Hasznos tesztek az új prognosztikai markerek klinikai értékének felmérésére: a szívelégtelenség példája

Bevezetés: Napjaink klinikai kutatásainak egyik fő iránya a megbetegedések hátterében álló kockázati tényezők azonosítása. Közlemények százai számolnak be „szignifikáns” és „független” prognosztikai faktorokról különböző humán megbetegedésekben, azonban ezek egy részében nem vagy nem megfelelően vizsgálták, hogy az új prognosztikai faktor javította-e, és ha igen, milyen mértékben az addig ismert prognosztikai modellt. A legújabb statisztikai módszertani ajánlások szerint az úgynevezett reklasszifikációs analízissel a fenti kérdést érdemben vizsgálni lehet. Célkitűzés: A reklasszifikációs analízis kivitelezésére több módszer is van, a közleményben a szerzők ezek alkalmazását saját, korábban publikált vizsgálataik újraelemzésével mutatják be. Módszer: Két marker, a vörösvértestátmérő-eloszlás szélessége és a szérum-hősokkfehérje-70 prognosztikai szerepét vizsgálták krónikus szívelégtelenségben szenvedő betegek körében. Korábban publikált eredményeik szerint mind a vörösvértestátmérő-eloszlás szélessége, mind a hősokkfehérje-70 szignifikáns, független prognosztikai markernek bizonyult többváltozós Cox-regressziós vizsgálatok alapján. Mindkét esetben újraértékelték a markerek szerepét reklasszifikációs tesztekkel. Eredmények: A szívelégtelen betegek prognosztikai modelljének diszkriminatív képessége lényegesen javult a korábbi modellhez képest, ha a vörösvértestátmérő-eloszlás szélességével egészítették ki a modellt, míg a hősokkfehérje-70 esetén ez nem volt egyértelmű. Következtetések: Az új prognosztikai faktorokat kritikusan kell kezelni mindaddig, míg alkalmas vizsgálatokkal elemzésre és bizonyításra nem kerül, mekkora a valós klinikai haszon, amely a marker már ismert prognosztikai modellhez való hozzáadásából származik. A hasznosságot a prognosztikai modell javulása során tesztelhetjük a reklasszifikáció módszereivel. Orv. Hetil., 2013, 154, 1374–1380.Introduction: Identification of risk factors is one of the most frequent questions in medical research currently. Several reports showed “significant” and “independent” prognostic factors in a variety of human conditions, however, those were not tested about predictive information in addition to standard risk markers. Recently novel statistical approaches (reclassification) have been developed to test the performance and usefulness of new risk factors and prognostic markers. There are several established methods to test the prognostic models. Aim: The aim of this work was to present the application of these novel statistical approaches by re-analyzing previously reported results of the authors. Method: The authors analyzed the prognostic role of two markers: red cell distribution width and heat shock protein 70 in patients with heart failure. Using Cox regression analyses the authors have reported previously that both markers are independent predictors. In the present study they re-analyzed the role of red cell distribution width and heat shock protein 70 by reclassification tests. Results: Incorporating red cell distribution width to the reference model the authors found a significant improvement in discrimination . However, the reclassification analysis provided ambiguous results with heat shock protein 70. Conclusions: Interpretation of results on new prognostic factors has to be done carefully, and appropriate reclassification approaches may help to confirm clinical usefulness only. Orv. Hetil., 2013, 154, 1374–1380

Extracting geometric information from images with the novel Self Affine Feature Transform

Based on our research, the Self Affine Feature Transform (SAFT) was introduced as it extracts quantities which hold information of the edges in the investigated image region. This paper gives details on algorithms which extract various geometric information from the SAFT matrix. As different image types should be analysed differently, a classification procedure must be performed first. The main contribution of this paper is to describe this classification in details. Information extraction is applied for solving different 2-dimensional image processing tasks, amongst them the detection of con­ver­gent lines, circles, ellipses, parabolae and hiperbolae or localizing corners of calibration grids in a robust and accurate manner

Design of an embedded microcomputer based mini quadrotor UAV

This paper describes the design and realization of a mini quadrotor UAV (Unmanned Aerial Vehicle) that has been initiated in the Systems and Control Laboratory at the Computer and Automation Research institute of the Hungarian Academy of Science in collaboration with control departments of the Budapest University of Technology and Economics. The mini quadrotor UAV is intended to use in several areas such as camera-based air-surveillance, traffic control, environmental measurements, etc. The paper focuses upon the embedded microcomputer-based implementation of the mini UAV, describes the elements of the implementation, the tools realized for mathematical model building, as well as obtains a brief outline of the control design

Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia.

The activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease is low in several conditions, including HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. As HELLP syndrome develops in most cases on the basis of preeclampsia, our aim was to determine whether plasma ADAMTS13 activity is decreased in preeclampsia. Sixty-seven preeclamptic patients, 70 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Plasma ADAMTS13 activity was determined with the FRETS-VWF73 assay, while VWF antigen (VWF:Ag) levels with an enzyme-linked immunosorbent assay. The multimeric pattern of VWF was analyzed by SDS-agarose gel electrophoresis. There was no significant difference in plasma ADAMTS13 activity between the preeclamptic and the healthy pregnant and non-pregnant groups (median [25-75 percentile]: 98.8 [76.5-112.8] %, 96.3 [85.6-116.2] % and 91.6 [78.5-104.4] %, respectively; p > 0.05). However, plasma VWF:Ag levels were significantly higher in preeclamptic patients than in healthy pregnant and non-pregnant women (187.1 [145.6-243.1] % versus 129.3 [105.1-182.8] % and 70.0 [60.2-87.3] %, respectively; p < 0.001). The multimeric pattern of VWF was normal in each group. Primiparas had lower plasma ADAMTS13 activity than multi-paras (92.6 [75.8-110.6] % versus 104.2 [92.1-120.8] %; p = 0.011). No other relationship was found between clinical characteristics, laboratory parameters and plasma ADAMTS13 activity in either study group. In conclusion, plasma ADAMTS13 activity is normal in preeclampsia despite the increased VWF:Ag levels. However, further studies are needed to determine whether a decrease in plasma ADAMTS13 activity could predispose preeclamptic patients to develop HELLP syndrome

Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies

(Full text is available at http://www.manu.edu.mk/prilozi). In thrombotic microangiopathies (TMA) pathological changes of the small vessels are present, which lead to ischaemia of the affected tissues, low platelet-count and intravascular haemolytic anaemia with fragmentocytes. Two main clinical syndromes belong to the group of TMAs: the haemolytic uraemic syndrome (HUS) with kidney failure, mainly affecting children, and the thrombotic thrombocytopenic purpura (TTP), starting primarily in adulthood. HUS can be clinically classified into two forms: typical and atypical HUS, the latter being caused by defective regulation of the complement system. However, acccording to recent studies, complement activation is also present in other TMAs. Complement activation products (C3a, C5a, MAC) are able to activate endothelial cells, which results in loss of their antiinflammatory and antithrombotic potential. Activation of the complement system can also lead to direct activation of platelets and granulocytes. The consequent endothelial damage and thrombosis forms the pathological basis of the TMAs. Exploring the exact pathogenetic role of the complement system in these diseases makes the development of new therapeutic methods possible. Key words: TMA, aHUS, D+ HUS, TTP, complement system, endothelial cell activation

Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure.

Decreased activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease, was recently reported in cardiovascular diseases and in hepatic failure. Chronic heart failure (CHF) is characterised by abnormalities of left ventricular function accompanied by the failure of the liver and dysregulation of endothelial activation. Therefore, the aim of our study was to measure ADAMTS13 activity in CHF, and determine the prognostic value of VWF and ADAMTS13 on major clinical events in CHF. ADAMTS13 activity (measured by FRETS-VWF73 substrate) was decreased in CHF (n = 152, left ventricular ejection fraction <45%), and it correlated negatively with B-type natriuretic peptide (BNP) NYHA (New York Heart Association) classes, markers of synthetic capacity of the liver and endothelial dysfunction (all p < 0.005). Both, high VWF:Ag levels (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.189-1.943), and low ADAMTS13/VWF:Ag ratios (HR 0.70, 95% CI 0.58-0.84) independently and significantly predicted short-term (1 year follow-up) clinical adverse events in heart failure (HF). Decreased activity of ADAMTS13 with concomitant high VWF:Ag levels is a significant independent predictor of clinical events in CHF. The levels of the two molecules may integrate the impaired synthetic capacity of the liver and the disturbed endothelial regulation and can therefore be a useful tool to predict clinical events in CHF

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis

Background—Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (Cpn), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. Methods and Results—A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, Cpn, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and Cpn but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and Cpn did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and Cpn, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). Conclusions—High levels of antibodies to hHSP60 and Cpn are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development