tbuckley/cabot-search huggingface dataset:
Abstract 19003: Long-term Outcomes After Subcutaneous Defibrillator Implantation in Patients With a Previous Device Infection
Authors: Ahmed Shahab, Adam Oesterle, Andrew Beaser, Zaid Aziz, Leigh Friedman, Ryan Deboer, Cevher Ozcan, Michael Broman, Gaurav Upadhyay, Roderick Tung, Hemal Nayak
Journal: Circulation (2017)

Introduction: Long-term outcomes for S-ICD reimplantation after a prior CIED infection are unknown. Hypothesis: S-ICD infection and death are not increased in those with a prior CIED infection. Met...
Abstract 18196: Aldehyde Oxidase is a Potent Source of Superoxide Generation and Can Modulate Cardiac Contractile Function
Authors: Tapan K Kundu, Levy Reyes, Saradhadevi Varadharaj, Jay L Zweier
Journal: Circulation (2011)

Aldehyde oxidase (AO) is a cytosolic enzyme belonging to the xanthine oxidoreductase (XOR) family. A variety of aldehyde substrates are known to be formed in cardiovascular disease secondary to inflammation and oxidative stress that are efficient AO substrates. While XOR has been reported to influence heart function in heart failure and is well known to be an important source of superoxide (O 2 • - ), little is known regarding the role of AO in cardiac oxidant signaling. In order to assess the presence of AO in the heart and its potential role in cardiovascular pathophysiology, we studied the distribution of AO in rat myocardium and isolated cardiac myocytes as well as its levels and activities in heart tissue. Furthermore, in isolated perfused rat hearts we measured the functional effect of AO activation or inhibition. Immunohistochemistry, using an AO specific antibody, showed a myofibrillar / sarcomere distribution for AO. In control rat myocardium, the activity of AO was found to be 1.5-fold higher than that of total XOR (0.21±0.02 vs . 0.14±0.01 nmol min -1 mg -1 of protein), and the levels of protein 2.5-fold higher than that of XOR (30.26±2.42 vs . 11.86±1.07 nM), while O 2 • - production (measured by cytochrome c assay) in the presence of optimal substrate levels was estimated to be &gt;10-fold higher for AO than XOR. In isolated perfused rat hearts, infusion with the AO substrate 4-(dimethylamino)cinnamaldehyde ( p -DMAC) (10 μM) resulted in a significant increase in left ventricular developed pressure (LVDP) of 14±3% (p&lt;0.05), while treatment with the potent inhibitor amadone (10 μM) completely inhibited this increase. Thus, AO is present in cardiac myocytes adjacent to the contractile proteins and in the presence of aldehyde substrates it can function as an important source of O 2 • - modulating contractile function. Further studies will be needed to assess the potential role of AO in modulating cardiac function in ischemic syndromes and heart failure.
Abstract 20444: Betrixaban Reduces Not Only the Presence of Thrombus but Also Extent of Thrombus: An APEX Trial Substudy
Authors: Gerald Chi, Tarek Nafee, Samuel Z Goldhaber, Adrian F Hernandez, Russell D Hull, Alex Gold, Serge Korjian, Yazan Daaboul, Alexander T Cohen, Robert A Harrington, C. Michael Gibson
Journal: Circulation (2017)

Background: While extended duration betrixaban has been associated with a reduction in the frequency of thrombus, it was hypothesized that it would reduce the extent of thrombus burden relative to ...
Impact of genomic alterations (GAs) on outcomes and their distribution by age groups in metastatic colorectal cancer (mCRC) patients (pts).
Authors: Ibrahim Halil Sahin, Wanqi H Chen, Zhengjia Chen, Mehmet Akce, Olatunji B. Alese, Walid Labib Shaib, Bassel F. El-Rayes, Christina Wu
Journal: Journal of Clinical Oncology (2019)

560 Background: Although clinical outcomes has substantially improved over the last decade, long term survival in mCRC remains rare. Molecular profiling (MP) of CRC is routinely conducted to identify potential therapeutic targets. The aim of this project is to evaluate the impact of uncommon GAs on outcomes and characterize their distribution by age. Methods: Pts were eligible if they had mCRC (synchronous or metachronous) and underwent MP between 01/2013 and 05/2018. GAs were obtained from Foundation Medicine reports. Clinical data were collected by trained personnel by detailed chart review. Multivariable survival analyses (MA) with Cox model were conducted for survival outcomes and Fisher’s exact test was used to assess the differences among age groups (&lt; 45, 45-60, &gt; 60). The study was reviewed by Institutional IRB ( IRB00097021 ). Results: 161 patients with mCRC had MP, and 159 of those patients had survival data. The most commonly detected GAs were APC (133/161, 82.6%) TP53 (128/161, 79.5%). In univariate analyses mutations in BRCA 1/2, RB1, SOX9, CDK8, FLT3, and IRS2 amplification were associated with worse survival outcomes. In MA, including initial stage of disease, GAs in BRCA1/2, RB1, FLT3, SOX9, and IRS2 remained statistically significant (Table). When we performed MA by age groups, mutations SOX9 in age group &lt; 45 and BRCA1/2 in age group 45-60 were significant predictors of worse outcomes. We also compared the frequency of mutations among age groups and FAM123B was significantly more common in age group 45-60 (P = 0.038). Conclusions: Our data suggests that GAs in BRCA1/2, RB1, FLT3, SOX9, and IRS2 may predict worse outcomes in mCRC. Therapeutic approaches targeting these pathways should be investigated. Differences in distribution and prognostic significance of mutations were observed based on age. [Table: see text]
Productivity Loss Among Parent Caregivers Is Associated with Poor Health-Related Quality of Life (HRQL) at the Intial Diagnosis of Pediatric Advanced Stage Hodgkin Lymphoma (HL)
Authors: Susan K Parsons, Sharon M. Castellino, Angie Mae Rodday, Frank G Keller, Kara M. Kelly, Rena M Conti, Debra Lerner, Tara O. Henderson
Journal: Blood (2018)
Abstract A020: Integrative analysis of the proteome in primary and advanced prostate cancer
Authors: Leena Latonen, Ebrahim Afyounian, Antti Jylhä, Janika Nättinen, Ulla Aapola, Matti Annala, Kati Kivinummi, Teuvo Tammela, Roger W. Beuerman, Hannu Uusitalo, Matti Nykter, Tapio Visakorpi
Journal: Cancer Research (2018)

Abstract To fully understand the output of alterations in cancer genomes and transcriptomes, we need to know how these aberrations are translated into the functional protein units in cells. We assessed proteomic changes during disease formation and progression in prostate cancer by performing high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC), and castration-resistant prostate cancer (CRPC). With SWATH-MS quantitation-based proteomics we found that each of these sample groups show a distinct protein profile. By integrative analysis of this mass spectrometry dataset with genetic, epigenetic, and transcriptional data from the same samples, we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. From our analysis, we have identified sets of novel expression changes occurring primarily at the protein level, in addition to identification of several miRNA-target correlations present at protein but not at mRNA level. We find novel expression changes in previously unrecognized pathways in prostate cancer that are likely to affect disease development and progression. For example, we identify two metabolic shifts in the citric acid cycle (TCA cycle), one occurring during primary cancer development and the second during castration resistance, having implications on drug targeting against cancer metabolism. Our proteogenomic analysis of prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression, reveals new disease mechanisms, and significantly extends understanding of prostate cancer biology. Citation Format: Leena Latonen, Ebrahim Afyounian, Antti Jylhä, Janika Nättinen, Ulla Aapola, Matti Annala, Kati Kivinummi, Teuvo Tammela, Roger W. Beuerman, Hannu Uusitalo, Matti Nykter, Tapio Visakorpi. Integrative analysis of the proteome in primary and advanced prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A020.
Abstract 20190: Cervical Sympathetic Chain Stimulation Attenuates the Hypoxic-Hypercapnic Response in Anesthetized Zucker-Fat Rats
Authors: Yee Hsee Hsieh, Woineshet Zenebe, Arun Sridhar, Stephen Lewis
Journal: Circulation (2017)

Cervical sympathetic chain controls sympathetic drive to the carotid baro- and chemo-sensors. Zucker fat rats (ZFRs) are a model of sleep apnea with both obstructive and central apneas. We hypothesized that electrical stimulation of the cervical sympathetic stimulation in anesthetized ZFRs will lead to improvement in airway patency and prevent the blood pressure drop during a hypoxic-hypercapnic challenge. Under urethane, male ZFRs (Age:16 wks, n=6), were instrumented for mean blood pressure (MAP), diaphragmatic and genioglossus electromyogram (EMG), and upper airway pressure (UAP) measurements. Both CSC were dissected, isolated and prepared for bipolar stimulation. ZFRs had a high incidence of sighs at baseline (room air) and exposure to hypoxic-hypercapnia exposure (10% O2, 8% CO2) for 1 min lead to increase in airway pressure (30% increase) and drop in blood pressure (40% decrease) (Panel A). Bilateral stimulation of CSC during hypoxic-hypercapnic challenge reduced the collapse of the airway and the bl...
Abstract P2-03-10: Not presented
Authors: A Mallinger, F Dalenc, M Poirot, S Silvente-Poirot
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Mallinger A, Dalenc F, Poirot M, Silvente-Poirot S. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-03-10.
A phase II, open-label pilot study evaluating the safety and activity of Nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study) (NCT03483038).
Authors: Hiral D. Parekh, Jessica L. Cioffi, Kathryn Hitchcock, Ji-Hyun Lee, Z. Hugh Fan, Carmen Joseph Allegra, Steven J. Hughes, Jose Gilberto Trevino, David L. DeRemer, Thomas J. George
Journal: Journal of Clinical Oncology (2020)

TPS790 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board, adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive FOLFNal-IRINOX regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30 day postoperative complication rate. Clinical trial information: NCT03483038 . [Table: see text]
Outcomes in pancreatic adenocarcinoma (PDA) patients (pts) with genetic alterations in DNA damage repair (DDR) pathways: Results from the Know Your Tumor (KYT) program.
Authors: Michael J. Pishvaian, Edik Matthew Blais, Jonathan Robert Brody, Davendra Sohal, Andrew Eugene Hendifar, Vincent Chung, Sameh Mikhail, Lola Rahib, Emily Lyons, Lisa Tibbetts, Subha Madhavan, Lynn McCormick Matrisian, Emanuel Petricoin
Journal: Journal of Clinical Oncology (2019)

191 Background: Up to 17% of PDAs harbor mutations in the DDR pathway. However, the purely prognostic relevance of these mutations is unclear. Furthermore, outcomes in response to platinum-based therapies in PDA pts harboring mutations in a broad range of DDR genes, particularly beyond BRCA1/2 and PALB2, remain unexplored. Methods: We evaluated PDA pts enrolled in the KYT registry for whom we collected cancer related exome sequencing and clinical outcomes. Pts were categorized as resected and advanced (LAPC and metastatic pts), and tumor genomic profiles were categorized as DDR mutated (DDRmut) based on the presence of pathogenic alterations in BRCA1/2, PALB2 (Group 1), ATM, ATR, ATRX (Group 2), or BAP1, BARD1, BRIP1, CHEK1/2, RAD50/51/51B, or FANCA/C/D2/E/F/G/L (Group 3). Tumors harboring no DDR mutations were labelled DDR proficient (pDDR). Median overall survival (OS) was measured from the date of diagnosis until death. Results: The OS was similar in all resected pts, irrespective of exposure to platinum therapy (see Table). However, for the pts with advanced disease, OS was significantly longer for DDRmut vs. pDDR pts, particularly in the platinum-treated group; but no such difference was identified in the platinum-naïve pts. Detailed outcomes for the 3 Groups will be presented, but in general the OS in pts with mutations in all 3 DDRmut Groups was greater than for the pDDR pts; but again this difference was lost in the platinum-naïve pts. Conclusions: Advanced DDRmut pts have an improved OS when treated with platinums, compared to pDDR pts. But, in the absence of platinum-based therapy, there is no OS difference observed in DDRmut vs. pDDR pts, suggesting that DDR status has no pure prognostic value. These findings support the need to test all pts with advanced PDA, to ensure that DDRmut pts are treated with platinum-based therapy. [Table: see text]
CO.28: <i>N</i>eoadjuvant Chemotherapy, <i>E</i>xcision and <i>O</i>bservation (<i>NEO</i>) for early rectal cancer.
Authors: Hagen F. Kennecke, Carl J Brown, Rebecca Auer, Sebastien Drolet, Cathy Eng, Vallerie Lynn Gordon, David J Hochman, Hussein Moloo, Alice C Wei, Kelvin Chan, Alexander Montenegro, Jonathan M. Loree, Dongsheng Tu, Derek J. Jonker
Journal: Journal of Clinical Oncology (2019)

TPS724 Background: CO.28 is a phase II study which aims to determine if patients with stage I/II rectal cancer can be treated with induction chemotherapy (FOLFOX/CAPOX) and organ-preserving transanal microsurgery. Prior studies have explored the use of pelvic chemoradiation followed by transanal microsurgery as a means to increase organ preservation. However, pre-operative radiation may have acute and prolonged impacts such as wound complications and adverse on sphincter, sexual and urinary function. Moreover, patients who develop recurrence following this strategy are difficult to salvage as re-irradiation is not usually an option. There is virtually no prospective experience of neoadjuvant FOLFOX/CAPOX chemotherapy and excision for early rectal tumors. Methods: The primary objective is to determine the rate of organ preservation and the trial will be successful if more than 65% of patients avoid a formal rectal resection. In this two-staged phase II trial, patients are eligible if they have clinical N0 and T1-T3a/bN0M0 rectal tumors and no pathologic high risk features. After 6 cycles of q2weekly FOLFOX or 4 cycles of CAPOX, rectal endoscopy and pelvic MRI are repeated and if there is evidence of tumor response, patients proceed to tumor excision by Transanal Endoscopic Microsurgery (TEMS) or Transanal Minimally Invasive Surgery (TAMIS). It is required that participating surgeons have a minimum experience of 20 TEMS/TAMIS procedures and they are asked to submit an unedited video for central review. Pathologic ypT0 or ypT1N0 tumors are assigned to observation while ypT2+ or any ypN+ tumors are treated with radical surgery and total mesorectal excision (TME). Pre-operative pelvic radiation is suggested only for ypT3+ or node positive tumors. Endoscopic and cross-sectional imaging is repeated every 4-6 months for 36 months. Circulating tumor DNA (ctDNA) will be correlated with tumor response and relapse. A total of 58 patients will be accrued. Study Progress: The study was activated in Canada in late 2017 and at select US Cancer Centers in 2018, with total accrual to date of 4 patients. (NCT03259035) Clinical trial information: NCT03259035.
Abstract 142: Plasma Exchange Therapy in a Patient with Refractory Kawasaki Disease Initially Treated with Intravenous Immunoglobulin and Prednisolone
Authors: Kentaro Okunushi, Ryota Ebata, Noriyuki Hattori, Hironobu Kobayashi, Naoki Saito, Shigeto Oda, Naoki Shimojo
Journal: Circulation (2015)

Prednisolone combined with intravenous immunoglobulin (IVIG) is the standard option for the initial treatment of Kawasaki disease (KD) in Japan, as described in the 2012 Japanese guidelines for KD. However, there is still debate regarding treatment in patients with refractory KD initially treated with IVIG plus prednisolone, especially in those with comorbid coronary artery aneurysm (CAA). Here, we present the case of a 3 year-old-girl initially treated with IVIG plus prednisolone, whose clinical and laboratory parameters improved after plasma exchange therapy (PE). She was admitted to a local hospital on day 4 of illness and diagnosed as having severe KD (Kobayashi score, 7). Therefore, prednisolone plus IVIG was administered as initial treatment. The initial course was ineffective. She was treated with methylprednisolone pulse therapy, and a second and third round of additional IVIG, but low-grade fever persisted. After these treatments the patient’s general condition had improved and major KD symptoms improved by day 13 of illness, despite a high serum C-reactive protein level (19.9 mg/dl) and hypoalbuminemia (1.8 g/dl). Expanding medium-sized aneurysm was detected on the same day, so she was immediately referred to our hospital for further treatment. The CAA continued to expand, so PE was performed for 3 consecutive days and prednisolone was gradually reduced from day 15 of illness. After that, she became afebrile and CAA progression stopped. Laboratory findings such as serum C-reactive protein and albumin levels were dramatically improved after PE. This case suggests that PE might be effective for refractory KD initially treated with IVIG plus glucocorticoids and may stop the CAA development. Doctors must remain aware that patients treated with glucocorticoids may have masked clinical conditions, and take care not to underestimate the signs of refractory KD.
Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort
Authors: Christian R Kahrs, Katerina Chuda, German Tapia, Lars C Stene, Karl Mårild, Trond Rasmussen, Kjersti S Rønningen, Knut E A Lundin, Lenka Kramna, Ondrej Cinek, Ketil Størdal
Journal: BMJ (2019)

To determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.Case-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016.Norwegian population.Children carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease.Enterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months.Coeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease.Among 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/μL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species Enterovirus A and Enterovirus B were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease.In this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease.
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Authors: Changjun Yin, Susanne Ackermann, Zhe Ma, Sarajo K. Mohanta, Chuankai Zhang, Yuanfang Li, Sandor Nietzsche, Martin Westermann, Li Peng, Desheng Hu, Sai Vineela Bontha, Prasad Srikakulapu, Michael Beer, Remco T. A. Megens, Sabine Steffens, Markus Hildner, Luke D. Halder, Hans-Henning Eckstein, Jaroslav Pelisek, Jochen Herms, Sigrun Roeber, Thomas Arzberger, Anna Borodovsky, Livia Habenicht, Christoph J. Binder, Christian Weber, Peter F. Zipfel, Christine Skerka, Andreas J. R. Habenicht
Journal: Nature Medicine (2019)