Control Centre for Intensive Care as a Tool for Effective Coordination, Real-Time Monitoring, and Strategic Planning During the COVID-19 Pandemic.

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named "Control Centre for Intensive Care," which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic.

Cancer incidence trends in the Czech Republic.

BACKGROUND: Evaluation of time trends is an integral part of a comprehensive analysis of cancer data. Our study aimed to assess trends in cancer incidence in the period 1977-2018 in the Czech Republic. METHODS: Cancer data were obtained from the Czech National Cancer Registry. Incidence trends were evaluated using the joinpoint regression. The overall trend for the entire analysed period and the current trend for the last 10 years were determined using the average annual percentage change. RESULTS: In the period 1977-2018, the age-standardised incidence (European standard) of malignant neoplasms excluding non-melanoma skin cancers increased from 518.2 to 681.9 cases per 100,000 population in men, and from 320.9 to 467.2 in women. The largest increase in trend in the analysed period was observed for melanoma, which showed an average annual increase of 4.0 % in men and 3.3 % in women. Over the last decade, a significant increase has been observed for head and neck cancer and oesophageal cancer, mainly in women. On the contrary, the largest decrease in trend in the analysed period was observed for stomach cancer, with an average decrease of 2.9 % in men and 2.8 % in women. Over the last 10 years, a highly significant decrease has also been observed for colorectal cancer: 3.2 % in men and 2.8 % in women. The largest difference in trend between the sexes was recorded in lung cancer: a steady decline of 1.3 % per year was observed for men, but an increase of 3.1 % per year was demonstrated for women. After the introduction of colorectal and cervical cancer screening programmes, a significant decrease of incidence rates for these diagnoses was observed. CONCLUSIONS: Knowledge of the current cancer burden in the population and its time trends will help to prioritise targets and future resource allocation to cancer control.

Development of the Czech Childhood Cancer Information System: Data Analysis and Interactive Visualization.

BACKGROUND: The knowledge of cancer burden in the population, its time trends, and the possibility of international comparison is an important starting point for cancer programs. A reliable interactive tool describing cancer epidemiology in children and adolescents has been nonexistent in the Czech Republic until recently. OBJECTIVE: The goal of this study is to develop a new web portal entitled the Czech Childhood Cancer Information System (CCCIS), which would provide information on childhood cancer epidemiology in the Czech Republic. METHODS: Data on childhood cancers have been obtained from the Czech National Cancer Registry. These data were validated using the clinical database of childhood cancer patients and subsequently combined with data from the National Register of Hospitalised Patients and with data from death certificates. These validated data were then used to determine the incidence and survival rates of childhood cancer patients aged 0 to 19 years who were diagnosed in the period 1994 to 2016 (N=9435). Data from death certificates were used to monitor long-term mortality trends. The technical solution is based on the robust PHP development Symfony framework, with the PostgreSQL system used to accommodate the data basis. RESULTS: The web portal has been available for anyone since November 2019, providing basic information for experts (ie, analyses and publications) on individual diagnostic groups of childhood cancers. It involves an interactive tool for analytical reporting, which provides information on the following basic topics in the form of graphs or tables: incidence, mortality, and overall survival. Feedback was obtained and the accuracy of outputs published on the CCCIS portal was verified using the following methods: the validation of the theoretical background and the user testing. CONCLUSIONS: We developed software capable of processing data from multiple sources, which is freely available to all users and makes it possible to carry out automated analyses even for users without mathematical background; a simple selection of a topic to be analyzed is required from the user.

Significant current epidemiological trend: Haematological malignancies as subsequent primary tumours in cancer patients.

BACKGROUND: Numbers of patients who develop subsequent primary tumours have markedly increased recently. This study aimed to carry out a comprehensive analysis documenting the risk of incidence of subsequent haematological malignancies. METHODS: The Czech National Cancer Registry was the main data source, containing records of 126,822 haematological malignancies diagnosed in the period 1977-2016. Subsequent haematological malignancies were identified according to IACR rules. Joinpoint regression was employed to assess the time trends. The risk of development of subsequent haematological malignancy was evaluated by the standardised incidence ratio. The Kaplan-Meier curves were used to assess the differences in survival. RESULTS: Age-standardised incidence of subsequent haematological malignancies increased from 0.5 in 1977 to 9.1 in 2016. In 1992, there was a significant change in the trend: a sharp increase by 7.7 % annually was revealed thereafter. The risk of development of a haematological malignancy was approximately 1.5 times higher in persons with history of any cancer than in the general Czech population. Patients with haematological malignancies - mainly myelodysplastic syndromes, polycythaemia vera and non-Hodgkin lymphoma - were shown to be at the highest risk of developing a subsequent haematological malignancy. While the median survival following a first haematological malignancy was 2.3 years, it was only 1.1 years for subsequent haematological malignancies (p < 0.001). CONCLUSIONS: Our study identified the highest-risk diagnoses in terms of development of subsequent haematological malignancy. The results might be useful to set up correctly follow-up procedures from which cancer patients could benefit.

Covidogram as a simple tool for predicting severe course of COVID-19: population-based study.

OBJECTIVES: COVID-19 might either be entirely asymptomatic or manifest itself with a large variability of disease severity. It is beneficial to identify early patients with a high risk of severe course. The aim of the analysis was to develop a prognostic model for the prediction of the severe course of acute respiratory infection. DESIGN: A population-based study. SETTING: Czech Republic. PARTICIPANTS: The first 7455 consecutive patients with COVID-19 who were identified by reverse transcription-PCR testing from 1 March 2020 to 17 May 2020. PRIMARY OUTCOME: Severe course of COVID-19. RESULT: Of a total 6.2% of patients developed a severe course of COVID-19. Age, male sex, chronic kidney disease, chronic obstructive pulmonary disease, recent history of cancer, chronic heart failure, acid-related disorders treated with proton-pump inhibitors and diabetes mellitus were found to be independent negative prognostic factors (Area under the ROC Curve (AUC) was 0.893). The results were visualised by risk heat maps, and we called this diagram a 'covidogram'. Acid-related disorders treated with proton-pump inhibitors might represent a negative prognostic factor. CONCLUSION: We developed a very simple prediction model called 'covidogram', which is based on elementary independent variables (age, male sex and the presence of several chronic diseases) and represents a tool that makes it possible to identify-with a high reliability-patients who are at risk of a severe course of COVID-19. Obtained results open clinically relevant question about the role of acid-related disorders treated by proton-pump inhibitors as predictor for severe course of COVID-19.

Complex Reporting of the COVID-19 Epidemic in the Czech Republic: Use of an Interactive Web-Based App in Practice.

BACKGROUND: The beginning of the coronavirus disease (COVID-19) epidemic dates back to December 31, 2019, when the first cases were reported in the People's Republic of China. In the Czech Republic, the first three cases of infection with the novel coronavirus were confirmed on March 1, 2020. The joint effort of state authorities and researchers gave rise to a unique team, which combines methodical knowledge of real-world processes with the know-how needed for effective processing, analysis, and online visualization of data. OBJECTIVE: Due to an urgent need for a tool that presents important reports based on valid data sources, a team of government experts and researchers focused on the design and development of a web app intended to provide a regularly updated overview of COVID-19 epidemiology in the Czech Republic to the general population. METHODS: The cross-industry standard process for data mining model was chosen for the complex solution of analytical processing and visualization of data that provides validated information on the COVID-19 epidemic across the Czech Republic. Great emphasis was put on the understanding and a correct implementation of all six steps (business understanding, data understanding, data preparation, modelling, evaluation, and deployment) needed in the process, including the infrastructure of a nationwide information system; the methodological setting of communication channels between all involved stakeholders; and data collection, processing, analysis, validation, and visualization. RESULTS: The web-based overview of the current spread of COVID-19 in the Czech Republic has been developed as an online platform providing a set of outputs in the form of tables, graphs, and maps intended for the general public. On March 12, 2020, the first version of the web portal, containing fourteen overviews divided into five topical sections, was released. The web portal's primary objective is to publish a well-arranged visualization and clear explanation of basic information consisting of the overall numbers of performed tests, confirmed cases of COVID-19, COVID-19-related deaths, the daily and cumulative overviews of people with a positive COVID-19 case, performed tests, location and country of infection of people with a positive COVID-19 case, hospitalizations of patients with COVID-19, and distribution of personal protective equipment. CONCLUSIONS: The online interactive overview of the current spread of COVID-19 in the Czech Republic was launched on March 11, 2020, and has immediately become the primary communication channel employed by the health care sector to present the current situation regarding the COVID-19 epidemic. This complex reporting of the COVID-19 epidemic in the Czech Republic also shows an effective way to interconnect knowledge held by various specialists, such as regional and national methodology experts (who report positive cases of the disease on a daily basis), with knowledge held by developers of central registries, analysts, developers of web apps, and leaders in the health care sector.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices.

Aims: To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results: The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion: Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

Predictors of quality of life in Czech female breast cancer survivors following treatment with special interest to coping strategies.

OBJECTIVES: This study examined the prognostic significance of breast cancer patients characteristics (coping strategies, BMI, age) and disease characteristics (stage of disease, relapse) with respect to quality of life (QoL) following treatment.Sample and settings: 120 breast cancer patients following treatment were recruited. Health-related QoL was assessed using the Czech version of FACT-B and SF-36; additionally, we used a life satisfaction questionnaire. Coping strategies were assessed using the SVF-78 method. In our sample of women, the average time from diagnosis to start of the study was 5.3 years. STATISTICAL ANALYSIS: Factors influencing QoL after treatment were analysed with univariate and multivariate linear regression. RESULTS: Overall negative strategy defined in SVF-78 (Flight tendency, Resignation and Self-accusation) was found to be associated with lower scores of most components of used QoL methods, while Resignation was found as the most negatively influencing strategy. Active problem confrontation (Situation control and Positive self-instruction) was associated with better QoL. More advanced stages and recurrence were related to a significant decrease in QoL for certain components only. CONCLUSION: Our findings suggest a significant predictive power of disease-related factors and of patients characteristics including coping strategies for QoL following treatment in Czech breast cancer survivors.Key words: breast cancer survivors - coping strategy - linear regression model - quality of life prediction - resignation.

Molecular dynamics study of Pseudomonas aeruginosa lectin-II complexed with monosaccharides.

We present the results of a series of 10-ns molecular dynamics simulations on Pseudomonas aeruginosa lectin-II (PA-IIL) and its complexes with four different monosaccharides. We compare the saccharide-free, saccharide-occupied, and saccharide- and ion-free forms of the lectin. The results are coupled with analysis of the water density map and calcium coordination. The water density pattern around the binding site in the free lectin molecular dynamics was fitted with that in the X-ray and with the hydroxyl groups of the monosaccharide within the lectin/monosaccharide complexes and the best ligand was predicted based on the best fit. Interestingly, the water density pattern around the binding site in the uncomplexed lectin exactly fitted the O2, O3, and O4 hydroxyl groups of the fucose complex with the lectin. This observation could lead to a hypothesis that the replacement of these three water molecules from the binding site by the monosaccharide decreases the entropy of the complex and increases the entropy of the water molecules, which favors the binding. It suggests that the high density peaks of the solvent around the binding site in the free protein could be the tool to predict hydroxyl group orientation of the sugar in the protein/sugar complexes. The high affinity of PA-IIL binding site is also attributed to the presence of two calcium ions, each of them making five to six coordinations with the protein part and two coordinations with either water or the monosaccharide. When the calcium ions are removed from the simulated system, they are replaced by sodium ions from the solvent. These observations rationalize the high binding affinity of PA-IIL towards fucose.

Structures and mechanisms of glycosyltransferases.

Glycosyltransferases (GTs) catalyze the transfer of a sugar moiety from an activated donor sugar onto saccharide and nonsaccharide acceptors. A sequence-based classification spreads GTs in many families thus reflecting the variety of molecules that can be used as acceptors. In contrast, this enzyme family is characterized by a more conserved three-dimensional architecture. Until recently, only two different folds (GT-A and GT-B) have been identified for solved crystal structures. The recent report of a structure for a bacterial sialyltransferase allows the definition of a new fold family. Progress in the elucidation of the structures and mechanisms of GTs are discussed in this review. To accommodate the growing number of crystal structures, we created the 3D-Glycosyltransferase database to gather structural information concerning this class of enzymes.

Molecular modeling and site-directed mutagenesis of plant chloroplast monogalactosyldiacylglycerol synthase reveal critical residues for activity.

Monogalactosyldiacylglycerol (MGDG), the major lipid of plant and algal plastids, is synthesized by MGD (or MGDG synthase), a dimeric and membrane-bound glycosyltransferase of the plastid envelope that catalyzes the transfer of a galactosyl group from a UDP-galactose donor onto a diacylglycerol acceptor. Although this enzyme is essential for biogenesis, and therefore an interesting target for herbicide design, no structural information is available. MGD monomers share sequence similarity with MURG, a bacterial glycosyltransferase catalyzing the transfer of N-acetyl-glucosamine on Lipid 1. Using the x-ray structure of Escherichia coli MURG as a template, we computed a model for the fold of Spinacia oleracea MGD. This structural prediction was supported by site-directed mutagenesis analyses. The predicted monomer architecture is a double Rossmann fold. The binding site for UDP-galactose was predicted in the cleft separating the two Rossmann folds. Two short segments of MGD (beta2-alpha2 and beta6-beta7 loops) have no counterparts in MURG, and their structure could not be determined. Combining the obtained model with phylogenetic and biochemical information, we collected evidence supporting the beta2-alpha2 loop in the N-domain as likely to be involved in diacylglycerol binding. Additionally, the monotopic insertion of MGD in one membrane leaflet of the plastid envelope occurs very likely at the level of hydrophobic amino acids of the N-terminal domain.

High affinity fucose binding of Pseudomonas aeruginosa lectin PA-IIL: 1.0 A resolution crystal structure of the complex combined with thermodynamics and computational chemistry approaches.

PA-IIL is a fucose-binding lectin from Pseudomonas aeruginosa that is closely related to the virulence factors of the bacterium. Previous structural studies have revealed a new carbohydrate-binding mode with direct involvement of two calcium ions (Mitchell E, Houles C, Sudakevitz D, Wimmerova M, Gautier C, Perez S, Wu AM, Gilboa-Garber N, Imberty A. Structural basis for selective recognition of oligosaccharides from cystic fibrosis patients by the lectin PA-IIL of Pseudomonas aeruginosa. Nat Struct Biol 2002;9:918-921). A combination of thermodynamic, structural, and computational methods has been used to study the basis of the high affinity for the monosaccharide ligand. A titration microcalorimetry study indicated that the high affinity is enthalpy driven. The crystal structure of the tetrameric PA-IIL in complex with fucose and calcium was refined to 1.0 A resolution and, in combination with modeling, allowed a proposal to be made for the hydrogen-bond network in the binding site. Calculations of partial charges using ab initio computational chemistry methods indicated that extensive delocalization of charges between the calcium ions, the side chains of the protein-binding site and the carbohydrate ligand is responsible for the high enthalpy of binding and therefore for the unusually high affinity observed for this unique mode of carbohydrate recognition.

Molecular dynamics simulations of glycosyltransferase LgtC.

Molecular dynamics simulations have been performed on fully solvated alpha-(1-->4)-galactosyltransferase LgtC from Neisseria meningitidis with and without the donor substrate UDP-Gal and in the presence of the manganese ion. The analysis of the trajectories revealed a limited movement in the loop X (residues 75-80) and a larger conformational change in the loop Y (residues 246-251) in the simulation, when UDP-Gal was not present. In this case, the loops X and Y open by almost 10A, exposing the active site to the solvent. The 'hinge region' responsible for the opening is composed of residues 246-247. We have also analyzed the behavior of the manganese ion in the simulations. The coordination number is 6 when UDP-Gal is present and it increases to 7 when it is absent. In the latter case, three water molecules become coordinated to the ion. In both cases, the coordination is very stable implying that the manganese ion is tightly bound in the active site of the enzyme even if UDP-Gal is not present. Further analysis of the structural water molecules location confirmed that the mobility of water molecules in the active site and the accessibility of this site for solvent are higher in the absence of the substrate.