Association between patent ductus arteriosus flow and home oxygen therapy in extremely preterm infants.

BACKGROUND: Central blood flow measurements include the estimation of right and left ventricular output (RVO, LVO), superior vena cava (SVC) flow, and calculated patent ductus arteriosus (PDA) flow. We aimed to provide an overview of the maturation patterns of these values and the relationship between PDA flow and the need for home oxygen therapy. METHODS: This prospective single-center study was conducted in infants born at <26 weeks of gestation. We performed echocardiographic measurements five times during their life (from the 4th post-natal day to the 36th postmenstrual week). RESULTS: Sixty patients with a mean birth weight of 680 (590, 760) g were included. Postnatal development of LVO and PDA flow peaked at the end of the second postnatal week (427 and 66 mL/kg/min, respectively). The RVO increased between days 4 and 7-8. The SVCF was most stable. The development curves of PDA flow differed between the groups with (n = 28; 47%) and without home oxygen therapy. CONCLUSION: We present the central blood flow values and their postnatal development in infants <26 weeks of gestation. This study demonstrates the association between PDA flow and the future need for home oxygen therapy. IMPACT: This study enriches our knowledge of the long-term development of central blood flow parameters and derived patent ductus arteriosus (PDA) flow in extremely preterm infants (<26 weeks). While pulmonary resistance decreased, PDA flow continued to increase from day 4 to the end of the second week of life. Similarly, left ventricular output increased as a marker of preload. The superior vena cava flow remained stable. The observed association between PDA flow and an unfavorable respiratory outcome is important for future studies focusing on the prevention of chronic lung disease.

Alarmins and Related Molecules in Elective Surgery.

Surgery is associated with alterations of alarmins' and related molecules' levels. The aim of this study was to investigate which biomarkers are most involved in surgery. The studied group consisted of 58 patients with inguinal or umbilical hernia or cholecystolithiasis and 21 healthy controls for compa-rison. We also added seven acute patients with appendicitis, cholecystitis and incarcerated hernia. Serum concentrations of soluble receptor of advanced glycation end-products (sRAGE), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE), calprotectin, high mobility group box 1 (HMGB1) and interleukin 6 (IL-6) were analysed by ELISA before and after surgery. Preoperative concentrations of calprotectin were significantly decreased while concentrations of sRAGE were significantly increased in patients compared to controls; the concentrations of EN-RAGE and HMGB1 did not differ significantly. IL-6 levels were undetectable in elective patients preoperatively and in controls. Postoperatively, there was a significant increase of EN-RAGE, calprotectin, HMGB1, and IL-6 and a significant decrease of sRAGE compared to preoperative levels. In acute patients, all tested molecules except for sRAGE were significantly increased preoperatively, and sRAGE was significantly decreased. In contrast, after surgery, we could observe a further increase in IL-6; the other biomarkers did not differ significantly. We can conclude that the concentrations of all tested biomarkers are significantly influenced by elective surgery. The postoperative levels of all tested molecules increase except for sRAGE, whose level is significantly decreased after surgery. In acute states, these molecules are already increased, and the influence of surgery is, apart from IL-6, insignificant.

Predicting the development of hemophilic arthropathy in patients with hemophilia based on patient age: a retrospective single-center database study.

BACKGROUND: Patients with hemophilia (PWH) develop hemophilic arthropathy of the major joints due to recurrent hemarthrosis. This study retrospectively estimated the age at which PWH may expect to develop hemophilic arthropathy and undergo joint replacement surgery. RESEARCH DESIGN AND METHODS: Using retrospective data from PWH at a Czech orthopedic center, Kaplan Meier analyses were used to estimate the cumulative proportions of patients with hemophilic arthropathy and undergoing joint replacement surgery as a function of age. RESULTS: Based on 1028 joint examinations in 167 PWH, hemophilic arthropathy of the knees, elbows, ankles and hips was estimated to develop by a median age of 48, 51, 52 and 61 years, respectively, with ≈80% of patients having such damage by ≈70 years of age. Hemophilic arthropathy of the shoulder occurred much later (median >80 years). In patients undergoing knee or hip replacement surgery, hemophilic arthropathy of the knee and hip occurred at a median age of ≈50 and ≈60 years, respectively, with replacement surgery occurring at a median of ≈70 and >75 years. CONCLUSIONS: In PWH, the risk of developing hemophilic arthropathy accumulates continuously over the patient's lifetime, allowing predictions about the ages at which such damage and joint replacement surgery may occur.

On the contact tracing for COVID-19: A simulation study.

BACKGROUND: Contact tracing is one of the most effective non-pharmaceutical interventions in the COVID-19 pandemic. This study uses a multi-agent model to investigate the impact of four types of contact tracing strategies to prevent the spread of COVID-19. METHODS: In order to analyse individual contact tracing in a reasonably realistic setup, we construct an agent-based model of a small municipality with about 60.000 inhabitants (nodes) and about 2.8 million social contacts (edges) in 30 different layers. Those layers reflect demographic, geographic, sociological and other patterns of the TTWA (Travel-to-work-area) Hodonín in Czechia. Various data sources such as census, land register, transport data or data reflecting the shopping behaviour, were employed to meet this purpose. On this multi-graph structure we run a modified SEIR model of the COVID-19 dynamics. The parameters of the model are calibrated on data from the outbreak in the Czech Republic in the period March to June 2020. The simplest type of contact tracing follows just the family, the second tracing version tracks the family and all the work contacts, the third type finds all contacts with the family, work contacts and friends (leisure activities). The last one is a complete (digital) tracing capable of recalling any and all contacts. We evaluate the performance of these contact tracing strategies in four different environments. First, we consider an environment without any contact restrictions (benchmark); second with strict contact restriction (replicating the stringent non-pharmaceutical interventions employed in Czechia in the spring 2020); third environment, where the measures were substantially relaxed, and, finally an environment with weak contact restrictions and superspreader events (replicating the situation in Czechia in the summer 2020). FINDINGS: There are four main findings in our paper. 1. In general, local closures are more effective than any type of tracing. 2. In an environment with strict contact restrictions there are only small differences among the four contact tracing strategies. 3. In an environment with relaxed contact restrictions the effectiveness of the tracing strategies differs substantially. 4. In the presence of superspreader events only complete contact tracing can stop the epidemic. INTERPRETATION: In situations, where many other non-pharmaceutical interventions are in place, the specific extent of contact tracing may not have a large influence on their effectiveness. In a more relaxed setting with few contact restrictions and larger events the effectiveness of contact tracing depends heavily on their extent.

Does sternal body shape reflect family relationships? A study on a genealogically documented Central European osteological sample (19th-20th centuries).

In forensic contexts, sternal anatomical varieties represent useful tools for the identification of an individual, either by comparison of ante-mortem and post-mortem data, or by potential comparison of data from biologically related individuals. Sternal body variation is also used to detect the biological affinity of individuals in bioarchaeology. However, no study has been made available to date on the degree to which the overall shape of the sternal body reflects the degree of biological relatedness. We, therefore, analyzed the sternal body shape of 10 individuals with known genealogical data, members of one family over three generations including inbred individuals (19th-20th centuries, Bohemia, Czech Republic), and a control sample of 12 biologically unrelated individuals. First, closely biologically related individuals were compared with unrelated individuals based on 10 variables expressing the morphological characteristics of the sternum, and then all individuals were compared based on Fourier analysis depending on their degree of relationship. The results showed that there is a greater degree of shape similarity in biologically related individuals than in unrelated individuals, and variability decreases with an increasing degree of relatedness. Inbred individuals showed the lowest sternum-shape distances and degree of variability, while unrelated individuals, showed the highest distances and variability. Moreover, in some cases, the documented relationships were also supported by a similar morphology of the ossified and fused xiphoid process. Thus, sternal shape analysis expands the possibilities for individual identification and the detection of the biological affinity of individuals for both the forensic sciences and bioarchaeology.

Retinoic acid associates with mortality of patients on long-term hemodialysis.

BACKGROUND: Retinol concentrations in serum are significantly higher in patients on hemodialysis (HD) compared to healthy controls. Its lower concentrations have been reported to be an independent predictor of mortality. ATRA - all-trans retinoic acid - is an important compound related to retinol. The objective was to determine ATRA concentrations in serum and to find their association with the prognosis of patients on long-term HD. METHODS: ATRA was determined by high-performance liquid chromatography in a group of 247 HD patients (follow-up five years) and 54 healthy controls. RESULTS: Although serum retinol concentrations were higher in the studied cohort of HD patients, ATRA was lower - median 1.13 (interquartile range 0.90-1.60) ng/mL in HD patients versus 1.42 (1.08-1.63) ng/mL in healthy controls, p = 0.02. Lower ATRA was significantly related to overall mortality of HD patients (HR (95%CI) 0.63 (0.47-0.85) per interquartile range, p = 0.003). The best prognosis was observed in patients with concentrations of both ATRA and retinol above the median (p = 0.003). CONCLUSIONS: We detected decreased retinoic acid levels in HD patients compared to healthy controls. Lower concentrations of ATRA represent a significant predictor of mortality and provide additional information to retinol.

New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold. We determined the value of TMB in tumor tissue (tTMB) and blood (bTMB) in 20 patients with early stage NSCLC using original custom gene panel LMB_TMB1. We evaluated various possibilities of TMB calculation and concluded that TMB should be counted from both somatic non-synonymous and synonymous mutations. Considering various factors, we established cut-offs of tTMB in/excluding HLA genes as ≥22 mut/Mb and 12 mut/Mb respectively, and cut-offs of bTMB were defined as ≥21 mut/Mb and ≥5 mut/Mb, respectively. We also observed trend in correlation of somatic mutations in HLA genes with overall survival of patients.

Hospital admissions to geriatric ward related to adverse drug events: a cross-sectional study from the Czech Republic.

Background Geriatric patients represent a vulnerable population in terms of adverse drug events (ADEs). Objective The aims of this study were to determine the prevalence and preventability of hospital admissions to a geriatric ward related to ADEs, to identify medications involved in these ADEs and to describe potential preventability aspects of ADE-related admissions. Setting University Hospital Hradec Králové, Czech Republic. Methods This cross-sectional study evaluated acute hospital admissions to the geriatric ward of University Hospital Hradec Králové over a period of nine months (April-December 2017). Medication reviews were performed in order to identify ADE-related hospital admissions. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. Modified Schumock-Thornton algorithm was used to assess the preventability of ADEs. Main outcome measure 9-month-prevalence of ADE-related hospital admissions. Results A total of 366 hospital admissions were included. The 9-month-prevalence of ADE-related hospital admissions was 11.75% [95% confidence interval 8.45-15.05]. Antithrombotic agents and diuretics represented the most common medication classes associated with ADEs (30.2% each). Electrolyte disturbances and gastrointestinal haemorrhages and ulcerations were the most frequently observed ADEs associated with hospital admission. Out of 43 ADE-related hospitalisations, 23 (53.5%) were considered potentially preventable. Conclusion The contribution of ADEs to hospital admission to the geriatric ward was not negligible. Our results also suggest that 53.5% of identified ADE-related admissions could be potentially prevented. This finding demonstrates just how important the research on the preventability of medication-related hospitalisations is. Further studies and implementations are still needed aiming to minimize the risk of medication-related harm.

Spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic.

Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic. Setting Retrospective observational pharmacovigilance study. Methods Adverse drug reaction reports were obtained from the State Institute for Drug Control between January 2005 and November 2017. Reports related to warfarin, dabigatran, apixaban, and rivaroxaban received from healthcare professionals and patients were analyzed. Main outcome measure Frequency and nature of adverse drug reactions reported to oral anticoagulants. Results In total, 297 reports containing 672 adverse drug reactions were received; 269 reports were sent by healthcare professionals (85% by physicians). In 65% of all reports, reactions were due to direct oral anticoagulants. A higher total number of adverse drug reactions was associated with direct oral anticoagulants than with warfarin [reporting odds ratio (ROR): 10.76; confidence interval (CI): 8.70-13.32; p < 0.001]. Along with the increasing utilization of direct oral anticoagulants, the reporting rate gradually declined over time, especially for rivaroxaban and apixaban. Fatal outcomes were reported in 7%, mostly for dabigatran. Hemorrhagic reactions were the most frequently reported adverse drug reactions (37% associated with dabigatran, 28% with apixaban, 24% with warfarin, and 23% with rivaroxaban), and compared to warfarin, they were significantly more often associated with direct oral anticoagulants (ROR: 14.36; CI: 9.57-21.54; p < 0.001). Conclusion The number of adverse drug reaction reports related to oral anticoagulants in the Czech Republic was relatively low, compared to other studies, but 96% of the cases were serious. Data from spontaneous adverse drug reactions reporting should be further analyzed in order to obtain additional information on the safety profile of oral anticoagulants.

Changes in Beliefs About Post-Transplant Immunosuppressants Over Time and Its Relation to Medication Adherence and Kidney Graft Dysfunction: A Follow-Up Study.

PURPOSE: The main aim was to evaluate the changes in beliefs about immunosuppressants over a 3-year period in patients after kidney transplantation. The second aim was to investigate the relationship between beliefs, medication adherence, and selected clinical outcomes such as graft functioning. PATIENTS AND METHODS: This observational follow-up study was conducted in the outpatient post-transplant clinic at the University Hospital Hradec Kralove in the Czech Republic. Adult patients, at least 4 weeks after kidney transplantation, were invited for the structured interview, which was followed by a self-administered questionnaire survey during their regularly scheduled visits at the clinic. Appropriate paired tests were used to compare two measurements of beliefs about immunosuppressants by BMQ-CZ© in 2016 (baseline) and in 2019 (follow-up). Self-reported adherence was measured by two validated tools (MARS-CZ© and BAASIS©) capturing implementation and discontinuation phases. A generalized linear model was used to investigate the relation between beliefs and the consecutive estimated glomerular filtration rate. RESULTS: The study involved 134 patients. Over time, their perceived treatment necessity beliefs of immunosuppressants decreased, while their treatment-related concerns increased. Overall self-reported non-adherence (ie, taking, dosing and discontinuation of immunosuppressants) was reported by 12% of the patients in both observation periods. In the follow-up period, timing non-adherence was reported by 52 (38.8%) patients. Higher baseline treatment concerns were associated with poor adherence whereas higher baseline treatment necessity beliefs corresponded with better kidney functioning, even after adjusting for age. CONCLUSION: Higher treatment necessity beliefs corresponded with better kidney functioning, whereas higher treatment concerns were related to non-adherence to immunosuppressants at the beginning of the observed period. Still, most patients accepted their medicines that do not come without risk. Nevertheless, decreasing treatment necessity beliefs on one hand, and increasing treatment concerns on the other, should be considered in clinical practice.

Analysis of the fall-related risk of pharmacotherapy in Czech hospitals: A case control study.

RATIONALE, AIMS, AND OBJECTIVES: Falls are among the major problems occurring in hospital setting, when drugs are viewed as important modifiable risk factor of falling. The aim was to analyse the effect of pharmacotherapy on the risk of falls in hospitalized patients. METHODS: A multicentre prospective case-control study was conducted in 2017 retrieving data from four hospitals in South Bohemia, Czech Republic. An online database was constructed to collect patient and fall-related data. Each fall that occurred during hospitalization was assigned to appropriate controls (no fall during hospitalization) based on gender, age, length of hospitalization, and the number of drugs. Univariate and multivariate correlations were performed with a significance level of P < .05. RESULTS: A total of 222 fall cases (107 males; median age, 81 y) and 1076 controls (516 males; median age, 80 y) were included. According to the first ATC level classification, drugs from groups S, N, and P were significantly associated with fall-related risk compared with controls (P < .05); further analysis of ATC levels showed that only psycholeptics (N05), antipsychotics (N05A), and tiapride were significantly associated with falls. Regression analysis revealed use of psycholeptics N05 (OR = 2.06; 95% CI, 1.56-2.76), or ophthalmologicals S01 (OR = 2.72; 95% CI, 1.37-5.41), as factors with the highest fall-related risk. CONCLUSIONS: Apart from the commonly considered fall-risk increasing drugs, other groups, such as ophthalmologicals, should also be considered; however, regarding clinical practice, it is difficult to evaluate the effects of individual drugs in the context of other risk factors of falls, due to the multifactorial nature of falls.

Pharmacotherapy as major risk factor of falls - analysis of 12 months experience in hospitals in South Bohemia.

This study aimed to analyze the effect of fall risk-increasing drugs (FRIDs) and drug-related factors relative to falls through clinical pharmacy service in hospitalized patients, focusing on the relevance of clinical pharmacist evaluation in the context of physician assessment. A prospective study of inpatient falls was conducted in 2017 retrieving data from 4 hospitals in South Bohemia, Czech Republic. An online database was developed to collect patient and fall-related data, and fall evaluation records. Healthcare professionals classified the overall effect of drugs on falls using Likert scale. Univariate and multivariate correlations were performed with a significance level of p < 0.05. Out of the total 280 falls (mean age of patients 77.0 years), a mean of 2.8 diagnoses with fall-related risk, 8.8 drugs, and 4.1 FRIDs per fall were identified. Incidence of falls decreased quarterly (p < 0.001). Use of FRIDs were positively associated with increasing age (p = 0.007). Clinical pharmacists were more likely to identify pharmacotherapy as the relevant fall-related risk, compared to physicians evaluation (p < 0.001). An increasing total number of prescribed drugs as well as higher number of FRIDs increased the suspicion in both professionals in the context of drug-related causes of falls.

Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients.

PURPOSE: Kidney transplant (KTx) recipients should strictly adhere to their lifelong complex therapeutic regimen, and any barriers to medication adherence can weaken correct patient behavior. This study aimed to determine the adherence to immunosuppressive therapy (IS) in KTx adult outpatients in the Czech Republic, and attempted to gain a greater insight into their attitudes toward IS and self-management tasks. MATERIALS AND METHODS: Pharmacist-led structured interviews were conducted to assess self-reported adherence to IS using the Czech version of the Medication Adherence Report Scale, in the context of attitudes toward IS in terms of necessity and concern scale of the Beliefs about Medicines Questionnaire. A specific questionnaire was developed to target IS self-management tasks. Medication records were also reviewed for IS serum levels, reflecting direct adherence measurement. Descriptive statistics were used to calculate adherence and self-management variables, and were analyzed by univariate and multivariate correlations, including the decision-tree method. RESULTS: The interview was completed by 211 (male 123; mean age 55.0±12.4 years, mean time 6.6±5.9 years after KTx) of the total of 235 patients. Full adherence to IS was reported by 173 (82.0%) patients. Most of them had IS serum levels within the therapeutic range, however, cyclosporine was associated with the highest variability (P<0.001). Non-adherence and concerns increased over time after KTx (P<0.05). Despite the more common unintentional non-adherence (P<0.001), relatively high concerns signified the risk of not taking IS as prescribed. Concerns also correlated with the perception of impaired health status (P<0.01), as well as the occurrence of IS-related adverse effects (P<0.001). The patients' awareness of their therapy was insufficient, and main gaps in self-management comprised inadequate sun protection, incorrect administration of IS, and unfamiliarity with the IS name, or their indications. CONCLUSION: Although self-reported adherence to IS therapy was satisfactory, the comprehensive evaluation enabled the detection of greater concerns about IS, as well as underestimated self-management tasks that posttransplant interventions should target in the future.

Range of motion after total knee arthroplasty in hemophilic arthropathy.

BACKGROUND: Outcomes of total knee replacement in cases of hemophilic patients are worse than in patients who undergo operations due to osteoarthritis. Previous publications have reported varying rates of complications in hemophilic patients, such as infection and an unsatisfactory range of motion, which have influenced the survival of prostheses. Our retrospective study evaluated the data of hemophilic patients regarding changes in the development of the range of motion. METHODS: The data and clinical outcomes of 72 total knee replacements in 45 patients with hemophilia types A and B were reviewed retrospectively. Patients were operated between 1998 and 2013. All of the patients were systematically followed up to record the range of motion and other parameters before and after surgery. RESULTS: The mean preoperative flexion contracture was 17° ± 11° (range, 0°-40°), and it was 7° ± 12° (range, 0°-60°) postoperatively. The mean flexion of the knee was 73° ± 30° (range, 5°-135°) before the operation and 80° ± 19° (range, 30°-110°) at the last follow-up. The mean range of motion was 56° ± 34° (range, 0°-130°) before the operation and 73° ± 24° (range, 10°-110°) at the last follow-up. CONCLUSIONS: Statistical analysis suggested that the range of motion could be improved until the 9th postoperative week. The patient should be operated on until the flexion contracture reaches 22° to obtain a contracture < 15° postoperatively or until the contracture reaches 12° to obtain less than 5°. The operation generally does not change the flexion of the knee in cases of hemophilic patients, but it reduces the flexion contracture and therefore improves the range.

Atmospheric metal pollution records in the Kovárská Bog (Czech Republic) as an indicator of anthropogenic activities over the last three millennia.

Three peat cores were extracted from the Kovárská Bog in the central Ore Mountains to study anthropogenic pollution generated by mining and metallurgy. The core profiles were 14C dated, and concentrations of selected elements were determined by ICP MS and HG-AAS. Principal component analysis indicated that Pb, Cu, As and Ag may be useful elements for the reconstruction of historical atmospheric pollution. Total and anthropogenic accumulation rates (ARs) of Pb, Cu and As estimated for the last ca. 3500years showed similar chronologies, and revealed twelve periods of elevated ARs of Pb, As and Cu related to possible mining and metallurgic activities. In total, four periods of elevated ARs of Pb, Cu and As were detected during the Middle and Late Bronze Ages, including a distinct Late Bronze Age pollution event between 1030BCE and 910BCE. The Iron Age included three episodes of increased ARs of Pb and As; the first and the most distinctive episode, recorded between 730 and 440BCE, was simultaneous with the Bylany culture during the Hallstatt Period. The Roman Age was characterized by one pollution event, two events were detected in the Middle Ages, and the last two during the modern period. Enhanced element ARs in the late 12th and 15th centuries clearly documented the onset of two periods of intense mining in the Ore Mountains. Metal ARs culminated in ca. 1600CE, and subsequently decreased after the beginning of the Thirty Years' War. The last boom of mining between 1700CE and 1830CE represented the last period of important metallurgical operations. Late Medieval and modern period metal ARs are in good agreement with written documents. Earlier pollution peaks suggest that local metal production could have a much longer tradition than commonly believed; however, archaeological or written evidence is scarce or lacking.

Are haplotypes in a single methotrexate pathway more predictive for response in rheumatoid arthritis than in different pathways?

Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs in methotrexate intracellular pathways are associated with methotrexate therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).

Pregnancy-Associated Plasma Protein A2 in Hemodialysis Patients: Significance for Prognosis.

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) is associated with adverse outcome of long-term hemodialysis patients (HD). The aim of the study was to test whether its homolog pregnancy-associated plasma protein A2 (PAPP-A2) can be detected in serum of HD patients and to define its significance. METHODS: The studied group consisted of 102 long-term HD patients and 25 healthy controls. HD patients were prospectively followed up for five years (2009-2014). PAPP-A2 was measured by surface plasmon resonance biosensor, PAPP-A by time resolved amplified cryptate emission. RESULTS: PAPP-A2, similarly as PAPP-A, was significantly increased in HD patients (median (interquartile range)) PAPP-A2: 6.2 (2.6-10.8) ng/mL, vs. 3.0 (0.7-5.9) ng/mL, p=0.006; PAPP-A: 18.9 (14.3-23.4) mIU/L, vs. 9.5 (8.4-10.5) mIU/L, p<0.001). In HD patients, PAPP-A2 correlated weakly but significantly with PAPP-A (τ=0.193, p=0.004). Unlike PAPP-A, PAPP-A2 was not significant for prognosis of HD patients when tested alone. There was a significant interaction between PAPP-A and PAPP-A2 on the mortality due to infection of HD patients (p=0.008). If PAPP-A was below median, mortality due to infection was significantly higher for patients with PAPP-A2 values above median than for patients with low PAPP-A2 levels (p=0.011). CONCLUSION: PAPP-A2 is increased in HD patients and interacts with PAPP-A on patients´ prognosis.

Polymorphisms of the receptor for advanced glycation end products and glyoxalase I and long-term outcome in patients with breast cancer.

Receptor for advanced glycation end products and glyoxalase I metabolizing advanced glycation end product precursors may play important role in the pathogenesis and progression of cancer. Potential relation between soluble forms of receptor for advanced glycation end products (sRAGE), receptor for advanced glycation end products, glyoxalase I polymorphisms, and long-term outcome (median follow-up of 10.3 years) was studied in 116 patients with breast cancer. Gly82Ser and 2184 A/G RAGE polymorphisms were related to the mortality due to the breast cancer and -419 A/C glyoxalase I polymorphism was related to the overall mortality of the patients suggesting their role not only in the risk of breast cancer but also in the outcome of patients with breast cancer.

Comparison of DNA isolation using salting-out procedure and automated isolation (MagNA system).

Isolation of genomic DNA is a key step in genetic analysis. The aim of the study was to evaluate the suitability of isolation of DNA from peripheral blood with manual salting-out procedure and automated MagNA system under specific conditions. The impact of storage conditions, type of material (whole blood or blood cells), and method used for DNA extraction were evaluated in terms of DNA yield, its purity, and integrity. Fresh material, and material stored at 2-8°C for 1-4 weeks and frozen at -80°C were tested. For fresh samples, salting-out method gives higher yield than MagNA, irrespectively, on material used. Neither the yield of salting-out method nor its purity decreases during the storage of the samples in the fridge (2-8°C) during 4 weeks. Concerning MagNA, storage of blood cells in the fridge decreases the yield of DNA as well as its purity. For frozen samples, for whole blood, MagNA gives better results while for blood cells, salting-out method seems to be better. For fresh samples, salting-out method is the preferred one, and both whole blood and blood cells can be used. For frozen samples, the preferred method depends on the material.