The tissue-specific regulation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) is coordinated by intronic and extragenic cis-acting elements that influence its transcriptional activity. The promoter apparently lacks sequences to drive cell-type specific expression. We previously identified a number of intronic elements that were associated with DNase I hypersensitive sites (DHS) and bound the hepatocyte nuclear factor 1 (HNF1) transcription factor. Moreover, we demonstrated the likely involvement of HNF1 in the regulation of CFTR expression in vivo. Here we investigate DHS in introns 16 and 17a of the CFTR gene, which are evident in intestinal and pancreatic cell lines, and determine the transcription factors that interact with these sites. Of particular interest were factors known to interact with HNF1 in co-ordinated expression of genes in the gastrointestinal tract. We demonstrate that though sequences within these DHS bind HNF1, CDX2 and PBX1 in vitro, only PBX1 show a robust in vivo interaction. These data contribute to our understanding of the complexity of cell-type-specific CFTR regulatory mechanisms. McCarthy, V. A. Ott, C. J. Phylactides, M. Harris, A. 0 2009-09-30T06:15:37Z 2009-09-24 2009-09-29 %0 Journal Article %A McCarthy, V. A. %A Ott, C. J. %A Phylactides, M. %A Harris, A. %D 2009 %T Interaction of intestinal and pancreatic transcription factors in the regulation of CFTR gene expression. %J Biochim Biophys Acta %V 1789 %N 11-12 %P 709-718 %M 19782160 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19782160 %X The tissue-specific regulation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) is coordinated by intronic and extragenic cis-acting elements that influence its transcriptional activity. The promoter apparently lacks sequences to drive cell type-specific expression. We previously identified a number of intronic elements that were associated with DNase I hypersensitive sites (DHS) and bound the hepatocyte nuclear factor 1 (HNF1) transcription factor. Moreover, we demonstrated the likely involvement of HNF1 in the regulation of CFTR expression in vivo. Here we investigate DHS in introns 16 and 17a of the CFTR gene, which are evident in intestinal and pancreatic cell lines, and determine the transcription factors that interact with these sites. Of particular interest were factors known to interact with HNF1 in coordinated expression of genes in the gastrointestinal tract. We demonstrate that though sequences within these DHS bind HNF1, CDX2, and PBX1 in vitro, only PBX1 show a robust in vivo interaction. These data contribute to our understanding of the complexity of cell-type-specific CFTR regulatory mechanisms. %+ Paediatric Molecular Genetics, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. 8415 false false 11-12 Biochimica et biophysica acta Biochim Biophys Acta 709-718 ppublish JOURNAL ARTICLE 19782160 In-Data-Review 2009-11-17T07:21:58Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19782160 1789 2009 Simon, M. A. Dong, X. Bennett, C. L. 0 2009-09-06T11:54:45Z 2009-06-12 %0 Journal Article %A Simon, M. A. %A Dong, X. %A Bennett, C. L. %D 2009 %T Partnering to promote equality in cancer care. %J Soc Work Public Health %V 24 %N 4 %P 355-359 %M 19517300 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19517300 %+ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. m-simon2@md.northwestern.edu Simon, Melissa A Dong, Xinqi Bennett, Charles L 236 false false 4 Social work in public health Soc Work Public Health 355-359 ppublish Journal Article 19517300 In-Process 2009-09-06T11:54:45Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19517300 24 2009 BACKGROUND: There is a paucity of research assessing the potential benefits of mannequin trainers when preparing students to interact with teaching associates. PURPOSE: The goal of this study was to better understand the effects of mannequin-based simulators on student comfort toward learning specific aspects of the clinical female pelvic exam. METHODS: First-year medical students (N = 344) were surveyed before and after a mannequin-based simulation curriculum to assess their comfort levels toward learning the female pelvic exam. RESULTS: Causing harm was the top cause of student anxiety toward learning the pelvic exam. Although the mannequin-based simulation curriculum was effective in significantly increasing (p < .001) student comfort levels toward learning the pelvic exam, the majority of students progressed from being "very uncomfortable" with the exam to being "somewhat comfortable." CONCLUSION: We suggest that mannequin-based simulators be used prior to students' learning experience with pelvic exam teaching associates. Pugh, C. M. Obadina, E. T. Aidoo, K. A. 0 2009-09-06T11:57:22Z 2009-03-31 %0 Journal Article %A Pugh, C. M. %A Obadina, E. T. %A Aidoo, K. A. %D 2009 %T Fear of causing harm: use of mannequin-based simulation to decrease student anxiety prior to interacting with female teaching associates. %J Teach Learn Med %V 21 %N 2 %P 116-120 %M 19330689 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19330689 %X BACKGROUND: There is a paucity of research assessing the potential benefits of mannequin trainers when preparing students to interact with teaching associates. PURPOSE: The goal of this study was to better understand the effects of mannequin-based simulators on student comfort toward learning specific aspects of the clinical female pelvic exam. METHODS: First-year medical students (N = 344) were surveyed before and after a mannequin-based simulation curriculum to assess their comfort levels toward learning the female pelvic exam. RESULTS: Causing harm was the top cause of student anxiety toward learning the pelvic exam. Although the mannequin-based simulation curriculum was effective in significantly increasing (p < .001) student comfort levels toward learning the pelvic exam, the majority of students progressed from being "very uncomfortable" with the exam to being "somewhat comfortable." CONCLUSION: We suggest that mannequin-based simulators be used prior to students' learning experience with pelvic exam teaching associates. %+ Department of Surgery, Northwestern University, Feinberg School of Medicine, 201 East Huron Street, Chicago, IL 60611-2908, USA. drpugh@northwestern.edu Pugh, Carla M Obadina, Eniola T Aidoo, Kofi A 4871 false false 2 Teaching and learning in medicine Teach Learn Med 116-120 ppublish Journal Article 19330689 In-Process 2009-09-06T11:57:22Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19330689 21 2009 This paper presents Mixed Reality Humans (MRHs), a new type of embodied agent enabling touch-driven communication. Affording touch between human and agent allows MRHs to simulate interpersonal scenarios in which touch is crucial. Two studies provide initial evaluation of user behavior with a MRH patient and the usability and acceptability of a MRH patient for practice and evaluation of medical students' clinical skills. In Study I (n=8) it was observed that students treated MRHs as social actors more than students in prior interactions with virtual human patients (n=27), and used interpersonal touch to comfort and reassure the MRH patient similarly to prior interactions with human patients (n=76). In the within-subjects Study II (n=11), medical students performed a clinical breast exam on each of a MRH and human patient. Participants performed equivalent exams with the MRH and human patients, demonstrating the usability of MRHs to evaluate students' exam skills. The acceptability of the MRH patient for practicing exam skills was high as students rated the experience as believable and educationally beneficial. Acceptability was improved from Study I to Study II due to an increase in the MRH's visual realism, demonstrating that visual realism is critical for simulation of specific interpersonal scenarios. Kotranza, A. Lok, B. Deladisma, A. Pugh, C. M. Lind, D. S. 0 2009-09-06T11:57:22Z 2009-03-14 %0 Journal Article %A Kotranza, A. %A Lok, B. %A Deladisma, A. %A Pugh, C. M. %A Lind, D. S. %D 2009 %T Mixed reality humans: evaluating behavior, usability, and acceptability. %J IEEE Trans Vis Comput Graph %V 15 %N 3 %P 369-382 %M 19282545 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19282545 %X This paper presents Mixed Reality Humans (MRHs), a new type of embodied agent enabling touch-driven communication. Affording touch between human and agent allows MRHs to simulate interpersonal scenarios in which touch is crucial. Two studies provide initial evaluation of user behavior with a MRH patient and the usability and acceptability of a MRH patient for practice and evaluation of medical students' clinical skills. In Study I (n=8) it was observed that students treated MRHs as social actors more than students in prior interactions with virtual human patients (n=27), and used interpersonal touch to comfort and reassure the MRH patient similarly to prior interactions with human patients (n=76). In the within-subjects Study II (n=11), medical students performed a clinical breast exam on each of a MRH and human patient. Participants performed equivalent exams with the MRH and human patients, demonstrating the usability of MRHs to evaluate students' exam skills. The acceptability of the MRH patient for practicing exam skills was high as students rated the experience as believable and educationally beneficial. Acceptability was improved from Study I to Study II due to an increase in the MRH's visual realism, demonstrating that visual realism is critical for simulation of specific interpersonal scenarios. %K Breast/*physiology %K *Computer Graphics %K Computer Simulation %K Consumer Satisfaction %K Diagnosis, Computer-Assisted/*methods %K Humans %K Imaging, Three-Dimensional/methods %K *Models, Biological %K Palpation/*methods %K Task Performance and Analysis %K Touch/*physiology %K *User-Computer Interface %+ University of Florida, Gainesville, FL, USA. akotranz@cise.ufl.edu Kotranza, Aaron Lok, Benjamin Deladisma, Adeline Pugh, Carla M Lind, D Scott 4873 false false 3 IEEE transactions on visualization and computer graphics IEEE Trans Vis Comput Graph Breast/*physiology; *Computer Graphics; Computer Simulation; Consumer Satisfaction; Diagnosis, Computer-Assisted/*methods; Humans; Imaging, Three-Dimensional/methods; *Models, Biological; Palpation/*methods; Task Performance and Analysis; Touch/*physiology; *User-Computer Interface 369-382 ppublish Evaluation Studies 19282545 MEDLINE 2009-09-06T11:57:22Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19282545 15 2009 There has been a dramatic sea change in the use of erythropoiesis-stimulating agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer patients undergoing chemotherapy. An important area that has not been addressed previously is a CKD patient who also has a malignancy. Clinical guidelines exist that outline recommended treatments for each disease, but the intersection of the two disease processes presents difficult decisions for patients and physicians. Herein, we review the background underlying recent revisions in clinical alerts and guidelines for ESAs, and provide guidance for treating anemia among CKD patients who are receiving no therapy, chemotherapy with curative intent, or chemotherapy with palliative intent. The guiding principle is that comprehensive assessment of risks and benefits in the relevant clinical setting is imperative. Bennett, C. L. Becker, P. S. Kraut, E. H. Samaras, A. T. West, D. P. 0 2009-09-06T11:54:46Z 2008-12-05 2009-01-30 %0 Journal Article %A Bennett, C. L. %A Becker, P. S. %A Kraut, E. H. %A Samaras, A. T. %A West, D. P. %D 2009 %T Intersecting guidelines: administering erythropoiesis-stimulating agents to chronic kidney disease patients with cancer. %J Semin Dial %V 22 %N 1 %P 1-4 %M 19175532 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19175532 %X There has been a dramatic sea change in the use of erythropoiesis-stimulating agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer patients undergoing chemotherapy. An important area that has not been addressed previously is a CKD patient who also has a malignancy. Clinical guidelines exist that outline recommended treatments for each disease, but the intersection of the two disease processes presents difficult decisions for patients and physicians. Herein, we review the background underlying recent revisions in clinical alerts and guidelines for ESAs, and provide guidance for treating anemia among CKD patients who are receiving no therapy, chemotherapy with curative intent, or chemotherapy with palliative intent. The guiding principle is that comprehensive assessment of risks and benefits in the relevant clinical setting is imperative. %K Anemia/*drug therapy/etiology %K Antineoplastic Agents/therapeutic use %K Drug Therapy, Combination %K Hematinics/*administration & dosage %K Humans %K Kidney Failure, Chronic/*complications/drug therapy %K Neoplasms/*complications/drug therapy %K *Practice Guidelines as Topic %K Treatment Outcome Bennett, Charles L Becker, Pamela S Kraut, Eric H Samaras, Athena T West, Dennis P 245 false false 1 Seminars in dialysis Semin Dial Anemia/*drug therapy/etiology; Antineoplastic Agents/therapeutic use; Drug Therapy, Combination; Hematinics/*administration & dosage; Humans; Kidney Failure, Chronic/*complications/drug therapy; Neoplasms/*complications/drug therapy; *Practice Guidelines as Topic; Treatment Outcome 1-4 ppublish Editorial 19175532 MEDLINE 2009-09-06T11:54:46Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19175532 22 2009 The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC. Mas, V. R. Maluf, D. G. Archer, K. J. Yanek, K. Kong, X. Kulik, L. Freise, C. E. Olthoff, K. M. Ghobrial, R. M. McIver, P. Fisher, R. 0 2009-09-06T12:00:38Z 2008-12-15 2008-12-23 %0 Journal Article %A Mas, V. R. %A Maluf, D. G. %A Archer, K. J. %A Yanek, K. %A Kong, X. %A Kulik, L. %A Freise, C. E. %A Olthoff, K. M. %A Ghobrial, R. M. %A McIver, P. %A Fisher, R. %D 2009 %T Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. %J Mol Med %V 15 %N 3-4 %P 85-94 %M 19098997 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19098997 %X The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC. %K Carcinoma, Hepatocellular/etiology/*genetics/pathology/*virology %K *Cell Transformation, Neoplastic %K Disease Progression %K Gene Expression Profiling %K *Gene Expression Regulation, Neoplastic %K Gene Regulatory Networks %K Hepacivirus/genetics/*pathogenicity %K Humans %K Liver Neoplasms/etiology/*genetics/pathology/*virology %K Oligonucleotide Array Sequence Analysis %K ROC Curve %K Reproducibility of Results %+ Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, Virginia, USA. vmas@mcvh-vcu.edu Mas, Valeria R Maluf, Daniel G Archer, Kellie J Yanek, Kenneth Kong, Xiangrong Kulik, Laura Freise, Chris E Olthoff, Kim M Ghobrial, Rafik M McIver, Paula Fisher, Robert 7704 false false 3-4 Molecular medicine (Cambridge, Mass.) Mol Med Carcinoma, Hepatocellular/etiology/*genetics/pathology/*virology; *Cell Transformation, Neoplastic; Disease Progression; Gene Expression Profiling; *Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Hepacivirus/genetics/*pathogenicity; Humans; Liver Neoplasms/etiology/*genetics/pathology/*virology; Oligonucleotide Array Sequence Analysis; ROC Curve; Reproducibility of Results 85-94 ppublish Journal Article 19098997 MEDLINE 2009-09-06T12:00:38Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19098997 15 2009 A therapy gaining rapid clinical adoption involves radioembolization with the use of Yttrium-90 (90Y) microspheres. The 20-60 microm-sized microspheres are injected trans-arterially and flow to hepatic tumors given their preferential blood supply from the hepatic artery. Once they lodge in the arterioles, they impart a very intense local radiotherapeutic effect. Given the combined radiation and embolic effect, the imaging findings imparted by this mode of action differ significantly from other treatments. This work represents a comprehensive review of the imaging findings following radioembolization in patients with primary liver tumors. The report discusses imaging response, benign secondary effects, and complications. This should help educate the radiologist on imaging findings that should be expected following radioembolization and therefore aid in the proper image interpretation. Ibrahim, S. M. Nikolaidis, P. Miller, F. H. Lewandowski, R. J. Ryu, R. K. Sato, K. T. Senthilnathan, S. Riaz, A. Kulik, L. Mulcahy, M. F. Omary, R. A. Salem, R. 0 2009-09-06T11:56:49Z 2008-09-09 %0 Journal Article %A Ibrahim, S. M. %A Nikolaidis, P. %A Miller, F. H. %A Lewandowski, R. J. %A Ryu, R. K. %A Sato, K. T. %A Senthilnathan, S. %A Riaz, A. %A Kulik, L. %A Mulcahy, M. F. %A Omary, R. A. %A Salem, R. %D 2009 %T Radiologic findings following Y90 radioembolization for primary liver malignancies. %J Abdom Imaging %V 34 %N 5 %P 566-581 %M 18777189 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18777189 %X A therapy gaining rapid clinical adoption involves radioembolization with the use of Yttrium-90 (90Y) microspheres. The 20-60 microm-sized microspheres are injected trans-arterially and flow to hepatic tumors given their preferential blood supply from the hepatic artery. Once they lodge in the arterioles, they impart a very intense local radiotherapeutic effect. Given the combined radiation and embolic effect, the imaging findings imparted by this mode of action differ significantly from other treatments. This work represents a comprehensive review of the imaging findings following radioembolization in patients with primary liver tumors. The report discusses imaging response, benign secondary effects, and complications. This should help educate the radiologist on imaging findings that should be expected following radioembolization and therefore aid in the proper image interpretation. %+ Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. Ibrahim, Saad M Nikolaidis, Paul Miller, Frank H Lewandowski, Robert J Ryu, Robert K Sato, Kent T Senthilnathan, Sean Riaz, Ahsun Kulik, Laura Mulcahy, Mary F Omary, Reed A Salem, Riad 4177 false false 5 Abdominal imaging Abdom Imaging 566-581 ppublish Journal Article 18777189 In-Process 2009-09-06T11:56:49Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18777189 34 2009 Graft choice remains an area of contention in anterior cruciate ligament reconstruction. Poorer cosmetic results and anterior knee pain remain a problem in the use of autologous patellar tendon grafts despite excellent clinical results when compared with autologous hamstring tendon grafts. Using a 2-incision technique to harvest the patellar tendon grafts has been shown to decrease the risk of anterior knee pain to a level comparable to hamstring tendon grafts. Proper graft tunnel placement and orientation also remain controversial with several recent researchers arguing the ability to perform an anatomic reconstruction using a conventional endoscopic transtibial technique. We will describe a relatively simple and cosmetically acceptable 2-incision technique for harvesting a bone-tendon-bone graft. In addition, we will describe the bony landmarks that should be used to ensure proper anatomic graft placement and the appropriate angles that need to be used for the tibial tunnel to drill the femoral tunnel in an anatomic position and carry out a successful endoscopic transtibial tunnel anterior cruciate ligament reconstruction. Purnell, M. L. Larson, A. I. 0 2009-11-18T07:17:28Z 2009-11-17 %0 Journal Article %A Purnell, M. L. %A Larson, A. I. %D 2009 %T Mini-incision patellar tendon harvest and anterior cruciate ligament reconstruction using critical bony landmarks. %J Sports Med Arthrosc %V 17 %N 4 %P 234-241 %M 19910781 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19910781 %X Graft choice remains an area of contention in anterior cruciate ligament reconstruction. Poorer cosmetic results and anterior knee pain remain a problem in the use of autologous patellar tendon grafts despite excellent clinical results when compared with autologous hamstring tendon grafts. Using a 2-incision technique to harvest the patellar tendon grafts has been shown to decrease the risk of anterior knee pain to a level comparable to hamstring tendon grafts. Proper graft tunnel placement and orientation also remain controversial with several recent researchers arguing the ability to perform an anatomic reconstruction using a conventional endoscopic transtibial technique. We will describe a relatively simple and cosmetically acceptable 2-incision technique for harvesting a bone-tendon-bone graft. In addition, we will describe the bony landmarks that should be used to ensure proper anatomic graft placement and the appropriate angles that need to be used for the tibial tunnel to drill the femoral tunnel in an anatomic position and carry out a successful endoscopic transtibial tunnel anterior cruciate ligament reconstruction. %+ Orthopaedic Associates of Aspen and Glenwood, 100 E. Main St., Aspen, CO 81611, USA. mark@purnell.com Purnell, Mark L Larson, Andrew I 8605 false false 4 Sports medicine and arthroscopy review Sports Med Arthrosc 234-241 2009-12-01 ppublish Journal Article 19910781 In-Process 2009-11-18T07:17:28Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19910781 17 2009 OBJECTIVE: MUC1, MUC5AC, and MUC6 are main constituents of the mucus barrier in the stomach, which protects the underlying epithelium from acid, proteases, mechanical trauma, and pathogenic microorganisms. Accumulating evidence implicates potential roles of MUC1, MUC5AC, and MUC6 genetic variation in the development of stomach cancer. METHODS: We evaluated the relationship between common genetic variations in these genes and stomach cancer risk, using an LD-based tagSNP approach in a population-based case-control study conducted in Warsaw, Poland, during 1994-1996. We genotyped 6, 8, and 14 tagSNPs in MUC1, MUC5AC, and MUC6 genes, respectively, among 273 cases newly diagnosed with stomach cancer and 377 controls. RESULTS: Each of the six tagSNPs tested across the MUC1 region showed statistically significant associations with an increased risk of stomach cancer. Carriers of the haplotype ACTAA rare alleles of rs4971052, rs4276913, rs4971088, rs4971092, and rs4072037 had a nearly doubled risk (OR = 1.93, 95% CI = 1.49-2.48) compared to the referent haplotype GTAAG. Out of the eight tagSNPs across MUC5AC region, only minor allele of rs868903 was significantly associated with an increased risk of stomach cancer (OR = 1.80, 95% CI = 1.22-2.63). CONCLUSIONS: Overall, our data provide evidence that some common variations in MUC1 and MUC5AC genes contribute to an elevated risk of stomach cancer. Further studies are needed to confirm these novel findings. Jia, Y. Persson, C. Hou, L. Zheng, Z. Yeager, M. Lissowska, J. Chanock, S. J. Chow, W. H. Ye, W. 0 2009-11-21T07:19:54Z 2009-11-19 2009-11-20 %0 Journal Article %A Jia, Y. %A Persson, C. %A Hou, L. %A Zheng, Z. %A Yeager, M. %A Lissowska, J. %A Chanock, S. J. %A Chow, W. H. %A Ye, W. %D 2009 %T A comprehensive analysis of common genetic variation in MUC1, MUC5AC, MUC6 genes and risk of stomach cancer. %J Cancer Causes Control %M 19924550 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19924550 %X OBJECTIVE: MUC1, MUC5AC, and MUC6 are main constituents of the mucus barrier in the stomach, which protects the underlying epithelium from acid, proteases, mechanical trauma, and pathogenic microorganisms. Accumulating evidence implicates potential roles of MUC1, MUC5AC, and MUC6 genetic variation in the development of stomach cancer. METHODS: We evaluated the relationship between common genetic variations in these genes and stomach cancer risk, using an LD-based tagSNP approach in a population-based case-control study conducted in Warsaw, Poland, during 1994-1996. We genotyped 6, 8, and 14 tagSNPs in MUC1, MUC5AC, and MUC6 genes, respectively, among 273 cases newly diagnosed with stomach cancer and 377 controls. RESULTS: Each of the six tagSNPs tested across the MUC1 region showed statistically significant associations with an increased risk of stomach cancer. Carriers of the haplotype ACTAA rare alleles of rs4971052, rs4276913, rs4971088, rs4971092, and rs4072037 had a nearly doubled risk (OR = 1.93, 95% CI = 1.49-2.48) compared to the referent haplotype GTAAG. Out of the eight tagSNPs across MUC5AC region, only minor allele of rs868903 was significantly associated with an increased risk of stomach cancer (OR = 1.80, 95% CI = 1.22-2.63). CONCLUSIONS: Overall, our data provide evidence that some common variations in MUC1 and MUC5AC genes contribute to an elevated risk of stomach cancer. Further studies are needed to confirm these novel findings. %+ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 17177, Stockholm, Sweden. 8612 false false Cancer causes & control : CCC Cancer Causes Control 2009-11-19 aheadofprint JOURNAL ARTICLE 19924550 Publisher 2009-11-21T07:19:54Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19924550 2009 Antonova, P. Jacobs, D. I. Bojar, M. Cerny, R. Ciharova, K. Frick, M. A. Fintel, B. Dehovitz, J. Bennett, C. L. 0 2009-11-18T07:15:56Z 2009-11-11 2009-11-17 %0 Journal Article %A Antonova, P. %A Jacobs, D. I. %A Bojar, M. %A Cerny, R. %A Ciharova, K. %A Frick, M. A. %A Fintel, B. %A Dehovitz, J. %A Bennett, C. L. %D 2009 %T Czech health two decades on from the Velvet Revolution. %J Lancet %M 19913289 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19913289 %+ Cardiovascular Centre, University Hospital Motol, Prague, Czech Republic. 8596 false false Lancet Lancet 2009-11-11 aheadofprint JOURNAL ARTICLE 19913289 Publisher 2009-11-18T07:15:56Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19913289 2009 PURPOSE: There is considerable variation in the quality of cancer care delivered in the United States. Assessing care by using quality indicators could help decrease this variability. The objectives of this study were to formally develop valid quality indicators for melanoma and to assess hospital-level adherence with these measures in the United States. METHODS: Quality indicators were identified from available literature, consensus guidelines, and melanoma experts. Thirteen experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. Adherence with individual valid indicators and a composite measure of all indicators were assessed at 1,249 Commission on Cancer hospitals by using the National Cancer Data Base (NCDB; 2004 through 2005). RESULTS: Of 55 proposed quality indicators, 26 measures (47%) were rated as valid. These indicators assessed structure (n = 1), process (n = 24), and outcome (n = 1). Of the 26 measures, 10 are readily assessable by using cancer registry data. Adherence with valid indicators ranged from 11.8% to 96.5% at the patient level and 3.7% to 83.0% at the hospital level. (Adherence required that >/= 90% of patients at a hospital receive concordant care). Most hospitals were adherent with 50% or fewer of the individual indicators (median composite score, five; interquartile range, four to seven). Adherence was higher for diagnosis and staging measures and was lower for treatment indicators. CONCLUSION: There is considerable variation in the quality of melanoma care in the United States. By using these formally developed quality indicators, hospitals can assess their adherence with current melanoma care guidelines through feedback mechanisms from the NCDB and can better direct quality improvement efforts. Bilimoria, K. Y. Raval, M. V. Bentrem, D. J. Wayne, J. D. Balch, C. M. Ko, C. Y. 0 2009-10-16T06:14:25Z 2009-10-13 2009-10-15 %0 Journal Article %A Bilimoria, K. Y. %A Raval, M. V. %A Bentrem, D. J. %A Wayne, J. D. %A Balch, C. M. %A Ko, C. Y. %D 2009 %T National assessment of melanoma care using formally developed quality indicators. %J J Clin Oncol %V 27 %N 32 %P 5445-5451 %M 19826131 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19826131 %X PURPOSE: There is considerable variation in the quality of cancer care delivered in the United States. Assessing care by using quality indicators could help decrease this variability. The objectives of this study were to formally develop valid quality indicators for melanoma and to assess hospital-level adherence with these measures in the United States. METHODS: Quality indicators were identified from available literature, consensus guidelines, and melanoma experts. Thirteen experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. Adherence with individual valid indicators and a composite measure of all indicators were assessed at 1,249 Commission on Cancer hospitals by using the National Cancer Data Base (NCDB; 2004 through 2005). RESULTS: Of 55 proposed quality indicators, 26 measures (47%) were rated as valid. These indicators assessed structure (n = 1), process (n = 24), and outcome (n = 1). Of the 26 measures, 10 are readily assessable by using cancer registry data. Adherence with valid indicators ranged from 11.8% to 96.5% at the patient level and 3.7% to 83.0% at the hospital level. (Adherence required that >OR= 90% of patients at a hospital receive concordant care.) Most hospitals were adherent with 50% or fewer of the individual indicators (median composite score, five; interquartile range, four to seven). Adherence was higher for diagnosis and staging measures and was lower for treatment indicators. CONCLUSION: There is considerable variation in the quality of melanoma care in the United States. By using these formally developed quality indicators, hospitals can assess their adherence with current melanoma care guidelines through feedback mechanisms from the NCDB and can better direct quality improvement efforts. %+ Department of Surgery, American College Surgeons, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3211, USA. kbilimoria@facs.org 8481 false false 32 Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol 5445-5451 2009-11-10 ppublish JOURNAL ARTICLE 19826131 In-Process 2009-11-13T07:19:17Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19826131 27 2009 PURPOSE: Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention. METHODS: A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates. RESULTS: Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates. CONCLUSION: A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost-effective. Shankaran, V. Luu, T. H. Nonzee, N. Richey, E. McKoy, J. M. Graff Zivin, J. Ashford, A. Lantigua, R. Frucht, H. Scoppettone, M. Bennett, C. L. Sheinfeld Gorin, S. 0 2009-10-16T06:14:22Z 2009-10-13 2009-10-15 %0 Journal Article %A Shankaran, V. %A Luu, T. H. %A Nonzee, N. %A Richey, E. %A McKoy, J. M. %A Graff Zivin, J. %A Ashford, A. %A Lantigua, R. %A Frucht, H. %A Scoppettone, M. %A Bennett, C. L. %A Sheinfeld Gorin, S. %D 2009 %T Costs and cost effectiveness of a health care provider-directed intervention to promote colorectal cancer screening. %J J Clin Oncol %V 27 %N 32 %P 5370-5375 %M 19826133 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19826133 %X PURPOSE: Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention. METHODS: A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates. RESULTS: Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates. CONCLUSION: A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost effective. %+ Veterans Affairs (VA) Chicago Healthcare System and VA Center for Management of Complex and Chronic Care, Chicago, IL, USA. 8480 false false 32 Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol 5370-5375 2009-11-10 ppublish JOURNAL ARTICLE 19826133 In-Process 2009-11-13T07:19:14Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19826133 27 2009 The regulated expression of large human genes can depend on long-range interactions to establish appropriate three-dimensional structures across the locus. The cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encompasses 189 kb of genomic DNA, shows a complex pattern of expression with both spatial and temporal regulation. The flanking loci, ASZ1 and CTTNBP2, show very different tissue-specific expression. The mechanisms governing control of CFTR expression remain poorly understood, although they are known to involve intronic regulatory elements. Here, we show a complex looped structure of the CFTR locus in cells that express the gene, which is absent from cells in which the gene is inactive. By using chromatin conformation capture (3C) with a bait probe at the CFTR promoter, we demonstrate close interaction of this region with sequences in the middle of the gene about 100 kb from the promoter and with regions 3' to the locus that are about 200 kb away. We show that these interacting regions correspond to prominent DNase I hypersensitive sites within the locus. Moreover, these sequences act cooperatively in reporter gene constructs and recruit proteins that modify chromatin structure. The model for CFTR gene expression that is revealed by our data provides a paradigm for other large genes with multiple regulatory elements lying within both introns and intergenic regions. We anticipate that these observations will enable original approaches to designing regulated transgenes for tissue-specific gene therapy protocols. Ott, C. J. Blackledge, N. P. Kerschner, J. L. Leir, S. H. Crawford, G. E. Cotton, C. U. Harris, A. 0 2009-11-11T07:23:01Z 2009-11-06 2009-11-10 %0 Journal Article %A Ott, C. J. %A Blackledge, N. P. %A Kerschner, J. L. %A Leir, S. H. %A Crawford, G. E. %A Cotton, C. U. %A Harris, A. %D 2009 %T Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus. %J Proc Natl Acad Sci U S A %M 19897727 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19897727 %X The regulated expression of large human genes can depend on long-range interactions to establish appropriate three-dimensional structures across the locus. The cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encompasses 189 kb of genomic DNA, shows a complex pattern of expression with both spatial and temporal regulation. The flanking loci, ASZ1 and CTTNBP2, show very different tissue-specific expression. The mechanisms governing control of CFTR expression remain poorly understood, although they are known to involve intronic regulatory elements. Here, we show a complex looped structure of the CFTR locus in cells that express the gene, which is absent from cells in which the gene is inactive. By using chromatin conformation capture (3C) with a bait probe at the CFTR promoter, we demonstrate close interaction of this region with sequences in the middle of the gene about 100 kb from the promoter and with regions 3' to the locus that are about 200 kb away. We show that these interacting regions correspond to prominent DNase I hypersensitive sites within the locus. Moreover, these sequences act cooperatively in reporter gene constructs and recruit proteins that modify chromatin structure. The model for CFTR gene expression that is revealed by our data provides a paradigm for other large genes with multiple regulatory elements lying within both introns and intergenic regions. We anticipate that these observations will enable original approaches to designing regulated transgenes for tissue-specific gene therapy protocols. %+ Human Molecular Genetics Program, Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza #211, Chicago, IL 60614. 8582 false false Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A 2009-11-06 aheadofprint JOURNAL ARTICLE 19897727 Publisher 2009-11-11T07:23:01Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19897727 2009 BACKGROUND:: Studies have demonstrated volume-outcome relationships for numerous operations, providing an impetus for regionalization; however, volume-based regionalization may not be feasible or necessary. Our objective was to determine if low-risk patients undergoing surgery at Community Hospitals have perioperative mortality rates comparable with Specialized Centers. METHODS:: From the National Cancer Data Base, 940,718 patients from approximately 1430 hospitals were identified who underwent resection for 1 of 15 cancers (2003-2005). Patients were stratified by preoperative risk according to age and comorbidities. Separately for each cancer, regression modeling stratified by high- and low-risk groups was used to compare 60-day mortality at Specialized Centers (National Cancer Institute-designated and/or highest-volume quintile institutions), Other Academic Institutions (lower-volume, non-National Cancer Institute), and Community Hospitals. RESULTS:: Low-risk patients had statistically similar perioperative mortality rates at Specialized Centers and Community Hospitals for 13 of 15 operations. High-risk patients had significantly lower perioperative mortality rates at Specialized Centers compared with Community Hospitals for 9 of 15 cancers. Regardless of risk group, perioperative mortality rates were significantly lower for pancreatectomy and esophagectomy at Specialized Centers. Risk-based referral compared with volume-based regionalization of most patients would require fewer patients to change to Specialized Centers. CONCLUSIONS:: Perioperative mortality for low-risk patients was comparable at Specialized Centers and Community Hospitals for all cancers except esophageal and pancreatic, thus questioning volume-based regionalization of all patients. Rather, only high-risk patients may need to change hospitals. Mortality rates could be reduced if factors at Specialized Centers resulting in better outcomes for high-risk patients can be identified and transferred to other hospitals. Bilimoria, K. Y. Bentrem, D. J. Talamonti, M. S. Stewart, A. K. Winchester, D. P. Ko, C. Y. 0 2009-11-11T07:21:39Z 2009-11-05 2009-11-10 %0 Journal Article %A Bilimoria, K. Y. %A Bentrem, D. J. %A Talamonti, M. S. %A Stewart, A. K. %A Winchester, D. P. %A Ko, C. Y. %D 2009 %T Risk-based Selective Referral for Cancer Surgery: A Potential Strategy to Improve Perioperative Outcomes. %J Ann Surg %M 19898231 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19898231 %X BACKGROUND:: Studies have demonstrated volume-outcome relationships for numerous operations, providing an impetus for regionalization; however, volume-based regionalization may not be feasible or necessary. Our objective was to determine if low-risk patients undergoing surgery at Community Hospitals have perioperative mortality rates comparable with Specialized Centers. METHODS:: From the National Cancer Data Base, 940,718 patients from approximately 1430 hospitals were identified who underwent resection for 1 of 15 cancers (2003-2005). Patients were stratified by preoperative risk according to age and comorbidities. Separately for each cancer, regression modeling stratified by high- and low-risk groups was used to compare 60-day mortality at Specialized Centers (National Cancer Institute-designated and/or highest-volume quintile institutions), Other Academic Institutions (lower-volume, non-National Cancer Institute), and Community Hospitals. RESULTS:: Low-risk patients had statistically similar perioperative mortality rates at Specialized Centers and Community Hospitals for 13 of 15 operations. High-risk patients had significantly lower perioperative mortality rates at Specialized Centers compared with Community Hospitals for 9 of 15 cancers. Regardless of risk group, perioperative mortality rates were significantly lower for pancreatectomy and esophagectomy at Specialized Centers. Risk-based referral compared with volume-based regionalization of most patients would require fewer patients to change to Specialized Centers. CONCLUSIONS:: Perioperative mortality for low-risk patients was comparable at Specialized Centers and Community Hospitals for all cancers except esophageal and pancreatic, thus questioning volume-based regionalization of all patients. Rather, only high-risk patients may need to change hospitals. Mortality rates could be reduced if factors at Specialized Centers resulting in better outcomes for high-risk patients can be identified and transferred to other hospitals. %+ From the *Cancer Programs, Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, IL; daggerDepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL; double daggerDepartment of Surgery, NorthShore University Health System, Evanston, IL; and section signDepartment of Surgery, University of California, Los Angeles (UCLA) and VA Greater Los Angeles Healthcare System, Los Angeles, CA. 8578 false false Annals of surgery Ann Surg 2009-11-05 aheadofprint JOURNAL ARTICLE 19898231 Publisher 2009-11-11T07:21:39Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19898231 2009 HYPOTHESIS: Specific complications occur more frequently in elderly patients undergoing major gastrointestinal (GI) tract operations that may represent opportunities for quality improvement. DESIGN: Retrospective cohort study. SETTING: One hundred twenty-one hospitals participating in American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). PATIENTS: Using the ACS-NSQIP participant use file (2005-2006), patients undergoing upper gastrointestinal tract (n = 4115), hepatobiliary or pancreatic (n = 3364), and colorectal (n = 17 268) operations at 121 hospitals were examined. MAIN OUTCOME MEASURES: Risk-adjusted 30-day outcomes were assessed using regression modeling adjusting for patient characteristics, comorbidities, and surgical procedures. The elderly were defined as those older than 75 years. RESULTS: Between January 1, 2005, and December 31, 2006, a total of 54 747 patients who underwent major GI tract operations were identified from the ACS-NSQIP data file. In the elderly, overall perioperative morbidity was 1.2 to 2 times higher and mortality was 2.9 to 6.7 times higher than in younger patients after adjusting for differences in preoperative comorbidities. Irrespective of procedure type, the elderly were significantly more likely to experience cardiac (acute myocardial infarction and cardiac arrest), pulmonary (pneumonia, pulmonary embolism, and respiratory failure), and urologic (urinary tract infection and renal failure) complications. However, surgical site infections, postoperative bleeding events, deep venous thromboses, and rates of return to the operating room did not differ significantly by age. CONCLUSIONS: Morbidity and mortality are markedly higher in older patients. Quality measures for the elderly currently address only myocardial infarction, surgical site infection, and deep venous thrombosis. If care for the elderly is to be improved, quality improvement initiatives need to be expanded to include postoperative pulmonary and renal complications. Bentrem, D. J. Cohen, M. E. Hynes, D. M. Ko, C. Y. Bilimoria, K. Y. 0 2009-11-19T07:22:08Z 2009-11-18 %0 Journal Article %A Bentrem, D. J. %A Cohen, M. E. %A Hynes, D. M. %A Ko, C. Y. %A Bilimoria, K. Y. %D 2009 %T Identification of specific quality improvement opportunities for the elderly undergoing gastrointestinal surgery. %J Arch Surg %V 144 %N 11 %P 1013-1020 %M 19917937 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19917937 %X HYPOTHESIS: Specific complications occur more frequently in elderly patients undergoing major gastrointestinal (GI) tract operations that may represent opportunities for quality improvement. DESIGN: Retrospective cohort study. SETTING: One hundred twenty-one hospitals participating in American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). PATIENTS: Using the ACS-NSQIP participant use file (2005-2006), patients undergoing upper gastrointestinal tract (n = 4115), hepatobiliary or pancreatic (n = 3364), and colorectal (n = 17 268) operations at 121 hospitals were examined. MAIN OUTCOME MEASURES: Risk-adjusted 30-day outcomes were assessed using regression modeling adjusting for patient characteristics, comorbidities, and surgical procedures. The elderly were defined as those older than 75 years. RESULTS: Between January 1, 2005, and December 31, 2006, a total of 54 747 patients who underwent major GI tract operations were identified from the ACS-NSQIP data file. In the elderly, overall perioperative morbidity was 1.2 to 2 times higher and mortality was 2.9 to 6.7 times higher than in younger patients after adjusting for differences in preoperative comorbidities. Irrespective of procedure type, the elderly were significantly more likely to experience cardiac (acute myocardial infarction and cardiac arrest), pulmonary (pneumonia, pulmonary embolism, and respiratory failure), and urologic (urinary tract infection and renal failure) complications. However, surgical site infections, postoperative bleeding events, deep venous thromboses, and rates of return to the operating room did not differ significantly by age. CONCLUSIONS: Morbidity and mortality are markedly higher in older patients. Quality measures for the elderly currently address only myocardial infarction, surgical site infection, and deep venous thrombosis. If care for the elderly is to be improved, quality improvement initiatives need to be expanded to include postoperative pulmonary and renal complications. %+ Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. Bentrem, David J Cohen, Mark E Hynes, Denise M Ko, Clifford Y Bilimoria, Karl Y 8606 false false 11 Archives of surgery (Chicago, Ill. : 1960) Arch Surg 1013-1020 2009-11-01 ppublish Journal Article 19917937 In-Data-Review 2009-11-19T07:22:08Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19917937 144 2009 Benson, A. B. 0 2009-10-30T06:21:56Z 2009-10-29 %0 Journal Article %A Benson, A. B. %D 2009 %T Chemotherapy: Adding oxaliplatin to the equation. %J Nat Rev Clin Oncol %V 6 %N 11 %P 620-622 %M 19861991 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861991 Benson, Al B 8537 false false 11 Nature reviews. Clinical oncology Nat Rev Clin Oncol 620-622 2009-11-01 ppublish Journal Article 19861991 In-Process 2009-10-31T06:19:28Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861991 6 2009 Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length-related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean +/- SD relative telomere length, 1.25 +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (P(trend) < 0.001). Telomere length-associated risks were higher among individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95% CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3103-9). Hou, L. Savage, S. A. Blaser, M. J. Perez-Perez, G. Hoxha, M. Dioni, L. Pegoraro, V. Dong, L. M. Zatonski, W. Lissowska, J. Chow, W. H. Baccarelli, A. 0 2009-10-30T06:22:15Z 2009-10-27 2009-10-29 %0 Journal Article %A Hou, L. %A Savage, S. A. %A Blaser, M. J. %A Perez-Perez, G. %A Hoxha, M. %A Dioni, L. %A Pegoraro, V. %A Dong, L. M. %A Zatonski, W. %A Lissowska, J. %A Chow, W. H. %A Baccarelli, A. %D 2009 %T Telomere length in peripheral leukocyte DNA and gastric cancer risk. %J Cancer Epidemiol Biomarkers Prev %V 18 %N 11 %P 3103-3109 %M 19861514 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861514 %X Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length-related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean +/- SD relative telomere length, 1.25 +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (P(trend) < 0.001). Telomere length-associated risks were higher among individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95% CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population. %+ Department of Preventive Medicine, Feinberg School of Medicine, and The Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, USA. l-hou@northwestern.edu 8539 false false 11 Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Cancer Epidemiol Biomarkers Prev 3103-3109 2009-11-01 ppublish JOURNAL ARTICLE 19861514 In-Process 2009-11-13T07:19:34Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19861514 18 2009 Spontaneous antitumor T cell responses in cancer patients are strongly controlled by Tregs, and increased numbers of tumor-infiltrating Tregs correlate with reduced survival. However, the tumor antigens recognized by Tregs in cancer patients and the impact of these cells on tumor-specific T cell responses have not been systematically characterized. Here we used a broad panel of long synthetic peptides of defined tumor antigens and normal tissue antigens to exploit a newly developed method to identify and compare ex vivo the antigen specificities of Tregs with those of effector/memory T cells in peripheral blood of colorectal cancer patients and healthy subjects. Tregs in tumor patients were highly specific for a distinct set of only a few tumor antigens, suggesting that Tregs exert T cell suppression in an antigen-selective manner. Tumor-specific effector T cells were detectable in the majority of colorectal cancer patients but not in healthy individuals. We detected differences in the repertoires of antigens recognized by Tregs and effector/memory T cells in the majority of colorectal cancer patients. In addition, only effector/memory T cell responses against antigens recognized by Tregs strongly increased after Treg depletion. The selection of antigens according to preexisting T cell responses may improve the efficacy of future immunotherapies for cancer and autoimmune disease. Bonertz, A. Weitz, J. Pietsch, D. H. Rahbari, N. N. Schlude, C. Ge, Y. Juenger, S. Vlodavsky, I. Khazaie, K. Jaeger, D. Reissfelder, C. Antolovic, D. Aigner, M. Koch, M. Beckhove, P. 0 2009-10-09T06:14:10Z 2009-10-05 2009-10-08 %0 Journal Article %A Bonertz, A. %A Weitz, J. %A Pietsch, D. H. %A Rahbari, N. N. %A Schlude, C. %A Ge, Y. %A Juenger, S. %A Vlodavsky, I. %A Khazaie, K. %A Jaeger, D. %A Reissfelder, C. %A Antolovic, D. %A Aigner, M. %A Koch, M. %A Beckhove, P. %D 2009 %T Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. %J J Clin Invest %V 119 %N 11 %P 3311-3321 %M 19809157 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19809157 %X Spontaneous antitumor T cell responses in cancer patients are strongly controlled by Tregs, and increased numbers of tumor-infiltrating Tregs correlate with reduced survival. However, the tumor antigens recognized by Tregs in cancer patients and the impact of these cells on tumor-specific T cell responses have not been systematically characterized. Here we used a broad panel of long synthetic peptides of defined tumor antigens and normal tissue antigens to exploit a newly developed method to identify and compare ex vivo the antigen specificities of Tregs with those of effector/memory T cells in peripheral blood of colorectal cancer patients and healthy subjects. Tregs in tumor patients were highly specific for a distinct set of only a few tumor antigens, suggesting that Tregs exert T cell suppression in an antigen-selective manner. Tumor-specific effector T cells were detectable in the majority of colorectal cancer patients but not in healthy individuals. We detected differences in the repertoires of antigens recognized by Tregs and effector/memory T cells in the majority of colorectal cancer patients. In addition, only effector/memory T cell responses against antigens recognized by Tregs strongly increased after Treg depletion. The selection of antigens according to preexisting T cell responses may improve the efficacy of future immunotherapies for cancer and autoimmune disease. %K Amino Acid Sequence %K Antigens, Neoplasm/chemistry/*immunology %K Colorectal Neoplasms/*immunology %K Histocompatibility Testing %K Humans %K Lymphocyte Depletion %K Molecular Sequence Data %K Peptides/metabolism %K T-Lymphocytes/*immunology %K T-Lymphocytes, Regulatory/*immunology %+ Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany. 8456 false false 11 The Journal of clinical investigation J Clin Invest Amino Acid Sequence; Antigens, Neoplasm/chemistry/*immunology; Colorectal Neoplasms/*immunology; Histocompatibility Testing; Humans; Lymphocyte Depletion; Molecular Sequence Data; Peptides/metabolism; T-Lymphocytes/*immunology; T-Lymphocytes, Regulatory/*immunology 3311-3321 2009-11-01 ppublish JOURNAL ARTICLE 19809157 MEDLINE 2009-11-18T07:17:15Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19809157 119 2009 PURPOSE OF REVIEW: Cancer immunology became scientifically credible only some 20 years ago with the demonstration of the existence of human tumor antigens. In this short time span, outcomes of cancer vaccine trials have raised hopes and also surfaced disappointments. This review focuses on the prospects of peptide-based vaccines in cancer immunotherapy. RECENT FINDINGS: Accurate descriptions of the natural immune responses to cancer allow for a more precise targeting of such tumors by boosting preexisting antitumor immune responses in patients. The development of synthetic long-peptide vaccines avoids many of the pitfalls of previous vaccination trials through the presence of multiple epitopes that may elicit memory antitumor immune responses. Furthermore, the combination of standard therapy with newly developed immunomodulating agents, such as antibodies blocking cytotoxic T lymphocyte-associated antigen-4 or programmed death receptor-1, and more efficient immune adjuvants has shown promising results. SUMMARY: Immunotherapy is becoming an effective means of targeting human cancers, and the application of such approaches in combination with current standard schemes of treatment can lead to a significant benefit in survival and quality of life for cancer patients. Khazaie, K. Bonertz, A. Beckhove, P. 0 2009-09-24T06:16:14Z 2009-09-23 %0 Journal Article %A Khazaie, K. %A Bonertz, A. %A Beckhove, P. %D 2009 %T Current developments with peptide-based human tumor vaccines. %J Curr Opin Oncol %V 21 %N 6 %P 524-530 %M 19770763 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19770763 %X PURPOSE OF REVIEW: Cancer immunology became scientifically credible only some 20 years ago with the demonstration of the existence of human tumor antigens. In this short time span, outcomes of cancer vaccine trials have raised hopes and also surfaced disappointments. This review focuses on the prospects of peptide-based vaccines in cancer immunotherapy. RECENT FINDINGS: Accurate descriptions of the natural immune responses to cancer allow for a more precise targeting of such tumors by boosting preexisting antitumor immune responses in patients. The development of synthetic long-peptide vaccines avoids many of the pitfalls of previous vaccination trials through the presence of multiple epitopes that may elicit memory antitumor immune responses. Furthermore, the combination of standard therapy with newly developed immunomodulating agents, such as antibodies blocking cytotoxic T lymphocyte-associated antigen-4 or programmed death receptor-1, and more efficient immune adjuvants has shown promising results. SUMMARY: Immunotherapy is becoming an effective means of targeting human cancers, and the application of such approaches in combination with current standard schemes of treatment can lead to a significant benefit in survival and quality of life for cancer patients. %+ Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Robert Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA. khazaie@northwestern.edu 8393 false false 6 Current opinion in oncology Curr Opin Oncol 524-530 2009-11-01 ppublish JOURNAL ARTICLE 19770763 In-Process 2009-10-16T06:15:38Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19770763 21 2009 Dithiocarbamates (dtcs) have been implicated as important gold-binding groups in molecular electronics. Dtcs have two alkane branches connected at a single anchoring point that has a bidentate resonance structure. Forming readily in situ by the combination of secondary amines and CS(2), dtcs adsorb quickly onto gold surfaces. Electroactive self-assembled monolayers (eSAMs) were prepared by the coadsorption of ferrocene dialkyldithiocarbamates (Fc dtcs) with diluent dtcs on gold electrodes. Short and long alkane chains were used (11 and 16 methylene groups, respectively), and a polar ester group was incorporated. Cyclic voltammetry (CV) shows that the electrochemistry is quasi-reversible. At high surface coverage, the peak separations and full widths at half-maximum for Fc dtcs deviate from theoretical values and are analogous to that of ferrocene alkane thiols on gold at high surface coverage. Importantly, these features do not change at low Fc dtc surface coverage as observed for ferrocene alkane thiols. Ferrocene dtcs were used to label monolayer defect sites and to demonstrate the exchange of surface-bound dtcs with solution dtcs. Finally, the rate of electron transfer was analyzed using Tafel plots and ac voltammetric methods. The results for both techniques are consistent with a kinetically disperse population of redox sites. The length of the diluent alkane chain appears to have an effect on the distribution of electron-transfer rates, likely because of the eSAM structure. This work indicates that structurally, Fc dtc eSAMs are fundamentally different from alkane thiol SAMs on gold. Eckermann, A. L. Shaw, J. A. Meade, T. J. 0 2009-11-04T07:18:56Z 2009-10-30 2009-11-03 %0 Journal Article %A Eckermann, A. L. %A Shaw, J. A. %A Meade, T. J. %D 2009 %T Kinetic Dispersion in Redox-Active Dithiocarbamate Monolayers. %J Langmuir %M 19877702 %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19877702 %X Dithiocarbamates (dtcs) have been implicated as important gold-binding groups in molecular electronics. Dtcs have two alkane branches connected at a single anchoring point that has a bidentate resonance structure. Forming readily in situ by the combination of secondary amines and CS(2), dtcs adsorb quickly onto gold surfaces. Electroactive self-assembled monolayers (eSAMs) were prepared by the coadsorption of ferrocene dialkyldithiocarbamates (Fc dtcs) with diluent dtcs on gold electrodes. Short and long alkane chains were used (11 and 16 methylene groups, respectively), and a polar ester group was incorporated. Cyclic voltammetry (CV) shows that the electrochemistry is quasi-reversible. At high surface coverage, the peak separations and full widths at half-maximum for Fc dtcs deviate from theoretical values and are analogous to that of ferrocene alkane thiols on gold at high surface coverage. Importantly, these features do not change at low Fc dtc surface coverage as observed for ferrocene alkane thiols. Ferrocene dtcs were used to label monolayer defect sites and to demonstrate the exchange of surface-bound dtcs with solution dtcs. Finally, the rate of electron transfer was analyzed using Tafel plots and ac voltammetric methods. The results for both techniques are consistent with a kinetically disperse population of redox sites. The length of the diluent alkane chain appears to have an effect on the distribution of electron-transfer rates, likely because of the eSAM structure. This work indicates that structurally, Fc dtc eSAMs are fundamentally different from alkane thiol SAMs on gold. %+ Departments of Chemistry, Biochemistry and Molecular and Cell Biology, Neurobiology and Physiology, and Radiology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208. 8553 false false Langmuir : the ACS journal of surfaces and colloids Langmuir 2009-10-30 aheadofprint JOURNAL ARTICLE 19877702 Publisher 2009-11-04T07:18:56Z http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19877702 2009