the rating of the associated technologies leads to the conclusion that - if adequately implemented and installed - the caregivers could potentially receive noticeable relief from them. Nevertheless, as next steps, the examined technologies and ideas must be completely implemented, thoroughly fused with each other, and evaluated to provide a real support system for clinical care and assisted documentation.

Social phenomenological analysis is presented as a research method to study gallery talks or guided tours in art museums. The research method is based on the philosophical considerations of Edmund Husserl and sociological/social science concepts put forward by Max Weber and Alfred Schuetz. Its starting point is the everyday lifeworld; the researcher interprets the phenomena that can be observed there as an individual, intersubjectively accessible reflection of subjective meaning. This approach is suitable for research projects that seek correlations and structures of certain typical situations in domains that are theoretically few prestructured. The article explains the methodological principles, the use and the profit of this research method.

Social phenomenological analysis is presented as a research method for museum and art education. After explaining its methodological background, it is shown how this method has been applied in a study of gallery talks or guided tours in art museums: Analyzing the situation by description and interpretation, a model for understanding gallery talks is developed: "Pedagogical Art Communication". Results: The interplay among the recipient group, the aesthetic object, and educator is characterized by the participants acquiring (i.e. by aesthetic experience) and the educator imparting (especially) knowledge. In the future, art education and museum education need to focus less on dissolving this difference (in the sense of "methods that work") and spend more time on finding ways of sensibly dealing with the difference between imparting and acquirement of art. So the practice would be a pedagogical art communication in which art educators impart what can be imparted (to the extent that it is "impartable"), while at the same time stimulating and enabling the acquirement of knowledge--and, at a broader level, coordinating the interplay of imparting and acquirement in social, performative and spatial dimensions.

Meta-Generalized Gradient Approximations (meta-GGAs) can, in principle, include spatial and temporal nonlocality in time-dependent density functional theory at a much lower computational cost than functionals that use exact exchange. We here test whether a meta-GGA that has recently been developed with a focus on capturing nonlocal response properties and the particle number discontinuity can realize such features in practice. To this end, we extended the frequency-dependent Sternheimer formalism to the meta-GGA case. Using the Krieger–Li–Iafrate (KLI) approximation, we calculate the optical response for the selected paradigm molecular systems and compare the meta-GGA Kohn–Sham response to the one found with exact exchange and conventional (semi-)local functionals. We find that the new meta-GGA captures important properties of the nonlocal exchange response. The KLI approximation, however, emerges as a limiting factor in the evaluation of charge-transfer excitations. [ABSTRACT FROM AUTHOR]

The Sternheimer approach to time-dependent density functional theory in the linear response regime is attractive because of its computational efficiency. The latter results from avoiding the explicit calculation of unoccupied orbitals and from the basic structure of the Sternheimer equations, which naturally lend themselves to far-reaching parallelization. In this article, we take a fresh look at the frequency-dependent Sternheimer equations. We first give a complete, self-contained derivation of the equations that complements previous derivations. We then discuss several aspects of an efficient numerical realization. As a worked example, we compute the photoabsorption spectra of small hydrogenated silicon clusters and confirm that for these the quality of the Kohn-Sham eigenvalues is more important than the effects of the exchange-correlation kernel. Finally, we demonstrate how triplet excitations can readily be computed from the Sternheimer approach. [ABSTRACT FROM AUTHOR]

The technological capabilities and ubiquity of smart mobile devices favor the combined utilization of Ecological Momentary Assessments (EMA) and Mobile Crowdsensing (MCS). In the healthcare domain, this combination particularly enables the collection of ecologically valid and longitudinal data. Furthermore, the context in which these data are collected can be captured through the use of smartphone sensors as well as externally connected sensors. The TrackYourTinnitus (TYT) mobile platform uses these concepts to collect the user's individual subjective perception of tinnitus as well as an objective environmental sound level. However, the sound level data in the TYT database are subject to several possible sensor errors and therefore do not allow a meaningful interpretation in terms of correlation with tinnitus symptoms. To this end, a data-centric approach based on Principal Component Analysis (PCA) is proposed in this paper to cleanse MCS mHealth data sets from erroneous sensor data. To further improve the approach, additional information (i.e., responses to the EMA questionnaire) is considered in the PCA and a prior check for constant values is performed. To demonstrate the practical feasibility of the approach, in addition to TYT data, where it is generally unknown which sensor measurements are actually erroneous, a simulation with generated data was designed and performed to evaluate the performance of the approach with different parameters based on different quality metrics. The results obtained show that the approach is able to detect an average of 29.02% of the errors, with an average false-positive rate of 14.11%, yielding an overall error reduction of 22.74%. [ABSTRACT FROM AUTHOR]

To examine the association between surgical waiting times (SWTs) and all-cause mortality (ACM) in non-metastatic patients with RCC, in relation to tumour stage. This nation-wide population-based cohort study included 9,918 M0 RCC patients registered in the National Swedish Kidney Cancer Register, between 2009 and 2021, followed-up for ACM until 9 December 2021, and having measured SWTs. The associations between primarily SWTs from date of radiological diagnosis to date of surgery (WRS) and secondarily SWTs from date of radiological diagnosis to date of treatment decision (WRT) and date of treatment decision to date of surgery (WTS), in relation to ACM, were analysed using Cox regression analysis, adjusted for clinical and demographic characteristics, stratified and unstratified according to T-stage. During a mean follow-up time of 5 years (49,873 person-years), 23% (n = 2291) of the patients died. The adjusted hazard ratio (AHR) for WRS (months) for all patients was 1.03 (95% confidence interval [CI] = 1.02–1.04; p < 0.001). When subdividing WRS on T-stage, the AHRs were 1.03 (95% CI = 1.01–1.04; p < 0.001) and 1.05 (95% CI = 1.02–1.08; p = 0.003) for stages T1 and T3, respectively, while non-significant for T2 (p = 0.079) and T4 (p = 0.807). Similar results were obtained for WRT and WTS. Prolonged SWTs significantly increased the risk of early overall death among patients with RCC. The increased risk of early death from any cause show the importance of shortening SWTs in clinical work of patients with this malignant disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Facemasks proved to be an additional layer of protection in limiting the spread of SARS-CoV-2 onboard commercial airplanes. Therefore, since the start of the COVID-19 pandemic, most countries and airlines implemented mask mandates. However, published data on the effect of mask wear on in-flight O2-saturation of flight crews is scarce. METHODS: We conducted a small case series of volunteers (pilots and cabin crew) to examine the above-mentioned effect. Volunteers were asked to assess their peripheral O2 saturation (SpO2) (using a personal pulse oximeter) on ground as well as during different flight phases while wearing a surgical mask (SFM), FFP2 respirator or no mask. We evaluated the average SpO2 according to mask type, wear time and ambient pressure. We used Mann--Whitney U test to assess statistical significance and Pearson's correlation coefficient to determine correlation. RESULTS: Eight volunteers participated in this series. A total of n= 481 measurements was taken during 39 flight legs. SpO2 aground did not differ between the mask groups (unmasked: μ (mean) = 97.6%, σ (standard deviation) = 1.5%; SFM μ = 97.6%, σ = 0.9%; FFP2 μ = 97.6%, σ = 0.9%). Airborne use of FFP2 respirators resulted in a slight but significant (Δ = 1.1%, p = 0.00004) reduction of SpO2 (unmasked: μ = 95.6%, σ = 1.9%; SFM: μ = 96.2% σ = 1.2% and FFP2: μ = 94.6%, σ = 0.9%). No relevant correlation between the duration of mask use and oxygenation could be demonstrated (r = -0.16, p = 0.12). Airborne SpO2 was significantly lower than aground independent of mask type (p < 0.0001 for each). DISCUSSION: Our exploratory case study suggests, to our knowledge for the first time, that SpO2 in flight crews is slightly impaired while using FFP2 respirators. This impairment is however minimal (1.1%) and therefore unlikely to have any effect on performance or health. The underlying reasons require further investigation. Limitations to this study exist due to the limited number of participants and measurement data as well as the assumption of statistical independence. Learning Objectives 1. The audience learns about O2 saturation in aircrews aground as well as airborne while using different mask types. As a byproduct the audience learns about physilogical responses in spO2 to a change in ambient pressure. 2. The audience should be sensitized that there are still questions unanswered that sparked during airline travel throughout the COVID19 pandemic. [ABSTRACT FROM AUTHOR]

Aza-Diels–Alder reactions are straightforward processes for the construction of N -heterocycles, featuring inherent atom-economy and stereospecificity. Intramolecular strategies allow the formation of bicyclic core structures with up to three stereocenters within a single step. Herein, this concept is combined with the chemistry of chiral Brønsted acid bound ortho -quinone methide imines to generate a range of interesting fused tetrahydroquinolines in a diastereo- and enantioselective- manner. [ABSTRACT FROM AUTHOR]

Abstract: Most research on pollination has focussed on a subset of insect taxa within a narrow time window during daylight hours. As a consequence, we have a limited understanding of the diversity and activity of flower visitors during the night or belonging to taxa other than bees or syrphid flies. Here, we quantified the abundance and species richness of flower visitors in ruderal meadows over repeated 24‐h cycles (i.e. day and night), and identified abiotic factors influencing these patterns. From the plant perspective, we investigated the likelihood of being visited by an insect across a 24‐h cycle. Activity of flower‐visiting insects never dropped to zero over 24‐h. During the day, non‐syrphid Diptera and Hymenoptera were the most abundant, and species‐rich groups of flower visitors, Lepidoptera and Coleoptera during night. While two of the seven most frequently visited plant species were most likely to be visited during the day, five also had a high likelihood to be visited during the night. The abundance and species richness of flower visitors was positively related to temperature during both the day and the night, whereas there was only a positive relationship with brightness during the day. We conclude that non‐syrphid Diptera and nocturnal flower visitors are currently underappreciated. As the latter seem to respond differently to abiotic factors compared to diurnal species, they may potentially increase response diversity and resilience of plant‐pollinator communities. There is an urgent need to improve our understanding of their ecological role and potential decline due to global change. [ABSTRACT FROM AUTHOR]

Abstract: Aza‐Diels‐Alder‐Reaktionen (ADARs) sind leistungsfähige Prozesse zum schnellen und stereoselektiven Aufbau von Stickstoffheterocyclen. Intramolekulare Varianten bieten darüber hinaus die Möglichkeit, bi‐ und polycyclische Ringsysteme in einem Schritt mit hoher Stereoselektivität zu generieren. In dem hier entwickelten Brønsted‐Säure‐katalysierten Verfahren können nun erstmals ortho‐Chinonmethidimine, die über den Iminsubstituenten an ein Dienophil gebunden sind, in einer enantioselektiven ADAR mit inversem Elektronenbedarf zu komplexen Chinolizidin‐ und Oxazinochinolin‐Ringsystemen umgesetzt werden. Die Reaktionen laufen unter milden Bedingungen in sehr guten Ausbeuten und mit guten bis sehr guten Diastereo‐ und Enantioselektivitäten ab. Das Verfahren kann darüber hinaus zu einem Domino‐Prozess erweitert werden, der Substratsynthese, ortho‐Chinonmethid‐Bildung und ADAR effizient vereinigt. [ABSTRACT FROM AUTHOR]

Abstract: Aza‐Diels–Alder reactions (ADARs) are powerful processes that furnish N‐heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi‐ and polycyclic systems with high stereoselectivity. We report herein a novel Brønsted acid catalyzed process in which ortho‐quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one‐step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo‐ and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho‐quinone methide imine formation, and ADAR. [ABSTRACT FROM AUTHOR]

Context While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. Objective To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. Evidence acquisition Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. Evidence synthesis The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03–1.92 and 1.41, 95% CI: 0.88–2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67–2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9–2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91–1.86). Sunitinib was associated with more Grade 3–4 adverse events than everolimus, although this was not statistically significant. Conclusions This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. Patient summary We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need. [ABSTRACT FROM AUTHOR]

A new enantiopure heteroscorpionate ligand HOPhbpm3menth ( 2) was synthesized in a one-pot synthesis. Ligand 2 was obtained in a pyridine-catalysed Peterson rearrangement starting from menthopyrazole, thionyl chloride, and salicylaldehyde. The evidence of κ3-coordination of the ligand was shown by the formation of a tetrahedral zinc complex [Zn-κ3-(OPhbpm3menth)CH3] ( 3) as well as an molybdenum complex [Mo-κ3-(OPhbpm3menth)O2Cl] ( 4). [ABSTRACT FROM AUTHOR]

This prospective study aimed to compare the efficacy of epidural (EDA) versus intravenous (PCA) application of analgesics after lumbar fusion. Fifty-two patients scheduled for elective posterior instrumented lumbar fusion were randomized into two groups. EDA patients received an epidural catheter intraoperatively, and administration of ropivacain and sulfentanil was started after a normal postoperative wake-up test in the recovery room area. PCA patients received intravenous opioids in the post-operative period. Differences between EDA and PCA groups in terms of patient satisfaction with respect to pain relief were not significant. Nevertheless, EDA patients reported less pain on the third day after surgery. There were significantly more side effects in the EDA group, including complete reversible loss of sensory function and motor weakness. There were no major side effects, such as infection or persisting neurological deficits, in either group. The routine use of epidural anesthesia for lumbar spine surgery has too many risks and offers very little advantage over PCA. [ABSTRACT FROM AUTHOR]

In power systems, flow allocation (FA) methods enable to allocate the usage and costs of the transmission grid to each single market participant. Based on predefined assumptions, the power flow is split into isolated generator-specific or producer-specific sub-flows. Two prominent FA methods, Marginal Participation (MP) and Equivalent Bilateral Exchanges (EBEs), build upon the linearized power flow and thus on the Power Transfer Distribution Factors (PTDFs). Despite their intuitive and computationally efficient concepts, they are restricted to networks with passive transmission elements only. As soon as a significant number of controllable transmission elements, such as high-voltage direct current (HVDC) lines, operate in the system, they lose their applicability. This work reformulates the two methods in terms of Virtual Injection Patterns (VIPs), which allows one to efficiently introduce a shift parameter q to tune contributions of net sources and net sinks in the network. In this work, major properties and differences in the methods are pointed out, and it is shown how the MP and EBE algorithms can be applied to generic meshed AC-DC electricity grids: by introducing a pseudo-impedance ω ¯ , which reflects the operational state of controllable elements and allows one to extend the PTDF matrix under the assumption of knowing the current flow in the system. Basic properties from graph theory are used to solve for the pseudo-impedance in dependence of the position within the network. This directly enables, e.g., HVDC lines to be considered in the MP and EBE algorithms. The extended methods are applied to a low-carbon European network model (PyPSA-EUR) with a spatial resolution of 181 nodes and an 18% transmission expansion compared to today's total transmission capacity volume. The allocations of MP and EBE show that countries with high wind potentials profit most from the transmission grid expansion. Based on the average usage of transmission system expansion, a method of distributing operational and capital expenditures is proposed. In addition, it is shown how injections from renewable resources strongly drive country-to-country allocations and thus cross-border electricity flows. [ABSTRACT FROM AUTHOR]

Certain excitations, especially ones of long-range charge transfer character, are poorly described by time-dependent density functional theory (TDDFT) when typical (semi-)local functionals are used. A proper description of these excitations would require an exchange-correlation response differing substantially from the usual (semi-)local one. It has recently been shown that functionals of the generalized gradient approximation (GGA) type can yield unusual potentials, mimicking features of the exact exchange derivative discontinuity and showing divergences on orbital nodal surfaces. We here investigate whether these unusual potential properties translate into beneficial response properties. Using the Sternheimer formalism we closely investigate the response obtained with the 2013 exchange approximation by Armiento and Kümmel (AK13) and the 1988 exchange approximation by Becke (B88), both of which show divergences on orbital nodal planes. Numerical calculations for Na2 as well as analytical and numerical calculations for the hydrogen atom show that the response of AK13 behaves qualitatively different from usual semi-local functionals. However, the AK13 functional leads to fundamental instabilities in the asymptotic region that prevent its practical application in TDDFT. Our findings may help the development of future improved functionals. They also corroborate that the frequency-dependent Sternheimer formalism is excellently suited for running and analyzing TDDFT calculations. [ABSTRACT FROM AUTHOR]

Pembrolizumab improves disease-free survival in high-risk clear cell renal cell carcinoma and is the first immune checkpoint inhibitor to be recommended in this setting. Overall survival data are immature. Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery. [ABSTRACT FROM AUTHOR]

The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer. Longer follow-up data and new trial data from phase III randomised controlled trials investigating immune checkpoint blockade (programmed death-receptor [PD]-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) in combination with tyrosine kinase inhibitors or dual immunotherapy have recently been released. The RCC Guidelines Panel recommends the combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all International Metastatic Database Consortium (IMDC) risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. [ABSTRACT FROM AUTHOR]

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer. Longer follow-up data and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. A recent update of Keynote-426 demonstrated an ongoing overall survival benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a progression-free survival benefit seen across all International Metastatic RCC Database Consortium (IMDC) subgroups. The RCC Guidelines Panel continues to recommend this combination across IMDC risk groups in advanced first-line RCC. [ABSTRACT FROM AUTHOR]

Abstract Cytoreductive nephrectomy (CN) has been the standard of care in patients with metastatic clear-cell renal cancer who present with the tumour in place. The CARMENA trial compared systemic therapy alone with CN followed by systemic therapy. This article outlines the new guidelines based on these data. Patient summary The CARMENA trial demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in patients diagnosed with intermediate and poor risk metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden poor risk patients experience hearing that removal of their primary tumour will not be beneficial, should be carefully considered. Take Home Message CARMENA demonstrates that immediate cytoreductive nephrectomy should no longer be considered the standard of care in intermediate- and poor-risk patients with metastatic renal cell carcinoma when medical treatment is required. However, the psychological burden that poor-risk patients experience on hearing that removal of their primary tumour will not be beneficial should be carefully considered. The renal cell carcinoma guidelines panel has revisited their treatment recommendations for Memorial Sloan Kettering Cancer Center intermediate- and poor-risk patients. [ABSTRACT FROM AUTHOR]

The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. Patient summary The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate- and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients. [ABSTRACT FROM AUTHOR]

People with asymptomatic bacteriuria (ABU) are often unnecessarily treated with antibiotics risking adverse effects and antimicrobial resistance. We performed a systematic review to determine any benefits and harms of treating ABU in particular patient groups. Relevant databases were searched and eligible trials were assessed for risk-of-bias and Grading of Recommendations, Assessment, Development and Education quality. Where possible, a meta-analysis of extracted data was performed or a narrative synthesis of the evidence was presented. After screening 3626 articles, 50 studies involving 7088 patients were included. Overall, quality of evidence ranged from very low to low. There was no evidence of benefit for patients with no risk factors, patients with diabetes mellitus, postmenopausal women, elderly institutionalised patients, patients with renal transplants, or patients prior to joint replacement, and treatment was harmful for patients with recurrent urinary tract infection (UTI). Treatment of ABU resulted in a lower risk of postoperative UTI after transurethral resection surgery. In pregnant women, we found evidence that treatment of ABU decreased risk of symptomatic UTI, low birthweight, and preterm delivery. ABU should be treated prior to transurethral resection surgery. In addition, current evidence also suggests that ABU treatment is required in pregnant women, although the results of a recent trial have challenged this view. Patient summary We reviewed available scientific studies to see if people with bacteria in their urine but without symptoms of urinary tract infection should be treated with antibiotics to eliminate bacteria. For most people, treatment was not beneficial and may be harmful. Antibiotic treatment did appear to benefit women in pregnancy and those about to undergo urological surgery. [ABSTRACT FROM AUTHOR]

Context Overall, 4–10% of patients with renal cell carcinoma (RCC) present with venous tumour thrombus. It is uncertain which surgical technique is best for these patients. Appraisal of outcomes with differing techniques would guide practice. Objective To systematically review relevant literature comparing the outcomes of different surgical therapies and approaches in treating vena caval thrombus (VCT) from nonmetastatic RCC. Evidence acquisition Relevant databases (Medline, Embase, and the Cochrane Library) were searched to identify relevant comparative studies. Risk of bias and confounding assessments were performed. A narrative synthesis of the evidence was presented. Evidence synthesis The literature search identified 824 articles. Fourteen studies reporting on 2262 patients were included. No distinct surgical method was superior for the excision of VCT, although the method appeared to be dependent on tumour thrombus level. Minimal access techniques appeared to have better perioperative and recovery outcomes than traditional median sternotomy, but the impact on oncologic outcomes is unknown. Preoperative renal artery embolisation did not offer any oncologic benefits and instead resulted in significantly worse perioperative and recovery outcomes, including possibly higher perioperative mortality. The comparison of cardiopulmonary bypass versus no cardiopulmonary bypass showed no differences in oncologic outcomes. Overall, there were high risks of bias and confounding. Conclusions The evidence base, although derived from retrospective case series and complemented by expert opinion, suggests that patients with nonmetastatic RCC and VCT and acceptable performance status should be considered for surgical intervention. Despite a robust review, the findings were associated with uncertainty due to the poor quality of primary studies available. The most efficacious surgical technique remains unclear. Patient summary We examined the literature on the benefits of surgery to remove kidney cancers that have spread to neighbouring veins. The results suggest such surgery, although challenging and associated with high risk of complications, appears to be feasible and effective and should be contemplated for suitable patients if possible; however, many uncertainties remain due to the poor quality of the data. [ABSTRACT FROM AUTHOR]

Context The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety. Objective We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade. Evidence acquisition Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (κ) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2). Evidence synthesis A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (κ = 0.683) and a fair (κ = 0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien ≥2 complications was reported. Study limitations included selection and differential-verification bias. Conclusions RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required. Patient summary We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer. [ABSTRACT FROM AUTHOR]

Context The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. Objectives To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. Evidence acquisition For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. Evidence synthesis All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10 862 articles. A total of 151 studies reporting on 78 792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence. Conclusions The 2014 guideline has been updated by a multidisciplinary panel using the highest methodological standards, and provides the best and most reliable contemporary evidence base for RCC management. Patient summary The European Association of Urology Guideline Panel for Renal Cell Carcinoma has thoroughly evaluated available research data on kidney cancer to establish international standards for the care of kidney cancer patients. [ABSTRACT FROM AUTHOR]

Context The introduction of novel molecular-targeted agents has revolutionised the management of patients with metastatic renal cell carcinoma (mRCC). However, uncertainties remain over sequential or simultaneous combination therapies. Objective To systematically review relevant literature comparing the clinical effectiveness and harms of different sequencing and combinations of systemic targeted therapies for mRCC. Evidence acquisition Relevant databases (including Medline, Cochrane Library, trial registries, and conference proceedings) were searched (January 2000 to September 2013) including only randomised controlled trials (RCTs). Risk of bias assessment was performed. A qualitative and quantitative synthesis of the evidence was presented. Evidence synthesis The literature search identified 5149 articles. A total of 24 studies reporting on 9589 patients were eligible for inclusion; data from four studies were included for meta-analysis. There were generally low risks of bias across studies; however, clinical and methodological heterogeneity prevented pooling of data for most studies. Overall, the data showed several targeted therapies were associated with an improvement in progression-free survival in patients with mRCC. There were limited data from RCTs regarding the issue of sequencing; studies on combination therapies have been hampered by difficulties with tolerability and safety. Conclusions Although the role of vascular endothelial growth factor/vascular endothelial growth factor receptor targeting therapies and mammalian target of rapamycin inhibition in the management of mRCC is now established, limited reliable data are available regarding sequencing and combination therapies. Although data from retrospective cohort studies suggest a potential benefit for sequencing systemic therapies, significant uncertainties remain. Presently, mRCC systemic treatment should follow international guidelines (such as the European Society for Medical Oncology, National Comprehensive Cancer Network, and European Association of Urology) for patients fit to receive several lines of systemic therapies. Patient summary We thoroughly examined the literature on the benefits and harms of combining drugs for the treatment of kidney cancer that has spread and on the sequence in which the drugs should be given. [ABSTRACT FROM AUTHOR]

Background: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review., Objectives: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy., Search Methods: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020., Selection Criteria: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy., Data Collection and Analysis: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach., Main Results: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants.  3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants.  4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants., Authors' Conclusions: Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. PATIENT SUMMARY: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naïve). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)