BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is still a very dangerous and life-threatening disease with an extremely heterogeneous course. Older patients and those with comorbidities are at increased risk of death from the disease but young patients can develop potentially lethal complications too. For those reasons, numerous recent studies focus on the analysis of markers associated with early assessment of COVID-19 prognosis. Previous publications provided evidence for the Intensive Care Infection Score (ICIS) as an easy to use tool to assess the risk for bacterial infection in ICU patients based on a combination of haematologic parameters. This study evaluated the performance of ICIS as a prognostic marker of stages of disease in COVID-19 patients. METHODS: A total of 205 COVID-19 patients admitted to the University Hospital Hradec Kralove, Czech Republic, with symptoms of respiratory tract infection and a positive RT-PCR test for SARS-CoV-2 virus were enrolled in this study. Forty-nine patients developed mild COVID-19 symptoms (no oxygen therapy needed), 156 patients developed moderate or severe symptoms (supplemental oxygen therapy or death). RESULTS: ICIS predicted the mild or moderate/severe course with the highest AUC (0.773). The cut-off value (ICIS = 3.5) was selected as the value with the highest Youden index (0.423). The cut-off value could predict a mild or moderate/severe course of the disease with the highest specificity (77.6%) and positive predictive value (90.2%) of all markers used in this study. Sensitivity was 64.7%. CONCLUSION: ICIS is a reliable, cheap, fast and simply interpretable score for the early identification of moderate/severe course of COVID-19 in an early stage of the disease. ICIS> 3 predicts a severe course of the disease with high specificity and positive predictive value.

• Klíčová slova
• COVID-19, Coronavirus, ICIS, Infection score, Prognosis,
• MeSH
• COVID-19 * MeSH
• hospitalizace MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Despite all the effort, infections remain one of the major causes of morbidity and mortality in clinically ill patients, and novel diagnostic markers detecting infections in early stages are searched for. Intensive Care Infection Score (ICIS) was developed as such a marker. METHODS: A total of 102 patients admitted to intensive care units (ICU) in the University Hospital Hradec Kralove, Czech Republic were enrolled in this study. ICIS along with relevant biochemical markers (procalcitonin, C-reactive protein and Interleukin 6) was analyzed on the day of the admission. Individual parameters used to calculate ICIS were analyzed too. Infection was subsequently confirmed in 30 patients. RESULTS: ICIS predicted infections with the highest AUC (0.958) of all analyzed markers. The cut-off value (< 4) was selected as the value with the highest Youden index, and it predicted sepsis with high specificity (84.2%) and sensitivity (93.3%). Negative predictive value was very high too (96.8%). Positive predictive value was 71.8%. CONCLUSIONS: ICIS is a reliable, cheap, fast, and simply interpretable score for the early identification of infection in patients admitted to ICUs. ICIS ≥ 4 predicts infection with high sensitivity, specificity, and negative predictive value.

• Klíčová slova
• Sysmex, infection score, infections, prediction,
• MeSH
• biologické markery krev   MeSH
• C-reaktivní protein MeSH
• dospělí MeSH
• infekce * diagnóza   krev   MeSH
• interleukin-6 krev   MeSH
• jednotky intenzivní péče * MeSH
• lidé středního věku MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu * MeSH
• příjem pacientů MeSH
• prokalcitonin krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sepse * diagnóza   krev   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• biologické markery MeSH
• C-reaktivní protein MeSH
• interleukin-6 MeSH
• prokalcitonin MeSH

BACKGROUND: The pan-European human biomonitoring initiative HBM4EU targets the harmonization of human biomonitoring (HBM) procedures and data for both environmental and occupational exposure, including chromium. The determination of chromium in urine (U-Cr), plasma (P-Cr) and whole blood (WB-Cr) is a common HBM application in employees occupationally exposed to chromium (VI) compounds. METHODS: European laboratories which have registered as candidate laboratories for chromium analysis within HBM4EU were invited to participate in a quality assurance/qualitycontrol (QA/QC) programme comprising interlaboratory comparison investigations (ICI) for the parameters U-Cr, P-Cr and WB-Cr. Participating laboratories received two samples of different concentrations in each of four rounds and were asked to analyse the samples using their standard analytical procedure. The data were evaluated by the Z-score approach and were reported to the participants after each round. RESULTS: The majority of the 29 participating laboratories obtained satisfactory results, although low limits of quantification were required to quantify chromium concentrations in some of the ICI materials. The robust relative standard deviation of the participants' results (study RSDR) obtained from all ICI runs ranged from 6 to 16 % for U-Cr, 7-18 % for P-Cr and 4-47 % for WB-Cr. The application of both inductively coupled plasma mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (EAAS) appeared appropriate for the determination of chromium in urine, plasma and whole blood with regard to occupational exposure levels. CONCLUSION: This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of chromium across Europe.

• Klíčová slova
• Chromium, Electrothermal atomic absorption spectrometry (EAAS), HBM4EU, Human biomonitoring (HBM), Inductively coupled plasma mass spectrometry (ICP-MS), Interlaboratory comparison investigation (ICI), Occupational exposure, Plasma, Red blood cells, Urine, Whole blood,
• MeSH
• biologický monitoring * MeSH
• chrom analýza   MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• pracovní expozice * analýza   MeSH
• spektrofotometrie atomová MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chrom MeSH

The European Human Biomonitoring Initiative (HBM4EU) is coordinating and advancing human biomonitoring (HBM). For this purpose, a network of laboratories delivering reliable analytical data on human exposure is fundamental. The analytical comparability and accuracy of laboratories analysing flame retardants (FRs) in serum and urine were investigated by a quality assurance/quality control (QA/QC) scheme comprising interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs). This paper presents the evaluation process and discusses the results of four ICI/EQUAS rounds performed from 2018 to 2020 for the determination of ten halogenated flame retardants (HFRs) represented by three congeners of polybrominated diphenyl ethers (BDE-47, BDE-153 and BDE-209), two isomers of hexabromocyclododecane (α-HBCD and γ-HBCD), two dechloranes (anti-DP and syn-DP), tetrabromobisphenol A (TBBPA), decabromodiphenylethane (DBDPE), and 2,4,6-tribromophenol (2,4,6-TBP) in serum, and four metabolites of organophosphorus flame retardants (OPFRs) in urine, at two concentration levels. The number of satisfactory results reported by laboratories increased during the four rounds. In the case of HFRs, the scope of the participating laboratories varied substantially (from two to ten) and in most cases did not cover the entire target spectrum of chemicals. The highest participation rate was reached for BDE-47 and BDE-153. The majority of participants achieved more than 70% satisfactory results for these two compounds over all rounds. For other HFRs, the percentage of successful laboratories varied from 44 to 100%. The evaluation of TBBPA, DBDPE, and 2,4,6-TBP was not possible because the number of participating laboratories was too small. Only seven laboratories participated in the ICI/EQUAS scheme for OPFR metabolites and five of them were successful for at least two biomarkers. Nevertheless, the evaluation of laboratory performance using Z-scores in the first three rounds required an alternative approach compared to HFRs because of the small number of participants and the high variability of experts' results. The obtained results within the ICI/EQUAS programme showed a significant core network of comparable European laboratories for HBM of BDE-47, BDE-153, BDE-209, α-HBCD, γ-HBCD, anti-DP, and syn-DP. On the other hand, the data revealed a critically low analytical capacity in Europe for HBM of TBBPA, DBDPE, and 2,4,6-TBP as well as for the OPFR biomarkers.

• Klíčová slova
• External quality assurance scheme (EQUAS), HBM4EU, Halogenated flame retardants (HFRs), Human biomonitoring (HBM), Interlaboratory comparison investigation (ICI), Organophosphorus flame retardants (OPFRs),
• MeSH
• biologický monitoring MeSH
• halogenované difenylethery analýza   MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• retardanty hoření * analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• halogenované difenylethery MeSH
• retardanty hoření * MeSH

Exposure to aromatic amines may occur via tobacco smoke, hair dyes or tattoo inks, but also in the workplace during certain manufacturing processes. As some aromatic amines are known or suspected carcinogens, human biomonitoring (HBM) is essential to assess their exposure. Aromatic amines were among the selected chemicals in HBM4EU, a European-wide project to harmonise and advance HBM within 30 European countries. For this purpose, the analytical comparability and accuracy of participating laboratories were assessed by a QA/QC programme comprising interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs). This paper presents the evaluation process and discusses the results of three ICI/EQUAS rounds for the determination of aromatic amines in urine conducted in 2019 and 2020. The final evaluation included ten participants which analysed the following six targeted aromatic amines over three rounds: aniline, ortho-toluidine (TOL), 4,4'-methylenedianiline (MDA), 4,4'-methylenebis(2-chloroaniline) (MOCA), 2,4-diaminotoluene (2,4-TDA), and 2,6-diaminotoluene (2,6-TDA). Most participants achieved satisfactory and highly comparable results, although low quantification limits were required to quantify the parameters at the level of exposure in the general population. Hydrolysis of the sample followed by liquid-liquid extraction and subsequent analysis of the derivatised analytes by means of GC-MS/MS were preferred for the sensitive and precise determination of aromatic amines in urine. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of aromatic amines in Europe.

• MeSH
• aminy * moč   analýza   MeSH
• aniliny moč   MeSH
• biologický monitoring * metody   MeSH
• fenylendiaminy MeSH
• laboratoře normy   MeSH
• lidé MeSH
• methylenbis(chloranilin) MeSH
• řízení kvality MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• toluidiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• 2-toluidine MeSH Prohlížeč
• 2,4-diaminotoluene MeSH Prohlížeč
• 4,4'-diaminodiphenylmethane MeSH Prohlížeč
• aminy * MeSH
• aniline MeSH Prohlížeč
• aniliny MeSH
• fenylendiaminy MeSH
• methylenbis(chloranilin) MeSH
• toluidiny MeSH

Perfluoroalkyl substances (PFASs) are of very high concern due to their persistence and accumulative behaviour as well as their manifold adverse health effects. Human biomonitoring (HBM) based on the determination of PFASs in serum samples is an adequate and established strategy for exposure and risk assessment of the population. The suspected health risks associated with exposure levels in the general population call for reliable HBM data verified by Quality Assurance and Quality Control (QA/QC) measures. PFASs were among the chemicals selected as priority substances in HBM4EU, a pan-European project to harmonize and advance HBM within 30 European countries. For this purpose, the analytical comparability and accuracy of PFASs-analysing laboratories was assessed in a QA/QC programme comprising Interlaboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs). This paper presents the evaluation process and discusses the results of four ICI/EQUAS rounds for the determination of eight perfluoroalkyl carboxylic acids and four perfluoroalkyl sulfonic acids (PFBS, PFHxS, PFHpS, PFOS) in serum. All 21 participating laboratories achieved satisfactory results for at least six of these biomarkers, although low limits of quantification (of about 0.1 μg/L) were required to quantify serum PFAS levels at general population exposure levels. The mean relative standard deviation of the participants' results (study RSDR) significantly improved from 22 % to 13 % over all PFAS biomarkers in the course of the four rounds. This QA/QC programme succeeded in establishing a network of laboratories with high analytical comparability and accuracy for the analysis of PFASs across 12 European countries.

• Klíčová slova
• Analytical methods, HBM4EU, Internal exposure, Perfluoroalkyl carboxylic acids, Perfluoroalkyl sulfonic acid, Z-scores,
• MeSH
• biologické markery MeSH
• biologický monitoring MeSH
• fluorokarbony * analýza   MeSH
• kyseliny alkansulfonové * analýza   MeSH
• kyseliny karboxylové MeSH
• kyseliny sulfonové analýza   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• fluorokarbony * MeSH
• kyseliny alkansulfonové * MeSH
• kyseliny karboxylové MeSH
• kyseliny sulfonové MeSH

Polycyclic aromatic hydrocarbons (PAHs) were included as priority substances for human biomonitoring (HBM) in the European Human Biomonitoring Initiative (HBM4EU), which intended to harmonise and advance HBM across Europe. For this project, a specific Quality Assurance and Quality Control (QA/QC) programme applying Inter-laboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) was developed to ensure the comparability and accuracy of participating analytical laboratories. This paper presents the results of four ICI/EQUAS rounds for the determination of 13 PAH metabolites in urine, i.e. 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene, 2-, 3- and 9-hydroxyfluorene, 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene. However, 4 PAH metabolites could not be evaluated as the analytical capacity of participating laboratories was too low. Across all rounds and biomarkers, 86% of the participants achieved satisfactory results, although low limits of quantification were required to quantify the urinary metabolites at exposure levels of the general population. Using high-performance liquid or gas chromatography coupled with mass spectrometry (HPLC-MS; GC-MS) and isotope dilution for calibration as well as performing an enzymatic deconjugation step proved to be favourable for the accurate determination of PAHs in urine. Finally, the HBM4EU QA/QC programme identified an international network of laboratories providing comparable results in the analysis of urinary PAH biomarkers, although covering all parameters initially selected was still too challenging.

• Klíčová slova
• 1-Hydroxypyrene, Analytical method, HBM4EU, Human biomonitoring, Quality control, Z-score,
• MeSH
• biologické markery moč   MeSH
• biologický monitoring MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• polycyklické aromatické uhlovodíky * moč   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• biologické markery MeSH
• polycyklické aromatické uhlovodíky * MeSH

PURPOSE: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication. EXPERIMENTAL DESIGN: We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts. RESULTS: We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden. CONCLUSIONS: Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.

• MeSH
• CD8-pozitivní T-lymfocyty * imunologie   účinky léků   MeSH
• ektopické lymfoidní struktury * imunologie   patologie   MeSH
• hepatocytární jaderný faktor 1-alfa * genetika   metabolismus   MeSH
• inhibitory kontrolních bodů * terapeutické užití   farmakologie   MeSH
• karboplatina aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   účinky léků   MeSH
• nádory vaječníků * farmakoterapie   imunologie   patologie   MeSH
• neoadjuvantní terapie metody   MeSH
• paclitaxel aplikace a dávkování   terapeutické užití   farmakologie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   farmakologie   MeSH
• serózní cystadenokarcinom farmakoterapie   patologie   imunologie   MeSH
• stres endoplazmatického retikula účinky léků   imunologie   MeSH
• tumor infiltrující lymfocyty imunologie   účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hepatocytární jaderný faktor 1-alfa * MeSH
• inhibitory kontrolních bodů * MeSH
• karboplatina MeSH
• paclitaxel MeSH

Tidal interactions play a key role in the dynamics and evolution of icy worlds. The intense tectonic activity of Europa and the eruption activity on Enceladus are clear examples of the manifestation of tidal deformation and associated dissipation. While tidal heating has long been recognized as a major driver in the activity of these icy worlds, the mechanism controlling how tidal forces deform the different internal layers and produce heat by tidal friction still remains poorly constrained. As tidal forcing varies with orbital characteristics (distance to the central planet, eccentricity, obliquity), the contribution of tidal heating to the internal heat budget can strongly change over geological timescales. In some circumstances, the tidally-produced heat can result in internal melting and surface activity taking various forms. Even in the absence of significant heat production, tidal deformation can be used to probe the interior structure, the tidal response of icy moons being strongly sensitive to their hydrosphere structure. In the present paper, we review the methods to compute tidal deformation and dissipation in the different layers composing icy worlds. After summarizing the main principle of tidal deformation and the different rheological models used to model visco-elastic tidal response, we describe the dissipation processes expected in rock-dominated cores, subsurface oceans and icy shells and highlight the potential effects of tidal heating in terms of thermal evolution and activity. We finally anticipate how data collected by future missions to Jupiter's and Saturn's moons could be used to constrain their tidal response and the consequences for past and present activities.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• arterioskleróza MeSH
• fenylethery terapeutické užití   MeSH
• hodnocení léčiv MeSH
• klinické zkoušky jako téma MeSH
• koronární nemoc farmakoterapie   MeSH
• lidé MeSH
• praktolol terapeutické užití   MeSH
• propanolaminy terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH
• Názvy látek
• fenylethery MeSH
• praktolol MeSH
• propanolaminy MeSH