• MeSH
• diagnostické techniky oftalmologické MeSH
• nemoci retiny MeSH
• oftalmologické chirurgické výkony MeSH
• sklivec MeSH

• Konspekt
• Ortopedie. Chirurgie. Oftalmologie
• NLK Obory
• oftalmologie

Cíl Přestože již bylo prokázáno, že inhibitory tyrosinkináz (tyrosine kinase inhibitor, TKI) receptoru epidermálního růstového faktoru (epidermal growth factor receptor, EGFR) jsou u pacientů s adenokarcinomem plic s aktivující mutací EGFR účinnější než u pacientů s tímto genem divokého typu, je v první skupině přítomno zhruba 30 % pacientů, kteří na TKI neodpovídají. Molekulární základ této zásadní heterogenity odpovědí není znám. Naším cílem bylo najít molekulární aberace, které na celogenomové úrovni přispívají k progresi onemocnění, a určit prognostickou signaturu specifi ckou pro pacienty s aktivující mutací EGFR. Pacienti a metody Nejprve jsme pomocí microarray pro vysokodenzitní komparativní genomovou hybridizaci (high-density array comparative genomic hybridization) v souboru 138 tkání adenokarcinomu prozkoumali molekulární rozdíly mezi nádory s aktivující mutací EGFR a nádory s genem divokého typu. Potom jsme u jiné nezávislé skupiny 114 pacientů validovali klinický význam alterací počtu kopií (copy-number alteration, CNA) pro predikci celkového přežití a přežití bez známek onemocnění (disease-free survival, DFS). V posledním kroku jsme u 23 pacientů s mutací EGFR léčených EGFR TKI zkoumali spojení mezi CNA a odpovědí na EGFR-TKI. Výsledky Určili jsme chromosomové oblasti s rozdíly v CNA mezi nádory s aktivující mutací EGFR a nádory divokého typu a zjistili jsme přítomnost vysoké míry shlukování aberací na chromosomu 7p. Klastr šesti reprezentativních genů na chromosomu 7p předpovídal celkové přežití a přežití bez známek onemocnění pacientů s aktivující mutací EGFR, ale ne u pacientů s genem divokého typu. Důležité je zjištění, že současná přítomnost většího počtu genů se zvýšenou hodnotou CNA v tomto klastru u pacientů s aktivující mutací EGFR korelovala s méně příznivou odpovědí na EGFR-TKI. Závěr Naše výsledky významným způsobem přispívají k objasnění příčin heterogenních odpovědí pacientů s aktivující mutací EGFR na léčbu EGFR-TKI. Mohly by přispět ke zlepšení léčby pacientů v této populaci.

PURPOSE: Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation. PATIENTS AND METHODS: We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs. RESULTS: We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation. CONCLUSION: Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population.

• MeSH
• adenokarcinom farmakoterapie   genetika   MeSH
• chromozomální aberace MeSH
• DNA nádorová genetika   MeSH
• erbB receptory genetika   MeSH
• financování organizované MeSH
• genom lidský MeSH
• genová dávka MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 7 genetika   MeSH
• míra přežití MeSH
• mutace genetika   MeSH
• mutační analýza DNA MeSH
• nádory plic farmakoterapie   genetika   MeSH
• následné studie MeSH
• nemalobuněčný karcinom plic farmakoterapie   genetika   MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• senioři MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the IdyllaTM EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of IdyllaTM EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

• MeSH
• erbB receptory genetika   MeSH
• formaldehyd MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• malobuněčný karcinom plic * genetika   MeSH
• mutace MeSH
• mutační analýza DNA metody   MeSH
• nádory plic * diagnóza   MeSH
• nemalobuněčný karcinom plic * diagnóza   MeSH
• parafín MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• Publikační typ
• tisková chyba MeSH

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.

• MeSH
• cholesterol krev   MeSH
• cytochrom P-450 CYP2D6 metabolismus   MeSH
• dospělí MeSH
• fenotyp MeSH
• genotyp MeSH
• hormonální protinádorové látky krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu krev   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tamoxifen analogy a deriváty   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• beta-laktamová rezistence MeSH
• cefotaxim MeSH
• finanční podpora výzkumu jako téma MeSH
• infekce spojené se zdravotní péčí epidemiologie   MeSH
• mnohočetná bakteriální léková rezistence MeSH
• Serratia marcescens izolace a purifikace   patogenita   účinky léků   MeSH

This research explores the kinematics performance of children with ADHD on the Pursuit Test at four speeds (i.e., 30, 50, 80, 100 millimeters per second) to assess their movement flexibility and its quality. The study consists of 23 children with ADHD and 38 normal children. The results have shown that children with ADHD demonstrate a faster speed in movement, along with greater acceleration, and the entire movement process tends to be less smooth. Children with ADHD also demonstrated greater difficulty in motor control while the speeds of pursuit test increased. Discussion regarding children with ADHD had difficulty in implementing close-loop movements, higher-level cognitive processing, and higher-speed activities were proposed. Clinical implications, study limitations and suggestions for future study were provided.

• MeSH
• časové faktory MeSH
• dítě MeSH
• hyperkinetická porucha * komplikace   MeSH
• lidé MeSH
• plnění a analýza úkolů * MeSH
• pohybová aktivita MeSH
• poruchy motorických dovedností * diagnóza   komplikace   MeSH
• pozornost MeSH
• psychomotorický výkon MeSH
• reakční čas MeSH
• statistika jako téma MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

BACKGROUND: Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. OBJECTIVE: To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. METHODS: We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. RESULTS: A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. CONCLUSION: There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.

• MeSH
• adenom komplikace   chirurgie   MeSH
• akromegalie etiologie   chirurgie   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru chirurgie   MeSH
• mladý dospělý MeSH
• nádory hypofýzy komplikace   chirurgie   MeSH
• radiační poranění epidemiologie   etiologie   MeSH
• radiochirurgie škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: There are presently no grading scales that specifically address the outcomes of cranial dural arteriovenous fistula (dAVF) after stereotactic radiosurgery (SRS). OBJECTIVE: To design a practical grading system that would predict outcomes after SRS for cranial dAVFs. METHODS: From the International Radiosurgery Research Foundation (University of Pittsburgh [41 patients], University of Pennsylvania [6 patients], University of Sherbrooke [2 patients], University of Manitoba [1 patient], West Virginia University [2 patients], University of Puerto Rico [1 patient], Beaumont Health System 1 [patient], Na Homolce Hospital [13 patients], the University of Virginia [48 patients], and Yale University [6 patients]) centers, 120 patients with dAVF treated with SRS were included in the study. The factors predicting favorable outcome (obliteration without post-SRS hemorrhage) after SRS were assessed using logistic regression analysis. These factors were pooled with the factors that were found to be predictive of obliteration from 7 studies with 736 patients after a systematic review of literature. These were entered into stepwise multiple regression and the best-fit model was identified. RESULTS: Based on the predictive model, 3 factors emerged to develop an SRS scoring system: cortical venous reflux (CVR), prior intracerebral hemorrhage (ICH), and noncavernous sinus location. Class I (score of 0-1 points) predicted the best favorable outcome of 80%. Class II patients (2 points score) had an intermediate favorable outcome of 57%, and class III (score 3 points) had the least favorable outcome at 37%. The ROC analysis showed better predictability to prevailing grading systems (AUC = 0.69; P = .04). Kaplan-Meier analysis showed statistically significant difference between the 3 subclasses of the proposed grading system for post-SRS dAVF obliteration (P = .001). CONCLUSION: The proposed dAVF grading system incorporates angiographic, anatomic, and clinical parameters and improves the prediction of the outcomes following SRS for dAVF as compared to the existing scoring systems.

• MeSH
• cévní malformace centrálního nervového systému patologie   chirurgie   MeSH
• dítě MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prognóza MeSH
• radiochirurgie * MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Dural arteriovenous fistulas (DAVFs) can be categorized based on location. OBJECTIVE: To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. METHODS: This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). RESULTS: The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). CONCLUSION: After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.

• MeSH
• cévní malformace centrálního nervového systému patologie   radioterapie   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• radiochirurgie metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sinus cavernosus patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH