TASK DEFINITION: In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
PROBLEM: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

SOLUTION: Whole genomes redefine the mutational landscape of pancreatic cancer

PROBLEM: OBJECTIVE To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care.
DESIGN Prospective cohort study.
SETTING Five US teaching hospitals between 1989 and 1994. SUBJECTS A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories.
MAIN OUTCOME MEASURES Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results.
RESULTS By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful.
CONCLUSION In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.

SOLUTION: The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.

PROBLEM: BACKGROUND Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI. CASE PRESENTATION Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib.
CONCLUSION NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.

SOLUTION:
Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer