BACKGROUND: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations, and sensitivities may differ among these methods. METHODS: As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. RESULTS: Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. CONCLUSIONS: If a negative result was obtained from methods with lower sensitivity (e.g., Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, to identify T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Both anastomotic leak (AL) and conduit necrosis (CN) after oesophagectomy are associated with high morbidity and mortality. Therefore, the identification of preoperative, modifiable risk factors is desirable. The aim of this study was to generate a risk scoring model for AL and CN after oesophagectomy. METHODS: Patients undergoing curative resection for oesophageal cancer were identified from the international Oesophagogastric Anastomosis Audit (OGAA) from April 2018-December 2018. Definitions for AL and CN were those set out by the Oesophageal Complications Consensus Group. Univariate and multivariate analyses were performed to identify risk factors for both AL and CN. A risk score was then produced for both AL and CN using the derivation set, then internally validated using the validation set. RESULTS: This study included 2247 oesophagectomies across 137 hospitals in 41 countries. The AL rate was 14.2% and CN rate was 2.7%. Preoperative factors that were independent predictors of AL were cardiovascular comorbidity and chronic obstructive pulmonary disease. The risk scoring model showed insufficient predictive ability in internal validation (area under the receiver-operating-characteristic curve [AUROC] = 0.618). Preoperative factors that were independent predictors of CN were: body mass index, Eastern Cooperative Oncology Group performance status, previous myocardial infarction and smoking history. These were converted into a risk-scoring model and internally validated using the validation set with an AUROC of 0.775. CONCLUSION: Despite a large dataset, AL proves difficult to predict using preoperative factors. The risk-scoring model for CN provides an internally validated tool to estimate a patient's risk preoperatively.

• MeSH
• anastomóza chirurgická * MeSH
• chronická obstrukční plicní nemoc MeSH
• ezofagektomie * MeSH
• ezofágus chirurgie   patologie   MeSH
• hodnocení rizik MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jícnu * chirurgie   patologie   MeSH
• nekróza * MeSH
• netěsnost anastomózy * epidemiologie   etiologie   MeSH
• rizikové faktory MeSH
• ROC křivka MeSH
• senioři MeSH
• žaludek chirurgie   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• MeSH
• analýza potravin MeSH
• bezpečnost potravin MeSH
• prolaminy MeSH
• testy toxicity MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH
• zprávy MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• environmentální vědy
• zemědělství a potravinářství

BACKGROUND: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

• MeSH
• celosvětové zdraví MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• látky znečišťující vzduch * škodlivé účinky   analýza   MeSH
• lidé MeSH
• nemoci dýchací soustavy * mortalita   MeSH
• ozon * škodlivé účinky   analýza   MeSH
• požáry v divočině * MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění ovzduší škodlivé účinky   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Model-estimated air pollution exposure products have been widely used in epidemiological studies to assess the health risks of particulate matter with diameters of ≤2.5 μm (PM2.5). However, few studies have assessed the disparities in health effects between model-estimated and station-observed PM2.5 exposures. METHODS: We collected daily all-cause, respiratory and cardiovascular mortality data in 347 cities across 15 countries and regions worldwide based on the Multi-City Multi-Country collaborative research network. The station-observed PM2.5 data were obtained from official monitoring stations. The model-estimated global PM2.5 product was developed using a machine-learning approach. The associations between daily exposure to PM2.5 and mortality were evaluated using a two-stage analytical approach. RESULTS: We included 15.8 million all-cause, 1.5 million respiratory and 4.5 million cardiovascular deaths from 2000 to 2018. Short-term exposure to PM2.5 was associated with a relative risk increase (RRI) of mortality from both station-observed and model-estimated exposures. Every 10-μg/m3 increase in the 2-day moving average PM2.5 was associated with overall RRIs of 0.67% (95% CI: 0.49 to 0.85), 0.68% (95% CI: -0.03 to 1.39) and 0.45% (95% CI: 0.08 to 0.82) for all-cause, respiratory, and cardiovascular mortality based on station-observed PM2.5 and RRIs of 0.87% (95% CI: 0.68 to 1.06), 0.81% (95% CI: 0.08 to 1.55) and 0.71% (95% CI: 0.32 to 1.09) based on model-estimated exposure, respectively. CONCLUSIONS: Mortality risks associated with daily PM2.5 exposure were consistent for both station-observed and model-estimated exposures, suggesting the reliability and potential applicability of the global PM2.5 product in epidemiological studies.

• MeSH
• dospělí MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• látky znečišťující vzduch * škodlivé účinky   analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• mortalita trendy   MeSH
• nemoci dýchací soustavy mortalita   MeSH
• pevné částice * škodlivé účinky   analýza   MeSH
• senioři MeSH
• strojové učení MeSH
• velkoměsta * epidemiologie   MeSH
• vystavení vlivu životního prostředí * škodlivé účinky   MeSH
• znečištění ovzduší * škodlivé účinky   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Geografické názvy
• velkoměsta * epidemiologie   MeSH

• MeSH
• chromozomální aberace MeSH
• metaanalýza jako téma MeSH
• mezinárodní spolupráce MeSH
• prenatální diagnóza MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Pediatrie
• NLK Obory
• perinatologie a neonatologie
• genetika, lékařská genetika

• MeSH
• kontraceptiva orální škodlivé účinky   MeSH
• nádory prsu epidemiologie   etiologie   MeSH
• riziko statistika a číselné údaje   MeSH
• statistika jako téma MeSH

• Konspekt
• Gynekologie. Porodnictví
• NLK Obory
• gynekologie a porodnictví
• onkologie
• demografie
• gynekologie a porodnictví

Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenic mechanisms from multiple perspectives.We analyzed a Huntington's disease transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in Huntington's disease and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation.In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.

• MeSH
• genové regulační sítě MeSH
• Huntingtonova nemoc * genetika   MeSH
• lidé MeSH
• stanovení celkové genové exprese * metody   MeSH
• transkriptom * MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cílem studie CARDS (Collaborative Atorvastatin Diabetes Study) bylo kriticky zhodnotit účinnost atorvastatinu podávaného v dávce 10 mg denně oproti placebu v primární prevenci kardiovaskulárních onemocnění u pacientů s diabetem 2. typu.

• Klíčová slova
• Sorbis,
• MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   prevence a kontrola   MeSH
• interpretace statistických dat MeSH
• kardiovaskulární nemoci komplikace   prevence a kontrola   MeSH
• lidé MeSH
• riziko MeSH
• statiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

UNLABELLED: Human age estimation from trace samples may give important leads early in a police investigation by contributing to the description of the perpetrator. Several molecular biomarkers are available for the estimation of chronological age, and currently, DNA methylation patterns are the most promising. In this study, a QIAGEN age protocol for age estimation was tested by five forensic genetic laboratories. The assay comprised bisulfite treatment of the extracted DNA, amplification of five CpG loci (in the genes of ELOVL2, C1orf132, TRIM59, KLF14, and FHL2), and sequencing of the amplicons using the PyroMark Q48 platform. Blood samples from 49 individuals with ages ranging from 18 to 64 years as well as negative and methylation controls were analyzed. An existing age estimation model was applied to display a mean absolute deviation of 3.62 years within the reference data set. KEY POINTS: Age determination as an intelligence tool during investigations can be a powerful tool in forensic genetics.In this study, five laboratories ran 49 samples and obtained a mean absolute deviation of 3.62 years.Five markers were analyzed on a PyroMark Q48 platform.

• Publikační typ
• časopisecké články MeSH