The distribution of the high concentrations of arsenic (As) and fluoride (F-) in groundwater on a Pan-European scale could be explained by the geological European context (lithology and structural ...faults). To test this hypothesis, seventeen countries and eighteen geological survey organizations (GSOs) have participated in the dataset. The methodology has used the HydroGeoToxicity (HGT) and the Baseline Concentration (BLC) index. The results prove that most of the waters considered in this study are in good conditions for drinking water consumption, in terms of As and/or F- content. A low proportion of the analysed samples present HGT≥ 1 levels (4% and 7% for As and F-, respectively). The spatial distribution of the highest As and/or F- concentrations (via BLC values) has been analysed using GIS tools. The highest values are identified associated with fissured hard rock outcrops (crystalline rocks) or Cenozoic sedimentary zones, where basement fractures seems to have an obvious control on the distribution of maximum concentrations of these elements in groundwaters.
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•Geological context is crucial in the spatial analysis of arsenic and fluoride.•HydroGeoToxicity (HGT) assesses quality of groundwater as drinking-water.•BaseLine Concentration (BLC) give the most significant geogenic anomalies.•Structural control is relevant in the distribution of arsenic in porous aquifers.•Lithology is pivotal in fluoride distribution (e.g. fissured hard rocks).
“Canaralele din Portul Hârșova” geosite is integrated into ‘Canaralele Dunarii’ Natura 2000 site (ROSCI0022), and represents the northern part of the geologic profile in Jurassic deposits that is ...exposed along the Danube River valley between Hârșova and Capidava. This sector exhibits Middle and Upper Jurassic deposits, developed in biohermal (in situ spongalgal, coralgal reefs and stromatolits) and biostromal facies. All around Hârșova, on the right bank of the Danube, the landscape is dominated by ruiniform shapes of this spongalgal limestones, formed through differential dissolution. The Callovian and Oxfordian fossil fauna contents are of biostratigrafic and paleoecological importance.
Modern advances in technology such as next-generation sequencing and digital PCR make detection of minor circulating cell-free tumor DNA amounts in blood from cancer patients possible. Samples can be ...obtained minimal-invasively, tested for treatment-determining genetic alterations and are considered to reflect the genetic constitution of the whole tumor mass. Furthermore, tumor development can be determined by a time course of the quantified circulating cell-free tumor DNA. However, systematic studies which prove the clinical relevance of monitoring patients using liquid biopsies are still lacking. In this study, we collected 115 samples from 47 late stage melanoma patients over 1.5 years alongside therapy-associated clinical routine monitoring. Mutation status was confirmed by molecular analysis of primary tumor material. We can show that detectable levels of circulating cell-free tumor DNA correlate with clinical development over time. Increasing levels of circulating cell-free tumor DNA during melanoma treatment with either targeted therapy (BRAF/MEK inhibitors) or immunotherapy, during recovery time or the intervals between last treatment cycle and second-line treatment point towards clinical progression before the progression becomes obvious in imaging. Therefore, this is a further possibility to closely screen our patients for tumor progression during therapy, in therapy-free phases and in earlier stages before therapy initiation.
Pyrexia is a frequent adverse event of BRAF/MEK-inhibitor combination therapy in patients with metastasized malignant melanoma (MM). The study's objective was to identify laboratory changes which ...might correlate with the appearance of pyrexia. Initially, data of 38 MM patients treated with dabrafenib plus trametinib, of which 14 patients developed pyrexia, were analysed retrospectively. Graphical visualization of time series of laboratory values suggested that a rise in C-reactive-protein, in parallel with a fall of leukocytes and thrombocytes, were indicative of pyrexia. Additionally, statistical analysis showed a significant correlation between lactate dehydrogenase (LDH) and pyrexia. An algorithm based on these observations was designed using a deductive and heuristic approach in order to calculate a pyrexia score (PS) for each laboratory assessment in treated patients. A second independent data set of 28 MM patients, 8 with pyrexia, was used for the validation of the algorithm. PS based on the four parameters CRP, LDH, leukocyte and thrombocyte numbers, were statistically significantly higher in pyrexia patients, differentiated between groups (F = 20.8; p = <0.0001) and showed a significant predictive value for the diagnosis of pyrexia (F = 6.24; p = 0.013). We provide first evidence that pyrexia in patients treated with BRAF/MEK-blockade can be identified by an algorithm that calculates a score.
Although the role of sentinel lymph node biopsy (SLNB) as a prognostic factor is well established, its consequences for therapy are controversial. The aim of this study was to analyze if complete ...lymph node dissection (CLND) in patients with more than one positive sentinel lymph node (SLN) significantly improves melanoma‐specific survival (MSS) and progression‐free survival (PFS). Medical records of patients who underwent SLNB between 2001 and 2016 at the University Hospital of Cologne were reviewed, and patients with positive SLN were identified. Patient and tumor characteristics, patterns of recurrence, progression‐free and melanoma‐specific survival were analyzed. Seventy‐eight patients with multiple positive and 197 patients with one positive SLN were included in this study. Patients with multiple positive SLN had significantly more positive non‐SLN compared with patients with only one positive SLN (26.9% vs 8.6%, P = 0.01). However, in the subgroup of patients with multiple positive SLN, CLND did not significantly improve MSS (mean MSS 95 vs 75 months, P = 0.5) and PFS (mean PFS 59 vs 68 months P = 0.167). CLND did not result in a significant improvement in PFS and MSS in patients with multiple positive SLN.
Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the ...best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for long-term survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.
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