tbuckley/cabot-search huggingface dataset:
Changes in Antiemetic Overuse in Response to Choosing Wisely Recommendations
Authors: William Encinosa, Amy J. Davidoff
Journal: JAMA Oncology (2016)

Antiemetics are used to prevent chemotherapy-induced nausea and vomiting in patients with cancer. Newer antiemetic agents (serotonin and neurokinin-1 receptor antagonists) have increased efficacy but are expensive. The American Society of Clinical Oncology's first guideline in the 2013 Choosing Wisely (CW) campaign discouraged overuse of expensive antiemetics in patients with low risk of chemotherapy-induced nausea and vomiting. However, little is known about patterns or trends in antiemetic overuse or whether any change has occurred with the publication of the CW recommendations.To estimate the baseline prevalence, trends, determinants, and costs of antiemetic overuse from January 1, 2008, through March 31, 2015.From January 1, 2008, through March 31, 2015, this observational study applied descriptive (univariate and bivariate) and multivariable logistic regression analyses to longitudinal health insurance enrollment and nationwide MarketScan insurance claims data for 678 220 privately insured patients receiving chemotherapy before and after the October 29, 2013, announcement of the CW guidelines. The baseline prevalence, trends, determinants, and costs of antiemetic overuse were estimated in cases stratified by risk for chemotherapy-induced nausea and vomiting.Antiemetic use, overuse measure, and expenses before and after the publication of the CW recommendation, with adjustment for patient and health care professional characteristics.The sample included 678 220 adults who started chemotherapy during the observation period. The average age of the sample was 59.5 years, with 58.2% (n = 394 724) female. Antiemetic overuse occurred in 24.1% (n = 163 451) of patients, with highest rates among those receiving intravenous chemotherapy with high chemotherapy-induced nausea and vomiting risk (32.4% [n = 106 795]). Compared with baseline before the CW, patients had 7.0% lower odds of antiemetic overuse (95% CI, 4.4%-9.5%) during the 6 months after the CW, but this decrease was transitory: the odds of antiemetic overuse were 7.4% (95% CI, 4.6%-10.2%) higher than baseline at 6 months after the CW. Low-risk intravenous chemotherapy agents had overuse that continued to decrease 6 months after the CW. Antiemetic overuse was associated with higher costs. Reducing antiemetic overuse could have paid for 6.1% (95% CI, 5.8%-6.4%) of the chemotherapy drug costs.Antiemetic overuse is prevalent and results in unnecessary spending associated with systemic chemotherapy treatment. Short-term decreases in antiemetic overuse were associated with the CW recommendation, but sustained decreases occurred in only one risk group.
Outcome of patients with rare tumors included in phase l clinical trials.
Authors: D. Barrios Gonzales, Y. Loriot, C. Gomez-Roca, C. Massard, T. de La Motte Rouge, R. Bahleda, J. Soria
Journal: Journal of Clinical Oncology (2010)

e13109 Background: Few clinical trials are conducted in patients with rare types of cancer. Phase I clinical trials could be a great opportunity for patients with advanced rare tumors who fail to respond to standard therapy. The aim of this study was to assess the outcome of patients with rare tumors included in phase I trials at the Institut Gustave Roussy. Methods: Among the 667 patients included in phase I clinical trials between 2005 and 2009, 30 patients were diagnosed with rare tumors. We reviewed patients' demographic characteristics and type of agents studied. Outcome was assessed in terms of response rate, progression-free survival (PFS), and overall survival (OS). Safety evaluation was based on NCI CTC toxicity scale version 3.0. Results: Median age was 45 years (range: 29-70). 63% of patients had ≤1 previous chemotherapy lines (CL), and 37% had ≥2 CL. The histological types were mainly adenoid cystic carcinoma (n=14), adrenal carcinoma (n=7), thymoma (n=6), ACUP (n=1), and mucoepidermoid carcinoma of the lacrimal sac (n=2). The types of agents studied were: anti-angiogenic (n=7), growth-factor inhibitors (n=12), mTOR inhibitors (n=1), CDK inhibitors (n=1), or new chemotherapy (n=9). A partial response was observed in 1 patient (3%) and stable disease was observed in 29 patients (97%), from which 80% had SD at 3 months (n=24), 43% had SD at 6 months (n=13) and 3% at 12 months (n=1). The median PFS and OS were: 5.6 months (CI95%: 4.4-6.9) and 23.2 months (CI95%: 8.3-37), respectively. Grade III toxicity was observed in 5 patients (17%). The most frequent side effects were neutropenia (n=2), diarrhea (n=2), and cytolysis (n=1). Conclusions: Our study shows that the patients with rare tumors, rarely included in devoted large clinical trials, benefit from phase I clinical trials. This benefit is better than the outcome reported for overall population included in phase I trials (Italiano.2007). No significant financial relationships to disclose.
Circulating Oxidized LDL is a Useful Marker for Cardiovascular Risk Assessment
Authors: Ann Mertens, Peter P Verhamme, Raymond Verhaeghe, Erik Muls, Desire Collen, Frans Van de Werf, Paul Holvoet
Journal: Circulation (2001)

0032 BACKGROUND: Coronary artery disease is associated with an increase in circulating oxidized (Ox)LDL (Circulation 1998; 98:1487-1494). OBJECTIVES: 1) To determine the usefulness of OxLDL for identifying cardiovascular disease patients and 2) to study the relation of OxLDL with cardiovascular risk factors. METHODS: 1) To determine the diagnostic value of OxLDL 308 subjects were studied: 178 patients with angiographically proven coronary artery disease and 130 age-matched subjects without cardiovascular disease (controls) confirmed by B mode ultrasonography of their carotid arteries. 2) Additional 307 patients without cardiovascular disease were studied to determine the relation of OxLDL with cardiovascular risk factors. Levels of OxLDL were directly measured in plasma using a mAb-4E6 based competition ELISA. RESULTS: Compared with controls, patients had 2.3-fold higher levels of circulating OxLDL. At a cutoff value of 2.30 mg/dL, the sensitivity of OxLDL for cardiovascular disease was 73% with a specificity of 90%. The Global Risk Assessment Score (GRAS) was calculated using age, total and HDL cholesterol, systolic blood pressure, diabetes mellitus and smoking. GRAS was 8.65±3.41 for patients versus 6.09±5.10 (p≤0.001) for controls. Compared with subjects with low OxLDL (≤2.30 mg/dL) and low GRAS (≤12), risk of having cardiovascular disease was 3.2 times higher for subjects with low OxLDL and high GRAS, 6.4 times higher for subjects with high OxLDL and low GRAS and 27 times higher for subjects with both high OxLDL and high GRAS. Among patients without cardiovascular disease, stepwise multivariate analysis showed that Body Mass Index (p&lt;0.001), LDL cholesterol (p&lt;0.001), diabetes type 2 (p=0.003), triglycerides (p=0.017) and smoking (p=0.046) were the strongest predictors of OxLDL. Conclusion: Circulating OxLDL is a sensitive marker of cardiovascular disease. Circulating oxidized LDL correlates with obesity, hypercholesterolemia, diabetes and smoking. Addition of OxLDL to the established risk factors may improve cardiovascular risk prediction. Inclusion of OxLDL in prospective studies of risk factors of cardiovascular disease seems to be warranted.
Integrative Genomic Analysis Identifies the Core Transcriptional Hallmarks of Human Hepatocellular Carcinoma
Authors: Coralie Allain, Gaëlle Angenard, Bruno Clément, Cédric Coulouarn
Journal: Cancer Research (2016)

Abstract Integrative genomics helped characterize molecular heterogeneity in hepatocellular carcinoma (HCC), leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here, we performed a meta-analysis of 15 independent datasets (n = 784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared with the surrounding nontumor tissue. In the HCC signature, upregulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer. Cancer Res; 76(21); 6374–81. ©2016 AACR.
Phase II study of 90y Ibritumomab Tiuxetan (Zevalin) in Patients with Previously Untreated Marginal Zone Lymphoma
Authors: Jesus C Fabregas, James E. Hoffman, Tulay Koru-Sengul, Miao Feng, Deborah Goodman, Aldo Serafini, Peter J Hosein, Alexandra Stefanovic, Joseph D. Rosenblatt, Izidore S. Lossos
Journal: Blood (2014)
Ketamine use in sedation management in patients receiving extracorporeal membrane oxygenation
Authors: Amy L. Dzierba, Daniel Brodie, Matthew Bacchetta, Justin Muir, Lauren Wasson, Michael Colabraro, Whitney Gannon, Kathleen Connolly, Mauer Biscotti, Wim Rietdijk, Vivek Moitra, Jan Bakker
Journal: Intensive Care Medicine (2016)
Efficacy of Endoscopic Minor Papilla Sphincterotomy for Symptomatic Santorinicele
Authors: Stefano Francesco Crinò, Laura Bernardoni, Maria Cristina Conti Bellocchi, Giuseppe Malleo, Riccardo Manfredi, Irene Breoni, Antonio Amodio, Luca Frulloni, Armando Gabbrielli
Journal: Clinical Gastroenterology and Hepatology (2016)
Workforce in hepatology: Update and a critical need for more information
Authors: Mark W. Russo, Ayman A. Koteish, Michael Fuchs, K. Gautham Reddy, Oren K. Fix
Journal: Hepatology (2016)

The field of hepatology has experienced dramatic changes since the last workforce study in hepatology over 15 years ago. Hepatology practice has been dominated by hepatitis C but is now being overtaken by patients with nonalcoholic fatty liver disease. Expertise once attainable only through informal training, hepatology now has an accredited fellowship pathway and is recognized as a distinct discipline from gastroenterology with its own board certification. These changes that have occurred since the last workforce study in the prevalence and therapy of liver diseases and training may impact workforce needs. The time has come to conduct an updated analysis of the state of the hepatology workforce. The purpose of this article is to discuss the current issues facing training and workforce in hepatology and propose the next steps in conducting a workforce study. (Hepatology 2017;65:336-340).
Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study
Authors: Annalisa Ruggeri, Giorgia Battipaglia, Myriam Labopin, Gerhard Ehninger, Dietrich Beelen, Johanna Tischer, Arnold Ganser, Rainer Schwerdtfeger, Bertram Glass, Jurgen Finke, Mauricette Michallet, Matthias Stelljes, Pavel Jindra, Renate Arnold, Nicolaus Kröger, Mohamad Mohty, Arnon Nagler
Journal: Journal of Hematology & Oncology (2016)

Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3–157) months. Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II–IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)). Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.
A Novel DNA Repair Chip Assay Allows Rapid Identification of DNA Repair Abnormalities Induced By BCR-ABL
Authors: Ali G Turhan, Fanny Sarrazy, Marie Laure Bonnet, Angelina Bertrand, Marie Claude Meunier, Djamel Aggoune, Jean-Claude Chomel, Olivier Feraud, Sylvain Caillat, Annelise Bennaceur-Griscelli, Sylvie Sauvaigo
Journal: Blood (2014)
Prognostic Value of JAK2V617F, Calr and MPL Mutational Status on Outcome and Thrombotic Risk in a Retrospective Cohort of 138 Patients with Essential Thrombocythemia
Authors: Giulia Benevolo, Ludovica Riera, Barbara Nicolino, Andrea Evangelista, Eloise Beggiato, Chiara Aguzzi, Maura Nicolosi, Chiara Frairia, Umberto Vitolo
Journal: Blood (2014)
The role of TP, TS, and DPD as potential predictors of outcome following capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Biomarker findings from study NO16968 (XELOXA).
Authors: Hans-Joachim Schmoll, Josep Tabernero, Jean Alfred Maroun, Filippo G. De Braud, Timothy Jay Price, Eric Van Cutsem, Mark Hill, Silke Hoersch, Karen Rittweger, David Chen, Daniel G. Haller
Journal: Journal of Clinical Oncology (2012)

3578 Background: In NO16968, XELOX was superior in terms of disease-free survival (DFS) and overall survival (OS) to bolus 5-FU/LV as adjuvant therapy for stage III colon cancer (Schmoll et al. ASCO GI 2012). Three key enzymes appear to have the potential to predict efficacy and/or safety of fluoropyrimidine-based treatment: thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). We evaluated the association between baseline TP, TS and DPD and outcome (DFS and OS). Methods: Pts with stage III colon cancer received either XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles, 24w; Roswell Park, 4 cycles, 32w). The primary study endpoint was DFS; secondary endpoints included OS. TP, TS and DPD expression levels were determined in formalin-fixed, paraffin-embedded tissues by RT-PCR, and the median used as a cut-off point: high (above median) vs. low (below median). Results: The biomarker population included 498 (26%) of 1886 pts entered (XELOX, n=242; 5-FU/LV, n=256). Baseline demographics, tumor characteristics, cancer history and efficacy (DFS and OS) were similar to those in the main study population. Cox regression analysis for DFS (Table). In the XELOX group pts with low DPD and TP levels and a high TP/DPD ratio appeared to have significantly better DFS; this effect was not observed with 5-FU/LV. Subgroup analysis shows that the difference between XELOX and 5-FU/LV was also higher in pts with low DPD levels. Conclusions: These exploratory findings suggest that tumor DPD and TP RNA levels could be used to predict outcomes of adjuvant treatment with fluoropyrimidine/oxaliplatin combinations, and should be validated prospectively. Analysis of the current dataset is ongoing and further details on potential biomarkers will be available. [Table: see text]
Cardiovascular and Thrombotic Complications of Novel Multiple Myeloma Therapies
Authors: Weijuan Li, David Garcia, R. Frank Cornell, David Gailani, Jacob Laubach, Michelle E. Maglio, Paul G. Richardson, Javid Moslehi
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Multiple myeloma (MM) is the second most common hematological malignant abnormality. The introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has greatly improved the overall survival of patients with MM. Prevention and treatment of cardiovascular and thrombotic issues associated with novel MM therapies have emerged as important aspects of supportive care in patients with MM. <h3>Observations</h3> We searched PubMed and the Cochrance database for studies published from March 2001 to January 2016. Emerging evidence suggests that both IMiDs and PIs can have cardiovascular (CV) sequelae, which include thromboembolic complications, cardiac, and vascular toxic effects. These complications occur against the backdrop of a high prevalence of CV disease in the MM population as well as the adverse cardiac and vascular effects of MM itself. <h3>Conclusions and Relevance</h3> This review provides an overview of the incidences, clinical presentations, and mechanisms of CV complications in the MM population. We conclude that more research is needed for better screening and preventive strategies to abrogate these toxic effects and improve patient care.
Axial tubule junctions control rapid calcium signaling in atria
Authors: Sören Brandenburg, Tobias Kohl, George S.B. Williams, Konstantin Gusev, Eva Wagner, Eva A. Rog-Zielinska, Elke Hebisch, Miroslav Dura, Michael Didié, Michael Gotthardt, Viacheslav O. Nikolaev, Gerd Hasenfuss, Peter Kohl, Christopher W. Ward, W. Jonathan Lederer, Stephan E. Lehnart
Journal: Journal of Clinical Investigation (2016)

The canonical atrial myocyte (AM) is characterized by sparse transverse tubule (TT) invaginations and slow intracellular Ca2+ propagation but exhibits rapid contractile activation that is susceptible to loss of function during hypertrophic remodeling. Here, we have identified a membrane structure and Ca2+-signaling complex that may enhance the speed of atrial contraction independently of phospholamban regulation. This axial couplon was observed in human and mouse atria and is composed of voluminous axial tubules (ATs) with extensive junctions to the sarcoplasmic reticulum (SR) that include ryanodine receptor 2 (RyR2) clusters. In mouse AM, AT structures triggered Ca2+ release from the SR approximately 2 times faster at the AM center than at the surface. Rapid Ca2+ release correlated with colocalization of highly phosphorylated RyR2 clusters at AT-SR junctions and earlier, more rapid shortening of central sarcomeres. In contrast, mice expressing phosphorylation-incompetent RyR2 displayed depressed AM sarcomere shortening and reduced in vivo atrial contractile function. Moreover, left atrial hypertrophy led to AT proliferation, with a marked increase in the highly phosphorylated RyR2-pS2808 cluster fraction, thereby maintaining cytosolic Ca2+ signaling despite decreases in RyR2 cluster density and RyR2 protein expression. AT couplon "super-hubs" thus underlie faster excitation-contraction coupling in health as well as hypertrophic compensatory adaptation and represent a structural and metabolic mechanism that may contribute to contractile dysfunction and arrhythmias.
Lichen amyloidosus as a sweat gland/duct-related disorder: resolution associated with restoration of sweating disturbance
Authors: Y. Shimoda, Y. Sato, Y. Hayashida, Y. Yamazaki, Y. Mizukawa, K. Nakajima, T. Shiohara, Y. Aoyama
Journal: British Journal of Dermatology (2016)

Although a number of pathological processes resulting in amyloid deposition have been described in lichen amyloidosus (LA), no attention has been paid to the involvement of sweat glands/ducts in the pathogenesis of LA. According to recent studies, follicular structures are usually spared in serial histological sections of LA, and deposits of amyloid are likely to be confined to areas that display xerosis, suggesting that decreases in skin wetness by sweating disturbance seem to initiate LA. To investigate whether sweating disturbance could represent an early event that triggers LA, and whether resolution of LA could be induced by restoring the sweating disturbance. By using the impression mould technique, which allows an accurate quantification of individual sweat glands/ducts actively delivering sweat, we examined sweat responses to thermal stimulus in LA lesions before and after treatment with a moisturizer. Sweating disturbance was most profoundly detected in the ‘hub’ structure of the LA papule, and this disturbance due to leakage of sweat could be restored by short‐term treatment with a moisturizer, particularly when used under occlusion. This study was limited by the relatively small sample size. Treatment of LA should be primarily directed at preventing leakage of sweat into the dermis or epidermis and therefore sweat delivery to the skin surface could be made easier.
Harnessing bacteriocin biology as targeted therapy in the GI tract
Authors: Sushma Kommineni, Christopher J. Kristich, Nita H. Salzman
Journal: Gut Microbes (2016)

Recently, our laboratory demonstrated that bacteriocins produced by commensal enterococci provide an advantage in niche maintenance in the highly competitive environment of the gastrointestinal (GI) tract. Bacterial production of bacteriocins is a conserved defense strategy to help establish an ecological niche. Bacteriocin-encoding genes in enterococci are often carried on mobile genetic elements, including conjugative plasmids, enabling the transfer of such traits to other community members in a shared niche. Use of a novel mouse model for enterococcal colonization of the GI tract allowed us to investigate enterococcal dynamics and the role of enterococcal bacteriocins in the mouse GI tract. We examined the role of bacteriocin-21, carried on the pPD1 plasmid, in enterococcal colonization of the gut. We discovered that Enterococcus faecalis (EF) harboring pPD1 effectively colonizes the GI tract by using Bac-21 to eliminate its competition. In our study, we also present evidence for active conjugation in the GI tract, a strategy EF uses to enhance the number of bacteriocin producers in a given niche and eliminate bacteriocin-susceptible populations. Using an engineered strain of EF that is capable of producing Bac-21 but impaired in its conjugation ability, we were able to reduce pre-existing colonization by vancomycin-resistant enterococci in the mouse gut. Thus, our results suggest a novel therapeutic strategy to de-colonize antibiotic-resistant enterococci from the GI tract of patients and thereby prevent the emergence of resistant enterococcal infections that are otherwise difficult, or impossible, to treat.