tbuckley/cabot-search huggingface dataset:
Alternating versus continuous “FOLFIRI” in advanced colorectal cancer (ACC): A randomized “GISCAD” trial
Authors: R. Labianca, I. Floriani, E. Cortesi, L. Isa, A. Zaniboni, M. Marangolo, L. Frontini, S. Barni, G. D. Beretta, A. Sobrero
Journal: Journal of Clinical Oncology (2006)

3505 Background: In ACC “FOLFIRI” is one of the standard regimens and is able to obtain about 40% response rate (RR) with an overall survival (OS) of 17–18 months. Experimental studies (Sobrero, 2000) indicate that an alternating chemotherapy could delay the appearance of cell resistance and reduce the therapeutic load for patients (pts). Methods: In order to evaluate whether intermittent “FOLFIRI” (CPT-11: 180 mg/sqm d1 + l-folinic acid -FA: 100 mg/sqm in 2 hr + 5fluorouracil-5FU: 400 mg/sqm bolus + 600 mg/sqm 22 hr infusion, d 1 and 2 every 2 weeks, for 2 months on and 2 months off) (arm A) was at least as effective as continuous “FOLFIRI” (same regimen, every month) (arm B), until progression in both arms, 336 pts from 27 Centers were randomised from 7/2001 to 6/2005. The characteristics of pts were: median age 64 years (r 29–75), males 214 (63%), PS 0: 222 (66%), liver mets only 166 (49%), multiple mts including liver 80 (24%). Results: RR was 29% in arm A and 35% in arm B, with a median progression-free survival (PFS) of 8.8 and 7.3 months respectively (HR = 1.00, 95% CI: 0.74 - 1.36). At a median follow-up of 27 months, median overall survival (OS), the primary endpoint of the trial, was 16.9 months in arm A and 17.6 in arm B (HR = 1.11, 95% CI: 0.83 - 1.48). Toxicity was acceptable and similar in the 2 arms (WHO grade 3–4 toxicity: neutropenia in 12% pts, diarrhoea in 11%, nausea/vomiting in 4% and fatigue in 3%). Conclusions: Our results demonstrate that alternating “FOLFIRI” obtains the same survival as a continuous treatment, thus reducing the discomfort to pts and the economic costs. No significant financial relationships to disclose.
ELECTIVE INTRA-AORTIC BALLOON PUMP VERSUS OPTIMAL MEDICAL THERAPY FOR HIGH-RISK PERCUTANEOUS CORONARY INTERVENTION
Authors: Hasan Javed, Nauman Khalid, Rebecca Torguson, Cheng Zhang, Evan Shlofmitz, Yuefeng Chen, Anees Musallam, Jaffar Khan, Toby Rogers, Hayder Dhafir Hashim, Chava Chezar-Azerrad, Charan Yerasi, Itsik Ben-Dor, Brian Forrestal, Brian Case, Nelson L. Bernardo, Ron Waksman
Journal: Journal of the American College of Cardiology (2020)
REGRESSION OF SEVERE LEFT VENTRICLE HYPERTROPHY AFTER MEDICAL TREATMENT OF GLUCOCORTICOID-SUPPRESSIBLE PRIMARY ALDOSTERONISM
Authors: Luiz Aparecido Bortolotto, Raif R. Simao, Marcus Agrela, Madson Q. Almeida, Maria C.B.V. Fragoso
Journal: Journal of the American College of Cardiology (2020)
COMPARISON OF LEFT TRANSRADIAL AND TRANSFEMORAL ACCESS FOR CORONARY ANGIOGRAPHY IN PATIENTS WITH PRIOR CORONARY ARTERY BYPASS GRAFTS: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Tanawan Riangwiwat, Nath Limpruttidham, Narut Prasitlumkum, Gregory Walter Yost
Journal: Journal of the American College of Cardiology (2020)
Quality of life (QOL) and cognitive status among irradiated brain tumor survivors treated with donepezil or placebo.
Authors: Doug Case, Michelle Joy Naughton, Volker W. Stieber, Gerald K. Bayer, Paul A. Bilodeau, Dennis Frederic Moore, Steven Charles Falchuk, Burton M. Needles, James Piephoff, William Jeffery Edenfield, Jeffrey K. Giguere, Nicholette Erickson, Monica Elena Loghin, Edward G. Shaw, Stephen R. Rapp
Journal: Journal of Clinical Oncology (2013)

2051 Background: Cognitive problems after cancer therapy can decrease QOL. This phase III randomized trial tested the effect of donepezil (5-10 mg daily for 24 weeks) on cognition and QOL in brain cancer patients. Methods: Between 2/2008-12/2011, 198 (99 placebo; 99 donepezil) adult primary and metastatic brain tumor survivors &gt; 6 months post radiation (&gt; 30 Gy) were recruited at 24 sites affiliated with the Wake Forest CCOP Research Base, 3 CTSU sites, and M.D. Anderson. Outcomes were assessed at baseline, 12 and 24 weeks. Regression analyses examined the association of demographics, fatigue (FACIT-Fatigue), and a cognitive performance composite score (CC) (comprised of the Controlled Oral Word Association Test, Hopkins Verbal Learning Test-Revised, Digit Span Test, Trail Making Test A&amp;B, Rey-Osterreith Complex Figure-modified, Grooved Pegboard) on QOL, measured by the FACT-Brain (FACT-Br) total score. Results: Participants had a median age of 55, were predominantly female (54%) and non-Hispanic White (91%), with a median time from diagnosis of 38 months. Study completion was 74%. At 12 and 24 weeks, treatment had no significant effect on QOL, unadjusted and adjusted for race/ethnicity, age, sex, fatigue, baseline FACT-Br, and baseline CC. However, for those below the median on the baseline FACT-Br subscale (i.e., greater cognitive symptoms), donepezil was associated with higher (better) post-tx FACT-Br total scores (p =0.004), unadjusted for covariates. After adjustment for covariates, donepezil was borderline significantly associated with higher post-tx QOL (p=0.052). Improvement in QOL was associated with being female (p=0.017) and less baseline fatigue (p=0.005). For participants with baseline FACT-Br subscale scores above the median, only lower baseline FACT-Br total scores (p=0.015) were significantly related to greater improvements in FACT-Br. Donepezil treatment was not significant (p=0.48). Conclusions: The impact of donepezil on QOL was greater in survivors with more cognitive symptoms at baseline, although the results were borderline significant. Fatigue continued to be a major factor in lower QOL. Other interventions to better manage survivors’ symptoms are needed. Clinical trial information: NCT00369785.
Computational limits don't fully explain human cognitive limitations
Authors: Ernest S Davis, Gary F Marcus
Journal: Behavioral and Brain Sciences (2020)

Abstract The project of justifying all the limits and failings of human cognition as inevitable consequences of strategies that are actually “optimal” relative to the limits on computational resources available may have some value, but it is far from a complete explanation. It is inconsistent with both common observation and a large body of experimentation, and it is of limited use in explaining human cognition.
Vitamin D Metabolism Is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease
Authors: David A. Jolliffe, Christos Stefanidis, Zhican Wang, Nazanin Z. Kermani, Vassil Dimitrov, John H. White, John E. McDonough, Wim Janssens, Paul Pfeffer, Christopher J. Griffiths, Andrew Bush, Yike Guo, Stephanie Christenson, Ian M. Adcock, Kian Fan Chung, Kenneth E. Thummel, Adrian R. Martineau
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Vitamin D deficiency is common in patients with asthma and chronic obstructive pulmonary disease (COPD). Low 25-hydroxyvitamin D (25[OH]D) levels may represent a cause or a consequence of these conditions.Objectives: To determine whether vitamin D metabolism is altered in asthma or COPD.Methods: We conducted a longitudinal study in 186 adults to determine whether the 25(OH)D response to six oral doses of 3 mg vitamin D3, administered over 1 year, differed between those with asthma or COPD versus control subjects. Serum concentrations of vitamin D3, 25(OH)D3, and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) were determined presupplementation and postsupplementation in 93 adults with asthma, COPD, or neither condition, and metabolite-to-parent compound molar ratios were compared between groups to estimate hydroxylase activity. Additionally, we analyzed 14 datasets to compare expression of 1α,25(OH)2D3-inducible gene expression signatures in clinical samples taken from adults with asthma or COPD versus control subjects.Measurements and Main Results: The mean postsupplementation 25(OH)D increase in participants with asthma (20.9 nmol/L) and COPD (21.5 nmol/L) was lower than in control subjects (39.8 nmol/L; P = 0.001). Compared with control subjects, patients with asthma and COPD had lower molar ratios of 25(OH)D3-to-vitamin D3 and higher molar ratios of 1α,25(OH)2D3-to-25(OH)D3 both presupplementation and postsupplementation (P ≤ 0.005). Intergroup differences in 1α,25(OH)2D3-inducible gene expression signatures were modest and variable if statistically significant.Conclusions: Attenuation of the 25(OH)D response to vitamin D supplementation in asthma and COPD associated with reduced molar ratios of 25(OH)D3-to-vitamin D3 and increased molar ratios of 1α,25(OH)2D3-to-25(OH)D3 in serum, suggesting that vitamin D metabolism is dysregulated in these conditions.
INDEX PD/PA PROVIDES EFFECTIVE RISK STRATIFICATION IN PATIENTS DEFERRED BASED ON NON-ISCHEMIC FFR
Authors: Linle Hou, Kulin Shah, Bobby Ghosh, Mohan Mallikarjuna Rao Edupuganti, Naga Venkata Pothineni, Ahmed A. Almomani, Jason J. Payne, Zubair Ahmed, Sabha Bhatti, Barry F. Uretsky, Abdul Hakeem
Journal: Journal of the American College of Cardiology (2020)
AMPLIFICATION OF INFLAMMATORY AND HEMOSTATIC DYSREGULATION RESPONSES IN ATRIAL FIBRILLATION PATIENTS WITH END-STAGE RENAL DISEASE
Authors: Alyssandra Abrenica, Meriam Ben Hadj Tahar, Emily Bontekoe, Debra A. Hoppensteadt, Mushabbar A. Syed, Vinod Bansal, Jawed Fareed
Journal: Journal of the American College of Cardiology (2020)
Abstract 15567: Short-Term Effect on Cardiac Biomarkers of Initiation of Sacubitril/Valsartan in Hospitalized Patients With Heart Failure and Reduced Ejection Fraction: Results of the Transition Study
Authors: Domingo Pascual-Figal, Michele Senni, Jan Belohlavek, Dmytro Butylin, Adele Noe, Weibin Bao, Rolf Wachter
Journal: Circulation (2018)

Introduction: The benefit of sacubitril/valsartan (S/V) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is associated with a reduction of biomarkers of myocardial stret...
Abstract 14611: Trans-Catheter Septal Myectomy for Hypertrophic Cardiomyopathy: Results From an Innovative Design and Testing
Authors: Jiheum Park, Arnar Geirsson, Pramod Bonde
Journal: Circulation (2018)

Introduction: Surgical myectomy is highly invasive and sometimes a residual gradient means doing a re-do sternotomy with added morbidity and mortality. A trans catheter septal myectomy can greatly ...
Epithelial-mesenchymal transition markers in metastatic transitional cell carcinoma (mTCC) patients under vinflunine treatment.
Authors: Felipe Sacristan, Guadalupe Aparicio, Enrique Grande, Mar Haz-Conde, Vanessa Medina Villaamil, Angelica Figueroa, Manuel Valladares Ayerbes, Luis M. Antón Aparicio
Journal: Journal of Clinical Oncology (2013)

e15532 Background: Vinflunine (VFL) demonstrated in vitro antiproliferative effects in human tumour cell lines, and in vitro antitumor activities against subcutaneous tumour xenografts. Recently, we demonstrated that VFL causes these effects through tubulin instability, which is one of the leading intracellular molecular process that drives epithelial-mesenchymal transition (EMT). In addition, VFL may induce up-regulation in expression levels of E-cadherin/N-cadherin cocient. Methods: The study included a retrospective analysis of 18 patients with mTCC treated with carboplatin-based chemotherapy. The patients who demonstrated objective response (38.8%) continued with vinflunine 320 mg/m 2 one day every three weeks until progression. EMT protein expression (E-cadherin, beta-catenin, vimentin, CK18) was evaluated by Western blotting and also by immunohistochemistry (IHQ). Results: Overall mean age of patients was 71 years. The median overall survival was 3.5 years for the carboplatin-based chemotherapy (95% CI, 0.377-3.623). In patients treated with VFL, it was demonstrated a correlation of performance status and overall response with the histological type and age. We also found a relationship between different EMT markers in patients that received VFL. Conclusions: The above data provide evidence for an intrincate mechanism by which VFL could stop the transition from epithelial cells to the invasive mesenchymal phenotype. Molecular mechanism of Snail, Slug, Twist and Hakai will be reported.
HOW AN IMAGE CAN SOLVE THE CASE: RARE SOURCE OF INTRACARDIAC EMBOLI
Authors: Zackary Tushak, Jaideep Patel, Aaron Schatz, Rajiv Ashok Kabadi, Taha Al-Jubaishi, Taeshik Park, Antonio Abbate, Phoebe Ashley
Journal: Journal of the American College of Cardiology (2020)
IN VIVO IMAGING OF THE CULPRIT PLAQUES WITH HISTOPATHOLOGY-DERIVED CHOLESTEROL CRYSTAL IN PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Hiroshi Ueda, Yusuke Nishida, Motoyoshi Maenaka, Kojiro Yoshimura, Hideshi Ishii, Seiji Matsuhisa, Naohiro Yoshida, Yukiko Kuga, Kazuya Ueda, Yasunori Nishida
Journal: Journal of the American College of Cardiology (2020)
LONG-TERM INCIDENCE OF THROMBOEMBOLISM AND MAJOR BLEEDING IN PATIENTS WHO UNDERWENT CATHETER ABLATION FOR ATRIAL FIBRILLATION: JACRE-EX REGISTRY
Authors: Koichi Inoue, Koichiro Kumagai, Keizo Hirao, Masaomi Kimura, Yasushi Miyauchi, Eiki Tsushima, Mitsuru Ohishi, Masahiro Yasaka, Hirosuke Yamaji, Keisuke Ohkawa, Manabu Fujimoto, Itsuro Morishima, Takanao Mine, Wataru Shimizu, Masatsugu Ohe, Ken Okumura
Journal: Journal of the American College of Cardiology (2020)
TRENDS, PREDICTORS AND IMPACT OF ARRHYTHMIAS IN CARDIAC AMYLOIDOSIS: A 16-YEAR ANALYSIS (1999-2014)
Authors: Ameesh Isath, Deepak Padmanabhan, Stuthi Perimbeti, Bharat Narasimhan, Ashish Correa, Claire Huang Lucas, Anwar Chahal, Davendra Mehta
Journal: Journal of the American College of Cardiology (2020)
DUAL RVAD-ECMO CIRCUITS TO TREAT CARDIOGENIC SHOCK AND PROFOUND HYPOXEMIA DUE TO NECROTIZING LUNG INFECTION
Authors: Andrew Rosenbaum, Kyle Bohman, John Stulak, Richard Daly, Allan Klompas, Atta Behfar, Suraj Yalamuri
Journal: Journal of the American College of Cardiology (2020)
Genetic Pathways in Nonalcoholic Fatty Liver Disease: Insights From Systems Biology
Authors: Silvia Sookoian, Carlos J. Pirola, Luca Valenti, Nicholas O. Davidson
Journal: Hepatology (2020)

Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning worldwide epidemic whose etiology reflects multiple interactions between environmental and genetic factors. Here, we review the major pathways and dominant genetic modifiers known to be relevant players in human NAFLD and which may determine key components of the heritability of distinctive disease traits including steatosis and fibrosis. In addition, we have employed general assumptions which are based on known genetic factors in NAFLD to build a systems biology prediction model that includes functional enrichment. This prediction model highlights additional complementary pathways that represent plausible intersecting signaling networks that we define here as an NAFLD-Reactome. We review the evidence connecting variants in each of the major known genetic modifiers (variants in patatin-like phospholipase domain containing 3, transmembrane 6 superfamily member 2, membrane-bound O-acyltransferase domain containing 7, glucokinase regulator, and hydroxysteroid 17-beta dehydrogenase 13) to NAFLD and expand the associated underlying mechanisms using functional enrichment predictions, based on both preclinical and cell-based experimental findings. These major candidate gene variants function in distinct pathways, including substrate delivery for de novo lipogenesis; mitochondrial energy use; lipid droplet assembly, lipolytic catabolism, and fatty acid compartmentalization; and very low-density lipoprotein assembly and secretion. The NAFLD-Reactome model expands these pathways and allows for hypothesis testing, as well as serving as a discovery platform for druggable targets across multiple pathways that promote NAFLD development and influence several progressive outcomes. In conclusion, we summarize the strengths and weaknesses of studies implicating selected variants in the pathophysiology of NAFLD and highlight opportunities for future clinical research and pharmacologic intervention, as well as the implications for clinical practice.
A retrospective safety analysis of adult patients treated with high-dose methotrexate for osteosarcoma in Stockholm, Sweden.
Authors: Daniel Alm, Christina Linder Stragliotto, Annika Folin, Jonas Bergh, Theodoros Foukakis
Journal: Journal of Clinical Oncology (2012)

10083 Background: Patients with osteosarcoma are routinely treated with pre- and post-operative chemotherapy that includes high-dose methotrexate. The treatment is associated with a risk of severe renal and hepatic toxicity. Methods: All patients with osteosarcoma that had received at least one cycle of high-dose methotrexate at the adult oncology department, Karolinska University Hospital were retrospectively identified. Treatment toxicity, including hematologic, renal, hepatic toxicity, infections and oral mucositis were registered and graded according to CTCAE v 4.0. A possible relationship between methotrexate blood concentration and toxicity was investigated. Results: Sixteen eligible patients that had received a total of 103 cycles of high-dose methotrexate were identified. Ten patients experienced a severe hepatic toxicity, (Grade 3, n=5 and Grade 4, n=5). Grade 3 renal toxicity was seen in one patient and although reversible, it led to treatment interruption. Reversible, grade 2 elavation of serum creatinine occured in 5 cases. Four grade 3 infections were seen in 2 patients and 8 patients had at least one occurrence of Grade 3 oral mucositis. Thrombocytopenia was a common event (Grade 3, n=5 and Grade 4, n=2) but no severe bleeding complications were observed. One patient died as a result of multi-organ failure two days after methotrexate administration. Methotrexate blood concentration at 24 hours from administration could predict for renal toxicity (p&lt;0.005, by chi-square test), but not for other toxicity. Conclusions: High-dose methotrexate in adult patients with osteosarcoma was frequently associated with severe, however reversible toxicity.
A prospective registry study assessing decision impact and patient outcomes following gene-expression profiling for tumor-site origin.
Authors: Irina Degtiar, Raji Pillai, Gerald Colvin, Mikhail Shtivelband, Qianyi Li, William David Henner, Shawn Becker, John C. Hornberger
Journal: Journal of Clinical Oncology (2013)

e22172 Background: A retrospective registry study has shown that gene-expression profiling (GEP) of the tissue of origin (Pathwork Tissue of Origin Test) of metastatic or poorly differentiated cancer changes the working diagnosis and management for the majority of patients. The FDA-cleared GEP test determines similarity of tumors of uncertain origin to gene expression patterns representing 60 morphologies in 15 cancer types. Inability to identify cancer primary sites presents challenges for patient treatment, outcomes, and prognosis. This study aims to prospectively assess impact of GEP on physician decisions and patient outcomes. Methods: A prospective, observational study is examining GEP’s impact on treatment changes and outcomes in adult patients with difficult-to-diagnose cancers. The study is assessing changes in diagnosis, management, oncologist confidence and perception of the test’s clinical utility, survival, therapy response, and other outcomes over 2 years of follow-up. Results before and after GEP are presented here for 18 patients. The study is designed to enroll 300 patients overall. Results: The primary working diagnosis changed for 37% of patients: 4 whose physicians obtained a working diagnosis while previously not having a tissue-specific diagnosis, and 3 for whom the primary diagnosis changed. After GEP, all patients had a working diagnosis. At least one aspect of management plans changed for 65% patients after GEP. Chemotherapy was ordered for 2 more patients and the regimen changed for 3 others; surgery was performed for 4 fewer, radiation for 1 fewer, and hospice for 2 more patients. After obtaining results from GEP, 58% of the treating oncologists “agreed” or “strongly agreed” that they were confident in both their diagnosis and treatment. Seventy-two percent believed that their changes in management would lead to improvement in at least one outcome (survival, response rate, time to relapse, quality of life, or patient anxiety). Conclusions: Current results of this prospective study are consistent with results of the prior retrospective study: GEP significantly changed and improved physician confidence in their diagnosis and treatment. Clinical trial information: NCT01649453.
THE ROLE OF NON-INVASIVE IMAGING IN TAKAYASU ARTERITIS ASSOCIATED WITH ATYPICAL ANGINA AND SILENT MYOCARDITIS
Authors: Julio Francisco Mamani-Tito, Nilda Espinola-Zavaleta, Sergio A. Zuñiga-Mendoza, Erick Alexanderson Rosas
Journal: Journal of the American College of Cardiology (2020)
Make mission impossible successful: clip-with-line traction facilitates difficult pancreatic duct cannulation in a patient with duodenal duplication
Authors: Wei-hui Liu, Zhao-shen Li, Dong Wang
Journal: Endoscopy (2020)

We describe a novel clip-with-line traction method to rescue a difficult pancreatic cannulation that failed with traditional techniques during endoscopic retrograde cholangiopancreatography (ERCP) in a patient with duodenal duplication ([Video 1]).
Hepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation
Authors: Thoetchai (Bee) Peeraphatdit, Jennifer Wang, Matthew A. Odenwald, Shaomin Hu, John Hart, Michael R. Charlton
Journal: Hepatology (2020)

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are an immunotherapy for the treatment of many advanced malignancies. The advent of ICIs has been a major breakthrough in the field of oncology, a fact recognized by the 2018 Nobel Prize in Physiology or Medicine being awarded for the discovery. The Food and Drug Administration approved the first ICI, ipilimumab, in 2011 for the treatment of metastatic melanoma. Seven ICIs are now used in clinical practice, including nivolumab and pembrolizumab for treatment of advanced hepatocellular carcinoma. ICIs are increasingly used across the spectrum of hepatobiliary neoplasia. The utility of ICI therapy has been limited by immune-related adverse reactions (irAEs) affecting multiple organ systems. Hepatotoxicity is an important irAE, occurring in up to 16% of patients receiving ICIs. Optimizing outcomes in patients receiving ICI therapy requires awareness of and familiarity with diagnosing and management of ICI-induced immune-mediated hepatotoxicity (IMH), including approaches to treatment and ICI dose management. The aim of this review article is to (1) provide a comprehensive, evidence-based review of IMH; (2) perform a systematic review of the management of IMH; and (3) present algorithms for the diagnosis and management of IMH.
ATHEROSCLEROTIC CARDIOVASCULAR DISEASE EVENT RATES AMONG ADULTS WITH CHRONIC KIDNEY DISEASE TAKING MODERATE- OR HIGH-INTENSITY STATINS ACCORDING TO THEIR RISK CATEGORY IN THE 2018 AHA/ACC BLOOD CHOLESTEROL GUIDELINE
Authors: Bharat Poudel, Robert S. Rosenson, Vera Bittner, Orlando Gutiérrez, Amanda Anderson, Mark Woodward, Rajat Deo, April Carson, Katherine Mues, Paul Dluzniewski, Bernard Jaar, Claudia M. Lora, Jonathan Taliercio, Paul Muntner, Lisandro Colantonio
Journal: Journal of the American College of Cardiology (2020)