Pojem „personalizovaná medicína“ sa v posledných rokoch spomína čoraz častejšie v súvislosti so snahami čo najlepšie prispôsobiť medikamentóznu, ale aj režimovú liečbu potrebám a požiadavkám jednotlivých pacientov. Personalizácia antidiabetickej liečby prekonala svoj vývoj v kontexte nárastu poznatkov týkajúcich sa cukrovky. Od úrovne empirickej sa posunula na úroveň fenotypickú, ktorá umožnila rozlišovanie medzi jednotlivými typmi diabetu. V rámci diabetu 2. typu sa od 60. rokov minulého storočia aplikovala patogenetická personalizácia, ktorá vychádzala z predpokladov, že u niektorých pacientov prevažuje inzulínová rezistencia a u iných deficit sekrécie inzulínu. Bioštatistická personalizácia (medicína dôkazov) viedla k dôkazom, na základe ktorých bol metformín zaradený do odporúčaní pre liečbu diabetu 2. typu ako liek prvej voľby. Randomizované štúdie v prvom desaťročí 21. storočia síce nedokázali superioritu žiadnej z iných liečebných modalít ako prídavnej liečby k metformínu, ale viedli k individualizácii cieľov glykemickej kompenzácie. V súčasnej dobe sa personalizácia posúva na úroveň farmakogenetickú, od ktorej môžeme v najbližších rokoch očakávať individualizáciu liečby v zmysle výberu liekov prvej, druhej a tretej voľby v závislosti od panelu kľúčových génových polymorfizmov charakterizujúcich citlivosť jedinca na konkrétne antidiabetiká. V konečnom dôsledku by mala byť „liečba ušitá na mieru“ vybratá na podklade syntézy patogenetických, bioštatistických a farmakogenetických poznatkov, čo bude reflektovať transláciu výsledkov základného biomedicinískeho výskumu do klinickej praxe. Kľúčové slová: diabetes 2. typu – farmakogenetika – medicína dôkazov – patogenéza – personalizovaná liečba, In recent years, the term “personalized medicine“ has been increasingly mentioned in relation to the endeavours to tailor the pharmaceutical as well as regimen therapy to the needs and requirements of individual patients. The personalization of antidiabetic treatment has undergone a dramatic advancement in relation to the expansion of knowledge about diabetes. From the empirical it moved forward to the phenotypic level which made it possible to differentiate between individual types of diabetes. The pathogenetic personalization which began to be used within Type 2 diabetes in the 1960s, was based on the assumption that while insulin resistance predominates in some patients, others are mainly affected by insulin secretion deficit. Biostatistics-personalized medicine (evidence based medicine) gathered evidence based on which metformin was included in recommendations on the therapy for Type 2 diabetes as a first-line drug. Although randomized studies during the first decade of the 21st century did not prove superiority of any other treatment modality as an adjunctive therapy used with metformin, they brought with them individualization of the goals of glycemic control. At present, personalization is heading towards the pharmacogenetic level that will enable in the near future individualized therapy in terms of choice of first-, second- and third-line drugs depending on the panel of key gene polymorphisms which characterize sensitivity of an individual to specific antidiabetics. Finally, the “tailor-maded therapy“ should be chosen based on a synthesis of pathogenetic, biostatistic and pharmacogenetic knowledge that will reflect the translation of results of the basic biomedical research into the clinical practice. Key words: evidence based medicine – pathogenesis – personalized therapy – pharmacogenetics – type 2 diabetes, and Ivan Tkáč
Úvod: Reverzný, liver-first prístup je alternatívou pre pacientov s komplikovanými synchrónnymi pečeňovými metastázami, kde by progresia v pečeni viedla k inoperabilite, alebo pre pacientov s lokálne pokročilým nálezom v malej panve, kde by komplikácia resekcie primárneho tumoru mohla ohroziť včasnú resekciu pečeňových metastáz. Metódy: Retrospektívna unicentrická analýza 32 pacientov liečených reverzným prístupom v období rokov 2011−2015. Reverzný prístup bol v tomto období indikovaný na základe konsenzu členov multioborovej onkologickej komisie ako preferovaný u všetkých pacientov s iniciálne, alebo potenciálne resekabilným synchrónnym izolovaným metastatickým postihom pečene pri adenokarcinóme kolorekta. Výsledky: 26 pacientov (81,3 %) úspešne absolvovalo kompletnú resekciu nádorovej masy (resekciu pečeňových metastáz a resekciu primárneho tumoru), ale iba 16 pacientov (50 %) absolvovalo kompletný onkochirurgický liečbený plán (hepatektómia, resekcia primárneho tumoru a plánovaná dávka a dĺžka perioperačnej, alebo adjuvantnej onkologickej liečby). Medián prežívania bol 50,5 mesiacov, trojročné prežívanie v súbore bolo 83,7 %. U 20 pacientov (62,5 %) došlo počas sledovania k progresii ochorenia s mediánom do progresie 21,6 mesiaca. Najčastejším miestom progresie bola pečeň, nasledovaná pľúcami (65 resp. 20 % všetkých rekurencií nádorového ochorenia). Záver: Aj keď reverzný, liver-first prístup umožňuje kompletné odstránenie masy tumoru u väčšiny pacientov, iba polovica z nich absolvuje kompletný onkochirurgický liečebný plán. Najproblematickejším aspektom reverzného postupu je načasovanie a dĺžka perioperačnej (bio)chemoterapie. Dôkladné zváženie rizika progresie metastatického procesu počas liečby ako aj rizika kompletnej rádiologickej odpovede by malo viesť k uváženej indikácii perioperačnej (bio)chemoterapie najmä u pacientov s iniciálne resekabilnými pečeňovými metastázami., Introduction: Reverse, liver-first strategy is an alternative for patients with complicated liver metastases where disease progression would prove inoperable, or for patients with locally advanced pelvic disease where postoperative complications after primary tumour resection may lead to delayed treatment of metastatic disease. Methods: Retrospective unicenter analysis of 32 patients approached liver-first approach between 2011 and 2015. During this period reverse strategy was considered a preferred approach for all initially or potentially resectable synchronous colorectal liver metastases based on multidisciplinary team consensus. Results: 26 patients (81.3%) completed their surgical plan (hepatectomy and primary tumour resection) but only 16 (50%) completed their oncosurgical plan (hepatectomy, primary tumour resection and full dose and length of perioperative or adjuvant systemic (bio)chemotherapy). Median overall survival was 50.5 months with the survival rate of 83.7% at 3 years. 20 patients (62.5%) progressed during the follow-up with median time to progression of 21.6 months. The liver was the most common site of recurrent disease followed by the lungs (65% and 20% of all recurrences, respectively). Conclusion: While reverse strategy may allow complete tumour removal in the majority of patients, only half of them complete their oncosurgical plan even with the liver-first approach. The most problematic aspect of the liver-first strategy is the timing and length of perioperative (bio)chemotherapy. When deciding on preoperative chemotherapy in up-front resectable lesions one should take into account the risk of disease progression while on chemotherapy as well as the risks of complete radiologic response., and M. Straka, M. Migrová, R. Soumarová, L. Burda, I. Selingerová
Conceptual degree-day snow models are often calibrated using runoff observations. This makes the snow models dependent on the rainfall-runoff model they are coupled with. Numerous studies have shown that using Snow Cover Area (SCA) remote sensing observation from MODIS satellites helps to better constrain parameters. The objective of this study was to calibrate the CemaNeige degree-day snow model with SCA and runoff observations. In order to calibrate the snow model with SCA observations, the original CemaNeige SCA formulation was revisited to take into account the hysteresis that exists between SCA and the snow water equivalent (SWE) during the accumulation and melt phases. Several parametrizations of the hysteresis between SWE and SCA were taken from land surface model literature. We showed that they improve the performances of SCA simulation without degrading the river runoff simulation. With this improvement, a new calibration method of the snow model was developed using jointly SCA and runoff observations. Further analysis showed that the CemaNeige calibrated parameter sets are more robust for simulating independent periods than parameter sets obtained from discharge calibration only. Calibrating the snow model using only SCA data gave mixed results, with similar performances as using median parameters from all watersheds calibration.
Analyzing the process of keeping promise we identify its sequence structure and its phase sequences in time. This allows us to arrive at a time order principle forming according to which obligation performance cannot precede in time its sufficient or necessary conditions performance. We further observe that a given promise must always be taken as an element of a certain system of promises. As a result we review definitions of the terms sufficient condition and necessary condition as no more allowing their mutual defining, or symmetry (conversion). We try to discover the compliance rules concerning the condition - the conditioned vector, the course of events vector and the time vector. We conclude that it indicates an incorrect use if, provided the condition - the conditioned vector complies with the course of events vector, the negative time difference in the descriptive use of sentences involving either the if-then connective or the only if connective is obtained. Only when using sentences for abductive explanation with a dominating epistemic vector the negative difference of time does not indicate erroneous use; however, this is possible only for the term of sufficient condition. We further suggest reviewed definition generalization involving the terms of sufficient condition and necessary condition containing always a parameter element denot-ing a given modality type, or a particular system of rules, laws, etc. Such definition satisfies Brennan’s requirement of a ''general formal scheme'' where the notion of sufficient condition and necessary condition symmetry (conversion) does not apply., Analýzou procesu dodržení příslibu identifikujeme jeho sekvenční strukturu a její fázové sekvence v čase. To nám umožňuje dospět k principu tvorby časového řádu, podle něhož plnění závazku nemůže včas předcházet jeho dostatečným nebo nezbytným výkonovým podmínkám. Dále pozorujeme, že daný slib musí být vždy považován za prvek určitého systému slibů. Jako výsledek přezkoumáváme definice pojmů dostatečná podmínka a nezbytná podmínka, protože již neumožňují jejich vzájemné vymezení nebo symetrii (konverzi). Snažíme se zjistit, jaká pravidla se týkají podmínky - podmíněný vektor, průběh vektoru událostí a časový vektor. Došli jsme k závěru, že indikuje nesprávné použití, pokud podmínka splňuje podmínku vektoru událostí, záporný časový rozdíl v popisném použití vět zahrnujících buď spojku if-then, nebo pouze tehdy, pokud je získáno spojení. Pouze pokud použijete věty pro abduktivní vysvětlení s dominantním epistemickým vektorem, negativní časový rozdíl neznamená chybné použití; to je však možné pouze po dostatečnou dobu. Dále navrhujeme zrevidovat definici definic zahrnující podmínky dostatečné podmínky a nezbytnou podmínku obsahující vždy prvek parametru označující daný typ modality nebo určitý systém pravidel, zákonů atd. Tato definice splňuje požadavek Brennanové na ,,obecný formální systém ''.Tam, kde se nepoužije pojem dostatečná podmínka a nezbytná symetrie podmínky (konverze)., and František Gahér
In this paper, the risk zone mapping of declining lowland forests belonging to „Morović“, management unit „Varadin-Županja“ (northern Serbia) is performed using geostatistics analysis. Based on the monitoring of groundwater level, the Kriging method has been performed for the spatial distribution of groundwater level for a multiyear period (2010–2013) – reference level and characteristic levels for the wettest and the driest year during the analyzed period. Risk assessment was determined by the variance of characteristics compared to reference levels. Then, multi-criteria decision analysis methods (AHP, PROMETHEE II) were applied to define the rank of each department (smaller forest management units) located in the research area. These analyses are very important because they enable to locate of the area with a high risk of forest decline and to rank departments using criteria: deviation from water level recorded during dry periods, species demand for water, conservation status and purpose of the unit (seed stands or technical wood). The proposed methodology is usable for the determination of the primary localities for the application of management measures conducting on the level of lower planned units (departments) and thus lead to the successful planning and more efficient forest management. Obtained results at the researched area showed that a negative influence on the watering regime has groundwater level decreasing compared to the reference level because it directly affects available water for the plants. Based on multicriteria analysis methods, it was deduced that the most endangered parts are located at the edge, while this risk is much lower in the central part of the management unit. A combination of applied methods (geostatistics and multicriteria analysis) is of great importance for forestry management.