Medicine and Health Sciences Commons^™

Daclatasvir In Combination With Asunaprevir And Beclabuvir For Hepatitis C Virus Genotype 1 Infection With Compensated Cirrhosis., Andrew J Muir, Fred Poordad, Jacob Lalezari, Gregory Everson, Gregory J Dore, Robert Herring, Aasim Sheikh, Paul Kwo, Christophe Hézode, Paul J Pockros, Albert Tran, Joseph L. Yozviak Do, Facp, Nancy Reau, Alnoor Ramji, Katherine Stuart, Alexander J Thompson, John Vierling, Bradley Freilich, James Cooper, Wayne Ghesquiere, Rong Yang, Fiona Mcphee, Eric A Hughes, E Scott Swenson, Philip D Yin

Joseph L Yozviak DO, FACP

IMPORTANCE: Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis.

OBJECTIVE: All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis.

DESIGN, SETTING, AND PARTICIPANTS: The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients …

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …

Association Between Chlorinated Pesticides In The Serum Of Prepubertal Russian Boys And Longitudinal Biomarkers Of Metabolic Function, Jane Burns, Paige Williams, Susan Korrick, Russ Hauser, Oleg Sergeyev, Boris Revich, Thuy Lam, Mary Lee

Mary M. Lee

Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Gaelle Eve Doucet

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

Barriers And Facilitators For Colorectal Cancer Screening Practices In The Latino Community: Perspectives From Community Leaders, Ana Natale-Pereira, Jonnie Marks, Marielos Vega, Dawne Mouzon, Shawna Hudson, Debbie Salas-Lopez

Debbie Salas-Lopez MD, MPH

BACKGROUND: Colorectal cancer (CRC) is the second-leading cause of cancer-related death in the United States and the third most commonly diagnosed cancer among Latinos. While Latinos represent one of the fastest-growing ethnic groups in the United States, their participation in cancer prevention and treatment trials is low. METHODS: Thirty-six Latino community leaders participated in five focus groups that examined factors affecting CRC screening practices among Latinos. RESULTS: The top four barriers identified were low knowledge and awareness of CRC, language barriers, lack of insurance, and undocumented legal status. Additional barriers included seeking health care only when sick, fatalism, fear, denial …

Perspectives On Cancer Screening Among Latino Community Members And Internal Medicine Residents, Debbie Salas-Lopez, Dawne Mouzon, Jonnie Marks, Neil Kothari, Ana Natale-Pereira

Debbie Salas-Lopez MD, MPH

BACKGROUND: Latinos have lower rates of cancer screening, partially because of cultural beliefs that conflict with those of health care professionals. Moreover, established programs for training physicians in cultural competency often fail to incorporate input from the community.

METHODS: To explore beliefs about cancer and cancer screening among Latino community members and internal medicine residents. Three focus groups of Latino community members (n = 31) and one focus group of internal medicine residents (n = 9) were conducted to compare ideas regarding cancer and cancer screening.

RESULTS: We identified clear disconnects between residents and Latino community members regarding their understandings …

Comparison Of Insulin Infusion Protocols Targeting 110-140 Mg/Dl In Patients After Cardiac Surgery., Vasudev Magaji, Shriddha Nayak, Amy Donihi, Lauren Willard, Srinivasa Jampana, Parachur Nivedita, Raymond Eder, Jann Johnston, Mary Korytkowski

Vasudev G Magaji MD, MS

BACKGROUND: Continuous intravenous insulin infusion (CII) following coronary artery bypass graft (CABG) surgery reduces postoperative complications and hospitalization duration. Because of limited data evaluating outcomes of CII with revised glycemic targets (110-140 mg/dL) in cardiac surgery, this study compared efficacy and safety of two different CII protocols having revised targets. SUBJECTS AND METHODS: This is a retrospective study comparing two different protocols between August 2009 and March 2010. Protocol 1 consists of four algorithms, and Protocol 2 is a table to adjust CII. Blood glucose (BG) and CII rates were recorded for 48 h postoperatively or CII discontinuation. Efficacy was …

Angiographic Recognition Of Ostial Left Main Coronary Artery Stenosis: Case Report., R M Macmillan, Bruce Feldman, V Maranhao

Bruce A. Feldman DO

Ostial left main coronary stenosis has a poor prognosis and increased mortality rate with coronary arteriography. Due to its anatomic location, visualization of the stenosis may be difficult. A high index of suspicion based upon only a few signs should prompt the physician to perform certain maneuvers to obtain the correct diagnosis. Four illustrative cases are presented and discussed.

Addressing The Controversy Of Rate-Versus-Rhythm Control In Atrial Fibrillation, Tahmeed Contractor, Vadim Levin, Ravi Desai, Francis E Marchlinski

Vadim A Levin MD

Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases patient risk of stroke, cardiomyopathy, and mortality. Rate versus rhythm control as the "best" treatment strategy remains an issue of considerable, ongoing debate. A multitude of clinical trials have compared the 2 strategies and have not shown any benefit of one approach over the other. However, the trials were conducted in specific subgroups of patients and demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that successful rhythm control with sinus rhythm restoration is …

Addressing The Controversy Of Rate-Versus-Rhythm Control In Atrial Fibrillation, Tahmeed Contractor, Vadim Levin, Ravi Desai, Francis E Marchlinski

Ravi V Desai MD

Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases patient risk of stroke, cardiomyopathy, and mortality. Rate versus rhythm control as the "best" treatment strategy remains an issue of considerable, ongoing debate. A multitude of clinical trials have compared the 2 strategies and have not shown any benefit of one approach over the other. However, the trials were conducted in specific subgroups of patients and demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that successful rhythm control with sinus rhythm restoration is …

Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias Schnell, Laurence Eisenlohr, Scott Waldman

Adam E Snook

Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory …

Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …

Prognostic Factors For Male Breast Cancer: Similarity To Female Counterparts, Edward Yu, Larry Stitt, Olga Vujovic, Kurian Joseph, Avi Assouline, Joseph Au, Jawaid Younus, Francisco Perera, Patricia Tai

Edward Yu

Abstract. Aim: To assess whether prognostic factors in male (MBC) and female (FBC) breast cancer have similar impact on survival. Patients and Methods: Charts for men and women diagnosed with breast cancer referred to the London Regional Cancer Program (LRCP) were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with/without hormone and radiation therapy (RT), overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female …

Intervention At The Level Of The Neuroendocrine-Immune Axis And Postoperative Pneumonia Rate In Long-Term Alcoholics, Claudia Spies, Verena Eggers, Gyongyi Szabo, Alexandra Lau, Vera Von Dossow, Helge Schoenfeld, Hilke Althoff, Katrin Hegenscheid, Birgit Bohm, Torsten Schroeder, Sebastian Pfeiffer, Sabine Ziemer, Christian Paschen, Martin Klein, Christian Marks, Peter Miller, Michael Sander, Klaus-D. Wernecke, Evelin Achterberg, Udo Kaisers, Hans-Dieter Volk

Gyongyi Szabo

RATIONALE: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily …

Comparative Planning Evaluation Of Intensity-Modulated Radiotherapy Techniques For Complex Lung Cancer Cases, Slav Yartsev, Jeff Chen, Edward Yu, Tomas Kron, George Rodrigues, Terry Coad, Kristina Trenka, Eugene Wong, Glenn Bauman, Jake Van Dyk

Edward Yu

Background and purpose: Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance. Patients and methods: Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to …

Does Sex Influence The Impact That Smoking, Treatment Interruption And Impaired Pulmonary Function Have On Outcomes In Limited Stage Small Cell Lung Cancer Treatment?, Gregory Videtic, Pauline Truong, Robert Ash, Edward Yu, Walter Kocha, Mark Vincent, Anna Tomiak, A Dar, Frances Whiston, Larry Stitt

Edward Yu

PURPOSE: To look for survival differences between men and women with limited stage small cell lung cancer (LS-SCLC) by examining stratified variables that impair treatment efficacy. METHODS: A retrospective review of 215 LS-SCLC patients treated from 1989 to 1999 with concurrent chemotherapy-radiotherapy modelled on the 'early-start' thoracic radiotherapy arm of a National Cancer Institute of Canada randomized trial. RESULTS: Of 215 LS-SCLC patients, 126 (58.6%) were men and 89 (41.4%) were women. Smoking status during treatment for 186 patients (86.5%) was: 107 (58%) nonsmoking (NS) (76 [71%] male [M]; 31 [29%] female [F]) and 79 (42%) smoking (S) (36 M …

Planning Evaluation Of Radiotherapy For Complex Lung Cancer Cases Using Helical Tomotherapy, Tomas Kron, Grigor Grigorov, Edward Yu, Slav Yartsev, Jeff Chen, Eugene Wong, George Rodrigues, Kris Trenka, Terry Coad, Glenn Bauman, Jake Van Dyk

Edward Yu

Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used …

Radiation Treatment Of Lung Cancer--Patterns Of Practice In Canada, Patricia Tai, Edward Yu, Jerry Battista, Jake Van Dyk

Edward Yu

BACKGROUND AND PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat lung cancers. PATIENTS AND METHODS: A questionnaire detailing different aspects of radiation treatment of lung cancer was mailed to all radiation oncologists treating lung cancer in Canada. Seventy-two percent (74/103) of radiation oncologists who treat lung cancer from all 34 Canadian cancer centres replied to the questionnaire. RESULTS: (a) Radiotherapy regimens in Canadian cancer centres are in accordance with several major randomised studies. There is still some variation in treatment practice that may be due to unresolved controversies or limited resources. The most frequently used …

Using Treatment Interruptions To Palliate The Toxicity From Concurrent Chemoradiation For Limited Small Cell Lung Cancer Decreases Survival And Disease Control, Gregory Videtic, Karen Fung, Anna Tomiak, Larry Stitt, A. Dar, Pauline Truong, Edward Yu, Mark Vincent, Walter Kocha

Edward Yu

BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, …

Radiation Treatment For Cervical Esophagus: Patterns Of Practice Study In Canada, 1996, Patricia Tai, Jake Van Dyk, Edward Yu, Jerry Battista, Matthew Schmid, Larry Stitt, Jon Tonita, Terry Coad

Edward Yu

PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat esophageal cancers, using a trans-Canada survey, completed at the end of 1996. METHODS AND MATERIALS: One of 3 case presentations of different stages of cervical esophageal cancer was randomly assigned and sent to participating radiation oncologists by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline target volumes for the boost phase of radiotherapy. Radiation oncologists from 26 of 27 (96%) of all Canadian centers participated. RESULTS: High-energy X-rays (>/= 10 MV) were employed by 68% of the respondents in part …

Variability Of Target Volume Delineation In Cervical Esophageal Cancer, Patricia Tai, Jake Van Dyk, Edward Yu, Jerry Battista, Larry Stitt, Terry Coad

Edward Yu

PURPOSE: Three-dimensional (3D) conformal radiation therapy (CRT) assumes and requires the precise delineation of the target volume. To assess the consistency of target volume delineation by radiation oncologists, who treat esophageal cancers, we have performed a transCanada survey. MATERIALS AND METHODS: One of three case presentations, including CT scan images, of different stages of cervical esophageal cancer was randomly chosen and sent by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline boost target volumes for the primary tumor on CT scans, using ICRU-50 definitions. RESULTS: Of 58 radiation oncologists who agreed to participate, 48 …