Changing climate shifts timing of European floods

A warming climate is expected to have an impact on the magnitude and timing of river floods; however, no consistent large-scale climate change signal in observed flood magnitudes has been identified so far. We analyzed the timing of river floods in Europe over the past five decades, using a pan-European database from 4262 observational hydrometric stations, and found clear patterns of change in flood timing. Warmer temperatures have led to earlier spring snowmelt floods throughout northeastern Europe; delayed winter storms associated with polar warming have led to later winter floods around the North Sea and some sectors of the Mediterranean coast; and earlier soil moisture maxima have led to earlier winter floods in western Europe. Our results highlight the existence of a clear climate signal in flood observations at the continental scale

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

Background: Beta-adrenergic signalling plays an important role in several cancer-related processes, including angiogenesis. The impact of beta-blocker use on prognosis of cancer patients treated with antiangiogenic agents is unclear. The aim of this study was to evaluate the association between the incidental use of beta-blockers and the outcomes of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based therapy. Methods: Clinical data from 514 mCRC patients treated with bevacizumab between 2005 and 2019 were analysed retrospectively. The association of progression-free survival (PFS) and overall survival (OS) with the incidental use of beta-blockers and other common antihypertensive drugs was assessed. Results: The median PFS and OS for patients using beta-blockers was 11.40 (95% confidence interval (CI) 10.10–13.61) months and 26.8 (95% CI 22.2–32.2) months compared with 8.30 (95% CI 7.80–9.57) and 21.0 (95% CI 17.8–23.8) months for patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate analysis, the use of beta-blockers was a significant factor predicting both PFS (hazard ratio (HR) = 0.763 (95% CI 0.606–0.960), p = 0.021) and OS (HR = 0.730 (95% CI 0.560–0.951), p = 0.020). Conclusions: The results of the present retrospective study suggest that there is a significant association between the use of beta-blockers and favourable outcomes of mCRC patients treated with bevacizumab-based therapy

Parkin (PARK 2) mutations are rare in Czech patients with early-onset Parkinson's disease.

The aim of the study is to determine the frequency of parkin allelic variants in Czech early-onset Parkinson's disease patients and healthy controls.A total of 70 early-onset Parkinson's disease patients (age at onset ≤40 years) and 75 controls were screened for the sequence variants and exon rearrangements in the parkin gene.Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous deletion of the exon 4. No mutations were obtained in control subjects. A novel sequence variant p.V380I (c.1138G>A) was identified in one control. Non-pathogenic polymorphisms p.S167N and p.D394N were seen in similar percentage in patients and controls, polymorphism p.V380L was almost twice as frequent in controls as in patients.Our study contributes to the growing body of evidence on the low frequency of the parkin mutations in the early-onset Parkinson's disease suggesting the potential role of other genes in the pathogenesis of the disease

Impact of Delaying the Addition of Anti-EGFR in First Line of RAS Wild-Type Metastatic Colorectal Cancer: A Propensity-Weighted Pooled Data Analysis

The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5–34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9–43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4–44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS (p = 0.24) or progression-free survival (p = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR

Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection

The liquid biopsy has the potential to improve current clinical practice in oncology byproviding real-time personalized information about a patient’s disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected aroundsurgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-DefinitionSingle Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC)enumeration, cellular morphology and kinetics between time-points of collection were considered inthe survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survivalwith an increase in cell count from pre-resection to post-resection. This study demonstrates thatCTC subcategorization based on morphological differences leads to nuanced results between thesubtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show thatfactoring in the time-point of each blood collection is critical, both for its static enumeration and forthe change in cell populations between draws. By integrating morphology and time-based analysisalongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into thepathophysiology of mCRC by highlighting the complexity of the disease across a patient’s treatment

Pembrolizumab plus enfortumab vedotin in urothelial cancer

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Outcomes According to MSKCC Risk Score with Focus on the Intermediate-Risk Group in Metastatic Renal Cell Carcinoma Patients Treated with First-Line Sunitinib: A Retrospective Analysis of 2390 Patients

Background: The Memorial Sloan–Kettering Cancer Center (MSKCC) prognostic model has been widely used for the prediction of the outcome of metastatic renal cell carcinoma (mRCC) patients treated with systemic therapies, however, data from large studies are limited. This study aimed at the evaluation of the impact of the MSKCC score on the outcomes in mRCC patients treated with first-line sunitinib, with a focus on the intermediate-risk group. Methods: Clinical data from 2390 mRCC patients were analysed retrospectively. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analysed according to the MSKCC risk score. Results: ORR, median PFS, and OS for patients with one risk factor were 26.7%, 10.1, and 28.2 months versus 18.7%, 6.2, and 16.2 months, respectively, for those with two risk factors (ORR: p = 0.001, PFS: p < 0.001, OS: p < 0.001). ORR, median PFS, and OS were 33.0%, 17.0, and 44.7 months versus 24.1%, 9.0, and 24.1 months versus 13.4%, 4.5, and 9.5 months in the favourable-, intermediate-, and poor-risk groups, respectively (ORR: p < 0.001, PFS: p < 0.001, OS: p < 0.001). Conclusions: The results of the present retrospective study demonstrate the suitability of the MSKCC model in mRCC patients treated with first-line sunitinib and suggest different outcomes between patients with one or two risk factors

Utilization and efficacy of second-line targeted therapy in metastatic renal cell carcinoma: data from a national registry

Abstract Background It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). Methods This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. Results The median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5–19.5 months), 17.1 months (95% CI 14.5–19.8), and 15.4 months (95% CI 11.0–19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus. Conclusions In this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib