Trastuzumab is a humanized monoclonal antibody directed against the HER-2 receptor. Trastuzumab-based therapy significantly improves response rate (RR), time to progression (TTP) and overall survival (OS) for women with HER-2 positive metastatic breast cancer. Despite its initial efficacy, acquired resistance to trastuzumab develops in a majority of patients with MBC, and a large subset never responds, demonstrating primary resistance. The purpose of this retrospective study was to determine prognostic factors applicable to clinical practice. METHODS: We enrolled 112 women with metastatic breast cancer, who started the trastuzumab-based therapy at Masaryk Memorial Cancer Institute until January 2007. Clinical and laboratory factors, such as: patients conditions, character ofmetastatic spread, histology, estrogen, progesterone and Her-2 receptor status, Her-2/neu gene amplification, and serum tumor markers CEA, CA 15-3 and extracellular domain of Her-2 receptor (S-HER-2 ECD) were monitored. The association of all factors to response to therapy, time to progression (TTP) and overall survival (OS) was assessed. RESULTS: In 95% patients, the trastuzumab was combined with cytostatics (83% taxanes), 88,4% of patients started the trastuzumab as the first or second-line anticancer treatment. The median TTP was 284 days (9,3 months) and the median OS was 612 days (20,1 months) for all patients, RR was 54,5%. The highest RR was associated with the first-line treatment (p<0.0001) and with HER-2 gene/Chromosome 17 ratio > 2,2 (p=0,0092). Eleven patients (9,8%) discontinued the treatment because of toxicity, 7 patients did it as a result of cardiotoxicity (6,2%). CNS metastases occurred in 31 patients (27,7%). The S-HER-2 ECD was the most frequently elevated serum marker at the time of the treatment initialization (72,5%) and at the time of the progression (55,9%). Cox regression analysis identified S-HER-2 ECD levels at the beginning and between day 90 and 130 of the trastuzumab therapy as the best predictors of TTP. On the other hand the best predictor of OS was level of CEA before the treatment started and level of S-HER-2 ECD between day 90 and 130 of the trastuzumab therapy. CONCLUSIONS: We confirmed that the only one predictive marker for response to trastuzumab therapy is a proof of HER-2 tumor positivity.The highest prevalence of S-HER-2 ECD positivity among serum tumor markers and the strong association between initial and subsequent S-HER-2 ECD serum concentrations and time to progression and overall survival make the S-HER-2 ECD the most significant prognostic marker., Svoboda Marek, Grell Peter, Šimíčková Marta, Fabian Pavel, Petráková Katarína, Palácpvá Markéta, Macková Dagmar, Trojanec Radek, Hajdúch Marián, Pavlík Tomáš, Nenutil Rudolf, Vyzula Rostislav, and Lit.: 37
Autoři uvádějí systematický přehled velkých randomizovaných studií z posledních let, které srovnávají krátkodobý i dlouhodobý efekt endovaskulární a chirurgické metody při léčbě stenózy odstupu vnitřní karotické tepny. Studie prokázaly podobný pozitivní dlouhotrvající efekt pro obě metody. Vyšší četnost komplikací v periprocedurálním období po angioplastice je způsobena častějšími drobnými neinvalidizujícími mozkovými ischemiemi, endarterektomie má větší riziko srdečního infarktu. Pro úspěch léčby je zásadní zkušenost operatéra a správná indikace nemocného k léčbě. Nemocní by měli být léčeni v centrech, která mají k dispozici obě metody a provádějí je s nízkým počtem komplikací., The authors present a systematic review of recent large randomized studies comparing short and long-term effect of endovascular and surgical treatment of the internal carotid artery stenosis at its origin. The studies showed similar beneficial long-term effect of both methods. Higher rate of complications in angioplasty is caused by minor debilitating ischemic strokes in the periprocedural period while the endarterectomy has higher risk of myocardial infarction. Experience of the operator and appropriate patient indication for therapy are crucial for treatment success. Patients should be treated in centers in which both methods are routinely available with lower rate of complications. Key words: carotid stenting – carotid endarterectomy –randomized study – periprocedural complications – long-term outcomes 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 “uniform requirements” for biomedical papers., and D. Krajíčková, A. Krajina
Cieľ: Veľká významnosť včasne prevedenej karotickej endarterektómie u indikovaných pacientov po tranzitornej ischemickej atake (TIA) z pohľadu sekundárnej prevencie iktu viedla k potrebe podrobnej analýzy našich dát, ich korelácie s všeobecne akceptovanými odporúčaniami AHA, prípadne hľadaní nápravy. Metodika: Do prospektívnej štúdie bolo zaradených 975 karotických endarterektomií operovaných na Neurochirurgickej klinike Masarykovej nemocnice v Ústí nad Labem v období od roku 2006 do roku 2013. Všetky operácie boli v lokálnej anestézii so selektívnym požitím skratu v závislosti na vývoji neurologického stavu po nasadení klipov na karotídu. Vyšetrenie mozgu pomocou MR DW bolo uskutočnené v deň príjmu pacienta k operácii a 24 hod po výkone. Z dostupných dát bola spätne vyselektovaná skupina symptomatických stenóz (n = 422) a podrobne analyzovaná skupina s priebehom ako TIA (n = 187). Sledované parametre boli: 1. čas prevedenia operácie od vzniku klinických príznakov a 2. počet a typ komplikácií vzhľadom k časovaniu operácie. Výsledky: 1. V skupine všetkých TIA je od roku 2007 medián doby od vzniku príznakov k prevedeniu operácie v akceptovateľnom rozmedzí 3,5–14 dní, pre skupinu hemisferálnych TIA je medián ešte nižší 3–13 dní, pre skupinu TIA len s prejavom amaurosis fugax (AF) medián presahuje hodnotu odporúčanií (14–25,5 dní). 2. Počet veľkých komplikácií je 2,5 % a nie je častejší pri časných indikáciách. Záver: Komplexné cerebrovaskulárne centrum spolu s iktovými jednotkami v ústeckom kraji managuje pacientov po hemisferálnej príhode TIA indikovaných CEA v súlade s odporúčaniami jak z pohľadu časovania, tak z pohľadu počtu komplikácií. Je potrebné zlepšiť informovanosť verejnosti o AF, a skrátiť tak dobu časovania CEA v týchto prípadoch., Aim: The importance of early endarterectomy (CEA) for secondary stroke prevention in patients after transient ischaemic attack (TIA) inspired an analysis of our data and their correlation with generally accepted recommendations to ascertain whether any improvements are needed. Material and methods: 975 CEA were performed within a prospective study from 2006 to 2013 at the Clinic of Neurosurgery, Masaryk Hospital in Usti nad Labem. All procedures were done under regional anaesthesia. Magnetic resonance of the brain in diffusion-weighted mode was performed within 24 hours before and after the surgical procedure. 187 procedures in patients with symptomatic TIAs were analysed in detail. We focused on: 1. period (in days) from the onset of symptoms until carotid endarterectomy itself; 2. number and type of perioperative complications in relation to operation timing. Results: 1. Since 2007, the mean symptom-to-surgery period in the all TIAs group was acceptable: 3.5–14 days. The mean values in the hemispheral TIAs group were even lower: 3–13 days. The mean symptom-to-surgery period exceeded the recommended values in the group of TIAs with amaurosis fugax (AF) only: 14–25.5 days. 2. Perioperative and early postoperative complications rate was 2.5% and was not higher in early surgeries. Conclusion: CEA management of post-hemispheral TIA patients by the Comprehensive Cerebrovascular Centre in Usti nad Labem in cooperation with other stroke units in Ustecky region, was in line with available recommendations with respect to timing as well as complication rate. Public should be better educated on AF in order to decrease symptom-to-surgery period for CEA in post-TIA patients. Key words: carotid endarterectomy timing – symptomatic stenosis – transient ischaemic attacks 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 “uniform requirements” for biomedical papers., and M. Orlický, P. Vachata, M. Sameš
Hyperglykemie je nezávislým rizikovým faktorem kardiovaskulární morbidity i mortality. Co nejlepší kompenzace diabetes mellitus by tedy měla vést ke snížení výskytu kardiovaskulárních příhod. U nových léků je potřeba k získání schválení léku dodat data z klinických studií, která zahrnují informace o vlivu léku na kardiovaskulární riziko. S gliptiny, které byly na trh uvedeny poměrně nedávno, byly již studie tohoto typu zčásti provedeny. Lze říci, že prokázaly bezpečnost těchto léků. Na výsledky studií, které by zcela splňovaly nová doporučení FDA, si však budeme muset ještě nějakou chvíli počkat., Hyperglycaemia is an independent risk factor for cardiovascular morbidity and mortality. The best possible control of diabetes should therefore lead to a reduction in the incidence of cardiovascular events. To obtain approval for the new drugs it is necessary to supply clinical trial data, including information about the effect of the drug on cardiovascular risk. For gliptins that have been marketed rather recently, some studies have already been conducted that can be said to have demonstrated the safety of these drugs. However, it will still take time before we have study results that would fully satisfy the new FDA guidelines., and Benešová R., Kvapil M.