Nelsonrees6591

BACKGROUND Organ allocation guidelines in many countries give children relative priority, but the normative justification of child priority is seldom articulated. METHODOLOGY We conducted a scoping review of the recent international literature (2013-2019) to identify moral positions and normative frameworks to justify or criticize pediatric priority in all kind of organ allocation. We identified 11 relevant papers. RESULTS Our analysis revealed a complex juxtaposition of pro and contra argumentations along three main normative lines a) equal treatment of each individual, b) individual benefit, and c) social benefit and the public good. The general type of argument can be found independent of the organ allocated. For each of these three lines we identified and categorized two types of argumentations those in favor and those critical of the priority rule. Additionally, we discuss a problematic issue that has not yet been mentioned in the literature, namely the effects of age thresholds related to child-priority rules in organ allocation. We illustrate this problem with an analysis of selected German data with allocated postmortal kidneys and livers. These data show non-normal distributions of organ transplantations and waiting times for patients between the ages of 16 and 19. DISCUSSION Our overview serves as a matrix to reconsider existing guideline policy. The review can assist policy makers or experts on organ allocation committees in increasing the transparency of child priority rules, in explaining their justifications, and in reforming existing guidelines. BACKGROUND/OBJECTIVES We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. METHODS We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group. To further characterize the migratory pattern, we assessed the distribution of clinical and pathologic T-stage and N-stage. RESULTS In our cohort of 28,338 patients who underwent resection for PDAC, AJCC clinical staging did not reliably predict pathologic stage. Stage migration after resection was responsible for discrepancies between the distribution of overall clinical stage and pathologic stage. The predominant migration was from patients with clinical stage I disease to pathologic stage II disease. Most patients with clinical T1 and T2 disease were upstaged to pathologic T3 disease and over half of patients with clinical N0 disease were upstaged to pathologic N1 disease after resection. DISCUSSION Clinical staging appears to overrepresent early T1, T2, and N0 disease, and underrepresent T3 and N1 disease. V.BACKGROUND There is limited data on the efficacy of adjuvant therapy (AT) in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMN). This single center retrospective cohort study aims to assess the impact of AT on survival in these patients. IDF-11774 price METHODS Patients undergoing surgery for invasive IPMN between 1993 and 2018 were included in the study. We compared the clinicopathologic features and evaluated overall survival (OS) using multivariate Cox regression adjusting for adjuvant therapy, age, T and N stage, perineural and lymphovascular invasion. We also assessed survival differences between surgery alone and AT in node negative (N0) and node positive (N+) subgroups. RESULTS 103 patients were included in the study; 69 underwent surgery alone while 34 also received AT. Patients in the AT group were significantly younger, presented at higher T and N stages and had more perineural and lymphovascular invasion. Median OS in the surgery alone group was 134 months and 65 months in the AT group, p = 0.052. On multivariate analysis, AT was not associated with improved OS; hazard ratio (HR) = 1.03 (0.52-2.05). In N0 patients, compared to surgery alone, AT was associated with a worse median OS (65 vs 167 months, p = 0.03), whereas in N+ patients there was a non-significant improvement (50.5 vs 20.4 months, p = 0.315). CONCLUSION AT did not improve survival in the overall cohort even after multivariate analysis. N0 patients have excellent survival, and AT should probably be avoided in them, whereas it may be considered in patients with N+ disease. V.Poly (ADP-ribose) polymerase (PARP) inhibitors have achieved great success in clinical application, especially for the prolonged survival of cisplatin-sensitive ovarian cancer patients. However, there are still many patients who do not respond to PARP inhibitors. Novel PARP inhibitors with higher activity are urgently needed. Herein we report a series of compounds by molecular hybridization PARP-1 inhibitor Olaparib (Ola) with HSP90 inhibitor C0817 (one curcumin derivative). All synthesized compounds were evaluated for their antiproliferative activity in vitro, and some were further assessed for their inhibitory activities of the PARP enzyme and HSP90 affinity. Our results indicated that compound 4 could bind to HSP90 and cause static quenching, indicating that compound 4 was able to bind to HSP90, moreover, downstream molecular breast cancer 1 (BRAC-1) was reduced. In conclusion, dual target inhibitors of PARP and HSP90 exhibited stronger selective cytotoxicities against cancer. The Petasis three-component reaction gives rise to diverse substituted α-aryl glycines from readily available amines, boronic acids and glyoxalic acid. Thus, this reaction is highly attractive for DNA-encoded small molecule screening library synthesis. The Petasis reaction is for instance promoted by a potentially DNA damaging copper(I)/bipyridine reagent system in dry organic solvents. We found that solid phase-coupled DNA strands tolerated this reagent system at elevated temperature allowing for synthesis of diverse substituted DNA-tagged α-aryl glycines from DNA-conjugated secondary amines.