Molecular testing of endometrial carcinoma in real-world clinical practice.

BACKGROUND: Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. MATERIALS AND METHODS: In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. RESULTS: A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8-36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. CONCLUSION: Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.

EFFECT OF RANIBIZUMAB AND AFLIBERCEPT ON RETINAL PIGMENT EPITHELIAL DETACHEMENT, SUBRETINAL AND INTRARETINAL FLUID IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The aim of the study was to compare the effect of three initial doses of the anti-VEGF ranibizumab and aflibercept medication on serous pigment epithelial detachment (PED), subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula of treatment naive neovascular AMD (nvAMD) patients. MATERIAL AND METHODS: The cohort consists of 148 patients, of which 74 patients were treated with ranibizumab (51 females and 23 males) and 74 with aflibercept (46 females and 28 males). The data was recorded prospectively from the moment of diagnosis and start of treatment for a period of 3 months. At the moment of diagnosis and 3 months later, an OCT examination (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was performed. The OCT examination included a macular scan with 25 scans. Using the OCT instrument software, we measured the maximum anterior-posterior elevation of serous PED, the highest thickness of SRF and the largest diameter of the intraretinal cystic space. The statistical significance of differences between groups was evaluated using the t-test for continuous data and the Fisher exact test for categorical data. Changes in values of continuous variables over time were evaluated using the Wilcoxon paired test. Paired comparisons of binary parameters were determined by the McNemar test. RESULTS: Full regression of PED, SRF and IRF occurred in 3 (4.1%), 25 (39%) and 20 (51%) patients treated with ranibizumab, and in 5 (7.9%, p = 0.470), 28 (47%, p = 0.470) and 25 (57%, p = 0.827) patients treated with aflibercept, respectively. The average regression of PED, SRF and IRF was -60.4 μm (median -37.5 μm), -84.3 μm (median -85 μm) and -109.3 μm (median -81 μm) in patients treated with ranibizumab, and -46.3 μm (median -30 μm, p = 0.389), -127.7 μm (median -104 μm, p = 0.096) and -204.4 μm (median -163 μm, p = 0.005) in patients treated with aflibercept, respectively. We did not show a statistically significant difference in the regression rates of PED, SRF and IRF between the ranibizumab and aflibercept groups. (in patients with IRF after adjustment of the higher baseline IRF volumes in patients treated with aflibercept, p = 0.891). CONCLUSION: We are convinced that ranibizumab and aflibercept have the same effect on serous PED, SRF and IRF in the macula in patients with treatment naive nvAMD during the initial loading phase.

Is the finding of endometrial hyperplasia or corporal polyp an mandatory indication for biopsy?

OBJECTIVE: The aim of our study was to analyze a group of patients referred for endometrial biopsy. To evaluate the ultrasound finding of hyperplasia/polyp, the symptomatology of patients related to the result of definitive histology, to determine the severity of individual variables in connection with the detection of precancerosis/cancer. Due to the complexity of information identify women who are suitable for conservative approach. DESIGN: Unicentric retrospective observational study. SETTING: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno. METHODS: All patients over 50 years who underwent surgical endometrial biopsy at our department in the period of 2017-2018 (n = 754) were included. We were interested in reasons of indication, the age of patients at the time of the procedure and at the menopause, the presence of risk factors for development precancerosis/cancer (hypertension, diabetes mellitus, using of tamoxifen), number of deliveries and pregnancies, symptomatology, the description of ultrasound scans, the result of histology examination, peroperative and postoperative complications. RESULTS: Perimenopause - the median of endometrial thickness in both benign and malignant histology was 8 mm (p = 0.448), the median of the largest polyp dimension was 18 mm. All patients with precancerosis/malignancy were symptomatic with irregular/excessive bleeding, no carcinoma was found in polyp. Postmenopause - the median of endometrial thickness in benign histology was 7 mm versus 16 mm in precancerosis/malignancy (p < 0.001), the median of the largest polyp dimension was the same in both histologies (13 mm, p = 0.274). The risk of malignancy was more than threefold in bleeding versus asymptomatic patients with both hyperplasia and polyp (OR 3.39, 3.79). In asymptomatic patients the risk of cancer was similar for selected cut-offs (5, 8 and 12 mm), statistically significant only for 12 mm (OR 3.54), while in symptomatic patients the risk was high for all cut-offs, however with wide confidence intervals, statistically significant for cut-offs of 8 mm (minimum 3.58) and 12 mm (minimum 4.94). CONCLUSION: We have shown that symptomatology is a strong risk factor for the presence of precancerosis/malignancy in patients with endometrial hyperplasia or polyp. The thickness of the endometrium or polyp size in asymptomatic patients does not play a major role. Ultrasound alone does not have sufficient accuracy for detection or even screening of endometrial cancer. We recommend a conservative procedure, monitoring changes in the ultrasound scan and symptomatology of the patient over time.

Importance of addition of HPV DNA testing to the cytology based cervical cancer screening and triage of findings with p16/Ki67 immunocytochemistry staining in 35 and 45 years old women LIBUSE trial data analysis.

OBJECTIVE: The study evaluates results of 2-years follow-up of patients in ages 35-36 and 45-46, who are participating in the project LIBUSE, that deals with efficacy of HPV DNA and Pap smear co-testing and p16/Ki67 dual staining in the Czech national cervical screening. DESIGN: Prospective observational study. SETTING: Department of Obstetrics and Gynecology, General University Hospital and 1st Medical Faculty, Charles University, Prague. MATERIALS AND METHODS: Out of all women enrolled in the project LIBUSE only those who were at the beginning of the study 35-36 and 45-46 years old were sellected. Conventional Pap smear and HPV DNA test (Cobas 4800, Roche Diagnostics) had been collected at the baseline. Women were stratified according to their results in the three risk groups: 1. low-risk, 2. high-risk and 3. intermediate risk, who subsequently underwent p16/Ki67 dual staining. All high-risk patients and those with positive result of dual staing were refered to the expert colposcopy. The cases with biopsy proven precancers or cancers were considered as „positive findings“. RESULTS: Altogether 352 women meet the age requirements. In 26 (7.6%) women had been proven HPV DNA positivity and out of the them 9 cases were HPV 16/18 positive. Severe cytological abnormality was found only in one patient (0.3%), who was simultaneously HPV positive. Ten women (2.8%) were classified as high-risk and directly refered to colposcopy. Another 18 patients underwent p16/Ki67 dual staining and 4 positive cases were refered to colposcopy too. After one year further 9 patients were classified as intermediate risk and 6 more were identified after two years of follow-up. Within two years 9 more patient were refered to colposcopy. After the entire period of follow-up in 10 patients biopsy confirmed precancer lesions, none of them had invasive cancer. CONCLUSIONS: Addition of HPV DNA testing with selective HPV 16/18 genotyping to the cytology based screening significantly increases sensitivity and safety of our cervical screening program.

High Level of Circulating Microparticles in Patients with BCR/ABL Negative Myeloproliferative Neoplasm - a Pilot Study.

BACKGROUND: Microparticles (MPs) are small (0.1-1 μm) cell-derived vesicles released during activation or apoptosis, with a surface-exposed phosphatidylserine along with antigens indicating the cellular origin. The level of MPs is known to be elevated in thromboembolic diseases and malignancies; it is believed that MPs are not only amplifying but can also initiate the thrombogenesis processes. BCR/ABL negative myeloproliferative neoplasms (MPNs) are clonal haematopoietic diseases, which include polycythemia vera, essential thrombocythemia and primary myelofibrosis. One of the main problems of MPN patients is high risk and incidence of thrombosis which affect the survival, quality of life and life expectancy. PATIENTS AND METHODS: The clinical significance of circulating MPs was assessed in a group of 179 patients with BCR/ABL-negative MPNs. Analysis of MPs was done using flow cytometry on 417 samples, and MPs procoagulation activity was performed using a functional assay called Zymuphen MP-activity (Hyphen Biomed, Neuville-sur-oise, France) on 274 samples. RESULTS: Significantly higher absolute and relative count of platelet MPs was found in MPN patients when compared with healthy group, respectively (p = 0.001, p = 0.043). Erythrocyte MPs were also significantly higher in MPN patients than in the healthy group (p < 0.001). Procoagulation activity of MPs was as well significantly higher in patients compared to the control group (p < 0.001). Patients with primary myelofibrosis had decreased absolute and relative count of platelet MPs compared to polycythemia vera and essential thrombocythemia patients, respectively (p = 0.008, p = 0.014). Presence of JAK2V617F mutation was associated with higher absolute and relative count of platelet MPs, respectively (p = 0.045, p = 0.029). CONCLUSION: Although some literature data support the hypothesis of a direct relation between MPs and thrombotic events in MPN patients, further studies are needed to evaluate the clinical implication of MPs in the hypercoagulation state of MPN patients.

[Can Analysis of Cellular Lipidome Contribute to Discrimination of Tumour and Non-tumour Colon Cells?] / Muze analýza bunecného lipidomu prispet k rozlisení nádorových a nenádorových bunek tlustého streva?

BACKGROUNDS: Colon cancer development is often characterized by abnormalities in lipid synthesis and metabolism, which may influence energetic balance, structure and function of biological membranes, or production of specific mediators and cell signalling. The changes in lipid profile and metabolism (lipidome) may significantly affect cell behaviour and response to therapy. Permanent epithelial cell lines at various stages of cancer development are used for better understanding of this topic on cellular and molecular levels. In our study, we hypothesized that detailed analyses of colon cancer cell line lipidomes may help to identify major alterations in the amount and profile of specific lipid classes/species, which can contribute to their different response to various stimuli. MATERIAL AND METHODS: Cellular lipids were isolated from six human epithelial cell lines derived from tissues at various stages of tumour development. Liquid chromatography coupled with tandem mass spectometry analyses were performed in order to determine amount and mass profiles of all phospholipid (PL), lysophospholipid (lysoPL) and sphingolipid classes. The data was statistically evaluated (cluster and discrimination analyses) with respect to mutual comparison of cell lines and to significantly discriminating lipid types. RESULTS: The results of cluster analysis arranged cell lines in order corresponding to their level of transformation (normal cells, adenoma, carcinoma and lymph node metastasis). The results of discrimination analyses revealed the most discriminating lipid types and distinction in PL: lysoPL ratios. Particularly, significant correlation of the amount and profiles of both specific lysoPL and sphingolipid classes with cell transformation level were observed. Similar approaches are now applied to compare lipidomes of colon epithelial cells isolated from tumour vs. non-tumour samples of colon cancer patients. CONCLUSION: Our results indicate that a) selected cancer cell lines are suitable model for lipidomic studies that can serve as a basis for subsequent clinical research, b) cellular lipidome analyses may help to discriminate tumour and non-tumour cells in clinical samples, where specific types of lipids could serve as biomarkers.Key words: colon cancer - cell lines - liquid chromatography - mass spektrometry - phospholipids - sphingolipids - bioinformatics 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. This work was supported by Czech Health Research Council, grant No. AZV 15-30585A.Submitted: 19. 3. 2018Accepted: 18. 4. 2018.

[Postoperative administration of octreotide to reduce lymphorrhea, lymphocele, lymphedema and lymphatic ascites after lymphadenectomy in gynecological malignancies]. / Vliv pooperacního podání oktreotidu na redukci lymforey a následne vzniku lymfocyst, lymfedému a lymfatického ascitu po lymfadenektomii u gynekologických malignit.

INTRODUCTION: Octreotide is a synthetic analogue of natural somatostatin. Octreotide effect on lymphorrhea reduction in gynecological malignancies has only been assessed in case studies. DESIGN: Original work. SETTING: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno. METHODS: In 2014 there was a prospective, randomized, one-institution study. Patients underwent surgery including pelvic or pelvic and paraaortic lymphadenectomy for cervical, uterine and ovarian cancer. The informed consent was signed. Octreotide was evaluated in relation to diagnosis, surgery (laparoscopy versus laparotomy), pelvic and/or paraaortic lymphadenectomy, number of removed lymph nodes and their positivity, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, albumin, BMI, number of days with drains postoperatively, number of days in hospital, blood loss during surgery, time of surgery, total number of drains placed into abdominal cavity. In follow up period, within 1 year after surgery, we searched for lymphocele, lymph-edema of lower extremities and lymphatic ascites in relation to lymphorrhea. RESULTS: 44 patients (9 cervical, 19 endometrial and 16 ovarian cancer) were enrolled in two statistically comparable randomized groups. "Octreotide group", which paradoxically showed lymphorrhea of 4082 ml on average, (without 1992 ml, p = 0.001), needed drainage for more days (p = 0.001). The diagnosis had no influence on lymphorrhea in both groups (p = 0.966). The neoadjuvant chemotherapy was administered (p = 0.026), the more lymph nodes were removed (p = 0.018), the more days the drainage was in place (p < 0.001), the bigger the lymphorrhea; no relationship between lymphorrhea and age (p = 0.631), albumin level (p = 0.584), BMI ( p= 0.966) or number of positive nodes (p = 0.259), length of surgery (p = 0.206), blood loss (p = 0.494). Nor lymphedema (p = 0.404), nor lymphocele (p = 0.086), correlated with postoperative lymphorrhea. Lymphatic ascites was associated with lymphorrhea (p = 0.048). CONCLUSION: Octreotide did not reduce lymphorrhea and the incidence of lymphocele, lymphedema of lower extremities and lymphatic ascites within one year of follow-up period after surgery. According to our results, we do not recommend to administer the octreotide in oncogynecological patients after pelvic and/or paraaortic lymphadenectomy.

Microenvironmental interactions between endothelial and lymphoma cells: a role for the canonical WNT pathway in Hodgkin lymphoma.

The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and ß-catenin in cHL cells. Furthermore, LEF-1- and ß-catenin-regulated cHL secretome promoted EC migration, sprouting and vascular tube formation involving vascular endothelial growth factor A (VEGF-A). Importantly, high VEGFA expression is associated with a worse overall survival of cHL patients. These findings strongly support the concept that WNTs might function as a regulator of lymphoma dissemination by affecting cHL cell chemotaxis and promoting EC behavior and thus angiogenesis through paracrine interactions.

Utilization of an automated pipetting system in the cell line-based screening of the activity of a DNA-damaging anti-tumour drug.

The principles of large screening strategies, which are developed by industrial companies, have been recently adopted by researchers in the fields of molecular biology and oncology as invaluable tools for translational medicine. The declining costs of laboratory robotic machines have allowed high-throughput screening to become more available to academic centres with limited resources. Here, we describe how a robotic conventional liquid handling system could be used on a daily basis in laboratories to obtain consistent and reproducible results. Our approach allowed us to quickly screen a panel of more than 20 tumorigenic and non-tumorigenic cell lines for their responses to hydroxyurea, which is a DNA-damaging anticancer therapeutic drug. The format of 384-well microplates was used for manual cell seeding, and the effect of hydroxyurea was screened at multiple concentrations. The fluorescence-based CyQuant assay was employed as the readout method to analyse the cellular DNA content. The effectiveness of our approach was demonstrated in the experimental results.

[The effectiveness of anagrelide treatment in patients with Ph negative myeloproliferative diseases: influence on the incidence of thrombosis in the data from the Registry of patients with essential thrombocythemia and thrombocythemia associated with other myeloproliferative diseases treated with Thromboreductin® to the end of 2012]. / Úcinnost lécby anagrelidem u nemocných s Ph negativními myeloproliferativními chorobami: ovlivnení výskytu trombózy ve výstupech Registru pacientu s dia-gnózou esenciální trombocytemie a trombocytemie provázející jiné myeloproliferativní onemocnení lécených Thromboreductinem® ke konci roku 2012.

In the Czech Republic, anagrelide (Thromboreductin®) [29] is used according to the recommendations of the Czech Working Group on Myeloproliferative Disorders (CZEMP) for treatment of thrombocythemia associated with Ph negative myeloproliferative disorders (MPDs). The patient data are collected in the Registry of patients with essential thrombocythemia (ET) and thrombocythemia associated with other MPDs treated with Thromboreductin®. At the end of 2012, the Registry contained data on 1,161 patients. Out of these, 1,159 patients with the dia-gnosis of a Ph negative MPD were evaluated. In 844 patients, precise WHO based dia-gnosis was known at start of therapy: 442 (52.4%) had ET, 108 (12.8%) had polycythaemia vera (PV) and 243 had primary myelofibrosis (PMF). The median age was 51 years at the time of diagnosis. At the time of the evaluation of the population, the median was 59 years. Every year, the proportion of patients newly treated with anagrelide as a firstline treatment in accordance with the CZEMP guidelines has been increasing. A growing proportion of patients has been treated with an additional cytoreducing drug, such as hydroxyurea and interferon. The majority of the patients received also an antiaggregant (or anticoagulant). More than a half of patients harbors the JAK2 mutation. A prompt decrease of platelet counts (as the response to Thromboreductin® treatment) was documented in most of the patients. After one year, 86.9% of patients had a full or partial response. In poorer responders, combination cytoreductive treatment was administered rather then the escalation of the Thromboreductin® dosage. There were 461 thrombotic manifestations in 363 patients and 61 haemorrhagic events in 57 patients recorded in the patients history. In the course of treatment (followup; F U), thrombosis was diagnosed only 179-times in 136 patients. There were more haemorrhagic events during F U: 109 events in 83 patients. Upon comparison of the number of events during F U to their numbers in history, we found a twofold decrease in arterial thrombosis, an almost twofold decrease in microvascular thrombosis and even a 6.6- fold decrease in venous thromboembolism events. Bleeding episodes increased 1.8-fold during F U. However, the vast majority of these hemorrhagic events were clinically insignificant. In conclusion, the treatment strategy according to the CZEMP guidelines incorporating anagrelide is highly effective in reducing the platelet counts, strongly prevents venous events, reduces arterial events, and leads to an increase of minor hemorrhages.

Activity of the tick Ixodes ricinus monitored in a suburban park in Brno, Czech Republic, in association with the evaluation of selected repellents.

The ever-increasing number of Lyme borreliosis patients led us to consider more effective procedures for disease prevention. The aim of our study was to monitor the annual activity and infectivity of Ixodes ricinus ticks in the Pisárky region, City of Brno, CR, and to test the responses of the locally-captured ticks to selected repellents. The result of regular one-hour-per-week monitoring in 2011 was the collection of ticks that directly reflected the highest number of Lyme disease patients (4,835) detected throughout the period of recording in the Czech Republic. The ticks were examined for spirochaetes by dark field microscopy. The positive samples were identified by PCR analysis, confirming that 76% of these were infected with Borrelia burgdorferi sensu lato. Ticks were most abundant in May and June, with August having the highest risk for spirochaetal infection. Tick activity was statistically correlated with temperature. The moving-object-bioassay was used to study repellent efficiency on the Ixodes ricinus nymphs captured in the above-mentioned suburban park. Five selected commercial repellents based on DEET (N, N-diethyl-3-thylbenzamide) showed statistically different effects on the non-repellent control group.

[The influence of some factors on presence of varices and variceal bleeding in liver cirrhosis patients]. / Faktory ovlivnující pritomnost varixu a varikóznnho krvácení u pacientu s jaterní cirhózou.

STUDY AIM: The aim of the study was to identify non-invasive investigations that would provide a sufficiently reliable prediction of the presence of varices in patients with liver cirrhosis (LC) and identification of patients in a risk of variceal bleeding. PATIENT SAMPLE AND METHODOLOGY: As part of a prospective evaluation, 165 patients with alcoholic LC admitted to the Department of Internal Hepatology and Gastroenterology of the Medical School, Masaryk University in Brno between 2007-2009 were divided according to the presence of varices and variceal bleeding into three groups: I. patients with LC and varices with no variceal bleeding (N = 50), II. patients with LC with no varices and thus no variceal bleeding (N = 51), III. patients with LC and varices with confirmed variceal bleeding (N = 64). A statistical evaluation was performed of a range of haematological and biochemical parameters, spleen size and a thrombocyte, leucocyte and erythrocyte count to spleen size ratio. RESULTS: Patients with varices (groups I and III) had, compared to patients with no varices (group II), a significantly larger spleen, lower thrombocyte count, lower plasma fibrinogen level, extended prothrombin time (higher INR), lower plasma GGT activity and lower erythrocyte, leucocyte and thrombocyte count to spleen size ratio. In the present cohort, statistically significant factors for the presence of variceal bleeding included lower erythrocyte count and lower level of haemoglobin, i.e. the expected effect of bleeding, lower fibrinogen serum levels, lower serum ALP activity, lower total serum protein and serum albumin, higher plasma levels of uric acid and lower leucocyte or erythrocyte count to spleen size ratio. CONCLUSION: Using common haematological and biochemical parameters together with spleen size enables, even without endoscopic examination, highly reliable prediction of the presence of varices and identification of patients in a high risk of variceal bleeding. When these non-invasive methods are used, it is possible to eliminate the need for the invasive endoscopic examination that is frequently poorly tolerated by the patients and economically demanding.

Registry of inherited bleeding disorders in Poland--current status and potential role of the HemoRec database.

We present data collected in HemoRec, an Internet-based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand's disease is largely under-registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.

[Recombinant activated factor VII in the treatment of life threatening post-partum haemorrhage; registry UniSeven in the Czech Republic]. / Rekombinantní aktivovaný faktor VII (rFVIIa) v lécbe závazného poporodního krvácení data z registru UniSeven v Ceské republice.

OBJECTIVE: To analyze the data related to the treatment of 80 Czech patients with life threatening postpartum haemorrhage recorded in the clinical registry UniSeven during years 2004-2009. DESIGN: Retrospective, observational, multicentre study. SETTINGS: ICU and Obstetrics departments of University and Regional hospitals in Czech Republic. MATERIAL AND METHODS: UniSeven is an international academic project of Masaryk University in Brno, Czech Republic, focused on recording of clinical data related to "off-label" use of rFVIIa (Novo Seven) in life threatening bleeding. Data of 80 case reports of post partum haemorrhage from the registry was analysed from the clinical (efficacy and safety) as well as laboratory aspects. RESULTS: In 97.5% of our patients the treatment with rFVIIa was able to control the bleeding. In 53 women (66.3%) only one dose of rFVIIa was sufficient to control the bleeding. The rest of the patient received two or more rFVIIa doses. First dose of rFVIIa given to patients who needed more than one dose was significantly lower (96.6 microg/kg) compared to patient succesfully treated with one dose only (110.6 microg/kg; p = 0.048). The mortality rate in our cohort of patients was 2.5%. We have not recorded any thrombembolic event as and adverse event related to the rFVIIa treatment. In 74.3% of patients where rFVIIa was administered before considering the hysterectomy, it was able to avoid hysterectomy what we consider to be a significant improvement of the patients' quality of life. CONCLUSIONS: Our data were also considered during the work up of national guidelines for the treatment of life threatening post-partum haemorrhage in the Czech Republic.

[Essential thrombocythaemia and other myeloproliferative disorders with thrombocythaemia treated with Thromboreductin. A report from the database of register for the 1st quarter of 2010]. / Esenciální trombocytemie a jiné myeloproliferate s trombocytemií lécené Thromboreductinem. Výstupy z databáze Registru k 1. ctvrtletí roku 2010.

In the Czech Republic, anagrelid is used according to the recommendations of the Czech Working Group on Myeloproliferative Disorders for treatment ofthrombocythaemias associated with chronic myeloproliferative disorders--mainly essential thrombocythaemia and, regularly, reports are being presented from the Register of Patients Treated with Thromboreductin, most recently last year (Vnitr Lék 2009; 55: I-XII). The Register commenced in 2005 and from then it aims to determine detailed clinical and laboratory profiles of the patients. The structure of the Register has changed significantly in the course of its existence, reflecting the reports from each of the analyses conducted so far. Also, the data entry in the database improves every year and it reaches 97% on some of the items. The longest evaluation period in some of the patients is 108 months. By April 2010, the Register database contained data on 717 patients. Of these, 672 patients with the diagnosis of a Ph-negative chronic myeloproliferative disorder were evaluated. This year's analysis included the patients with essential thrombocythaemia, polycythaemia vera and primary myelofibrosis only. The analysis included 418 women and 254 men with median age of50 years. Unlike the first years, 2/3 of the current sample are non pretreated patients, meaning that the patients reach the specialized centres early in their treatment. Also, patients, and the older patients in particular, are more frequently treated with combined regimens including Thromboreductin. We increasingly observe hypertension as one of the monitored risk factors preceding the disease and laboratory parameters showJAK2 mutation in more than a half of patients while some form ofthrombotic diathesis is found in the anamnesis of 7-10% of patients. Some bleeding is observed in 1-5% of the registered patients. In comparison to the previous years, this is a decrease in the prevalence of clinical symptoms prior to the disease onset; this is very likely associated with an earlier patient diagnosis within the asymptomatic phase of the disease. Therapeutically, we achieve a fast treatment response but there still are 16.3% of sufficient afterone year of treatment. Thromboreductin dose is increasing but even in this group it does not exceeds the mean of 2.38 mg per 24 hours. Complications are observed in 6.2% of patients in the first year of therapy, and ofthese, thrombotic events in about 2.5% and (small) bleeding complications in 4% of patients. The data suggest that we still do not reach treatment response in a certain proportion of patients after a year of their therapy. Even though the care results from the analysed data improve every year, the Register helps to uncover some issues that still remain, such as treatment intensification and other treatment modifications.