TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).

SOLUTION: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?

PROBLEM: The EuroSCORE (European System for cardiac operative risk evaluation) stratifies cardiac risk surgery in easy and accessible manner; it was validated in North America with good results but in many countries of Latin America is used routinely without prior validation. Our objective was to validate the EuroSCORE in patients with cardiac valve surgery at the Instituto Nacional de Cardiologia Ignacio Chavez (INCICh) in Mexico.', 'EuroSCORE additive and logistic models were used to predict mortality in adults undergoing cardiac valve surgery from march 2004 to march 2008. The goodness of fit test of Hosmer-Lemeshow was used to evaluate the calibration. The area under the ROC curve was calculated to determinate discrimination.', 'We included 1188 patients with ages of 51.314.5 years, 52% women. There were significant differences in the prevalence of risk factors among the INCICh and the EuroSCORE populations. Total mortality was 9.68% versus 5% and 5.6% predicted by additive and logistic EuroSCORE. According to additive EuroSCORE the risk was low in 11.3%, intermediate in 52.9% and high in 35.9%; for these groups the mortality was .7%, 6.34% and 17.4% against those predicted of 2%, 3.9% and 7.64%. Hosmer-Lemeshow test had a P<.001 for both models and the area under the ROC curve was .707 and .694 for additive and logistic EuroSCORE.

SOLUTION: Do [ EuroSCORE underestimate the mortality risk in cardiac valve surgery of Mexican population ]?

PROBLEM: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS.', 'We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans 90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05.', 'Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004).

SOLUTION:
Do large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients?