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Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PURPOSE OF THE STUDY Laboratory methods are central to prosthetic joint infection (PJI) diagnosis. Most research teams focus on detection of specific inflammatory markers, causative pathogens, or on assessment of the tissue response. This study sought to determine the optimal cut-off values and diagnostic performance of selected synovial markers in relation to the diagnosis of hip or knee PJI. The studied markers were synovial level of glucose, lactate, coefficient of energy balance (CEB) and NGAL (neutrophil gelatinase-associated lipocalin). MATERIAL AND METHODS This prospective study includes 89 patients who underwent revision total knee or hip arthroplasty for septic or aseptic reasons in the period from 2014 to 2017. Among these 89 patients, there are 2 cases of prosthetic hip infection, 22 cases of prosthetic knee infection, 31 aseptic revision total hip arthroplasties and 34 aseptic revision total knee arthroplasties. The diagnostic characteristics of the studied methods were set in relation to the reference standard, the 2013 MSIS (Musculoskeletal Infection Society) criteria. The cut-off values were calculated using the ROC (receiver operating characteristic curve) analysis. RESULTS The synovial glucose test is considered positive if the glucose level drops below 2.65 mmol/L. The area under the curve is 0.813, sensitivity 75.0%, specificity 83.1%. The synovial lactate test is considered positive if lactate level rises above 8.87 mmol/L. The area under the curve is 0.882, sensitivity 70.8%, specificity 95.4%. Synovial NGAL is considered positive if its level exceeds 998 μg/L. The area under the curve is 1.000, sensitivity 100.0%, specificity 100.0%. CEB is considered positive if its value is lower than +4.665. The area under the curve is 0.883, sensitivity 91.7% and specificity 69.8%. Combining of these tests with other synovial markers does not improve the diagnostic performance of the studied tests. CONCLUSIONS The glucose and lactate levels and CEB undoubtedly reflect the presence of an inflammatory process in a prosthetic joint. However, the diagnostic characteristics of these tests are not better than those of other modern diagnostic techniques. As opposed to these tests, synovial NGAL shows excellent diagnostic performance. Nonetheless, the potential of this method shall be verified on larger cohorts of patients. [ABSTRACT FROM AUTHOR]

This review focuses on the issue of the effectiveness of biological and targeted treatment in seropositive and seronegative patients with rheumatoid arthritis. Rando-mized trials preferentially enroll strongly active patients, i.e. mostly seropositive, with a minority of patients being seronegative. Therefore, the evidence of efficacy in seronegative patients comes primarily from meta-analyses of open-label extensions and registries. Due to different methodologies, results are sometimes inconsistent. However, a larger body of evidence demonstrates that rituximab and abatacept are more effective in seropositive patients, and a trend for efficacy has also been shown for tocilizumab. In contrast, anti-TNF drugs are as effective in both seropositive and seronegative patients. In randomized controlled trials, tofacitinib was more effective in seropositive than in seronegative patients. In conclusion, although some differences in the efficacy of biological and targeted drugs have been found between seropositive and seronegative patients, the differences are not so large as to be the only selection criterion in the selection of a biological or targeted drug. [ABSTRACT FROM AUTHOR]

Copyright of Otorhinolaryngology & Phoniatrics / Otorinolaryngologie a Foniatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PURPOSE OF THE STUDY Laboratory methods are central to prosthetic joint infection (PJI) diagnosis. Most research teams focus on detection of specific inflammatory markers, causative pathogens, or on assessment of the tissue response. This study sought to determine the optimal cut-off values and diagnostic performance of selected synovial markers in relation to the diagnosis of hip or knee PJI. The studied markers were synovial level of glucose, lactate, coefficient of energy balance (CEB) and NGAL (neutrophil gelatinase-associated lipocalin). MATERIAL AND METHODS This prospective study includes 89 patients who underwent revision total knee or hip arthroplasty for septic or aseptic reasons in the period from 2014 to 2017. Among these 89 patients, there are 2 cases of prosthetic hip infection, 22 cases of prosthetic knee infection, 31 aseptic revision total hip arthroplasties and 34 aseptic revision total knee arthroplasties. The diagnostic characteristics of the studied methods were set in relation to the reference standard, the 2013 MSIS (Musculoskeletal Infection Society) criteria. The cut-off values were calculated using the ROC (receiver operating characteristic curve) analysis. RESULTS The synovial glucose test is considered positive if the glucose level drops below 2.65 mmol/L. The area under the curve is 0.813, sensitivity 75.0%, specificity 83.1%. The synovial lactate test is considered positive if lactate level rises above 8.87 mmol/L. The area under the curve is 0.882, sensitivity 70.8%, specificity 95.4%. Synovial NGAL is considered positive if its level exceeds 998 μg/L. The area under the curve is 1.000, sensitivity 100.0%, specificity 100.0%. CEB is considered positive if its value is lower than +4.665. The area under the curve is 0.883, sensitivity 91.7% and specificity 69.8%. Combining of these tests with other synovial markers does not improve the diagnostic performance of the studied tests. CONCLUSIONS The glucose and lactate levels and CEB undoubtedly reflect the presence of an inflammatory process in a prosthetic joint. However, the diagnostic characteristics of these tests are not better than those of other modern diagnostic techniques. As opposed to these tests, synovial NGAL shows excellent diagnostic performance. Nonetheless, the potential of this method shall be verified on larger cohorts of patients. Key words: prosthetic joint infection, periprosthetic infection, total knee arthroplasty, total hip arthroplasty, diagnosis, glucose, lactate, CEB, NGAL.

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of leukemia, accounting for 25 % of childhood leukemias. By the presence of genetic mutations in hematopoietic/ progenitor stem cells, the bone marrow produces a large number of abnormal undifferentiated leukocytes (blasts), which significantly impairs the proper differentiation of cells. AML is induced by two interventions. Chromosomal translocation during hematopoiesis of intrauterine development is the first intervention. This creates preleukemic fusion genes (PFG), which can later be transformed by a second intervention (point genetic mutation - deletion, insertion ) into a functional malignant clone. Characteristic AML fusion genes include AML1-ETO, PML-RARA or MLL-AF9, which in turn produce hybrid proteins with altered function. Several studies suggest that these PFGs are considered an important prognostic tool in disease assessment. While the incidence of PFG characteristic of acute lymphoblastic leukemia (ALL) has been relatively well studied by several research groups and has been estimated at 1 to 5% in the umbilical cord blood of healthy neonates, PFG relevant to AML are still not sufficiently clarified.

Background: A long-term occupational exposure of healthcare staff to cytostatics and ionizing radiation is associated with a possible manifestation of their genotoxic, carcinogenic and teratogenic effects., Material and Methods: A total number of 101 employees working with cytostatics or ionizing radiation were examined (some of them repeatedly) in a cancer treatment facility. The control group consisted of 119 persons excluded from the risk exposure. Fluorescence in situ hybridization with three pairs of whole-chromosomal probes and a pancrossomeric probe was used and the translocation frequency was determined., Results: The total number of chromosomal rearrangements of healthcare professionals and control group correlates with age. Taking into account the age dependence, an increased level of chromosomal reconstruction was found in the case of 11 individuals, 10 of which were female, working on the positions of pharmacist, general nurse, physician. A total of 9 of those case involved the work with cytostatics. Five of these cases were re-examined two years later and the observed levels dropped to the control level., Conclusion: The results of biomonitoring should be evaluated on a group basis and individually, taking into account the personal history and possible non-professional effects on individuals - in particular those related to specific environmental measurement results.Key words: preventive medicine - occupational exposure - cytostatic agents - chromosome aberrations - in situ hybridization - fluorescence The authors declare they have no potential conflicts of interest concern ing drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This work was supported by project of Ministry of Health Czech Republic. reg. No. 15-33968A.Submitted: 12. 4. 2018Accepted: 16. 4. 2018.

Introduction: Corrosion casts (CCs) are used for the visualization and assessment of hollow structures. CCs with filled capillaries enable (with the help of imaging methods) to obtain data for mathematical organ perfusion modelling. As the processing is more difficult in case of organs with greater volume of the vasculature, mainly organs from small animals have been cast up to now. The aim of this study was to optimize the protocol of corrosion casting of different organs of pig. Porcine organs are relatively easily accessible and frequently used in experimental medicine., Method: Organs from 10 healthy Prestice Black-Pied pigs (6 females, body weight 35-45 kg), were used in this study (liver, spleen, kidneys and small intestine). The organs were dissected, heparin was administered into the systemic circulation and then the vascular bed of the organs was flushed with heparinized saline either in situ (liver) or after their removal (spleen, kidney, small intestine). All handling was done under the water surface to prevent air embolization. The next step was an intraarterial (in case of the liver also intraportal) administration of Biodur E20® (Heidelberg, Germany) resin. After hardening of the resin the organ tissue was dissolved by 15% KOH and the specimen was rinsed with tap water. Voluminous casts were stored in 70% denatured alcohol, the smaller ones were lyophilized. The casts were assessed with a stereomicroscope, computed and microcomputed tomography (CT and microCT), a scanning electron microscope (SEM) and high-resolution digital microscope (HRDM)., Results: High-quality CCs of the porcine liver, kidneys, spleen and small intestine were created owing to the sophisticated organ harvesting, the suitable resin and casting procedure. Macroscopic clarity was improved thanks to the possibility of resin dying. Scanning by CT was performed and showed to be a suitable method for the liver cast examination. MicroCT, SEM and HRDM produced images of the most detailed structures of vascular bed. Despite the fact that SEM seems to be an irreplaceable method for CCs quality control, it seems that this modality could be partly replaced by HRDM. MicroCT enabled to obtain data about three-dimensional layout of the vascular bed and data for mathematical modelling of organ perfusion. With regard to the quality of the CCs, they could also be used to teach human anatomy., Conclusions: The protocol of the corrosion casting of the porcine liver, kidneys, spleen and small intestine CCs was optimized. Thanks to different imaging methods, the CCs can be used as a source of data on three-dimensional architecture of the vascular bed. These data can be used for mathematical modeling of organ perfusion which can be helpful for example for optimization of organ resections.Key words: corrosion casts microvasculature Biodur E20® domestic pig animal model.

Background: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant tumours. Metastatic RCC (mRCC) is commonly treated with tyrosine kinase inhibitors (TKI). Effective TKIs administration can be achieved only by accurate prediction of therapeutical response. Therefore, the aim of this study was to analyse papers concerning predictive potential of microRNA (miRNA)., Material and Methods: We chose seven candidate miRNAs and analysed their expression on 44 patients divided into cohort with poor and good response to sunitinib treatment. Patients were divided into two groups according to progression-free survival. RNA from tissue samples was isolated and expression of selected miRNAs was measured using quantitative PCR with miRNA-specific TaqMan probes., Results: We successfully validated two miRNAs to be differentially expressed in responding and non-responding patients to sunitinib treatment. Other analysed miRNAs have not shown predictive potential., Conclusion: From miRNAs studied so far, two miRNAs had predictive value according to present study.Key words: microRNA - renal cell carcinoma - sunitib The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Supported by Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

Background: Currently, more than 200 hereditary cancer syndromes have been described, yet, in most countries genetic testing is restricted to a narrow spectrum of genes within a limited group of people tested., Methods: For this retrospective study we used the TruSight cancer panel (Illumina)--NGS panel targeting 94 cancer predisposition genes in order to analyze 50 high-risk cancer patients with significant personal and family history of cancer who did not carry mutations in BRCA1, BRCA2, MLH1, MSH2, MSH6, TP53 or APC genes. All pathogenic and potentially pathogenic mutations detected by NGS technology have been confirmed by Sanger sequencing., Results: There were several deleterious (frame-shift/nonsense) mutations detected in ATM, BAP1, FANCC, FANCI, PMS2, SBDS, ERCC2, RECQL4 genes. Various pathogenic or potentially pathogenic (missense, predicted splice site, in-frame insertion/deletion) mutations were detected in ATM, BRIP1, CDH1, CHEK2, ERCC2, ERCC3, ERCC4, FANCA, MC1R, MEN1, MRE11A, MUTYH, PALB2, RAD51C, RET, SDHB, STK11. These mutations affect highly conserved protein domains and affect their function as proved by the available functional assays. They were confirmed to be pathogenic as an "Parent No2 " in serious recessive diseases such as Ataxia telangiectasia or Fanconi anemia. The clinical significance of the majority of detected missense variants still remains to be identified., Conclusion: Moderate or low penetrance variants are of limited clinical importance. Panel genetic testing in high-risk individuals with cancer provides important information concerning the cause of the investigated cancer, and may assist in the risk assesment and optimal management of the cancer, as well as in further preventive care.

Background: The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process. Previous research shows that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signaling pathways downstream of EGFR. Of all relevant factors (mutation of KRAS, NRAS, BRAF, and PIK3CA oncogenes, inactivation of tumor suppressors PTEN and TP53, amplification of EGFR and HER2, and expression of epiregulin and amphiregulin, mikroRNA miR-31-3p, and miR-31-5p), only evaluation of KRAS and NRAS mutations has entered routine clinical practice. The role of the other markers still needs to be validated. The ongoing benefit of anti-EGFR therapy could be indicated by specific clinical parameters measured after the initiation of targeted therapy, including early tumor shrinkage, the deepness of the response, or hypomagnesemia. The accuracy of predictive dia-gnostic tools could be also increased by examining a combination of predictive markers using next generation sequencing methods. However, unjustified investigation of many molecular markers should be resisted as this may complicate interpretation of the results, particularly in terms of their specific clinical relevance., Aim: The aim of this review is to describe current possibilities with respect to predicting responses to EGFR blockade in the context of the EGFR pathway, and the utilization of such results in routine clinical practice.

Genetic testing for hereditary breast and ovarian cancer syndrome is indicated by a genetic counselor on the basis of personal and family history evaluation, with regards to consensual criteria, reflecting the current knowledge. The latest recommendation accepted by Czech Oncology Society and Society of Medical Genetics was published in the supplement 22 to the Journal of Clinical Oncology in 2009. Since the availability of PARP inhibitors for treatment of ovarian cancer in BRCA1/ 2 mutation carriers, an update of these guidelines is urgently needed. Another reason is a higher incidence of other malignancies in high-risk families, such as prostate or pancreatic cancer. The goal is to refine the detection of mutations in selected families, to improve preventive care and collect data necessary for targeted cancer treatment.

COPD is a serious pulmonary disease with rising global socioeconomic impact. From the perspective of the Czech Republic COPD was responsible for 21 000 acute hospitalizations and 3 500 deaths, mortality reaches 33/100 000 in 2015. Early stages of disease may be associated with a significant reduction of exercise capacity and the reduction of activities of daily living. Moreover early stages of bronchial obstruction are associated with the fastest lung function decline. Finally, early elimination of the risk of inhalation exposure is able to influence the course of the disease and to reduce its mortality. Most current treatment strategies and national recommendations attributed central role to bronchodilator drugs. Long-acting bronchodilators (LAMA and LABA) creates an essential component of the treatment of symptomatic individuals in the Czech COPD guidelines as well. Actual version of this document constitutes as standard therapy: long-lasting inhaled bronchodilators, targeted efforts to eliminate inhalation risk, vaccination, regular exercise, repeated inhalation technique training, identification, and treatment of relevant comorbidities. All other drugs (inhaled-corticosteroids, mucoactive medication, roflumilast, antibiotics), and non-pharmacological (lung volume reductions, nutrition support, long-term oxygen, home non-invasive ventilation, lung transplantation, palliative care) procedures are intended for a specific subgroups of patients only. The newest type of bronchodilator therapy is represented by a fixed dual bronchodilation. Currently we can use four original drug combinations: titropium + olodaterol, glycopyrronium + indacaterol, umeklidinium + vilanterol and aclidinium + formoterol in the Czech Republic. This area is an enterprising research. For example comprehensive scientific program covering eight studies on 15 000 COPD patients (TOviTO) assess the therapeutic benefits of tiotropium + olodaterolu in terms of lung function, quality of life, exercise tolerance, daily physical activity and the incidence of acute exacerbations. Meanwhile the published results of analyzed studies TONADO, OTEMTO, VIVACITO, and the first results of the study DYNAGITO have showed that fixed dual bronchodilation should be a mandatory treatment to all the symptomatic COPD patients. Unfortunately "face to face" comparison of different drug combinations is still missing. However, the treatment with tiotropium + olodaterol combination has been demonstrated to significantly (35 %) reduce the occurrence of clinically significant deterioration, which may lead to the stabilization of this multicomponent disease.Key words: COPD - hospitalizations - inhaled bronchodilators - mortality - treatment.