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Life in the city has changed on different levels in the past few years. Smart solutions are becoming a part of daily lives of citizens. This leads to an increase in the quality of life in the cities - ordinary cities are slowly transforming into the Smart Cities. On the other hand, in cities there are also devices which the ordinary citizen does not come directly to contact with, but these devices provide significant features like traffic management, oxygen distribution in the subway etc. Any unexpected failure can cause a large economic damage or jeopardize citizens’ lives. In order to prevent the failure, these key devices are subject to preventive maintenance which, on the other side, requires a huge amount of human and material resources. Predictive maintenance can be more effective. However, its application is not an easy task. The Smart City requires the deployment of a solution that can independently learn from previous fails and respond to unknown problems. As a solution, we propose an approach based on the utilization of machine learning techniques and recommendation systems., This article was supported thanks to the generous support under the Operational Program Integrated Infrastructure for the project: "Research Centre for Data Analysis and Protection - II. Stage", Project no. 313021W479, co-financed by the European Regional Development Fund.

Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease.A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings.0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions.Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) 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.

Deep sternal wound infection is a feared complication of cardiac surgery due to the negative impact on mortality, morbidity and long-term survival. Its incidence has remained more or less unchanged over the last three decades despite the significant increase in patients´ morbidity and complexity of cardiac surgery. The review summaries strategies to reduce the incidence of deep sternal wound reflecting general surgical site infection prevention and specificities of surgery performed through the median sternotomy. Furthermore, contemporary evidence-based recommendations for prevention of this complication are highlighted in the review. Key words: sternal infection - prevention - cardiac surgery.

PURPOSE OF THE STUDY Outcome analysis of penetrating cardiac and great vessels injury within the 15-year existence of the cardiac surgery service as a part of the major trauma centre of the University Hospital Olomouc MATERIAL AND METHODS Retrospective analysis of a group of a total of 16 patients who underwent a surgery for penetrating cardiac and great vessels injury since II/2002 to XI/2016. The dominant causes of penetrating trauma were stab injuries (15 patients, 94%), in one patient only (6%) it was a gunshot injury. The mean age of the patients included in the group was 42.9 ± 16.1 years, with men significantly prevailing (13 patients, 81%). A total of 7 injured persons (44%) were haemodynamically stable when admitted, 9 injured persons (56%) were unstable or in critical condition. The average transfer distance was 48.8 ± 34.5 km; the injured were admitted on average 115.9 ± 154.8 minutes after being injured. Preoperatively, all the injured suffered from pericardial effusion (5 mm) confirmed by TTE (81%) or CTA (19%). In 4 patients (25%) pericardial drainage for cardiac tamponade was performed before surgery. RESULTS All the penetrating cardiac and great vessels injuries were repaired by cardiac surgeon, in one case only (6%) the extracorporeal circulation support was used. The injury of coronary arteries was in one case managed by CABG and in the other case by ligation of the peripheral part of the coronary artery. In 4 patients (25%) also a penetrating injury of other organs was simultaneously managed. The mean ICU stay reached 85.8 ± 91.9 hours, on average 5.6 ± 9.3 units of red blood cells were administered during the in-hospital stay which lasted on average 7.1 ± 2.4 days. In the group a nonsignificant increase of left ventricular ejection fraction (44.1 ± 4.7 vs. 49.3 ± 3.2, p = 0.882) was reported at discharge of the injured patients. One patient died on the 78 th day of hypoxic brain damage (6% three-month mortality). The long-term survival analysis showed 94% one-year and 88% five-year cumulative survival in the group. DISCUSSION The incidence of the penetrating cardiac and great vessels injury is directly dependent on the crime level in the respective countries and regions. A cardiac arrest, severe hemodynamic instability, unconsciousness, serious concomitant injury, gunshot injury, multiple or atrial injury represent independent predictors of death in these injuries. The total three-month mortality in penetrating cardiac and great vessels injury ranges from 18 to 42%, the presence of vital signs at the time of hospital admission is associated with 78-92% probability of survival. The surviving patients show excellent long-term results with the exception of those who suffered a severe damage to valve apparatus or with significantly depressed left ventricular function. CONCLUSIONS Our experience proves a high survival rate of patients with penetrating cardiac and great vessels injury. The centralisation of the care into the major trauma centre with a cardiac surgery background, a unified treatment algorithm, and a vital interdisciplinary cooperation are the key goal of successful management of these injuries. Key words:penetrating injury, cardiac injury, great vessel injury, outcome. Práce byla podpořena programem institucionální podpor.

Due to the rise of terroristic attack threat, public buildings should be designed to ensure as much safety of its visitors as possible. This paper is focused mainly on understanding of blast wave dynamics in interaction with the solid building and its equipment. Especially pressure wave reflections inside a confined space are of particular interest. The effect of atmospheric overpressure on the human body is also studied. A method for computer modelling of explosive events was developed using LS-DYNA software. The FEM model was calibrated based on experimental data. Multiple arrangements and shapes of concrete barriers were then proposed for faster energy dissipation and effective reduction of the damage and injuries caused by the explosion. The most promising arrangements according to FEM modelling results were then selected for the experimental program. This paper also includes a comparison of the experimental data and results of numerical FEM analysis. The accuracy of the FEM model is then discussed. Thanks to use of TNT explosive charge, the experimental results can also be compared to other blast experiments without barriers. The effectiveness of different barrier arrangements are compared and evaluated.

Multiple myeloma, a plasma cell malignancy, still remains a hard-to-treat hematological disease that desperately needs new therapy targeting plasmocytes but also the bone marrow microenvironment. Clonal plasmocytes are characterized by increased regulation of ubiquitin-proteasome pathway which augments their sensitivity to proteasome inhibitors. Treatment strategies based on proteasome inhibitors belong to the era of new drugs, and they have become increasingly important for treatment of multiple myeloma in recent years. Bortezomib became the first proteasome inhibitor approved for the treatment of multiple myeloma and showed remarkable anti-myeloma activity. However, despite its high efficiency, a large proportion of patients have became bortezomib resistant. The second generation of proteasome inhibitors - carfilzomib, marizomib and MLN9708 - were developed in an effort to overcome bortezomib-resistance and find proteasome inhibitors with a better toxic profile. These drugs brought a chance that multiple myeloma would become a chronic disease.

Waldenström macroglobulinemia is a rare lymphoproliferative disease that is currently classified into lymphomas with incidence of 3 cases per million. This disease comprises about 1-2% of hematological malignancies and is characterized by infiltration of malignant B cells into the bone marrow and presence of monoclonal immunoglobulin IgM in serum. WM is still an incurable disease with median survival of 5 years. Molecular basis of this disease remains unclear even though deletion of 6q, trisomy of chromosomes 4 and 8, deletion of 13q and increased expression of IL-6 seem to be typical for this disease. The most important changes of microRNA are increased expression of miR-155 and decreased expression of miR-9*. This work aims to describe current knowledge about the molecular basis of this disease.

Multiple myeloma is a hematooncological disease characterized by malignant proliferation of plasma cells. These cells accumulate in the bone marrow where they suppress physiological hematopoiesis; at the same time, these cells interact with a wide variety of cytokines, growth factors and adhesion molecules. It is obvious that the bone marrow microenvironment plays an important role in disease pathogenesis as well as treatment resistance.

Multiple myeloma is the second most common hematological disease caused by clonal proliferation of B cells. Evaluation of number of plasmocytes in the bone marrow is still one of the basic diagnostic criteria. The aim of this study was to verify if this evaluation has prognostic value even in the era of new drugs.Two groups of MM patients were enrolled in this study. The group T - 45 newly diagnosed MM patients who underwent treatment with thalidomide. Group B - 86 patients in first relapse of MM without autologous transplantation of bone marrow that were treated with thalidomide and bortezomib in various combinations. Percentage of subtypes of plasmocytes in the bone marrow was evaluated based on progressive analysis of nucleus, chromatin and nucleo-cellular ratio (N/C).Mature plasma cells were found in 53.3% (group T) and 53.5% (group B) of patients; proplasmocytes I were found in 22.2% (group T) and 24.4% (group B) of patients; proplasmocytes II were found in 22.2% (group T) and 22.1% (group B) of patients and plasmablasts in 1% (group T) and 0% (group B). Patients who reached treatment response after first treatment had statistically significant number of proplasmocytes II when compared to group without treatment response (median 37% vs. 11%, p = 0.033). Group B patients with mature plasmocytes below 10% had significantly shorter overall survival than other patients when comparison of quartiles was performed. Group B patients with higher infiltration of proplasmocytes I than median of 15% had lower overall survival (median 50.3 months vs. 74.9 months, p = 0,024); the same was true for evaluation of proplasmocytes II (median OS 41.3 months vs. 74.9 months, p = 0,011).Numerical evaluations of plasma cells in the bone marrow remain basic diagnostic criteria of MM even in the era of new genomics analyses. More precise morphological evaluation of 8 subtypes of plasma cells brings important prognostic information that is necessary for new protocols for immunomodulatory drugs and proteasome inhibitors.

Recently, the term biomarker has become, especially in connection with the term clinical proteomics, one of the most frequent terms in the field of biomedical research. The aim of this work was to select an appropriate pre-fractionation method of blood plasma prior to a subsequent proteomic analysis of low-abundant fraction of proteins by two dimensional gel electrophoresis (2-DE) and mass spectrometry to improve the resolution of 2-DE maps and protein identification.First, we compared two prefractionation methods (MARS versus ProteoMiner) preceding 2-DE analysis using 10 blood plasma samples. Based on the results of the comparative experiments, low-abundant plasma protein fractions from 18 multiple myeloma patients treated with bortezomib were analyzed. Patients were divided into two groups: a group resistant to chemotherapy (9 patients--disease progression, stable disease) and a group with positive clinical response (9 patients--complete and partial remission).Samples prefractioned by ProteoMiner method yielded 2-DE maps with a significantly increased number of detected protein spots, as compared to immunodepletion method MARS (Multiple Affinity Removal System). Between groups of chemoresistant and sensitive patients treated with bortezomib, 15 differently intense spots were revealed by image analysis. These spots were found to correspond to 10 proteins, as confirmed by mass spectrometry. Seven proteins had significantly lower protein level in the group of chemosensitive patients (serum amyloid P, fibrinogen--gamma chain, retinol-binding protein 4, complement factor C4-A, apolipoprotein E, carboxypeptidase N and complement factor H-related protein 1) and 3 proteins showed significantly higher levels of protein (or were only detected) in the group of chemosensitive patients (serum paraoxonase 1, alpha-1-antitrypsin and complement factor B).

Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage.A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia.Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1-21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84-141) g/l. The median of D-dimer decreased to 9.3 (8.0-17) µg/mL.Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patients disease has been stable for 9 months.

Castleman disease is a rare non-clonal lymphoproliferative disorder with the etiopathogenesis not yet thoroughly clarified. Clinically, either unicentric (localized) or multicentric (generalized) forms are recognized while, histopathologically, hyaline-vascular, plasma-cell and mixed variants of the disease exist. These types vary one from another in their clinical courses and, importantly, in methods of therapeutic management. While the unicentric hyaline-vascular form usually manifests as benign growth of a single lymph node and treatment response to complete surgical excision reaches up to 100%, the multicentric plasmocellular variant is an aggressive disease with generalized symptoms, laboratory abnormalities and the need for systemic therapy.The paper provides an overview of information on Castleman disease from its clinical and histopathological signs to diagnostic and therapeutic options. It deals with the role of cytokines and HHV-8 virus infection in the disease pathophysiology and is supplied with ample pictorial documentation of radiographic findings including ultrasonography, computed tomography and hybrid imaging by positron emission tomography (PET) in combination with simultaneously taken full-body computed tomography (CT) scans, the so called PET/CT. We also present photographs of histological specimens taken from an HIV and HHV-8 negative patient with the plasmocellular multicentric form.Consequent to its low incidence, Castleman disease is often misdiagnosed or diagnosed with a delay. Therefore, it is always necessary to include this rare condition in differential diagnostics of lymphadenopathy, microcytic anemia as well as B-symptoms (night sweats, fevers and weight loss). In conclusion, we also stress the significance of full-body PET/CT scanning during staging and treatment response evaluation.

Erdheim-Chester disease is a very rare syndrome affecting adult population. It typically causes hyperostosis of long bones, retroperitoneal fibrosis and widening of the aortic wall. Patients frequently suffer from disease-associated fevers and pain in the lower limbs. No guidelines are available for the treatment of this rare ailment. Therefore, we describe our experience with lenalidomide in a patient with poor treatment response to 2-chlorodeoxyadenosine.Diabetes insipidus and neurological problems developing over 4 years were the first signs of the disease. The disease was diagnosed from histology of the bone marrow extracted from the ilium. At diagnosis, the patient had multiple infiltrates in the brain, widened wall of the thoracic and abdominal aorta, fibrotic changes to retroperitoneum and typical hyperostosis of the long bones of lower limbs with high accumulation of technetium pyrophosphate as well as fluorodeoxyglucose. First line treatment involved 2-chlorodeoxyadenosine 5 mg/m2 s.c. for 5 consecutive days every 28 days. There was no clear treatment response identifiable on the MR scan of the brain following the third cycle and thus 4th-6th cycle consisted of 2-chlorodexyadenosine 5 mg/m2 + cyclophosphamide 150 mg/m2 + dexamethasone 24 mg day 1-5 every 28 days. After the 6th cycle, MR showed partial regression of the brain lesions. PET-CT showed an increased accumulation of fluorodeoxyglucose in bone lesions. Second line treatment involved lenalidomide 25 mg/day days 1-21 every 28 days. Lenalidomide tolerance was excellent; the number of neutrophils and thrombocytes was within the physiological range throughout the treatment period. Follow-up MR showed complete remission of the brain lesions, while follow-up PET-CT showed further increase in fluorodeoxyglucose accumulation in the bones of lower limbs.Treatment with 2-chlorodeoxyadenosine-based regimen provided partial remission of Erdheim-Chester disease lesions in the brain, while treatment with lenalidomide resulted in complete remission of these lesions. Fluorodeoxyglucose continues to accumulate in the long bones of lower limbs. We are unable to elucidate the reasons for complete remission of the disease in the brain as per the MR and its progression in the long bones according to PET-CT. Further testing of lenalidomide in the treatment of this disease is required to support further use of this perspective treatment option.

In this paper, initial processing of biological material, cell separation algorithms and other procedures are discussed. For samples with initial infiltration of plasma cells5%, CD138 MicroBeads and Auto-Magnetic-Activated Cell Sorting program are used. Fluorescence-Activated Cell Sorting is used exclusively for cell populations with low-abundance; these samples are detected using fluorescently labeled antibodies only. Isolated plasma cells are further processed for molecular biological studies, for cytogenetics and protein analyses. Furthermore, this work examines the pitfalls of research related to multiple myeloma; some of them we have overcome, while the others are still problematic.

Multiple myeloma (MM) is a hematological disease caused by malignant proliferation of clonal plasma cells (PCs) known for its clinical and biological heterogeneity. Identification of chromosomal changes in genome of PCs plays a key role in MM pathogenesis and is supposed to have important prognostic significance for MM patients. There are two major genetic entities in MM. Hyperdiploid tumors (H-MM), which include about 50% of MM tumors, often have multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 and a substantially lower prevalence of IgH translocations. Nearly half of tumors are non-hyperdiploid (NH-MM), and mostly have one of five recurrent IgH translocations: 11ql13 (CCND1), 6p21 (CCND3), 16q23 (MAF), 20q12 (MAFB), and 4p16 (FGFR3 and MMSET). The development and expanded use of new technologies, such as genome-wide array-based comparative genomic hybridization (aCGH) has accelerated genomic research in MM. This technique is a powerful tool to globally analyze recurrent copy number changes in tumor genome in a single reaction and to study cancer biology and clinical behaviors. It widely overcame routinely used cytogenetic techniques (G-banding, FISH) both in minimal resolution of chromosomal changes and amount of obtained genomic data important for further analyses and clinical applications. Array CGH technique is now used to better understanding of molecular phenotypes, sensitivity to particular chemotherapeutic agents, and prognosis of these diseases. This paper brings brief literature and methodic overview of oligonucleotide-based array-CGH technique in MM diagnosis.

Multiple myeloma (MM) is a plasma cell (PC) disorder and associated with immune impairments. Flow cytometry based phenotyping and quantification of regulatory T cells (Tregs) enable to monitor the immune status of myeloma patients. Apart from enumeration of Tregs, functional characterization using proliferation or suppression assay adds key value in demonstrating the functional value ofTregs. Our study revealed that in MM patientsTregs are elevated compared to healthy subjects, which demonstrate the immune deregulation in MM.

The presence of multiple centrosomes in tumor cells is associated with the formation of multipolar mitotic spindles and results in aneuploidy of both daughter cells. Centrosome amplification is a feature of all cancer cells. We have previously described centrosome amplification in abnormal B cells. Further studies of centrosome amplification in different stages of B lineage development could provide important information about multiple myeloma pathogenesis.

The introduction of new drugs improved clinical response of patients with diagnosed multiple myeloma (MM); however, MM is still an incurable disease that leads to frequent relapses. Individual genetic variability can significantly affect therapeutic response, sensitivity and toxicity. Analysis of single nucleotide polymorphisms (SNPs) to study genetic changes is the genomic method that can obtain information for improving the effectiveness of treatment with minimum undesirable toxicity followed by individual treatments. The aim of this paper is to explain the possibility of detection and evaluation of polymorphisms associated with toxicity of treatment in patients with MM.

Monoclonal gammopathy of undetermined significance (MGUS) is a precancerosis comprising two different kinds of cancer: lymphoid/lymphoplasmocytoid MGUS and plasma cell MGUS that represents about 85% of all MGUS cases. This type of MGUS has low but persistent tendency to transform to malignant disease, mainly multiple myeloma (MM), with frequency of about 1% per year. Using known risk stratification models based on clinical parameters, it is possible to identify patients' groups with average rates of progression as low as 0.26% and as high as 12% per year. However, due to the lack of clear genetic and/or phenotypic markers distinguishing MGUS from MM, we are not able to predict if and when MGUS will progress to MM in individual patients. There are partially overlapping molecular pathogenic events shared by MGUS and MM. Better understanding of pathogenesis of MGUS and MM using molecular-genetic approaches will help disclose the mechanisms of myeloma genesis; it can be also useful for identification of novel molecular targets. The ultimate goal for the near future is to develop better markers for definition of high-risk MGUS patients who will be candidates for early treatment intervention.

Nestin, a marker of multipotent precursor cells, is an important dynamic structure; its polymerization/depolymerization influences intracellular signaling and participates in key cell processes such as proliferation, migration and cell survival. It is presumed that nestin plays a central role in carcinogenesis. It is suggested that nestin might be a suitable diagnostic and prognostic indicator of malignancy and a potential marker of cancer stem cells. Unexpectedly, nestin has been identified in mature CD138+CD38+ plasma cells (PC) of multiple myeloma patients (MM). Expression of nestin, a marker of stem/progenitor cells, in malignant PC, that are considered to be terminally differentiated, indicates that nestin might play a unique role in pathology of MM.

This manuscript is an introduction to the topic of multiple myeloma. Definition, incidence, etiology, pathogenesis and principles of diagnostics and treatment of multiple myeloma are described briefly in this work It corresponds with Guidelines for diagnostics and treatment of the myeloma section of the Czech Hematological Society and the Czech Myeloma Group.

The technological development of flow cytometry (FC) together with new findings reveal the need for immunophenotyping in research of monoclonal gammopathy (MG) because of its diagnostic, prognostic and predictive significance. The aim of the European Myeloma Network (EMN) is to standardize this analytical method and implement it into routine clinical examination. Since the overall significance and application of FC are still analysed, standardisation could help obtain more clinical relevant information in terms of MG pathophysiology.

The most important diagnostic criteria for Schnitzler syndrome include chronic urticaria, the presence of monoclonal IgM immunoglobulin, marked inflammation (leukocytosis, elevated CRP and erythrocyte sedimentation rate), subfebrile temperatures or fevers and bone and joint pains. It is a rare idiopathic disease that may lead to potentially life-threatening complications such as development of secondary amyloidosis or transformation into malignant lymphoproliferation. Schnitzler syndrome should be included in differential diagnostics of chronic urticaria and fevers of unknown origin. The diagnostic algorithm is based on clinical presentation and serum and urine electrophoreses to detect monoclonal components. Blockade of interleukin-1 (IL-1), key cytokine in the pathogenesis of the disease, dominates current therapeutic protocols. Anakinra (Kineret), recombinant human IL-1 receptor antagonist, is the most widely used treatment option. According to literature, disease remission was obtained in all treated patients. Therefore, anakinra represents a significant diagnostic possibility to differentiate Schnitzler syndrome from e.g. monoclonal gammopathy of unknown significance (MGUS) associated with urticaria of different aetiology. Biological therapy with rilonacept (Arcalyst) and canakinumab (Ilaris) represents a new treatment alternative for patients, allowing prolonged dosing intervals of 1 and 8 weeks, respectively (compared to 24 hours with anakinra). The review article also presents findings of various imaging methods (conventional radiography, computed tomography, traditional bone scintigraphy) and photographs of patients with Schnitzler syndrome before and after anakinra therapy.The aim of the review is to draw attention to the existence of this rare autoinflammatory and potentially premalignant condition, present a simple diagnostic algorithm and provide an overview of therapeutic options for the patients.Malign potential of Schnitzler syndrome, possible development into systemic amyloidosis and the fact that patients are frequently referred to oncology clinics for differential diagnostics of monoclonal gammopathy, are the main reasons why clinical oncologists should be aware of Schnitzler syndrome.

The aim of this paper is to present an algorithm for plasma cell separation from bone marrow samples of multiple myeloma patients. The main prerequisite for applying modern research methods in this disease is gaining pure cell populations.Bone marrow samples were collected from outpatients or inpatients of the Internal Haematology and Oncology Clinic of the Faculty Hospital Brno, after they had signed an Informed Consent Form. The bone marrow was first depleted of red cells (by density gradient centrifugation or erythrolysis), plasma cells were labelled by monoclonal antibody against syndecan-1 (CD138) and separated either magnetically or by cell sorter. The purity of separated population was evaluated by flow cytometry or, alternatively, morfologically.We processed 28 bone marrow samples, in parallel, by magnetic or fluorescence-based separation, and we evaluated the purity of the separated fractions. Based on a statistical evaluation of resulting purities in the entire sample set as well as the individual groups divided according to the initial plasma cell content, a separation algorithm was proposed with a cut-off value of 5% of plasma cells in mononuclear fraction of bone marrow: samples with less than 5% of plasma cells are henceforth separated on cell sorter, samples with more than 5% are separated magnetically.The effectiveness of this algorithm was evaluated after the first year of its application on a dataset of 210 bone marrow samples: median purity of the separated plasma cells increased from 62.4% (0.4-99.6%) to 94.0% (23.9-100%).The introduction of a fluorescence-based separation markedly increased the effectiveness of plasma cell separation from bone marrow samples, mainly in samples with low plasma cell content where magnetic separation used thus far is not sufficient. This finding also opened a door for plasma cell separation of bone marrow samples from patients with monoclonal gammopathy of undetermined significance, where plasma cell count is typically below or just over one percent.

Schnitzler syndrome is a rare idiopathic disease characterized by chronic urtica, presence of monoclonal IgM immunoglobuline and further, less common symptoms. This case report describes another case of this disease affecting a male adult born in 1963. The first symptoms, eruptions of non-pruritic urticarial rash, appeared in this patient at the age of 43. In addition, bone pains (mainly tibias) and joint pains (mainly knees) were present. Later on however, severe attacks of fever, chills and shaking together with bone and joint pains were added to during which new urticarial eruptions appeared. Primarily, the man was followed up without any substantial therapeutic results at a department of dermatovenerology, subsequently, due to a finding of monoclonal IgM kappa immunoglobulin (serum concentration 1.9 g/l) he was referred to our department for the reason of gammopathy being a differential diagnosis. On a CT scan hyperostosis in claviculae and pelvic bones was identified. Also on the CT, an increase in cortical thickness was described in the long bones of the lower extremities, where areas of technetium pyrophosphate accumulation were identified on a bone scintigraphy. These areas were found in the chest and sacral regions as well. From the blood exams, the proinflammatory status of the organism was apparent (CRP 35.9 mg/l, erythrocyte sedimentation rate 92 mm/h, leukocytes 12.4 x 10(9)/l). After excluding other differential diagnoses, the patient was diagnosed with Schnitzler syndrome. As regards therapy, we made initial use of the effect of corticoids which abated the symptoms, however, these were causing serious adverse reactions in the form of iatrogenous Cushing's syndrome. The therapy took a turn only after biologic therapy with anakinra (interleukin-1 receptor antagonist) had started, which minimized the Schnitzler symptoms with very good drug tolerance. In the work we measured serum levels of interleukins for disease activity monitoring. The most sensitive were interleukins IL-6 and especially IL-18 the levels of which were the highest at the time of clinical exacerbation of the disease, whereas the levels of IL-1beta and TNF-alpha (tumour necrosis factor) were during all measurements below the limit of detection. Concerning the growing numbers of the reports on successful biological therapy with anakinra and our positive experience, we propose that the therapeutic response to anakinra should be included within the diagnostic criteria of Schnitzler syndrome, which is significant above all in differential diagnosis thereof.

Our paper describes 5 patients with a vascular malformation - angiomatosis. In the first patient, a young man, angiomatosis affected the stomach, intestine, the area of mesenterium and retroperitoneum as well as mediastinum. Angiomatous mass had invaded pelvic bones and vertebrae. Treatment was initiated with interferon alpha in a maximum tolerated dose of 3 million units 3 times a week. Because of low efficacy of interferon alpha, thalidomide was added at a dose of 100 mg per day. Bone pain disappeared following a few applications of zoledronate administered in regular monthly intervals. After 3 years of concomitant administration of interferon alpha and thalidomide, we changed the regimen due to adverse effects and are administering thalidomide and interferon alternatively in 4-monthly intervals. Treatment has resulted in 50% reduction, according to imaging, of angiomatous mass, reduced intensity of disseminated intravascular coagulation and disappearance of clinical signs. The second was a case of multiple angiomatosis affecting the intestine only (multiple intestinal angiodysplasias) where we used thalidomide monotherapy. This treatment reduced blood losses and haemoglobin concentrations rose to normal levels. This male patient had consumed 120 transfusion units per year before the initiation of thalidomide. The third case was a slowly progressing vascular malformation of the face. This vascular malformation troubled its sufferer by spontaneous shortening that could not be resolved surgically because of its fragility. Two years of combined treatment with interferon a 6 million unites 3 times a week and thalidomide 100 mg daily led to a reduction and flattening of the malformation, paling of its colour and ceasing of spontaneous bleeding. This development enabled minor surgery--partial excision of this large vascular malformation. Histology examination confirmed that there was no evidence of new capillary formation. Histological examination thus confirmed efficacy of the treatment. The fourth case involved a patient with large vascular malformations affecting supraclavicular region of the neck and nape in whom radiotherapy was applied (54 Gy) leading to a reduction of the malformation mass by a at least 50%. The fifth is a case of an extensive periorbital lymphangioma that diminished following treatment with interferon alpha. These cases illustrate the benefits of combined treatment including thalidomide and interferon alpha in patients with multiple angiomatosis or large proliferating hemangioma (vascular malformation). If combined treatment with thalidomide and interferon a is not possible, it is beneficial to use thalidomide monotherapy. Radiotherapy is another alternative, although it is necessary to apply doses exceeding 50 Gy which may not be always possible.

Lenalidomide is a promising new drug in the treatment of patients with multiple myeloma. The analogue of thalidomide was created with the intention of improving the anticancer activity, its immunomodulatory properties as well as reducing the toxicity of the preparation. The mechanism of antitumor action of the preparation appears to be the effect on cells, tumour microenvironment and in particular the regulation of cytokinine production. Performed clinical studies Phase I and II have shown efficacy in patients with relapsed multiple myeloma. Subsequently, large randomized trials demonstrated the benefit of combined therapy in relapsed/refractory multiple myeloma patients with a combination of lenalidomide plus dexamethasone compared with dexamethasone treatment alone. Patients treated with a combination of lenalidomide and dexamethasone had significantly higher therapeutic response and overall survival than patients treated with dexamethasone alone. Profound toxicity seems to be the myelosuppressive effect of lenalidomide. The work gives a summary of the information available on lenalidomide in the treatment of multiple myeloma.

Central diabetes insipidus with an onset in adulthood is very rare. Unlike in children, central diabetes insipidus in adults is more frequently caused by inflammatory processes and neoplastic infiltrations that do not originate from the neuronal tissue than primary neuronal tissue tumours. Rare histiocytic neoplasias (Langerhans cell histiocytosis, xanthogranulomatosis and Erdheim-Chester disease) have a specific affinity to hypothalamus and the pituitary stalk not only in paediatric patients but also when occurring in adults. We describe 3 cases of central diabetes insipidus with an onset in adulthood. Diabetes insipidus was the first sign of Langerhans cell histiocytosis in 2 patients, and it was the first sign of Erdheim-Chester disease in one patient. MR imaging showed pathological infiltration and dilated pituitary stalks in all 3 patients. PET-CT proved useful in differential diagnosis, showing further extracranial pathological changes either on the basis of significant glucose accumulation or on the basis of CT imaging. The Langerhans cell histiocytosis in the first patient has also manifested itself as an infiltration of the perianal area with intensive accumulation of fluorodeoxyglucose (FDG) - SUV 8.6 and gingival inflammation indistinguishable from parodontosis. Histology of the perianal infiltrate confirmed Langerhans cell histiocytosis. Infiltration of the pituitary stalk disappeared from the MR image after 4 cycles of 2-chlordeoxyadenosin (5 mg/m2 5 consecutive days). The PET-CT of the 2nd patient showed only borderline accumulation of FDG in the ENT area, while simultaneously performed CT imaging showed cystic restructuring of the pulmonary parenchyma and nodulations consistent with pulmonary Langerhans cell histiocytosis. Bronchoalveolar lavage identified higher number of CD1 and S100 positive elements, consistent, once again, with pulmonary LCH also affecting pituitary stalk and ear canal. The PET-CT of the third patient showed increased activity in the long bones and ilium near the sacroiliac joint. Biopsy of the focus in the ilium confirmed foam histiocyte infiltration immunochemically corresponding to Erdheim-Chester disease. Additional imaging assessments revealed the presence of further signs of the disease. Pituitary infiltrate biopsy in this patient did not elucidate the diagnosis but resulted in complete panhypopituarism. Central diabetes insipidus in adulthood might be the first sign of so far undiagnosed extracranial disease, in our case of histiocytic neoplasias, and PET-CT has an excellent potential to detect extracranial symptoms of these conditions. Therefore, the high-risk pituitary stalk infiltrate biopsy should always be preceded by comprehensive examination aimed at identification of extracranial manifestations of the pituitary gland diseases.

The similarity solution is presented for laminar wall jets on bodies of revolution for power-law fluids. The functional dependence of the length and velocity similarity scales on a shape parameter and a flow behaviour index is determined. Discussion dealing with flow invariance, modified Mangler's transformation and with previously published results is carried out.

Monoclonal gammopathy of undetermined significance (MGUS) is the most common type of monoclonal gammopathies. Genetic changes, various cytokines and bone marrow angiogenesis play an important role in the pathogenesis. As far as the malignant transformation of MGUS is concerned, size and type of the serum M-protein, serum kappa and lambda free light chain ratio and number of plasma cells in peripheral blood seem to play a predictive role. A new possible risk-stratification model predicting progression of MGUS to multiple myeloma or other related disorders was presented in 2006. The model takes three parametres in consideration, type and initial size of the serum M-protein and serum kappa and lambda ratio. Patients are divided into four risk groups with different risk of progression, from 5% at 20 years in low risk group to 58% in high risk group. The interval from MGUS diagnosis to the evolution of multiple myeloma or other related malignancies ranges from 1 to 30 years. Nevertheless, the risk of progression persists even after more than 30 years after MGUS diagnosis.

Dendritic cells (DCs) are highly specialized antigen-presenting cells, which can be used for immunotherapy trials. Functionally normal DCs play a critical role in the activation and potentiation of antitumor antigen-specific responses.Maturation of DCs from 10 healthy donors, 14 monoclonal gammopathy of undetermined significance patients and 14 multiple myeloma patients was tested in an in vitro study.DCs were generated from adherent mononuclear precursors of peripheral blood and cultured in presence of IL-4 and GM-CSF with human CD40Ligand stimulation. Serum-free or autologous serum conditions were used and expression of significant surface antigens, chemokines receptors and production of IL-12p70, were compared. We found no difference between groups under serum-free conditions with or without CD40L stimulation. Under autologous conditions we found negative effect on patients DCs manifested by reduction of some markers. The production of IL-12p70 was low and no difference in serum IL-6 levels between individual groups was found.Under serum free conditions there was no difference between healthy volunteers, MGUS and patients, but CD40L stimulation did not lead to the full maturation ofDCs. Autologous patient serum had negative influence on DCs, with no definite dependance on the IL-6 level.

Multiple myeloma is a malignant disease caused by malign transformation of B-cells, their clonal proliferation and the accumulation of myeloma cells in the bone marrow. These cells are set apart by a pronounced genetic instability. Chromosomal abnormalities are probably the most important prognostic factors in myeloma which influence the division of the patients into individual sub-groups each with a different developmental process of the disease and thus a different approach during treatment. The study summarizes the methodological approaches and current options in classical and molecular cytogenetics during the examination of cytogenetic changes in multiple myeloma. It presents the most common types of numerical and structural chromosomal changes found in the karyotype of multiple myeloma patients, and their prognostic importance.

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.

BACKGROUND: Multiple myeloma is an incurable hematological disease. High-dose chemotherapy including autologous stem cell transplantation is recently considered a standard therapy for myeloma. Unfortunately, a relapse of the disease is inevitable. Therefore, new approaches such as immunotherapy have been considered recently. A specific activation of cytotoxic T cells can be reached using dendritic cells loaded with tumor-specific antigens. The HLA-A2-specific nonapeptides as hTERT derived from catalytic subunit of telomerase and MUC1 derived from mucin protein can be used. DESIGN AND SUBJECTS: Activation, identification, separation and expansion of myeloma-specific T cells from healthy HLA-A2 blood donors were tested in an in vitro study using hTERT and MUC1 nonapeptides as tumor-specific antigens. METHODS AND RESULTS: T cells and dendritic cells were obtained from peripheral blood. T cells were repeatedly stimulated with hTERT and MUC1 nonapeptide-loaded dendritic cells. Activated myeloma-specific T cells produced interferon gamma and were evaluated by flow cytometry. The activated T cells were immunomagnetically separated and in vitro expanded to the number usable in clinical trials. CONCLUSIONS: This study demonstrates feasibility of a specific activation, identification, separation and expansion of tumor-specific T cells that can be used in myeloma therapy.

The vacuum-asssited closure has represented an encouraging treatment modality in treatment of surgical site infection in cardiac surgery, providing superior results compared with conventional treatment strategies, particularly in the treatment of deep sternal wound infection.From November 2004 to January 2007, 40 patients, undergoing VAC therapy (VAC system, KCI, Austria, Hartmann-Rico Inc., Czech Republic) for surgical site infection following cardiac surgery, were prospectively evaluated. Four patients (10%) were treated for extensive leg-wound infection, 10 (25%) were treated for superficial sternal wound infection and 26 (65%) for deep sternal wound infection. The median age was 69.9 +/- 9.7 years and the median BMI was 33.2 +/- 5.0 kg/m2. Twenty-three patients (57%) were women and diabetes was present in 22 patients (55%). The VAC was employed after the previous failure of the conventional treatment strategy in 7 patients (18%).Thirty-eight patients (95%) were successfully healed. Two patients (5%) died, both of deep sternal infetion consequences. The overall length of hospitalization was 36.4 +/- 22.6 days. The median number of dressing changes was 4.6 +/- 1.8. The median VAC treatment time until surgical closure was 9.7 +/- 3.9 days. The VAC therapy was solely used as a bridge to the definite wound closure. Four patients (10%) with a chronic fistula were re-admitted with the range of 1 to 12 months after the VAC therapy.The VAC therapy is a safe and reliable option in the treatment of surgical site infection in the field of cardiac surgery. The VAC therapy can be considered as an effective adjunct to convetional treatment modalities for the therapy of extensive and life-threatening wound infection following cardiac surgery, particurlarly in the group of high-risk patients.

The authors present the case report of a Marfan syndrome patient with aneurysm of ascending, dissecting aneurysm of descending and abdominal aorta. Ascending aorta replacement with aortic valve sparing procedure was performed at first surgery. Later on descending and abdominal aorta were replaced. The patient was reoperated because of a chylus collection in retroperitoneal space. Three months following surgery the patient is completely recovered.

The understanding haematological malignancies at the protein level is important for the prediction of therapy response, the possibility for disease diagnostics, the development of targeted treatment, and it must be based on the knowledge regarding the molecular pathogenesis of the tumour. 'Proteomics' describes the analysis of the entire proteome of a cell or a tissue and incorporates multiple technologies, including - Western blotting, two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and ProteinChip-based technology. Although there is a limited number of studies to date in haematological malignancies, those performed highlight the potential impact of these technologies in the discovery of novel markers associated with the drug resistance and the identification of biomarkers which may facilitate the development of a rapid diagnostic test that would be easily applicable in the clinical setting. Thereby this article describes used proteomics techniques and highlights studies regarding proteomic research in haematological malignancies, namely the primarily publications concerning research of multiple myeloma, leukaemias and lymphomas.

The case-report of a 57-year-old patient with the symptoms of massive pulmonary embolism is presented. The patient was admitted to the hospital in the cardiogenic shock, ventilated and with high dose of inotropic support. It was impossible to find out the exact data from personal history. The patient was operated on urgently. The chronic occlusion of the right pulmonary artery due to the chronic tromboembolic disease was found out. Thromboendarterectomy of the pulmonary artery was successfully performed. Three month after operation the patient is in excellent clinical condition almost without any functional limitation. Some atypical features of this case are stressed in the discussion: the urgency of the operation for chronic tromboembolic disease with unilateral involvement, which simulated pulmonary embolism and operation in mild hypothermia without circulatory arrest.

Multiple myeloma is the second most prevalent and mostly fatal hematologic cancer. Further advances have been made in understanding the mechanisms involved in the myeloma pathogenesis and elucidation of critical signalling pathways as therapeutical targets. Proteasome inhibitors are the example of this new approach and bortezomib is the first agent in this class to enter clinical trials.In 6 hematological centers in Czech Republic 29 patients with refractory/relapsed myeloma had been treated with bortezomib (Velcade, Millennium Pharmaceuticals) in 2004. The initial dose 1.3 mg/m2 of Velcade was given, in 1 case the dose was adjusted due to pre-existing renal failure to 1 mg/m2. The response was achieved in 17 patients (59%). Four patients had complete, 11 partial and two minor responses. In 5 cases stabilization of disease was observed and 6 patients progressed during the therapy.Unfortunately, one patient died immediately after the start of therapy due to sepsis. The most common adverse events were thrombocytopenia, anaemia, neuropathy, gastrointestinal complication, renal failure and fatigue. Grade 4 adverse events occurred in 37.9% of patients (4x thrombocytopenia, 2x gastrointestinal, 2x renal failure, 1x sepsis, leucopenia, hepatopathy and anaemia, respectively). Peripheral neuropathic pain of grade 3 was reported in 4 cases, in one patient therapy had to be interrupted due to this complication. We confirmed promising results of phase II trials.

Cytogenetic abnormalities of chromosome 13 are emerging as important prognostic factors in multiple myeloma and have been associated with poor prognosis.The occurrence of 13q14 deletion and other standard laboratory parameters were determined in 40 patients with multiple myeloma. We found that interphase fluorescence in situ hybridization using a locus specific probe for RB1 gene on immunomagnetically selected myeloma cells was more sensitive than non selected cells. The 13q14 deletion was found in 10 of 40 (25.0%) of bone marrow samples without cell selection and in 25 of 40 (62.5%) of samples with CD138+ enriched myeloma cells. Negative correlation was found between albumin and the 13q14 deletion in separated (p = 0.003) as well as in cells without selection (p = 0.010). No significant correlation was found in overall survival of separated and unseparated cells (p = 0.830; p = 0.260) and a similar result was obtained for treatment response after transplantation of separated cells (p = 0.520) or non-separated cells (0.190).Our results confirm that immunomagnetic selection of CD138+ cells increases the probability of detection of the 13q14 deletion in bone marrow samples. The correlation was found between albumin and the 13q14 deletion in both of type of cells.