tbuckley/cabot-search huggingface dataset:
Long-term risks for chronic medical conditions and premature mortality in survivors of pediatric soft tissue sarcoma: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Emily L Mueller, Raymond J. Hutchinson, Pamela Goodman, Wendy M. Leisenring, Charles A. Sklar, Melissa M. Hudson, Kirsten K. Ness, Gregory T. Armstrong, Leslie L. Robison, Marilyn Stovall, Kevin C. Oeffinger, Paul C. Nathan
Journal: Journal of Clinical Oncology (2015)

10013 Background: Approximately 67% of children with soft tissue sarcoma (STS) survive 5+ years. Late mortality, subsequent malignant neoplasms (SMN), and frequency or severity of chronic medical conditions (CMC) have not been extensively assessed. Methods: The CCSS, a multi-institutional retrospective cohort study of 5+ year survivors of childhood cancer, assessed outcomes for 1,246 STS survivors and 4,023 siblings with up to five questionnaires over 14 years. Self-reported CMCs were graded using CTCAE v4.03. Cox proportional hazards models provided hazard ratios (HR) and associated 95% confidence intervals (CI) for CMC. SMNs ≥ 5 years from primary cancer diagnosis were confirmed by pathology report, medical record, or death certificate. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were generated using SEER and US mortality rates, respectively. Results: Median age at diagnosis was 8 years (range 0-20); median follow-up was 20 years (1.5-33.9). 243 survivors died, with SMR 5.3 (95% CI 4.7-6.0) and cumulative incidence 17.1% at 35 years from diagnosis. Compared with siblings, 42% of survivors reported ≥ 1 severe, disabling or life-threatening (grade 3-4) CMC (HR 3.5; 95% CI 2.9-4.2). Hearing, vision, and/or speech were the most prevalent severe chronic morbidities at 35 years post diagnosis (cumulative incidence at 35 years 17.0%, CI 14.7-19.3%), with survivors 2.6 times more likely to have experienced this CMC as compared to siblings (CI 1.8-3.8). Survivors who received radiation to the brain, head or neck (HR = 3.3, CI 1.8-6.4), pelvis (HR = 4.2, CI 2.2-7.8), or extremities (HR = 4.2, CI 2.2-8.1) were at particular risk for multiple (≥ 2) severe to life-threatening CMCs. The SIR of SMN was 5.6 (CI 4.6-7.0). The most frequent SMN was new (non-recurrent) soft tissue sarcoma (n = 22, SIR 22.6, CI 14.9-34.3), but risk was highest for the development of a secondary osteosarcoma (n = 12, SIR = 55.0, CI. 31.3-96.9). Conclusions: Survivors of pediatric STS, especially those exposed to radiation, experience significant long-term sequelae. This observation should guide long-term surveillance and inform the evolution of new therapies.
Failure to follow directions for prescription medications to save money among cancer survivors.
Authors: Ahmedin Jemal, Zhiyuan Zheng, Tengteng Wang, Xuesong Han
Journal: Journal of Clinical Oncology (2015)

9590 Background: To examine the patterns of not following prescription medication due to financial reasons among nonelderly and elderly cancer survivors in the US. Methods: The 2011 to 2013 National Health Interview Survey data was used to identity recently diagnosed ( ≤ 1 year; n = 639) and previously diagnosed (1 year; n = 8,292) cancer survivors, and individuals without a cancer history (n = 93,058). Survey questions about not following prescription medication asked whether a participant took the following measures to save money: 1) skipped medication doses; 2) took less medicine; 3) delayed filing a prescription; 4) asked doctor for lower cost medication; 5) bought prescription drugs from another country; and 6) used alternative therapies. All analyses were stratified by age (nonelderly: 18-64; elderly: 65+). Multivariable logistic regressions were fitted to estimate the adjusted percentage of individuals reporting not following prescription medication controlling for age, sex, race/ethnicity, marital status, education, number of comorbidities, health insurance, and geographic region. Results: Previously diagnosed cancer survivors were more likely to report not following prescription medication in order to save money compared to individuals without a cancer history, primarily among nonelderly cancer survivors (28.4% vs 22.8%), i.e. skipping medication doses (8.6% vs 6.7%), took less medicine (9.3% vs 7.0%), delayed filing a prescription (11.7% vs. 8.8%), asked for lower cost medicine (22.5% vs 17.2%), bought prescription drugs from another country (2.5% vs 1.9%), and used alternative therapies (6.3% vs 5.0%) to save money (all p < .05). In contrast, all recently diagnosed cancer survivors were not statistically different from individuals without a cancer history in terms of not following prescription medication due to financial reasons. Conclusions: Compared to nonelderly individuals with no history of cancer, nonelderly long time cancer survivors were less likely to follow their prescription medication as needed in order to save money.
THU-139-Real world experience of chronic hepatitis C retreatment with genotype specific regimens in non-responders to previous interferon-free therapy
Authors: Robert Flisiak, Dorota Zarębska-Michaluk, Pawel Pabjan, Iwona Orłowska, Simon Krzysztof, Magdalena Tudrujek, Ewa Janczewska, Dorota Dybowska, Marek Sitko, Witold Dobracki, Jerzy Jaroszewicz, Klapaczynski Jakub, Łukasz Laurans, Wlodzimierz Mazur, Łukasz Socha, Tronina Olga
Journal: Journal of Hepatology (2019)
Abstract 18177: Plasma Levels of Cancer Antigen-125 as a Biomarker of Paroxysmal or Persistent Atrial Fibrillation in Postmenopausal Women
Authors: Haruki Sekiguchi, Issei Ishida, Kentaro Jujo, Ken Shimamoto, Tsuyoshi Shiga, Masatoshi Kawana, Nobuhisa Hagiwara
Journal: Circulation (2016)

Introduction: Plasma cancer antigen (CA)-125 is a tumor marker that was recently shown to be associated with systolic heart failure and new-onset atrial fibrillation (AF) after myocardial infarctio...
Young patients with breast cancer: Comparison of molecular characteristics of pregnancy associated breast cancer with non-pregnancy associated breast cancer.
Authors: Zorica Tomasevic, Zoran Tomasevic, Zeljko Kovac, Zorka Milovanovic, Ivana Minic, Snezana Milosevic, Ivana Bozovic-Spasojevic, Zdravko Zdrale, Ivan Markovic, Radan Dzodic
Journal: Journal of Clinical Oncology (2015)

e12081 Background: It is known that young patients have different BC molecular characteristics: higher % of HER2 3+ and triple negative subtypes (TN), and lower % of Luminal A subtype. However, it is less known whether these BC characteristics are related only to the young patient’s age or might be related to current /recent pregnancy. The aim of this study is to analyze and compare molecular characteristics of pregnancy associated breast cancer (PABC) vs. non-PABC in patients up to 40 yrs of age. PABC subgroup is defined as BC diagnosed during or up to 36 months after pregnacy. Methods: Since January 2012 to December 2014, 39 patients with PABC (30,7% diagnosed while beeing pregnant) and 50 patients with non-PABC (54% nulliparous) were prospectively registered. Results: Median age in PABC subgroup was 32 yrs and 33 yrs in non-PABC. Median time from pregnancy in PABC subgroup was 12 months. Conclusions: There is no statistically significant difference in HER2 3+ status (28.2 vs. 34%) as well as luminal A subtype expression.(41 vs.52%).between PABC and non-PABC. However, there is striking difference in TN subtype between PABC and non-PABC, that is statistically significantly different (30,7 vs. 6.0% Fisher exact test p=0.01). Although obtain on small group of patients, results are strongly suggestive that PABC might have different mechanism of development than non-PABC. Current/recent pregnancy somehow increase susceptibility for TNBC subtype. This susceptibility seemingly, is not related to the young age itself or pregnancy if pregnancy occurred more than 36 months before BC diagnosis. BC type Luminal A HER23+ Triple negative PABC 16/39 (41%) 11/39 (28.2%) 12/39 (30.7%) non-PABC 26/50 (52%) 17/50 (34%) 3/50 (6.0%) Fisher exact test ns ns p = 0.01
HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration
Authors: Pravin U. Dugel, Adrian Koh, Yuichiro Ogura, Glenn J. Jaffe, Ursula Schmidt-Erfurth, David M. Brown, Andre V. Gomes, James Warburton, Andreas Weichselberger, Frank G. Holz
Journal: Ophthalmology (2019)

<h3>Purpose</h3> Two similarly designed phase 3 trials (HAWK and HARRIER) compared brolucizumab, a single-chain antibody fragment that inhibits vascular endothelial growth factor-A, with aflibercept to treat neovascular age-related macular degeneration (nAMD). <h3>Design</h3> Double-masked, multicenter, active-controlled, randomized trials. <h3>Participants</h3> Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye. <h3>Intervention</h3> Patients were randomized to intravitreal brolucizumab 3 mg (HAWK only) or 6 mg or aflibercept 2 mg. After loading with 3 monthly injections, brolucizumab-treated eyes received an injection every 12 weeks (q12w) and were interval adjusted to every 8 weeks (q8w) if disease activity was present; aflibercept-treated eyes received q8w dosing. <h3>Main Outcome Measures</h3> The primary hypothesis was noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to Week 48 (margin: 4 letters). Other key end points included the percentage of patients who maintained q12w dosing through Week 48 and anatomic outcomes. <h3>Results</h3> At Week 48, each brolucizumab arm demonstrated noninferiority to aflibercept in BCVA change from baseline (least squares [LS] mean, +6.6 [6 mg] and +6.1 [3 mg] letters with brolucizumab vs. +6.8 letters with aflibercept [HAWK]; +6.9 [brolucizumab 6 mg] vs. +7.6 [aflibercept] letters [HARRIER]; <i>P <</i> 0.001 for each comparison). Greater than 50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]). At Week 16, after identical treatment exposure, fewer brolucizumab 6 mg–treated eyes had disease activity versus aflibercept in HAWK (24.0% vs. 34.5%; <i>P</i> = 0.001) and HARRIER (22.7% vs. 32.2%; <i>P</i> = 0.002). Greater central subfield thickness reductions from baseline to Week 48 were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean −172.8 μm vs. −143.7 μm; <i>P</i> = 0.001) and HARRIER (LS mean −193.8 μm vs. −143.9 μm; <i>P <</i> 0.001). Anatomic retinal fluid outcomes favored brolucizumab over aflibercept. Overall, adverse event rates were generally similar with brolucizumab and aflibercept. <h3>Conclusions</h3> Brolucizumab was noninferior to aflibercept in visual function at Week 48, and >50% of brolucizumab 6 mg–treated eyes were maintained on q12w dosing interval through Week 48. Anatomic outcomes favored brolucizumab over aflibercept. Overall safety with brolucizumab was similar to aflibercept (ClinicalTrials.gov; NCT02307682, NCT02434328).
Quantifying the magnitude of pharyngeal obstruction during sleep using airflow shape
Authors: Dwayne L. Mann, Philip I. Terrill, Ali Azarbarzin, Sara Mariani, Angelo Franciosini, Alessandra Camassa, Thomas Georgeson, Melania Marques, Luigi Taranto-Montemurro, Ludovico Messineo, Susan Redline, Andrew Wellman, Scott A. Sands
Journal: European Respiratory Journal (2019)

Rationale and objectives Non-invasive quantification of the severity of pharyngeal airflow obstruction would enable recognition of obstructive versus central manifestation of sleep apnoea, and identification of symptomatic individuals with severe airflow obstruction despite a low apnoea–hypopnoea index (AHI). Here we provide a novel method that uses simple airflow- versus -time (“shape”) features from individual breaths on an overnight sleep study to automatically and non-invasively quantify the severity of airflow obstruction without oesophageal catheterisation. Methods 41 individuals with suspected/diagnosed obstructive sleep apnoea (AHI range 0–91 events·h −1 ) underwent overnight polysomnography with gold-standard measures of airflow (oronasal pneumotach: “flow”) and ventilatory drive (calibrated intraoesophageal diaphragm electromyogram: “drive”). Obstruction severity was defined as a continuous variable (flow:drive ratio). Multivariable regression used airflow shape features (inspiratory/expiratory timing, flatness, scooping, fluttering) to estimate flow:drive ratio in 136 264 breaths (performance based on leave-one-patient-out cross-validation). Analysis was repeated using simultaneous nasal pressure recordings in a subset (n=17). Results Gold-standard obstruction severity (flow:drive ratio) varied widely across individuals independently of AHI. A multivariable model (25 features) estimated obstruction severity breath-by-breath (R 2 =0.58 versus gold-standard, p&lt;0.00001; mean absolute error 22%) and the median obstruction severity across individual patients (R 2 =0.69, p&lt;0.00001; error 10%). Similar performance was achieved using nasal pressure. Conclusions The severity of pharyngeal obstruction can be quantified non-invasively using readily available airflow shape information. Our work overcomes a major hurdle necessary for the recognition and phenotyping of patients with obstructive sleep disordered breathing.
Abstract 17881: The Intriguing Relationship Between Skeletal Muscle Mass and Heart Function Is Present In Spite Of Ageing-Related Sarcopenia
Authors: Bryan M Keng, Louis L Teo, Jia-ing Wong, Serene J Chua, Ru San Tan, Fei Gao, Felix Y Keng, Woon-Puay Koh, Angela S Koh
Journal: Circulation (2017)

Introduction: The link between skeletal muscle and heart disease is intriguing. In sarcopenic states such as those associated with chronological ageing, it is unknown if the link between skeletal m...
SAT-305-Alignment between physician-estimated versus objectively derived fibrosis scores in non-alcoholic steatohepatitis: Real-world evidence suggests clinicians underestimate disease severity in secondary care
Authors: Quentin Anstee, Niall Lynch, Adrien Hauvespre, Juliana Bottomley, Claudia Knight, Nathan Williams, James Piercy, Victoria Higgins
Journal: Journal of Hepatology (2019)
Comparative risks of chronic inhaled corticosteroids and macrolides for bronchiectasis
Authors: Emily Henkle, Jeffrey R. Curtis, Lang Chen, Benjamin Chan, Timothy R. Aksamit, Charles L. Daley, David E. Griffith, Kevin L. Winthrop
Journal: European Respiratory Journal (2019)

Introduction Non-cystic fibrosis (CF) bronchiectasis (“bronchiectasis”) is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory infections in chronic users of inhaled corticosteroids (ICSs) versus macrolide monotherapy. Methods We identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models. Results We identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23–1.57) for hospitalised respiratory infection, 1.56 (95% 1.49–1.64) for acute exacerbation and 1.09 (95% 0.95–1.25) for mortality. Interpretation Among patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.
Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy
Authors: Anping Li, Ming Yi, Shuang Qin, Yongping Song, Qian Chu, Kongming Wu
Journal: Journal of Hematology & Oncology (2019)

During tumor progression, a subset of cancer cells escape from immune surveillance and eventually develop into measurable tumor mass. Cancer immunotherapy eradicates tumor cells by enhancing multiple steps in cancer-immunity cycle including antigen presentation, T cell priming, activation, and immune killing activity. Immunotherapy has been verified as an effective strategy in multiple cancers, but some problems still exist in actual clinical practice such as frequent primary and adaptive resistance. Combination with other adjuvant therapies gives us a new perspective to overcome the emerging obstacles in immunotherapy application. Recently, a series of studies demonstrated that the vital component of host innate immunity — cGAS-STING pathway might play an important role in anti-cancer immunity. It is generally acknowledged that the downstream signals of cGAS-STING especially type I interferon (IFN) bridge innate immunity and adaptive immunity. Given the functions of type I IFN in promoting the maturation and migration of dendritic cells, enhancing cytotoxic T lymphocyte- or natural killer cell-mediated cytotoxicity effect, and protecting effector cells from apoptosis, we believe cGAS-STING agonist might be used as sensitizer for multiple immunotherapies such as cancer vaccine, immune checkpoint blockade, and chimeric antigen receptor T cell therapy. In this review, we highlight the latest understanding of cGAS-STING pathway and the advances of the combination therapy of STING agonist and immunotherapy.
Sustaining pneumococcal vaccination after transitioning from Gavi support: a modelling and cost-effectiveness study in Kenya
Authors: John Ojal, Ulla Griffiths, Laura L Hammitt, Ifedayo Adetifa, Donald Akech, Collins Tabu, J Anthony G Scott, Stefan Flasche
Journal: The Lancet Global Health (2019)

In 2009, Gavi, the World Bank, and donors launched the pneumococcal Advance Market Commitment, which helped countries access more affordable pneumococcal vaccines. As many low-income countries begin to reach the threshold at which countries transition from Gavi support to self-financing (3-year average gross national income per capita of US$1580), they will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full cost or to discontinue PCV in their childhood immunisation programmes. Using Kenya as a case study, we assessed the incremental cost-effectiveness of continuing PCV use.
Descemet Membrane Endothelial Keratoplasty Failure Associated with Innate Immune Activation
Authors: Zala Lužnik, Silke Oellerich, Karin Roesch, Jia Yin, Markus Zumbansen, Lars Franken, Gerrit R.J. Melles, Reza Dana
Journal: Ophthalmology (2019)
Efficacy of Oral Cryotherapy During Oxaliplatin Infusion in Preventing Oral Thermal Hyperalgesia: A Randomized Trial
Authors: Brittany Bauman, Rosemarie Mick, Eileen Martinez, Theresa M. Lawless, Lindsey Zinck, Paige Sinclair, Mary Fuhrer, Mark O’Hara, Charles J. Schneider, Peter O’Dwyer, John Plastaras, Ursina Teitelbaum, Kim A. Reiss
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Chemotherapy-induced oral thermal hyperalgesia (OTH) is a common and debilitating side effect of platinum-based anticancer agents. This study evaluated the efficacy of oral cryotherapy in preventing OTH during oxaliplatin chemotherapy infusion. Methods: Patients with gastrointestinal cancer treated with biweekly oxaliplatin (85 mg/m 2 over 120 minutes) at Abramson Cancer Center at the University of Pennsylvania were randomized to receive oral cryotherapy (ice chips) during oxaliplatin infusion or standard-of-care treatment. All patients completed baseline questionnaires regarding oral and peripheral symptoms and on-treatment questionnaires on day 1 of each subsequent chemotherapy cycle. Those in the treatment arm were asked to document how long they kept the ice chips in their mouths (0, &lt;30, 30, 60, 90, or 120 minutes) and to report their discomfort associated with oral cryotherapy. Evaluable patients were those who had completed at least 2 cycles of oxaliplatin therapy. Results: Of 62 randomized patients with a variety of gastrointestinal malignancies, 50 (25 per treatment arm) were evaluable for efficacy. The rate of patients with oral symptoms after the first treatment cycle was significantly lower in the intervention arm (n=8; 32%) than in the control arm (n=18; 72%), meeting the primary study objective ( P =.01). The magnitude of difference in symptom scores before versus after the first treatment cycle was significantly less in the intervention versus control arm ( P =.001). No difference in oral symptoms over time was seen between the intervention and control groups ( P =.20), although a high attrition rate was noted. Duration of ice chip exposure was associated with improved oral symptoms over time ( P =.02). Conclusions: Oral cryotherapy is a tolerable and cost-effective method of diminishing OTH in patients receiving oxaliplatin chemotherapy, and seems to be most effective in the early stages of treatment.
THU-091-Acalcemic vitamin D analogues show antifibrotic effects in vitro while paricalcitol prevents progression of established fibrosis in the CCl4 mouse-model
Authors: Florian Paul Reiter, Liangtao Ye, Florian Bosch, Ralf Wimmer, Renate Artmann, Andreas Ziesch, Veronika Kanitz, Mayr Doris, Michael Trauner, Ivonne Regel, Alexander Gerbes, Julia Mayerle, Simon Hohenester, Enrico de Toni, Denk Gerald
Journal: Journal of Hepatology (2019)
Performance status and comorbidities on outcome of hypomethylating therapy in older adults (≥60 years old) with acute myeloid leukemia.
Authors: Anju Chana, Laurie Ann Ford, Elizabeth A. Griffiths, James E. Thompson, Meir Wetzler, Eunice S. Wang
Journal: Journal of Clinical Oncology (2015)

7058 Background: Outcomes of standard induction chemotherapy in older patients (pts) ≥ 60 years old with acute myeloid leukemia (AML) are significantly affected by medical co-morbidities and performance status. We asked whether these same factors impact the outcome of upfront hypomethylating therapy. Methods: We retrospectively reviewed 83 consecutive pts ≥ 60 yrs old with newly diagnosed AML who underwent induction therapy with hypomethylating agents at our institute between 2008-13. Sixty-nine patients received decitabine (20 mg/m2 daily for 5-10 days) and 14 received azacitidine (75 mg/m2 daily for 7 days). Number of underlying co-morbidities, Charlson Co-morbidity Index (CCI), Hematopoietic Cell Transplant- Comorbidity Index (HCT-CI), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and overall survival (OS) were assessed. Results: Median age was 75.5 (range 60-92) years. Three-quarters (63) were male. Median white blood cell count was 5 x 109/L (range 0-121). Over half (46, 55%) the pts had secondary AML, and 31 (40%) had adverse cytogenetics. Six pts (7%) had FLT-3 mutant and 8 (10%) had NPM-1 mutant AML. ECOG PS was assessed as 0 (13 pts, 16%), 1 (55 pts, 66%), 2 (12 pts, 14%), and ≥ 3 (3 pts, 4%). Co-morbidities were measured as 0 (19 pts, 23%), 1 (28 pts, 34%), 2 (19 pts, 23%) or ≥ 3 (17 pts, 20%). CCI was 2-3 (6 pts), 4-5 (39 pts), 6-7 (28 pts), and ≥ 8 (10 pts). Sixteen pts (20%) achieved a complete response with an overall response date of 28%. Median OS of all pts was 9.1 (95% CI 4.5-12.4) months. ECOG was significantly associated with OS (p = 0.039) with median durations of 12.6 (PS 0), 11.3 (PS 1), 3.5 (PS 2) and 0.5 (PS ≥ 3), months, respectively. Co-morbidities, CCI, or HCT-CI were not significantly associated with survival (p = NS). Conclusions: Our results suggest that PS, not co-morbidities, predicts outcomes in older AML pts receiving upfront decitabine/ azacitidine. These data contrast with prior studies showing that co-morbidities, CI, HCT-CI, and PS all significantly impact outcomes of intensive induction. Prospective studies of the potential benefit of hypomethylating therapy in older AML patients with multiple co-morbidities are warranted.