tbuckley/cabot-search huggingface dataset:
Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data
Authors: Naaheed Mukadam, Andrew Sommerlad, Jonathan Huntley, Gill Livingston
Journal: The Lancet Global Health (2019)

Nine potentially modifiable risk factors (less childhood education, midlife hearing loss, hypertension, and obesity, and later-life smoking, depression, physical inactivity, social isolation, and diabetes) account for 35% of worldwide dementia, but most data to calculate these risk factors come from high-income countries only. We aimed to calculate population attributable fractions (PAFs) for dementia in selected low-income and middle-income countries (LMICs) to identify potential dementia prevention targets in these countries.The study was an analysis of cross-sectional data obtained from the 10/66 Dementia Research surveys of representative populations in India, China, and six Latin America countries (Cuba, Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela), which used identical risk factor ascertainment methods in each country. Between 2004 and 2006 (and between 2007 and 2010 for Puerto Rico), all residents aged 65 years and older in predefined catchment areas were invited to participate in the survey. We used risk factor prevalence estimates from this 10/66 survey data, and relative risk estimates from previous meta-analyses, to calculate PAFs for each risk factor. To account for individuals having overlapping risk factors, we adjusted PAF for communality between risk factors, and used these values to calculate overall weighted PAFs for India, China, and the Latin American sample.The overall weighted PAF for potentially modifiable risk factors for dementia was 39·5% (95% CI 37·5-41·6) in China (n=2162 participants), 41·2% (39·1-43·4) in India (n=2004), and 55·8% (54·9-56·7) in our Latin American sample (n=12 865). Five dementia risk factors were more prevalent in these LMICs than worldwide estimates, leading to higher PAFs for dementia: less childhood education (weighted PAF of 10·8% in China, 13·6% in India, and 10·9% in Latin America vs 7·5% worldwide), smoking (14·7%, 6·4%, and 5·7%, respectively, vs 5·5% worldwide), hypertension (6·4%, 4·0%, and 9·3%, vs 2·0%), obesity (5·6%, 2·9%, and 7·9%, vs 0·8%), and diabetes (1·6%, 1·7%, and 3·2%, vs 1·2%).The dementia prevention potential in India, China, and this sample of Latin American countries is large, and greater than in high-income countries. Less education in early life, hypertension, hearing loss, obesity, and physical inactivity have particularly high PAFs and could be initial targets for dementia prevention strategies.No funding.
Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice
Authors: Lindsey E. Roeker, Christopher P. Fox, Toby A. Eyre, Danielle M. Brander, John N. Allan, Stephen J. Schuster, Chadi Nabhan, Brian T. Hill, Nirav N. Shah, Frederick Lansigan, Maryam Yazdy, Bruce D. Cheson, Nicole Lamanna, Arun K. Singavi, Catherine C. Coombs, Paul M. Barr, Alan P. Skarbnik, Mazyar Shadman, Chaitra S. Ujjani, Hande H. Tuncer, Allison M. Winter, Joanna Rhodes, Colleen Dorsey, Hannah Morse, Charlene Kabel, John M. Pagel, Annalynn M. Williams, Ryan Jacobs, Andre Goy, Sivraj Muralikrishnan, Laurie Pearson, Andrea Sitlinger, Neil Bailey, Anna Schuh, Amy A. Kirkwood, Anthony R. Mato
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.
FRI-380-Factors and models for predicting posthepatectomy liver failure in patients undergoing hepatic resection for hepatocellular carcinoma
Authors: So-hyun Kim, Jonggi Choi, Gwang Hyun Choi, Danbi Lee, Ju Hyun Shim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee, Kang Mo Kim
Journal: Journal of Hepatology (2019)
Risk assessment in children presenting with fever and chemotherapy-induced neutropenia.
Authors: Kristen Schratz, Melissa Beauchemin, Zhezhen Jin, Alice Lee, Maria Luisa Sulis
Journal: Journal of Clinical Oncology (2015)

10078 Background: Febrile neutropenia (FN) is a common complication of cancer treatment and predisposes children to develop severe infections. The purpose of this study was to identify clinical and laboratory factors predictive of a serious infectious complication in pediatric cancer patients with FN. Methods: A retrospective cohort study was performed in 188 children admitted for management of 381 episodes of febrile neutropenia. The primary outcome was development of a severe infectious complication (SIC), which included an infection diagnosed by clinical exam, a proven bacterial infection of the blood, urine or other sterile site or a radiologically diagnosed infection. Twenty-five variables assessable at the time of presentation to the oncology clinic or emergency department were analyzed for significance, and included patient-specific, treatment-related and episode-specific variables, as well as complete blood count results. Results: The cohort’s mean age was 8.4 years. The underlying diagnosis was a solid tumor in 57.1%, and a hematologic malignancy in 42.9% of patients. The rate of SIC was 30.6% with the most prevalent complication being bacteremia in 49% of those. Of the episodes of bacteremia gram-negative bacilli were isolated in 58.6%. Factors identified in univariate analysis to be significant predictors were maximum temperature, leukocyte count, hemoglobin level, platelet count, baseline disease activity and hypotension. Multivariate regression analysis identified relapsed or advanced disease status, presence of hypotension and degree of leukopenia as significant predictors for a SIC. Conclusions: This study identifies several predictors of SIC in pediatric patients with FN, which will enable the development of a prediction model to distinguish patients at low risk of developing SIC. Risk stratification will allow for the design of a prospective safe outpatient management for the low-risk group.
Identifying driver mutations in squamous cell lung cancer (SCC): The Lung Cancer Genomics Ireland (LCGI) study.
Authors: Shereen Rafee, Sinead Toomey, Yasir Elamin, Aoife Carr, Kathy Gately, Stephen Finn, Siobhan Nicholson, Sinead Cuffe, John Crown, Patrick G. Morris, William Grogan, Oscar S. Breathnach, Elaine Kay, Anthony O'Grady, Bryan Hennessy, Kenneth O'Byrne
Journal: Journal of Clinical Oncology (2015)

11078 Background: Targeting oncogenic drivers has transformed the care of lung adenocarcinoma. However, there is no approved targeted therapy for lung SCC. LCGI aims to identify potential targets in lung SCC. Methods: The LCGI study is being carried out in patients with surgically resected lung SCC. We used the platform of Sequenom’s MassArray to perform genotyping for 548 somatic hotspot mutations in 49 genes including genes in the MAPK and PI3K pathways. We also evaluated FGFR1 amplification by fluorescence in situ hybridization (FISH) and MET protein expression by immunohistochemistry (IHC). Results: Lung SCCs from 201 patients have been tested by Sequenom MassArray to date. Lung SCCs from 150 patients have been evaluated for MET protein expression and 89 for FGFR1 amplification. 134 (66.7%) patients were male. The median age of the cohort was 68. The majority of patients were either current (32.8%) or former (64.2%) smokers at the time of diagnosis. 104 (57.1%) were stage I, 68 (33.8%) were stage II, 29 (14.5%) were stage III SCCs. At least one aberrant, potentially targetable oncogene was identified in the SCC of 81 (40.3%) patients (see Table). The presence of PIK3CA or KRAS mutations, or FGFR1 amplification did not have a statistically significant impact on median overall survival or recurrence-free survival. However, the presence of two or more aberrations in driver oncogenes in a tumor (patients, n = 19) was associated with a worse median overall survival compared to patients with either a single driver aberration (p = 0.04) or no aberrations (p < .001). Conclusions: 40.3% of lung SCC patients have an aberrant, potentially targetable driver oncogene in their tumor. The presence of two or more aberrant oncogenes is a poor prognostic factor. These findings can be used to guide clinical trials in lung SCC. Frequency of driver mutations in LCGI compared to The Cancer Genome Atlas (TCGA) study. Mutation LCGI (n = 201) TCGA (n = 178) FGFR1 amp (n = 89) 12.4% 16.8% PIK3CA 12.4% 10.1% KRAS 6.5% 0.6% PTPN11 4% 1.7% STK11 1.9% 1.7% MYC 1.9% 0.0% NRAS 1.5% 0.0% BRAF 1.5% 3.9% HRAS 1.5% 1.7% CTNNB1 1.5% 1.7% FBXW7 1.5% 3.4% MET Overexpression (n = 150) 1.3% NA EGFR 0.9% 2.8% AKT1 0.5% 0.6% CDK4 0.5% 0.0% GNA11 0.5% 0.6% MAP2K1 0.5% 0.6% DDR2 0% 1.1%
FRI-118-Decreased cognitive performance is associated with reduced resting state connectivity and gray matter atrophy in patients with minimal hepatic encephalopathy
Authors: Raquel Garcia-Garcia, Juan José Gallego, Alvaro Javier Cruz-Gómez, María Pilar Ballester, Alba Mangas-Losada, Amparo Urios, Cristina Forn, Desamparados Escudero-García, Joan Tosca, César Ávila, Vicente Belloch, Vicente Felipo, Carmina Montoliu
Journal: Journal of Hepatology (2019)
The expression quantitative trait loci (eQTLs) and their association with melanoma clinical outcomes.
Authors: Matjaz Vogelsang, Carlos N Martinez, Artur Romanchuk, Chana Hecht, Olivia Richardson, Richard L. Shapiro, Russell S. Berman, Iman Osman, Tomas Kirchhoff
Journal: Journal of Clinical Oncology (2015)

9061 Background: Prognosis of cutaneous melanoma (CM) is modulated by tumor immunogenicity, which varies on the individual level. While this suggests a contributing role of germline genetic factors, current approaches suffer from difficulties in identifying biologically relevant germline prognostic biomarkers. Recent whole-genome scans have established comprehensive maps of eQTLs (i.e. gene expression correlating germline genetic variants) across different populations and human tissues. We hypothesize that the interrogation of inherited eQTLs in cells of the immune system may reveal biologically important germline markers of CM immunogenicity and clinical outcomes. Methods: Based on our computational analyses of publicly available eQTL data, we selected 43 genetic variants most significantly correlating with expression of 41 immune-modulating genes in lymphoblastoid cell lines derived from 857 healthy female twins from Multiple Tissue Human Expression Resource. Variants were genotyped in a prospective cohort of 1022 CM patients and analysed for their association with overall and recurrence-free survival using Cox regression model, adjusted by demographic and clinical covariates. Results: We have discovered novel and highly significant association of rs6673928, an IL19 eQTL variant, with favorable CM overall survival (OS)(HR 0.54, 95% CI 0.37 to 0.79; P= 0.00087). Associations with melanoma OS were also observed for other significant eQTLs: rs6695772 (HR 1.76, 95% CI 1.21 to 2.55; P= 0.002), rs11569345 (HR 0.35, 95% CI 0.14 to 0.91; P= 0.014) and rs841718 (HR 1.75, 95% CI 1.12 to 2.72; P= 0.018) strongly correlating with expression of BATF3, CD40 and STAT6, respectively. Conclusions: Our unique approach of interrogating lymphocyte-specific eQTLs from healthy twins was notably powerful in identifying several immunomodulatory eQTL variants as novel biologically relevant predictors of CM prognosis. These data suggest that eQTL-based strategy proposed here will be highly efficient in discovering the missing germline genetic component associated with risk, outcome or therapy response in other human cancers driven by specific molecular pathways.
Factors associated with long term survival of patients with metastatic adenocarcinoma of the lung.
Authors: Doru Paul, Dennis Timony, Nina Kohn, Rosemarie Buro-Cavasinni, Mohammed Aziz, Lawrence Glassman, Haralambos Raftopoulos
Journal: Journal of Clinical Oncology (2015)

e19130 Background: Several studies have shown thattyrosine kinase inhibitors and chemotherapy (C)improve the short term and median survival of patients with metastatic adenocarcinoma of the lung (MAL) but they are silent on the long term survival (LTS). Methods: We performed a univariate retrospective analysis on 233 patients with MAL treated at our institution during 2009-2011 with up to a 5-year follow-up. Most patients received multiple treatment modalities. Overall survival was estimated using the product-limit method and compared using the log-rank test (significant results listed in the table below); patients alive at last follow-up were censored. Results: In our series, 14% of all patients (233) received erlotinib (E) as part of their treatment (33); of which 40% presented with epidermal growth factor receptor (EGFR) mutations (13). Although the 2-year and median survival were superior in patients receiving E or C, neither improved the 5-year survival rate. LTS with a better 5-year survival was only found in lung confined MAL when patients received curative surgery (S) for their disease. For the patients treated with E or C, regardless of EGFR mutations, all observed deaths occurred within 5 years. Factors associated with LTS were: sex, smoking history, S, and presence of metastatic disease confined to the lungs. Conclusions: In our univariate retrospective analysis, MAL patients, who were treated with E or C, had improved 2-year and median survival rates, but no improvement in LTS. Factors such as: surgery, metastases limited to the lungs only, female sex and never smoking were associated with LTS in MAL patients, but larger prospective studies are needed to confirm our findings. Factor Estimated Survival (% alive) at: Median Survival in months (95% CI) p-value 24 mo 60 mo Treatment E 42.4% 0.0% 18.8 (12.9, 37.0) 0.0070 No E 17.8% 10.4% 7.6 (5.9, 8.9) C 22.5% 0.0% 10.1 (8.8, 14.0) 0.0017 No C 18.1% 13.6% 2.9 (1.8, 4.0) S 18.1% 30.4% 22.2 (8.7, 53.8) 0.0002 No S 17.4% 0.0% 8.1 (6.1, 9.3) Sex Male 15.4% 0.0% 6.0 (4.6, 8.1) 0.0065 Female 25.7% 10.8% 10.1 (8.7, 15.2) Smoking Never 24.1% 11.3% 9.3 (7.8, 12.5) 0.0420 Former/Current 13.0% 0.0% 6.2 (4.3, 8.9) Lung metastases only Yes 34.9% 26.0% 9.6 (5.1, 21.4) 0.0161 No 17.5% 4.4% 8.3 (6.6, 9.7)
FRI-111-Albumin modulates endosomal TLR9 signaling in human peripheral leukocytes: A mechanism for its anti-inflammatory role in ACLF
Authors: Mireia Casulleras, José Alcaraz-Quiles, Marta Duran-Güell, Roger Flores-Costa, Esther Titos, Cristina López-Vicario, Raquel Horrillo, Montserrat Costa, Richard Moreau, Javier Fernández, Vicente Arroyo, Joan Clària
Journal: Journal of Hepatology (2019)
FRI-142-Interferon regulatory factor 5 and soluble fibrinogen-like protein 2 in hepatitis B virus related liver diseases
Authors: Xuan Hoan Nghiem, Van Tong Hoang, Bui Tien Sy, Mai Thanh Binh, C.-Thomas Bock, Nguyen Linh Toan, Huu Song Le, Thirumalaisamy P Velavan
Journal: Journal of Hepatology (2019)
PS-024-Early TIPS with covered stent versus standard treatment for acute variceal bleeding among patients with advanced cirrhosis: A randomised controlled trial
Authors: Yong Lv, Zhiping Yang, Chuangye He, Kai Li, Zhengyu Wang, Jing Niu, Wengang Guo, Wei Bai, Hongbo Zhang, Huahong Xie, Liping Yao, Jianhong Wang, Hui Chen, Qiuhe Wang, Tainlei Yu, Xulong Yuan, Enxin Wang, Dongdong Xia, Bohan Luo, Xiaomei Li, Na Han, Ying Zhu, Hongwei Cai, Jielai Xia, Zhanxin Yin, Kaichun Wu, Daiming Fan, Guohong Han
Journal: Journal of Hepatology (2019)
Circadian oscillations of cytosine modification in humans contribute to epigenetic variability, aging, and complex disease
Authors: Gabriel Oh, Karolis Koncevičius, Sasha Ebrahimi, Matthew Carlucci, Daniel Erik Groot, Akhil Nair, Aiping Zhang, Algimantas Kriščiūnas, Edward S. Oh, Viviane Labrie, Albert H. C. Wong, Juozas Gordevičius, Peixin Jia, Miki Susic, Art Petronis
Journal: Genome biology (2019)

Maintenance of physiological circadian rhythm plays a crucial role in human health. Numerous studies have shown that disruption of circadian rhythm may increase risk for malignant, psychiatric, metabolic, and other diseases.Extending our recent findings of oscillating cytosine modifications (osc-modCs) in mice, in this study, we show that osc-modCs are also prevalent in human neutrophils. Osc-modCs may play a role in gene regulation, can explain parts of intra- and inter-individual epigenetic variation, and are signatures of aging. Finally, we show that osc-modCs are linked to three complex diseases and provide a new interpretation of cross-sectional epigenome-wide association studies.Our findings suggest that loss of balance between cytosine methylation and demethylation during the circadian cycle can be a potential mechanism for complex disease. Additional experiments, however, are required to investigate the possible involvement of confounding effects, such as hidden cellular heterogeneity. Circadian rhythmicity, one of the key adaptations of life forms on Earth, may contribute to frailty later in life.
THU-147-Improvement of neutrophil function in hepatitis C patients under direct acting anti-viral treatment is associated with hemolysis parameters
Authors: Irina Komarova, Bettina Leber, Angela Horvath, Andreas Posch, Andrea Streit, Walter Spindelböck, Philipp Stiegler, Rudolf E. Stauber, Vanessa Stadlbauer
Journal: Journal of Hepatology (2019)
Implementation of a supervised exercise rehabilitation program in breast cancer survivors to improve quality of life, exercise endurance and fatigue in a rural oncology clinic.
Authors: Angela D. Adams, Rose Harris, Brian Vaughan, Sridhar Srinivasan, Jawad Sheqwara, Asit Jha
Journal: Journal of Clinical Oncology (2015)

e20615 Background: Physical and psychosocial effects of breast cancer and its treatment can be debilitating. The benefit of physical activity include decrease fatigue and improvement in overall health and wellbeing. Barriers to exercise include lack of motivation; fear of injury; decreased knowledge of exercise programs and equipment, lack of access, intimidation of joining a community gym. A hospital-based cardiac-pulmonology rehabilitation program was modified for breast cancer patients to evaluate the effectiveness of a monitored exercise program. Methods: 19 women with stages IA to IIIA breast cancer were enrolled. Average age: 64 years. Six received hormone; 3 received chemotherapy; 10 received both. Average time from completion of chemotherapy or starting of hormone to enrollment was 13 months. Patients were assessed in 3 domains – Behavioral, Clinical and Health. Patient perception of QOL and fatigue were assessed with the Dartmouth QOL Index and Fatigue Symptom. Results: See table below. 100% had improvement in minutes exercised per week. 100% had improvement in distance walked in 6 minutes. 84% reported improvement in QOL. 78% reported improvement in fatigue. Patients reported less intimidation, less fear of injury, better understanding of exercise regimens and body mechanics, and improved motivation. Conclusions: Implementation of a supervised, modified cardio-pulmonary rehabilitation program reduced physical and psychosocial effects of breast cancer and its treatment. Behavioral Domain Measure Goal Pre Intervention Post Intervention Goal Achieved Exercise Minutes/Week > 120-150 14 159 Yes Attendance Sessions/6weeks 20 NA 22 Yes Clinical Domain Measure Goal Pre Post Goal Achieved Weight lbs Maintain 189 lbs 187 lbs Yes 6-min Walk (a) Total Distance ≥ 1312ft 1190 1477 Yes (b)Improved Distance ≥ 194ft NA 286 Yes Sit to Stand Reps in 1 minute Improve by 5 14 20 Yes Health Domain Measure Goal Pre Post Goal Achieved Quality of Life Dartmouth Index < 25 23 19 Yes Fatigue Fatigue Symptom Inventory ≤ 3 4 2 Yes
A phase III study of MEDI4736 (M), an anti-PD-L1 antibody, in monotherapy or in combination with Tremelimumab (T), versus standard of care (SOC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) who have received at least two prior systemic treatment regimens (ARCTIC).
Authors: David Planchard, Mikhail Shtivelband, Kelvin Shi, Ramy Ibrahim, Marc Ballas, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

TPS8104 Background: M is a human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to programmed cell death-1 and CD-80 with high affinity and selectivity, and T is a selective human IgG2 mAb inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4). Both PD-L1 and CTLA-4 are regulators, or checkpoints, of T cell activation. Preclinical data, including mouse models of transplantable solid tumors, suggest that targeting both pathways may have additive or synergistic antitumor activity. Furthermore the Phase Ib dose-escalation/expansion study of M+T in advanced NSCLC (NCT02000947) shows a manageable safety, and early signs of clinical activity. Methods: This randomised, open label, multi-centre, phase III study (NCT02352948) is designed to evaluate the efficacy and safety of M vs SOC (gemcitabine, vinorelbine or erlotinib) in NSCLC pts with PD-L1-positive tumours (based on archival tumour sample or recent tumour biopsy) (Sub-study A), and the combination of M+T vs M or T vs SOC in NSCLC pts with PD-L1-negative tumours (Sub-study B). Eligible pts include pts (PS of 0-1) with locally advanced or metastatic NSCLC, who have received at least 2 prior treatment regimens including 1 platinum-based chemotherapy. Pts with known EGFR mutations and ALK rearrangements are not eligible. Approximately 300 pts will be randomised 1:1 in sub-study A and 600 pts in sub-study B (randomised 1:1:1:1). The primary objective is to assess the efficacy of M (PD-L1-positive) and M+T (PD-L1-negative) compared with SOC in terms of OS and PFS (per RECIST 1.1 as assessed by the Blinded Independent Central Review). Secondary objectives include objective response rate, duration of response, safety, tolerability, pharmacokinetics, immunogenicity and health-related QoL. Tumour assessments will be performed every 8 weeks (first 48 weeks) then every 12 weeks. A confirmatory scan is required following the initial demonstration of PD. Recruitment in the study is ongoing since January 2015. Clinical trial information: NCT02352948.