RATIONALE: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. OBJECTIVES: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals. METHODS: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives in hospitals. MEASUREMENTS AND MAIN RESULTS: 1023 hospitals in 69 countries were included. Most of them, 835 (81.6%) were from Europe. Sepsis screening was used in 54.2% of emergency departments(EDs), 47.9% of wards, and 61.7% of intensive care units(ICUs). Sepsis management was standardized in 57.3% of EDs, 45.2% of wards and in 70.7% of ICUs. The implementation of comprehensive quality improvement initiatives(QIIs) was associated with increased screening (EDs +33.3%; wards +44.4%; ICUs +23.8% absolute difference) and increased standardized sepsis management (EDs +33.6%; wards +40.0%; ICUs: +17.7% absolute difference) compared to hospitals without QIIs. 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. CONCLUSIONS: The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regards to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

• Klíčová slova
• health care, quality improvement, quality of care, sepsis, sepsis program,
• Publikační typ
• časopisecké články MeSH

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

• Klíčová slova
• antithrombin, fibrinogen, hemorrhage, thrombin, tranexamic acid,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• dospělí MeSH
• hemokoagulace MeSH
• heparin * škodlivé účinky   MeSH
• krvácení chemicky indukované   terapie   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikoagulancia MeSH
• heparin * MeSH

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

• Klíčová slova
• benzene, lung cancer, occupational exposure,
• MeSH
• benzen toxicita   MeSH
• karcinogeny MeSH
• lidé MeSH
• nádory plic * chemicky indukované   epidemiologie   MeSH
• nemoci z povolání * chemicky indukované   epidemiologie   MeSH
• plíce MeSH
• pracovní expozice * škodlivé účinky   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzen MeSH
• karcinogeny MeSH

• Publikační typ
• dopisy MeSH

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

• Klíčová slova
• TOPMed, genetic association studies, interstitial lung disease, telomerase, whole-genome sequencing,
• MeSH
• exom MeSH
• idiopatická plicní fibróza * genetika   MeSH
• lidé MeSH
• sekvenování celého genomu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

• MeSH
• biologický monitoring přístrojové vybavení   metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxygenoterapie metody   MeSH
• plicní embolie diagnóza   patofyziologie   terapie   MeSH
• poměr plicní ventilace a perfuze * MeSH
• rychlost toku krve * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tomografie metody   MeSH
• vyšetření u lůžka 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
• úvodníky MeSH

• MeSH
• Betacoronavirus MeSH
• COVID-19 MeSH
• koronavirové infekce * MeSH
• kritický stav MeSH
• lidé MeSH
• mimotělní membránová oxygenace * MeSH
• pandemie * MeSH
• SARS-CoV-2 MeSH
• syndrom dechové tísně * terapie   MeSH
• virová pneumonie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.

• Klíčová slova
• diesel exhaust, epidemiology, lung neoplasms, occupational exposure,
• MeSH
• adenokarcinom plic epidemiologie   MeSH
• dospělí MeSH
• inhalační expozice MeSH
• kouření cigaret epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom epidemiologie   MeSH
• nádory plic epidemiologie   MeSH
• odds ratio MeSH
• pracovní expozice statistika a číselné údaje   MeSH
• senioři MeSH
• sexuální faktory MeSH
• spinocelulární karcinom epidemiologie   MeSH
• uhlík MeSH
• velkobuněčný karcinom epidemiologie   MeSH
• výfukové emise vozidel * 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
• Geografické názvy
• Evropa epidemiologie   MeSH
• Kanada epidemiologie   MeSH
• Názvy látek
• uhlík MeSH
• výfukové emise vozidel * MeSH

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.

• Klíčová slova
• crystalline silica, lung cancer, occupational exposure,
• MeSH
• adenokarcinom plic epidemiologie   MeSH
• dospělí MeSH
• inhalační expozice MeSH
• kouření cigaret MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom epidemiologie   MeSH
• nádory plic epidemiologie   patologie   MeSH
• oxid křemičitý * MeSH
• pracovní expozice statistika a číselné údaje   MeSH
• senioři MeSH
• silikóza epidemiologie   MeSH
• spinocelulární karcinom epidemiologie   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
• Geografické názvy
• Evropa epidemiologie   MeSH
• Kanada epidemiologie   MeSH
• Názvy látek
• oxid křemičitý * MeSH

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

• Klíčová slova
• computer-aided image analysis, early detection, lung cancer, neural networks, risk stratification,
• MeSH
• algoritmy MeSH
• deep learning * MeSH
• lidé MeSH
• mnohočetné plicní uzly diagnostické zobrazování   MeSH
• nádory plic diagnostické zobrazování   epidemiologie   patofyziologie   MeSH
• neuronové sítě (počítačové) MeSH
• počítačová rentgenová tomografie metody   MeSH
• rentgenový obraz - interpretace počítačová metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Spojené státy americké epidemiologie   MeSH