tbuckley/cabot-search huggingface dataset:
Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation
Authors: Emmanuel Gabriel, Kristopher Attwood, William Du, Rebecca Tuttle, Raed M. Alnaji, Steven Nurkin, Usha Malhotra, Steven N. Hochwald, Moshim Kukar
Journal: JAMA Surgery (2015)

While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS).To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status.A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed.The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality.A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22).Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.
Planning and reporting of quality-of-life outcomes in cancer trials
Authors: S. Schandelmaier, K. Conen, E. von Elm, J.J. You, A. Blümle, Y. Tomonaga, A. Amstutz, M. Briel, B. Kasenda, S. Schandelmaier, K. Conen, E. von Elm, J.J. You, A. Blümle, Y. Tomonaga, R. Saccilotto, A. Amstutz, T. Bengough, J.J. Meerpohl, M. Stegert, K.K. Olu, K.A.O. Tikkinen, I. Neumann, A. Carrasco-Labra, M. Faulhaber, S.M. Mulla, D. Mertz, E.A. Akl, X. Sun, D. Bassler, J.W. Busse, I. Ferreira-González, F. Lamontagne, A. Nordmann, V. Gloy, H. Raatz, L. Moja, R. Rosenthal, S. Ebrahim, P.O. Vandvik, B.C. Johnston, M.A. Walter, B. Burnand, M. Schwenkglenks, L.G. Hemkens, H.C. Bucher, G.H. Guyatt, M. Briel, B. Kasenda
Journal: Annals of Oncology (2015)
Prevalence of ultrasound synovial inflammatory findings in healthy subjects
Authors: Ilaria Padovano, Félicie Costantino, Maxime Breban, Maria Antonietta D'Agostino
Journal: Annals of the Rheumatic Diseases (2015)

To evaluate the prevalence of joint inflammatory abnormalities and erosions detected by grey-scale and Doppler ultrasound (US) in the small joints of hands and feet in healthy subjects.US of the dorsal surface of 32 joints (10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal (MTP) and 2 wrists) was performed in 207 healthy subjects without joint symptom. Synovial effusion (SE), synovial hypertrophy (SH) and power Doppler (PD) signal were scored using a semiquantitative grading scale (0-3) and erosion binary.One-hundred and eighty-two subjects had at least one US abnormality: 52% of the subjects had SE alone, 13% SH alone (5% with and 8% without PD) and 35% both SH and SE. US findings were detected in 9% of the total joints examined, mostly in the feet, and in particular in the MTP1 (33% of the positive joints). SE was the most frequently detected finding (68% of the positive joints), followed by SH (31%). Severity was mild (grade 1 in average) whatever the finding recorded (SH, SE or PD). Four erosions were detected (MTP1).This study describes for the first time, in a large cohort of healthy subjects, the prevalence and location of US signs of joint inflammation and of structural damage in small joints of hands and feet. US abnormalities were quite common, and mostly located in the feet. Further studies are needed to define which US components may allow to discriminate between pathological and physiological findings in the joints commonly affected by inflammatory arthritis conditions.
2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction
Authors: Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Henry H. Ting, Patrick T. O’Gara, Frederick G. Kushner, Deborah D. Ascheim, Ralph G. Brindis, Donald E. Casey, Mina K. Chung, James A. de Lemos, Deborah B. Diercks, James C. Fang, Barry A. Franklin, Christopher B. Granger, Harlan M. Krumholz, Jane A. Linderbaum, David A. Morrow, L. Kristin Newby, Joseph P. Ornato, Narith Ou, Martha J. Radford, Jacqueline E. Tamis-Holland, Carl L. Tommaso, Cynthia M. Tracy, Y. Joseph Woo, David X. Zhao
Journal: Circulation (2016)

regions, sexes, ethnicities, intellectual perspectives/biases, and scopes of clinical practice, and by inviting organizations and professional societies with related
Is it an E lesion or stage IV? An unsettled issue in Hodgkin's disease staging.
Authors: J M Connors, P Klimo
Journal: Journal of Clinical Oncology (1984)

To determine whether recognized experts in the area of Hodgkin's disease would agree on the determination of stage when various types of extranodal disease are present, we asked senior investigators at 15 major centers to assign a stage to four different patients. In general, these experts agreed in cases representing the extremes of difference between localized and distant extranodal disease. However, when presented with patients with nearby but not contiguous extranodal disease of lung or bone, one half of the experts classified this as an E lesion and one half as stage IV. This disagreement in stage assignment has implications not only for individual patient treatment, but also for reporting of clinical trials. Over-assignment of stage IV has the practical result of "improving" the results of treatment of both low stage (by removing higher risk patients) and advanced stage patients (by including better risk patients). Papers reporting the results of treatment of Hodgkin's disease should include information concerning how patients with extranodal disease were separated into those with E lesions and those with stage IV disease.
Guiding Principles for Diabetes Care
Authors: William T. Cefalu, Jane L. Chiang
Journal: Diabetes Care (2015)

With the use of editorial commentaries over recent years, our editorial team has provided significant comments and updates at routine intervals regarding our progress as a leading diabetes journal. Many of the editorials were geared to addressing specific areas of science, providing discussion on clinical care or clinical research focus in a particular issue, or informing readers of new initiatives. With this issue of Diabetes Care , we want to provide comment on the process by which we acquire, gain, and put into practice recommendations based on new evidence, or when the evidence is not quite complete, how we make practice decisions based on the best evidence to date from consensus. Specifically, we are referring to the dissemination of recent updates from the American Diabetes Association (ADA) in the form of position statements, scientific statements, and consensus reports (proceedings from ADA Consensus Conferences). It has been a special privilege for our journal to publish these important narratives.

In this regard, this issue is particularly noteworthy as two comprehensive narratives (a consensus report and a scientific statement) are included that provide an enhanced focus on the advances in pathophysiology and pathways for development of therapies for type 1 diabetes. In addition, an ADA position statement provides an update on disease management and policy recommendations for students with diabetes in the elementary and secondary school settings. The updates in these particular areas not only provide important clinical information but also complement extremely well the special article collection in Diabetes Care (June 2015) entitled “Type 1 Diabetes at a Crossroads” (1). In that issue, the journal specifically focused on issues pertaining to type 1 diabetes and published articles that commented on the latest update from studies, opinions, and perspectives in the field.

The fact that this issue highlights three specific narratives from the …
The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota
Authors: Jérôme Boursier, Olaf Mueller, Matthieu Barret, Mariana Machado, Lionel Fizanne, Felix Araujo‐Perez, Cynthia D. Guy, Patrick C. Seed, John F. Rawls, Lawrence A. David, Gilles Hunault, Frédéric Oberti, Paul Calès, Anna Mae Diehl
Journal: Hepatology (2015)

Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Fifty-seven patients with biopsy-proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism.NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre-/probiotics therapies.
Friday, 16 July 2010
Authors: M. Popovici, V. Kobets, N. Ciobanu, V. Ivanov, I. Popovici, L. Ciobanu, I. Moraru, M. Chiusa, F. Seifriz, F. Timolati, T. Suter, C. Zuppinger, S. Zbinden, A. Zoccarato, N. Surdo, M. Berrera, M. Zaccolo, I. Daissormont, M. Lipp, E. Biessen
Journal: Cardiovascular Research (2010)
Transition rates between amyloid and neurodegeneration biomarker states and to dementia: a population-based, longitudinal cohort study
Authors: Clifford R Jack, Terry M Therneau, Heather J Wiste, Stephen D Weigand, David S Knopman, Val J Lowe, Michelle M Mielke, Prashanthi Vemuri, Rosebud O Roberts, Mary M Machulda, Matthew L Senjem, Jeffrey L Gunter, Walter A Rocca, Ronald C Petersen
Journal: The Lancet Neurology (2015)
Distal Symmetric Polyneuropathy
Authors: Brian C. Callaghan, Raymond S. Price, Eva L. Feldman
Journal: JAMA (2015)

Peripheral neuropathy is a highly prevalent and morbid condition affecting 2% to 7% of the population. Patients frequently experience pain and are at risk of falls, ulcerations, and amputations. We aimed to review recent diagnostic and therapeutic advances in distal symmetric polyneuropathy, the most common subtype of peripheral neuropathy.Current evidence supports limited routine laboratory testing in patients with distal symmetric polyneuropathy. Patients without a known cause should undergo a complete blood cell count, comprehensive metabolic panel, vitamin B12 measurement, serum protein electrophoresis with immunofixation, fasting glucose measurement, and glucose tolerance test. The presence of atypical features such as asymmetry, non-length dependence, motor predominance, acute or subacute onset, and prominent autonomic involvement should prompt a consultation with a neurologist or neuromuscular specialist. Electrodiagnostic tests and magnetic resonance imaging of the neuroaxis contribute substantial cost to the diagnostic evaluation, but evidence supporting their use is lacking. Strong evidence supports the use of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, and voltage-gated calcium channel ligands in the treatment of neuropathic pain. More intensive glucose control substantially reduces the incidence of distal symmetric polyneuropathy in patients with type 1 diabetes but not in those with type 2 diabetes.The opportunity exists to improve guideline-concordant testing in patients with distal symmetric polyneuropathy. Moreover, the role of electrodiagnostic tests needs to be further defined, and interventions to reduce magnetic resonance imaging use in this population are needed. Even though several efficacious medications exist for neuropathic pain treatment, pain is still underrecognized and undertreated. New disease-modifying medications are needed to prevent and treat peripheral neuropathy, particularly in type 2 diabetes.
Gene amplification in a leukemic patient treated with methotrexate.
Authors: R C Horns, W J Dower, R T Schimke
Journal: Journal of Clinical Oncology (1984)

Resistance to methotrexate (MTX) has been shown in mouse, hamster, and human cell lines grown in sequentially increased MTX concentrations to be due to increased dihydrofolate reductase (DHFR) synthesis and a proportional increase in DHFR gene copy number. Leukemia cells of a patient were studied to assess change in DHFR gene copy number after MTX treatment. The patient presented with chronic myeloid leukemia which rapidly evolved into blast crisis; 90% of peripheral white cells were lymphoblasts. Treatment included intrathecal and intravenous MTX; the lymphoblasts were reduced to undetectable levels. Three months later a second blast crisis occurred; 90% of peripheral white cells were lymphoblasts. Cells from each blast crisis were obtained by leukapheresis and stored for study. Quantification of DHFR gene copy number in DNA from lymphoblasts before and after MTX treatment was done: a radiolabeled cloned cDNA constituting the mouse DHFR coding sequence was used to probe high molecular weight pretreatment and posttreatment DNA bound to nitrocellulose filters. Posttreatment DNA contained two- to three-fold more DHFR gene sequences than pretreatment DNA. Quantitative Southern blotting of EcoRI-digested pretreatment and posttreatment DNA confirmed amplification of the DHFR gene. Karyotype analysis showed no double minute chromosomes or homogeneously staining regions. This is the first study demonstrating DHFR gene amplification in leukemia cells sampled in vivo from a patient treated with MTX.
Identification of<i>BRAF</i>Kinase Domain Duplications Across Multiple Tumor Types and Response to RAF Inhibitor Therapy
Authors: Samuel J. Klempner, Rodolfo Bordoni, Kyle Gowen, Henry Kaplan, Philip J. Stephens, Sai-Hong Ignatius Ou, Siraj M. Ali
Journal: JAMA Oncology (2015)

This case report profiles a patient with advanced parotid gland cancer with BRAF kinase domain duplication whose disease responded to RAF-directed therapy; comprehensive genomic profiling identified this phenomenon across multiple tumor types.
Genetic Mechanisms Controlling the Induction of Polysubstrate Monooxygenase (P-450) Activities
Authors: D W Nebert, H J Eisen, M Negishi, M A Lang, L M Hjelmeland, A B Okey
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
A Dominant Evolutionary Theme Emerges to Better Predict Clinical Outcomes for Cancer
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2015)

Despite the decades long battle since the “war on cancer” was first declared, major breakthroughs toward improving clinical outcomes have remained elusive. Now, with advanced sequencing, scientists have increasingly entered the fray from an evolutionary perspective toward cancer in the hopes of gaining new insights. Chen and He (2015) have used a new computational approach to show that as tumors evolve, no matter what the tissue or cell type, a dominant theme has emerged. Those that are trending toward a more primitive, or embryonic stem cell (ESC) state—have a worse clinical outcome. The authors applied their systems biology approach to study global gene expression profiles from 107 cells types, and in more than 3,000 tumors representing 18 different types of solid tumor cancers. The authors performed their analysis and showed that, regardless of the origins of the tissue, this common and robust pattern emerged. Like in ancient times, where despite the distance, all roads led to Rome, they showed that the distance to the ESC state may represent a robust and predictive measurement for various types of cancer. This is in line with a cancer evolution model recently demonstrated by the same group that cancer is a reverse evolutionary process back to the unicellular “ground state” by erasing multicellularity-associated cellular features. “The essence of Darwin’s theory is that evolution is driven by purposeless mutations that are subsequently selected by environments, so there is often no predefined destination in organismal evolution,” said He. “In this study, we showed that, distinct from organismal evolution, cancers of various types evolve toward a predefined cellular destination, a finding with implications to both evolutionary biology and cancer prognosis.” For cancer evolution, regardless of the environment, the predefined final destination is the ESC state, and the closer the evolutionary distance, the poorer the prognosis.
Diagnosis of Peanut Allergy Using Component-Resolved Diagnosis in Asian Population From A Country with Low Prevalence
Authors: Sadudee Boonmee, Narissara Suratannon, Jarungchit Ngamphaiboon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee
Journal: Journal of Allergy and Clinical Immunology (2013)
Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6
Authors: Elizabeth K. Ziemke, Joseph S. Dosch, Joel D. Maust, Amrith Shettigar, Ananda Sen, Theodore H. Welling, Karin M. Hardiman, Judith S. Sebolt-Leopold
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The emerging need for rational combination treatment approaches led us to test the concept that cotargeting MEK and CDK4/6 would prove efficacious in KRAS-mutant (KRASmt) colorectal cancers, where upregulated CDK4 and hyperphosphorylated retinoblastoma (RB) typify the vast majority of tumors. Experimental Design: Initial testing was carried out in the HCT-116 tumor model, which is known to harbor a KRAS mutation. Efficacy studies were then performed with five RB+ patient-derived colorectal xenograft models, genomically diverse with respect to KRAS, BRAF, and PIK3CA mutational status. Tolerance, efficacy, and pharmacodynamic evaluation of target modulation were evaluated in response to daily dosing with either agent alone or concurrent coadministration. Results: Synergy was observed in vitro when HCT-116 cells were treated over a broad range of doses of trametinib and palbociclib. Subsequent in vivo evaluation of this model showed a higher degree of antitumor activity resulting from the combination compared to that achievable with single-agent treatment. Testing of colorectal patient-derived xenograft (PDX) models further showed that combination of trametinib and palbociclib was well tolerated and resulted in objective responses in all KRASmt models tested. Stasis was observed in a KRAS/BRAF wild-type and a BRAFmt model. Conclusions: Combination of trametinib and palbociclib was well tolerated and highly efficacious in all three KRAS-mutant colorectal cancer PDX models tested. Promising preclinical activity seen here supports clinical evaluation of this treatment approach to improve therapeutic outcome for patients with metastatic colorectal cancer. Clin Cancer Res; 22(2); 405–14. ©2015 AACR.
Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors.
Authors: J H Lundberg, R M Hansen, C R Chitambar, C A Lawton, M Gottlieb, T Anderson, R C Ash
Journal: Journal of Clinical Oncology (1991)

Twenty-two patients, ages 16.6 to 43.9 years (median age, 30 years), with relapsed or refractory lymphoma were treated by allogeneic bone marrow transplantation after high-dose chemotherapy with or without total body irradiation (TBI). Seven patients had Hodgkin's disease, four had low-grade histology non-Hodgkin's lymphoma (NHL), seven had intermediate-grade NHL, and four had high-grade NHL. Of the 22 patients, 17 received T-cell (CD-3)-depleted marrow after intensive pretransplant chemoradiotherapy, and five received T-cell-replete grafts after chemotherapy-based preparative regimens. Five patients were transplanted from donors other than genotypically HLA-identical siblings: four from partially HLA-matched relatives, and one from a phenotypically HLA-identical unrelated donor. Acute graft-versus-host disease (GVHD) was less than or equal to grade II in all patients, and chronic GVHD was limited or absent in all but one patient. Of the 21 assessable patients, 17 (80.9%) achieved complete remissions. Death due to transplant-associated complications occurred in five patients, and five patients have relapsed. Thirteen patients are alive, and 12 are continuously relapse-free at a median follow-up of longer than 28 months (range, greater than 10 to greater than 58 months) from transplant. The cumulative probability of treatment failure from relapse or progression of lymphoma was 29% (95% confidence interval [CI], 12% to 51%), while the actuarial lymphoma-free (ie, event-free) survival plateau is 54.6% (95% CI, 34% to 76%). For young patients with advanced malignant lymphoma, allogeneic bone marrow transplantation appears superior to salvage chemotherapy for achievement of long-term, lymphoma-free survival and may be preferable to autologous bone marrow transplantation for selected patients.