tbuckley/cabot-search huggingface dataset:
Abstract P401: Female Gender is a Significant Risk Factor for Functional Disability After Hemorrhagic Stroke but Not Ischemic Stroke Among Japanese Community-Dwelling Elderly Individuals
Authors: Kozo Tanno, Shuko Takahashi, Yuki Yonekura, Masaki Ohsawa, Shinichi Omama, Yasuhiro Ishibashi, Kazuyoshi Itai, Toshiyuki Onoda, Toru Kuribayashi, Kuniaki Ogasawara, Fumitaka Tanaka, Motoyuki Nakamura, Makoto Koshiyama, Kiyomi Sakata, Akira Okayama
Journal: Circulation (2019)

Introduction: Previous studies have indicated that the female gender is one of the important risk factors for disability after stroke; however, most studies have been conducted in Western countries, and the higher risk of disability after stroke observed in women is thought to be different in Japan, where the proportion of hemorrhagic stroke (HS) is relatively higher than that in Western countries. Hypothesis: We assessed the hypothesis that the higher risk of disability after stroke attributable to the female gender was different between ischemic stroke (IS) and HS. Methods: We used 10-year community-based cohort data of 8,698 participants aged 65 years or older without cardiovascular disease or long-term care insurance (LTCI) at the time of the baseline survey. The stroke incidence was confirmed by reviewing the Iwate Stroke Registry. Functional disability was defined as being newly certified by the LTCI system. Participants were classified into three groups: G1, event-free (no stroke and no disability, n=7,950); G2, no disability after stroke (IS=177, HS=55); and G3, disability after stroke (IS=346, HS=170). Multivariate-adjusted odds ratios (ORs) of the female gender in G2 and G3 (reference: G1) were calculated using multinomial logistic regression with adjustments for age, hypertension, diabetes, dyslipidemia, overweight, current smoking, regular alcohol consumption, and regular exercise separately in those with IS and HS. Results: The ORs of the female gender were not high in G3 in IS, while the OR (95% confidence interval) was significantly high in G3 (1.55 (1.03-2.34)) in HS (see table). Conclusions: The proportion of females in the subjects with disabilities after HS was significantly higher than the proportion of males after multivariate adjustment. This suggested that the female gender was a significant risk factor for disability after HS, but not after IS in Japanese community-dwelling individuals.
Getting to the bottom of things: The value of evolutionary approaches in discerning the origin of psychopathology
Authors: Jiaqing O, Martin Brüne
Journal: Behavioral and Brain Sciences (2019)

Abstract The network approach as a novel way of understanding psychopathology has helped address some of the existing issues associated with traditional biological interpretations. Nonetheless, it has similarly failed in explaining the fundamental etiology of mental conditions – a persistent conundrum that arguably could be adequately addressed only by evolutionary formulations, specifically evolutionary mismatch and life history theories.
Abstract 17035: Prognostic Significance of Magnetic Resonance Imaging Derived Coronary Flow Reserve for Heart Failure Patients
Authors: Shingo Kato, Naoki Asahina, Naoki Iinuma, Yuka Kusakawa, Shintaro Minegishi, Daisuke Kamimura, Tatsuya Nakachi, Kazuki Fukui, Masami Kosuge, Kazuo Kimura, Kouichi Tamura
Journal: Circulation (2017)

Introduction: Phase contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus emerged as a non-invasive method to quantify coronary flow reserve (CFR). Previous studies demonstrated...
Abstract MP44: Association of High-Sensitivity Troponin With Peripheral Neuropathy in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Caitlin W Hicks, Dan Wang, Natalie Daya, Beverly G Windham, Christie M Ballantyne, Kunihiro Matsushita, Elizabeth Selvin
Journal: Circulation (2019)

Introduction: High-sensitivity cardiac troponin (hs-cTnT) is a marker of myocardial damage and has been associated with diabetes and its major complications, particularly those with a microvascular etiology. The aim of this study was to assess the association of hs-cTnT and other cardiac, kidney, inflammation, and hyperglycemia biomarkers with peripheral neuropathy (PN) in both diabetic and non-diabetic populations. Methods: We conducted a cross-sectional analysis of 3,019 black and white participants in the ARIC study who underwent monofilament PN testing and had hs-cTnT and other nontraditional measures [NT-proBNP, high-sensitivity C-reactive protein, β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), cystatin C-based eGFR, urine albumin:creatinine ratio, fructosamine, glycated albumin, and 1,5-anhydroglucitol] assessed at ARIC visit 6 (2016-2017, age 71-94 years). We used logistic regression models to assess the associations of these biomarkers with the presence of PN in older adults with and without diabetes after adjusting for traditional diabetes and cardiovascular risk factors. Results: Overall, 38.0% of the 3,019 participants had evidence of PN (42.0% in persons with diabetes and 36.4% in persons without diabetes). After adjusting for traditional risk factors, there were significant and robust associations of hs-cTnT, NT-proBNP, and β-2 microglobulin with PN ( Table, Model 2 ). After further adjusting for hemoglobin A1c, only the association of hs-cTnT with PN remained significant (P=0.02; Model 3 ). Elevated hs-cTnT (≥14 ng/L) was associated with prevalent PN in persons with diabetes (OR 2.10, 95%CI 1.24-3.56) and without diabetes (OR 2.61, 95% CI 1.59-4.28) compared to persons without diabetes and non-elevated hs-cTnT (&lt;6 ng/L). Conclusions: Hs-cTnT is associated with the presence of PN in older adults independent of cardiovascular risk factors and glycemic control. These findings support the hypothesis that hs-cTnT may be a global marker of end organ damage.
Clinical outcomes of patients with gliomas treated with bevacizumab in British Columbia (BC).
Authors: Adeline Markarian, Mario De Lemos, Laurel Kovacic, Kimberly Schaff, Susan Walisser
Journal: Journal of Clinical Oncology (2015)

e13021 Background: Health Canada approved the use of Bevacizumab (Bev) in recurrent gliomas in Mar 2010. However, there is limited evidence for its use for this indication. In Canada, several provincial health jurisdictions do not fund this drug in this setting. BC Cancer Agency started covering Bev for recurrent brain tumors in Apr 2011 and this study was conducted to assess the clinical outcomes of patients (pts) outside clinical trials to help support the continuing funding of this therapy. Methods: This was a retrospective, multi-centre, review conducted at the BC Cancer Agency, a government funded, integrated care organization which delivers cancer care to the residents of BC, Canada. Cases were identified from the agency’s provincial registry and systemic therapy drug database. Pts were eligible if they were treated with one dose of Bev min with or without lomustine or etoposide for recurrent brain tumor between Apr 2011 and Mar 2014. Response was assessed using the Neuro-Oncology Working Group Response Assessment for High-Grade Gliomas. The primary end points were progression free survival (PFS). Secondary endpoints were overall survival (OS) and objective response rate (ORR). Results: A total of 160 pts were included: median age was 55 (range 26-84) and majority was males (64.4%). Most common diagnoses were glioblastoma multiforme (70.6%) and oligodendroglioma (10.6%). Half of pts had received prior metronomic temozolomide. Median therapy duration was 3 months (mo) (0.5-31 mo). Median PFS was 5 mo and 6-mo PFS was 37.2%. Median OS was 7 mo and 9-mo OS was 27.7%. ORR was 20%. Most common reasons for Bev discontinuation were disease progression (57.5%), death (13.8%) and toxicity (5%). Conclusions: Our data suggest Bev induced clinical responses in pts with recurrent brain tumors with similar PFS compared to clinical trials (median 4-4.2 mo, 6-mo 41-42.6%). However, our data showed a lower ORR and less survival benefits than on clinical trials (ORR 28-38%, median OS 9-11 mo, 9-mo OS 38-59%). Bev remains an appropriate therapy option for pts with advanced brain tumors who have failed or cannot tolerate metronomic dose temozolomide or experience symptoms associated with cerebral edema requiring high doses of corticosteroids.
Modulation of plasma lipidomic signature in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Blossom Mak, Kate Lynette Mahon, Martin R. Stockler, Anthony M. Joshua, Alison Yan Zhang, Francis Parnis, Peter Meikle, Lisa Horvath
Journal: Journal of Clinical Oncology (2019)

TPS331 Background: Altered lipid metabolism and its impact on prostate cancer (PC) is increasingly recognised, in light of the association between obesity and worse PC outcomes. Our exploratory study was the first to identify baseline plasma lipidomic profiles in men with mCRPC commencing docetaxel that were associated with survival. A prognostic three-lipid signature was derived, consisting of ceramide, sphingomyelin and phosphatidylcholine (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). This signature was independently prognostic when modelled with clinicopathological factors and metabolic characteristics. A key question is whether therapeutic modulation of a patient’s lipid profile is possible. Statins significantly reduce the plasma levels of ceramides, sphingomyelin and cholesterol in cardiovascular disease, suggesting that this therapy could change the poor prognostic lipid profile of mCRPC patients. This trial assesses whether addition of simvastatin to docetaxel for mCRPC can reverse the poor prognostic lipid signature with the aim of developing a precision medicine strategy for metabolic targeting. Methods: This investigator-initiated, multi-centre, open-label, single arm, pilot study enrols patients with mCRPC commencing docetaxel for disease progression, not already receiving a lipid-lowering agent. Patients are treated with simvastatin 40mg orally once daily for 12 weeks, commencing on day 1 of the first cycle of docetaxel. Blood is taken at baseline and after 12 weeks of simvastatin and the plasma lipidomic profile is determined using liquid chromatography and electrospray ionisation-tandem mass spectrometry. The lipidomic profile is classified as either good or poor prognostic as per our three-lipid signature model derived by logistic regression. The primary objective is to assess the rates of conversion from a poor prognostic lipid signature to good prognostic after simvastatin. A sample size of 60 men provides over 90% power, with a 1-sided type 1 error of 10%, to detect conversion to the good prognostic signature in 50% of patients, assuming 25% of patients have the poor prognostic signature at baseline as previously detected. To date, 6 patients have been enrolled to the trial. Clinical trial information: ACTRN12617000965303.
Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies
Authors: Jiwei Cui, Yi Ju, Zachary H. Houston, Joshua J. Glass, Nicholas L. Fletcher, Sheilajen Alcantara, Qiong Dai, Christopher B. Howard, Stephen M. Mahler, Adam K. Wheatley, Robert De Rose, Paul T. Brannon, Brett M. Paterson, Paul S. Donnelly, Kristofer J. Thurecht, Frank Caruso, Stephen J. Kent
Journal: Advanced Healthcare Materials (2019)

Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.
Relationship between metformin use and recurrence and survival in patients (pts) with resected stage III colon cancer (CC) receiving adjuvant chemotherapy: Results from NCCTG N0147 (Alliance).
Authors: Preet Paul Singh, Qian Shi, Nathan R. Foster, Axel Grothey, Suresh Nair, Emily Chan, Anthony Frank Shields, Richard M. Goldberg, Sharlene Gill, Morton S. Kahlenberg, Frank A. Sinicrope, Daniel J. Sargent, Steven R. Alberts
Journal: Journal of Clinical Oncology (2015)

3531 Background: Although preclinical and epidemiological data suggest that metformin may have antineoplastic properties in CC, the impact of metformin use on pt survival in stage III CC undergoing curative resection is unknown. Methods: Before randomization to FOLFOX +/- cetuximab, 1958 stage III CC pts enrolled on N0147 study completed a questionnaire that included information on diabetes mellitus (DM) and metformin use. Cox models assessed the association between metformin use and outcomes of disease free survival (DFS), overall survival (OS) and time to recurrence (TTR), adjusting for clinical/pathological factors. Results: 1691 (86%), 115 (6%) and 152 (8%) of 1958 pts reported no history of DM, DM with metformin use, or DM with no metformin use, respectively. The two treatment arms were pooled since metformin use showed homogeneous effects on outcomes across arms. There was no difference in DFS, OS and TTR irrespective of metformin use when DM pts were compared to non-DM pts, after adjusting for tumor/pt factors (Table). Within the cohort of DM pts (n = 267), DFS (HR = 0.90; 95% CI: 0.59-1.35; p = 0.595), OS (HR = 0.99; 95% CI: 0.65-1.49; p = 0.948) and TTR (HR = 0.87; 95% CI: 0.56-1.35; p = 0.534) were similar in metformin users compared to non-users. Survival outcomes were comparable regardless of duration of metformin use ( < 1, 1-5, 6-10, 11+ years) before randomization (p = 0.361 for DFS; p = 0.068 for OS). There were no interaction effects observed between metformin use and clinical/pathological factors (KRAS, BRAF mutation status, tumor site, T/N stage, gender, and age). Conclusions: Stage III CC patients treated with adjuvant chemotherapy who used metformin experienced similar DFS, OS, or TTR compared to non-DM pts or DM pts without metformin use. Group DFS OS TTR HR (95% CI) p value HR (95% CI) p value HR (95% CI) p value Non-DM Ref Ref Ref DM, metformin use 0.95 (0.67-1.36) 0.796 1.17 (0.82-1.67) 0.383 0.91 (0.62-1.33) 0.616 DM, no metformin use 1.15 (0.86-1.54) 0.361 1.26 (0.93-1.72) 0.138 1.14 (0.84-1.57) 0.401
Prognostic effect of tumor location in stage II and III colon cancer.
Authors: Ahmet Ozveren, Zeki Gokhan Surmeli, Asli Turgut, Burcak Karaca, Bulent Karabulut, Ulus Ali Sanli, Ruchan Uslu
Journal: Journal of Clinical Oncology (2015)

e14652 Background: Proximal and distal colon tumors have different pathological and molecular characteristics. Here we examined whether the tumor location has a prognostic impact for patients with colon cancer who received adjuvant chemotherapy. Methods: Records of patients with stage II and III colon cancer who received adjuvant chemotherapy between January 2008 and December 2012 were retrospectively reviewed. Patients were categorized into proximal (caecum, ascending colon, transverse colon) and distal (descending and sigmoid colon) tumor groups. Patient and tumor characteristics, and survival outcomes were compared according to tumor location. Results: A total of 234 patients were included. Of those, 153 patients (65.4%) had distal, 81 patients (34.6%) had proximal tumors. Gender distribution (males in distal/proximal 57.5% / 59.3%) and median age at diagnosis (distal / proximal 57.3 / 56.9 years) were similar among groups. Tumor invasion (T2, T3, T4: 2%, 75.5%, 22.5% in distal; 1.3%, 76.3%, 22.5 in proximal tumors, respectively) and lymph node status (N0, N1, N2: 30.7%, 48.4%, 20.9% in distal; 34.6%, 39.5%, 25.9% in proximal tumors, respectively) were similar among groups. More poorly differentiated tumors (24.6% vs 7.1%, p:0.002), and more mucinous adenocarcinomas (19.8% vs 9.8%, p:0.008) were observed in proximal tumors. Lymphatic and/or vascular invasion and perineural invasion were observed similarly among groups. 66% and 65.4% of patients received oxaliplatin containing; 34% and 34.6% of patients received fluoropyrimidine-based adjuvant treatment in distal and proximal tumors, respectively. At a median follow-up duration of 49 months, disease recurrences were observed in 28.8% of distal and 29.6% of proximal tumors. Disease-free survival rates at 2 and 5 years were 82% and 62.9% in distal; 77.1% and 64.8% in proximal tumor groups, respectively (p:0.994). Overall survival rates at 2 and 5 years were 94.4% and 75.1% in distal; 87.7% and 75.5% in proximal tumor groups, respectively (p:0.679). Conclusions: Although proximal colon cancers are more likely to be poorly differentiated and to have mucinous histology; no differences in disease-free and overall survival were observed between distal and proximal tumors.
Abstract 19988: Estrogen Receptorα Non-genomic Pathway is Essential to the Cardiac Benefits From Pde5 Inhibition During Pressure Overload
Authors: Nobuaki Fukuma, Eiki Takimoto, Richard H Karas, Issei Komuro, Robert M Blanton
Journal: Circulation (2017)

Introduction: The sex hormone estrogen protects cardiovascular system. The decline of estrogen levels underlies the prevalence of heart failure among postmenopausal women, and has been demonstrated...
The Critical Role of HDAC1-IRF4-Pim-2 Axis in Myeloma Cell Growth and Survival: Therapeutic Impacts of Targeting the HDAC1-IRF4-Pim-2 Axis
Authors: Takeshi Harada, Asuka Oda, Yohann Grondin, Jumpei Teramachi, Ariunzaya Bat-Erdene, Masami Iwasa, Masahiro Oura, Shingen Nakamura, Kumiko Kagawa, Yasunobu Okamoto, Kimiko Sogabe, Shiro Fujii, Hirokazu Miki, Shuji Ozaki, Teru Hideshima, Kenneth C. Anderson, Masahiro Abe
Journal: Blood (2018)
Deleterious Germline Mutations Are a Risk Factor for Neoplastic Progression Among High-Risk Individuals Undergoing Pancreatic Surveillance
Authors: Toshiya Abe, Amanda L. Blackford, Koji Tamura, Madeline Ford, Patrick McCormick, Miguel Chuidian, Jose Alejandro Almario, Michael Borges, Anne Marie Lennon, Eun Ji Shin, Alison P. Klein, Ralph H. Hruban, Marcia I. Canto, Michael Goggins
Journal: Journal of Clinical Oncology (2019)

To compare the risk of neoplastic progression by germline mutation status versus family history without a known germline mutation (familial risk) among individuals with an increased risk for pancreatic cancer who are undergoing surveillance.Of 464 high-risk individuals in the Cancer of the Pancreas Screening program at Johns Hopkins Hospital who were undergoing pancreatic surveillance, 119 had a known deleterious germline mutation in a pancreatic cancer susceptibility gene; 345 met family history criteria for pancreatic surveillance but were not known to harbor a germline mutation. We used next-generation sequencing to identify previously unrecognized germline mutations among these 345 individuals. We compared the development of pancreatic cancer, high-grade dysplasia, or clinically worrisome features, adjusting for competing mortality, among all germline mutation carriers with the risk of progression in a cohort without a known germline mutation.Fifteen (4.3%) of 345 individuals classified as having familial risk had a previously unrecognized pancreatic cancer susceptibility gene mutation (nine that involved ATM, two BRCA2, one BRCA1, one PALB2, one TP53, and one CPA1). The cumulative incidence of pancreatic cancer, high-grade dysplasia, or worrisome features on pancreatic imaging was significantly higher in the germline mutation risk group (n = 134) than in the familial risk group (n = 330 [for pancreatic cancer, hazard ratio, 2.85; 95% CI, 1.0 to 8.18; P = .05]).The cumulative incidence of pancreatic cancer is significantly higher among individuals with an identifiable deleterious germline mutation in a pancreatic cancer susceptibility gene than it is among individuals with a strong family history but no identified mutation. Gene testing of individuals who meet criteria for pancreatic surveillance on the basis of their family history may better define those most at risk for neoplastic progression.
MiCheck performance: Comparator trial of MiCheck with PHI, % free PSA and PSA—The impact on decision making for prostate biopsy.
Authors: Neal D. Shore, Daniel R. Saltzstein, Christopher Michael Pieczonka, Jennifer Lynn Beebe-Dimmer, Julie J. Ruterbusch, Douglas Campbell, Brad Walsh
Journal: Journal of Clinical Oncology (2019)

199 Background: A more accurate diagnostic test is still needed to enhance decision-making regarding prostate biopsy. MiCheck is a triage test to assist in a decision to proceed to prostate biopsy. It measures multiple cancer related proteins in blood while combining this information with clinical factors. It has been optimised to differentiate between aggressive (AgCaP) and non-aggressive (non-AgCaP) prostate cancer. The MiCheck-01 clinical trial collected samples from patients who proceeded to biopsy on the basis of an elevated age adjusted PSA. The performance of MiCheck was compared with PSA, %free PSA and PHI. Methods: Serum samples were tested according to the MiCheck manufacturer’s instructions. Patient samples were also tested using a standard PSA assay and additionally underwent PHI and % free PSA measurement. A range of different MiCheck cutpoints were examined for test performance and one chosen following consultation with Urologists and Clinical Chemists. This algorithm was applied to all evaluable patients from the trial and the outputs used for the development of a health economic model. The net cost impact of using MiCheck was assessed. Results: The best performing MiCheck algorithm demonstrated a high AUC when differentiating AgCaP from non-AgCaP. MiCheck demonstrated a higher AUC than PSA, %free PSA and PHI in this population. Furthermore, the algorithm was superior to the other tests in PSA 4-10ng/ml range. The derived algorithm was applied to patients from the trial using a high sensitivity cutpoint. At this cutpoint, 25% of biopsies were avoided while only 5 (4%) AgCaP patients underwent a later diagnosis. A diagnostic workflow model of how the test might be employed by the clinician was constructed. This was applied to a health economic analysis demonstrating significant cost savings (between $2,744 and 5,047 per patient in year one) when incorporating MiCheck to standard of care. Conclusions: The MiCheck test demonstrates a superior ability to discriminate between AgCaP and non-AgCaP in comparison to PSA,PHI, and % free PSA. Use of the MiCheck test would assist clinicians in assessing the need for a prostate biopsy and provide significant healthcare cost savings.
Abstract 18557: Helicopter-borne ECPR Team for Remote Refractory Cardiac Arrest
Authors: Alice Hutin, Jean Herlé Raphalen, Jean Pierre Orsini, Christelle Dagron, Romain Jouffroy, Kim An, Pierre Carli, Lionel Lamhaut
Journal: Circulation (2017)

Introduction: Extracorporeal Cardio-Pulmonary Resuscitation (ECPR) is a second line treatment in the management of cardiac arrest (CA). Prognosis is linked to the access time to this technique; 100...
Gasping for a Diagnosis
Authors: Kristin D’Silva, Sarah Brown, Gary M. Hunninghake, Marina Vivero, Joseph Loscalzo
Journal: New England Journal of Medicine (2019)

A 42-year-old man presented with progressive nonproductive cough, shortness of breath, and unintentional weight loss. He reported no fevers, chills, night sweats, hemoptysis, or wheezing.