tbuckley/cabot-search huggingface dataset:
Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT)
Authors: Sarah Hewlett, Celia Almeida, Nicholas Ambler, Peter S Blair, Ernest H Choy, Emma Dures, Alison Hammond, William Hollingworth, Bryar Kadir, John Richard Kirwan, Zoe Plummer, Clive Rooke, Joanna Thorn, Nicholas Turner, Jon Pollock
Journal: Annals of the Rheumatic Diseases (2019)

To see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone.Multicentre, 2-year randomised controlled trial in RA adults (fatigue severity>6/10, no recent major medication changes). RAFT (Reducing Arthritis Fatigue: clinical Teams using CB approaches) comprises seven sessions, codelivered by pairs of trained rheumatology occupational therapists/nurses. Usual care was Arthritis Research UK fatigue booklet. Primary 26-week outcome fatigue impact (Bristol RA Fatigue Effect Numerical Rating Scale, BRAF-NRS 0-10). Intention-to-treat regression analysis adjusted for baseline scores and centre.308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect -0.59, 95% CI -1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total -3.42 (95% CI -6.44 to -0.39), Living with Fatigue -1.19 (95% CI -2.17 to -0.21), Emotional Fatigue -0.91 (95% CI -1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect -0.49 (95% CI -0.83 to -0.14), BRAF MDQ Total -2.98 (95% CI -5.39 to -0.57), Living with Fatigue -0.93 (95% CI -1.75 to -0.10), Emotional Fatigue -0.90 (95% CI -1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored > 8/10 vs 54% controls rating usual care booklet (p<0.0001).Multiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches.ISRCTN52709998.
A comparison of elderly versus nonelderly patients in the CRITICS gastric cancer trial.
Authors: Astrid E Slagter, Benjamín Tudela, Romy van Amelsfoort, Karolina Sikorska, Johanna W. van Sandick, Cornelis J. H. Van De Velde, Nicole C.T. van Grieken, Pehr A. Lind, Marianne Nordsmark, Hein Putter, Elma Meershoek – Klein Kranenbarg, Edwin PM Jansen, Annemieke Cats, Marcel Verheij
Journal: Journal of Clinical Oncology (2019)

81 Background: Although the proportion of elderly cancer patients (pts) increases, few randomized trials provide separate results on this group. Here, we present a sub-analysis of the CRITICS trial, comparing elderly with non-elderly pts. Methods: Preoperative (preop) chemotherapy (CT) included three cycles of epirubicin, cisplatin/oxaliplatin and capecitabine (ECC/EOC); pts were upfront randomized between postoperative (postop) CT (3x ECC/EOC) and chemoradiotherapy (CRT; 45Gy + cisplatin/capecitabine). Elderly pts were defined as age ≥ 70 years at the time of randomization. We present tolerability and outcomes for elderly versus non-elderly pts. Results: Details on baseline characteristics, preop treatment, surgery, postop treatment and survival are shown in Table 1. Tumor type and localization did not differ between both groups. Conclusions: Age had a significant impact on toxicity and tolerability of preop CT, but did not affect surgical resection rates and complications. Although less elderly pts started postop treatment and elderly pts received lower dose in de CT arm, there were no differences in treatment related toxicities. Survival was not significantly different. Clinical trial information: NCT00407186. [Table: see text]
How Do ASH Guidelines Panels Make Decisions? Association between Decision Making Factors and the Strength of Recommendations
Authors: Benjamin Djulbegovic, Tea Reljic, Shira Elqayam, Adam Cuker, Iztok Hozo, Qi Zhou, Shelly-Anne Li, Paul Alexander, Nieuwlaat Robby, Wojtek Wiercioch, Holger Schünemann, Gordon Guyatt
Journal: Blood (2018)
Cardioprotection in cancer therapy: novel insights with anthracyclines
Authors: Inbar Raber, Aarti Asnani
Journal: Cardiovascular Research (2019)

Anthracyclines are a class of antineoplastic agents that remain critical to modern-day cancer treatment. However, their propensity to cause cardiotoxic effects limits their use and can cause increased morbidity and mortality among patients with cancer. Currently available methods to minimize the impact of anthracycline cardiotoxicity have not been widely successful. While it is largely accepted that the generation of oxygen radicals contributes to the development of anthracycline cardiotoxicity, the exact mechanisms of cardiomyocyte injury remain unclear. In this review, we discuss the current state of basic and translational research on the cardiotoxic mechanisms of anthracyclines that have led to the discovery of new therapeutic targets. Pending validation in patient populations, these recent advances have the potential to be translated into clinical approaches that will minimize anthracycline cardiotoxicity and improve outcomes in cancer survivors.
Machine Learning-based Development and Validation of a Scoring System for Screening High-Risk Esophageal Varices
Authors: Tien S Dong, Amir Kalani, Elizabeth S Aby, Long Le, Kayti Luu, Meg Hauer, Rahul Kamath, Keith D Lindor, James H Tabibian
Journal: Clinical Gastroenterology and Hepatology (2019)
Association of Left Ventricular Ejection Fraction and Symptoms With Mortality After Elective Noncardiac Surgery Among Patients With Heart Failure
Authors: Benjamin J. Lerman, Rita A. Popat, Themistocles L. Assimes, Paul A. Heidenreich, Sherry M. Wren
Journal: JAMA (2019)

<h3>Importance</h3> Heart failure is an established risk factor for postoperative mortality, but how left ventricular ejection fraction and heart failure symptoms affect surgical outcomes is not fully described. <h3>Objectives</h3> To determine the risk of postoperative mortality among patients with heart failure at various levels of echocardiographic (left ventricular systolic dysfunction) and clinical (symptoms) severity compared with those without heart failure and to evaluate how risk varies across levels of surgical complexity. <h3>Design, Setting, and Participants</h3> US multisite retrospective cohort study of all adult patients receiving elective, noncardiac surgery in the Veterans Affairs Surgical Quality Improvement Project database from 2009 through 2016. A total of 609 735 patient records were identified and analyzed with 1 year of follow-up after having surgery (final study follow-up: September 1, 2017). <h3>Exposures</h3> Heart failure, left ventricular ejection fraction, and presence of signs or symptoms of heart failure within 30 days of surgery. <h3>Main Outcome and Measure</h3> The primary outcome was postoperative mortality at 90 days. <h3>Results</h3> Outcome data from 47 997 patients with heart failure (7.9%; mean [SD] age, 68.6 [10.1] years; 1391 women [2.9%]) and 561 738 patients without heart failure (92.1%; mean [SD] age, 59.4 [13.4] years; 50 862 women [9.1%]) were analyzed. Compared with patients without heart failure, those with heart failure had a higher risk of 90-day postoperative mortality (2635 vs 6881 90-day deaths; crude mortality risk, 5.49% vs 1.22%; adjusted absolute risk difference [RD], 1.03% [95% CI, 0.91%-1.15%]; adjusted odds ratio [OR], 1.67 [95% CI, 1.57-1.76]). Compared with patients without heart failure, symptomatic patients with heart failure (n = 5906) had a higher risk (597 deaths [10.11%]; adjusted absolute RD, 2.37% [95% CI, 2.06%-2.57%]; adjusted OR, 2.37 [95% CI, 2.14-2.63]). Asymptomatic patients with heart failure (n = 42 091) (2038 deaths [crude risk, 4.84%]; adjusted absolute RD, 0.74% [95% CI, 0.63%-0.87%]; adjusted OR, 1.53 [95% CI, 1.44-1.63]), including the subset with preserved left ventricular systolic function (1144 deaths [4.42%]; adjusted absolute RD, 0.66% [95% CI, 0.54%-0.79%]; adjusted OR, 1.46 [95% CI, 1.35-1.57]), also experienced elevated risk. <h3>Conclusions and Relevance</h3> Among patients undergoing elective noncardiac surgery, heart failure with or without symptoms was significantly associated with 90-day postoperative mortality. These data may be helpful in preoperative discussions with patients with heart failure undergoing noncardiac surgery.
Abstract 16605: Intraventricular Vortex Interaction Between Transmitral Flow and Paravalvular Leak
Authors: Daisuke Morisawa, Eleonora Avenatti, Stephen H Little, Arash Kheradvar
Journal: Circulation (2017)

Introduction: Paravaluvular leak (PVL) is an important complication of transcatheter aortic valve replacement (TAVR). Despite its marked clinical impact, no previous study has reported how PVL affe...
Abstract P146: Serum Magnesium and Mortality in the General US Population: Results From the NHANES I Epidemiologic Follow-up Study
Authors: Xi Zhang, Jin Xia, Liana C. Del Gobbo, Adela Hruby, Ka He, Qi Dai, Yiqing Song
Journal: Circulation (2016)

Introduction: Low magnesium (Mg) intake and/or status has been associated with increased risk of chronic disease, including cardiovascular disease (CVD) and cancer. However, whether and to what extent low serum Mg levels are associated with all-cause or cause-specific mortality in the general population is uncertain. Hypothesis: We aimed to quantify the dose-response associations between low concentrations of serum Mg and mortality from all causes, cancer, CVD, and stroke in the general US population. Methods: We analyzed prospective data on 14,353 participants aged 25-74 years with baseline measures of serum Mg concentrations from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study 1971-2006. We estimated the mortality hazard ratios (HRs) for participants within predefined and clinically meaningful categories of serum Mg levels, including &lt;0.7, 0.7-0.74, 0.75-0.79, 0.8-0.9 (normal reference), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L, using Cox proportional hazards models. Restricted cubic spline models were applied to examine potentially nonlinear relationships between serum Mg and mortality. Results: During a mean follow-up of 27.6 years, 7,072 deaths occurred, 3,310 (47%) CVD deaths, 1,533 (22%) cancer deaths, and 281 (4%) stroke deaths. Twenty-one percent of all participants had low levels of serum Mg (&lt;0.8 mmol/L) and 1.5% had extremely low serum Mg (&lt;0.7 mmol/L). Age-adjusted all-cause mortality rates were 3845, 3491, 3471, 3400 (normal reference), 3531, 3525, and 3836 per 100,000 person-years for increasing categories of serum Mg; the HRs and 95% confidence intervals for increasing serum Mg were 1.32 (1.02-1.72), 0.93 (0.74-1.16), and 1.06 (0.96-1.18), 1.07 (0.97-1.18), 0.94 (0.77-1.13), and 0.93 (0.72-1.21), compared to the reference group (0.8-0.9 mmol/L). An L-shaped association between serum Mg concentrations and all-cause mortality was observed after adjusting for potential confounders (Figure). No statistically significant associations were observed between serum Mg and cancer, CVD, or stroke mortality. Conclusions: Very low serum Mg levels were significantly associated with all-cause mortality in the general US population. Our findings support the hypothesis that Mg deficiency as defined by very low serum Mg may have an important influence on mortality.
Targeted Assessment of <i>G0S2</i> Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma
Authors: Dipika R. Mohan, Antonio Marcondes Lerario, Tobias Else, Bhramar Mukherjee, Madson Q. Almeida, Michelle Vinco, Juilee Rege, Beatriz M. P. Mariani, Maria Claudia N. Zerbini, Berenice B. Mendonca, Ana Claudia Latronico, Suely K. N. Marie, William E. Rainey, Thomas J. Giordano, Maria Candida B. V. Fragoso, Gary D. Hammer
Journal: Clinical Cancer Research (2019)

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients with locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of patients with homogeneously rapidly recurrent or fatal disease bear a unique CpG island hypermethylation phenotype, "CIMP-high." We sought to identify a biomarker that faithfully captures this subgroup.Experimental Design: We analyzed ACC-TCGA data to characterize differentially regulated biological processes, and identify a biomarker that is methylated and silenced exclusively in CIMP-high ACC. In an independent cohort of 114 adrenocortical tumors (80 treatment-naive primary ACC, 22 adrenocortical adenomas, and 12 non-naive/nonprimary ACC), we evaluated biomarker methylation by a restriction digest/qPCR-based approach, validated by targeted bisulfite sequencing. We evaluated expression of this biomarker and additional prognostic markers by qPCR.We show that CIMP-high ACC is characterized by upregulation of cell cycle and DNA damage response programs, and identify that hypermethylation and silencing of G0S2 distinguishes this subgroup. We confirmed G0S2 hypermethylation and silencing is exclusive to 40% of ACC, and independently predicts shorter disease-free and overall survival (median 14 and 17 months, respectively). Finally, G0S2 methylation combined with validated molecular markers (BUB1B-PINK1) stratifies ACC into three groups, with uniformly favorable, intermediate, and uniformly dismal outcomes.G0S2 hypermethylation is a hallmark of rapidly recurrent or fatal ACC, amenable to targeted assessment using routine molecular diagnostics. Assessing G0S2 methylation is straightforward, feasible for clinical decision-making, and will enable the direction of efficacious adjuvant therapies for patients with aggressive ACC.
Phase I study of tramatinib combined with sorafenib in patients (pts) with advanced hepatocellular cancer (HCC).
Authors: Emilie Wang, Dae Won Kim, Amit Mahipal, Dung-Tsa Chen, Biwei Cao, Fadzai Masawi, Richard D. Kim
Journal: Journal of Clinical Oncology (2019)

431 Background: RAS/RAF/MEK/ERK (MAPK) signaling pathway is associated with proliferation, progression, and survival of HCC. Preclinical data suggests that activation of MAPK pathway may be one of resistant mechanisms of sorafenib, and the combination of MEK inhibitor and sorafenib can induce synergistic anticancer activity in HCC. We evaluated the safety and efficacy of trametinib (MEK inhibitor) combined with sorafenib in HCC. Methods: This was a phase I single center study with standard 3+3 design for pts with treatment naïve advanced HCC. The primary endpoints are determining dose limiting toxicities (DLT) and maximum tolerated dose (MTD). Secondary endpoints include overall survival (OS), progression free survival (PFS), and disease control rate (DCR). Initial plan was to enroll pts in 4 escalating dose levels (dl)—trametinib 1mg daily (qd)/sorafenib 200mg twice daily (bid)(dl 1), trametinib 1.5mg qd/sorafenib 200mg bid (dl 2), trametinib 1.5mg qd/sorafenib 400mg bid (dl 3), trametinib 2mg qd/sorafenib 400mg bid (dl 4). Eligible pts had advanced unresectable HCC, ECOG PS 1, Child-Pugh Score 6, and adequate organ function. Results: 17 pts were treated in 3 different dl of trametinib and sorafenib (3 in dl 1, 8 in dl 2, and 6 in dl 3). Median age was 65 years (range 40-80) with 64.7% male. All pts were evaluated for toxicity, but only 15 were evaluable for DLT. 2 pts were replaced as they came off of study within 1 month (1 pt in dl 3 due to varices unrelated to the study drug, 1 pt in dl 2 for voluntary withdrawal due to side effects). DLT was noted in dl 3 with 2 pts (grade 4 hypertension (HTN) and grade 3 elevated (elev) of bilirubin/AST/ALT &gt; 7 days). Most common grade 3/4 treatment related adverse events were elev AST (47.1%), HTN (23.5%), elev Alk Phos (17.6%), elev ALT (5.9%), elev bilirubin (5.9%), and diarrhea (5.9%). The median PFS was 4.0 months (mo), and median OS was 5.8 mo. 11 pts were evaluable for response after cycle 2 (8 stable disease (SD), 2 disease progression (PD), 1 partial response). 3 pts were evaluable for response after cycle 4 (1 SD, 2 PD). DCR was 63.6%. Conclusions: Trametinib and sorafenib can be safely administered up to trametinib 1.5mg qd and sorafenib 200mg bid for pts with advanced HCC. Clinical trial information: NCT02292173.
Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer
Authors: Mary L. Disis, Matthew H. Taylor, Karen Kelly, J. Thaddeus Beck, Michael Gordon, Kathleen M. Moore, Manish R. Patel, Jorge Chaves, Haeseong Park, Alain C. Mita, Erika P. Hamilton, Christina M. Annunziata, Hans Juergen Grote, Anja von Heydebreck, Jaspreet Grewal, Vikram Chand, James L. Gulley
Journal: JAMA Oncology (2019)

<h3>Importance</h3> Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy. <h3>Objective</h3> To assess the efficacy and safety of avelumab, an anti–programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer. <h3>Design, Setting, and Participants</h3> In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018. <h3>Intervention</h3> Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study. <h3>Main Outcomes and Measures</h3> Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression–based analyses, and safety. <h3>Results</h3> A total of 125 women (median age, 62.0 years [range, 27-84 years]) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 [13.6%]), diarrhea (15 [12.0%]), and nausea (14 [11.2%]). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 [2.4%]) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred. <h3>Conclusions and Relevance</h3> Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01772004
Unconventional ST2- and CD127-negative lung ILC2 populations are induced by Alternaria
Authors: Kellen J. Cavagnero, Jana H. Badrani, Luay H. Naji, Michael B. Amadeo, Veranca S. Shah, Karina N. Roman, Suzanna S. Gasparian, Taylor A. Doherty
Journal: Journal of Allergy and Clinical Immunology (2019)
Prospective comparative study of endoscopic ultrasonography-guided fine-needle biopsy and unroofing biopsy.
Authors: Sung Kwan Shin, Jun Chul Park, Eun Hye Kim, Sang Kil Lee, Yong Chan Lee
Journal: Journal of Clinical Oncology (2019)

38 Background: Adequate tissue acquisition is important in making treatment decisions for patients with upper gastrointestinal subepithelial tumors (SETs). This study aimed to compare the outcomes of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) with those of the unroofing biopsy technique. Methods: This study was a single-center, prospective comparative study conducted at Severance Hospital, Yonsei University College of Medicine. A total of 39 patients with SETs ≥15 mm were enrolled between January 2016 and August 2017. Results: Of the 39 patients, 28 underwent biopsy with both techniques (4 underwent only unroofing and 7 underwent only EUS-FNB). The mean tumor size was 21.0 mm (median, 19.0 mm; 15.0–45.0 mm). Histological diagnosis was made with EUS-FNB in 64.3% and with unroofing biopsy in 78.6% (p = 0.344), and immunohistochemical diagnosis was made with EUS-FNB in 46.4% and unroofing biopsy in 67.9% (p = 0.180). In the subgroup analysis (28 patients), there was no significant difference in diagnostic yield between the 2 methods. The mean procedural time with EUS-FNB was shorter than that with unroofing biopsy (p &lt; 0.001). The larger SET (≥ 20 mm) (p = 0.035) and satisfaction of procedure (p = 0.019) were positively associated with successful histological diagnosis by EUS-FNB. No complications were reported with both methods. Conclusions: There was no significant difference in the histological diagnostic yield for SETs between the EUS-FNB and unroofing biopsy techniques. Further study is needed to confirm the efficacy of EUS-FNB and unroofing biopsy in a larger study population. Clinical trial information: NCT02646241.
Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8 <sup>+</sup> T cells
Authors: Lelisa F. Gemta, Peter J. Siska, Marin E. Nelson, Xia Gao, Xiaojing Liu, Jason W. Locasale, Hideo Yagita, Craig L. Slingluff, Kyle L. Hoehn, Jeffrey C. Rathmell, Timothy N. J. Bullock
Journal: Science Immunology (2019)

In the context of solid tumors, there is a positive correlation between the accumulation of cytotoxic CD8
A Mendelian Randomization Approach for Assessing the Relationship Between Physical Activity and Depression
Authors: Adam Mourad Chekroud
Journal: JAMA Psychiatry (2019)

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Epigenetic Drift in Colorectal Cancer—It's Probably Later Than You Think
Authors: Carmen Sapienza
Journal: Cancer Research (2019)

Abstract The analysis of age-related methylation changes in patients with colorectal cancer indicates that tumors have their origins earlier in life than previously suspected. The implication is that healthy lifestyle modifications designed to prevent colorectal cancer should be adopted early in life. See related article by Luebeck et al., p. 495