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Importance Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration isrctn.org Identifier: ISRCTN44687907

Nuestro proyecto de investigación tiene el objetivo de cubrir los hiatos en las investigaciones de las relaciones culturales entre España y Hungría, abarcando y examinando en profundidad la presencia del teatro español en Hungría desde los siglos xviii-xix hasta nuestros días. Junto con dar un repertorio de las traducciones húngaras y los estrenos de las obras teatrales españolas en nuestro país queremos ofrecer también un análisis más complejo y un resumen exhaustivo sobre los aspectos más importantes de la recepción del teatro español en Hungría en los últimos dos siglos. Uno de los hitos importantes ha sido el examen de la presencia y la popularidad de los dramas de Calderón de la Barca en Hungría. Hemos buscado la primera huella de su nombre, el nacimiento de las traducciones —primero del alemán y luego directamente del español—, sus estrenos desde 1795 hasta nuestros días, y su resonancia crítica en la prensa teatral húngara. Este artículo tiene el objetivo de resumir los resultados de esta investigación, destacando a algunos traductores literarios y directores teatrales que hicieron memorable el nombre de Calderón de la Barca ante el público húngaro. My research project aims to investigate the cultural relations between Spain and Hungary, through an in-depth analysis of the presence of Spanish theatre in Hungary, from the 18th-19th century until today. Apart from compiling a data base comprising the Hungarian translations and the Hungarian performances of Spanish dramas, I also examine in detail the most important aspects of the reception of Spanish theatre in Hungary. The analysis of the popularity and the presence of the dramas of Calderón de la Barca was especially important. I have traced the first appearance of his name, the translations of his dramas (first these were translated from German, later directly from Spanish), the performances of his plays from 1795 until today, and also their critical reception in the Hungarian press. The goal of the present article is to summarise the findings of this research, emphasising the role of certain Hungarian translators and directors, thanks to whom the Hungarian public became familiar with the name of Calderón de la Barca.

Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) is located in the activation peptide (AP) just 3 amino acids away from the thrombin cleavage site. This mutation has been associated with a protective effect against occlusive arterial diseases and venous thrombosis; however, its biochemical consequences have not been explored. In the current study it was demonstrated that the intracellular stability and the plasma concentration of FXIII of different Val34Leu genotypes are identical, which suggests that there is no difference in the rate of synthesis and externalization of wild-type and mutant FXIII-A. In contrast, the release of AP by thrombin from the Leu34 allele proceeded significantly faster than from its wild-type Val34 counterpart. By molecular modeling larger interaction energy was calculated between the Leu34 variant and the respective domains of thrombin than between the Val34 variant and thrombin. In agreement with these findings, the activation of mutant plasma FXIII by thrombin was faster and required less thrombin than that of the wild-type variant. Full thrombin activation of purified plasma FXIII of different genotypes, however, resulted in identical specific transglutaminase activities. Similarly, the mean specific FXIII activity in the plasma was the same in the groups with wild-type, heterozygous, and homozygous variants. Faster activation of the Leu34 allele hardly could be associated with its presumed protective effect against venous thrombosis. No such protective effect was observed in a large group of patients with familial thrombophilia.