tbuckley/cabot-search huggingface dataset:
Abstract 2622: Plasma growth diefferentiation factor-15 is and independen marker for aggressive disease in endometrial cancer
Authors: Hilde Engerud
Journal: Cancer Research (2019)

Abstract Objective: Better biomarkers are needed in order to identify patients with endometrial carcinoma at risk of recurrence and who may profit from a more aggressive treatment regimen. Our objective was to explore the applicability of plasma growth differentiation factor 15 (GDF-15) as a marker for recurrent disease, as well as a marker for poor prognosis and lymph node metastases. Methods: EDTA-blood samples were obtained from 235 patients with endometrial cancer before primary surgery. For 36 of these patients, matching blood samples were collected at time of recurrence. Blood samples were also collected from 78 patients with endometrial hyperplasia. Plasma GDF-15 was measured by an enzyme-linked immunosorbent assay (ELISA). Preoperative pelvic MRI scans for 141 patients were investigated in parallel for imaging variables. Results: Preoperative plasma level of GDF-15 was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518-9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307-7030 ng/L) (p&amp;lt;0.001). Plasma levels of GDF-15 at recurrence (2818 ng/L, 95% CI 2088-3548 ng/L) were significantly higher than plasma levels of GDF-15 measured at time of primary diagnosis (1857 ng/L, 95% CI; 1317-2398 ng/L) (p=0.001). High plasma level GDF-15 independently predicts recurrent disease (OR=3.14; 95% CI 2.10-4.76) and lymph node metastases (OR=2.64; 95% CI 1.52-4.61). Patients with high plasma level of GDF-15 had significantly larger tumor volume (p=0.008). Conclusion: Elevated plasma level of GDF-15 is associated with aggressive disease and lymph node metastasis in endometrial carcinoma. GDF-15 may be helpful in indicating recurrent disease. Citation Format: Hilde Engerud. Plasma growth diefferentiation factor-15 is and independen marker for aggressive disease in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2622.
Supplements Improve Insulin Sensitivity
Authors: Anita Slomski
Journal: JAMA (2019)

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Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease
Authors: Bryan Zeitler, Steven Froelich, Kimberly Marlen, David A Shivak, Qi Yu, Davis Li, Jocelynn R Pearl, Jeffrey C Miller, Lei Zhang, David E Paschon, Sarah J Hinkley, Irina Ankoudinova, Stephen Lam, Dmitry Guschin, Lexi Kopan, Jennifer M Cherone, Hoang-Oanh B Nguyen, Guijuan Qiao, Yasaman Ataei, Matthew C Mendel, Rainier Amora, Richard Surosky, Josee Laganiere, B Joseph Vu, Anand Narayanan, Yalda Sedaghat, Karsten Tillack, Christina Thiede, Annette Gärtner, Seung Kwak, Jonathan Bard, Ladislav Mrzljak, Larry Park, Taneli Heikkinen, Kimmo K Lehtimäki, Marie M Svedberg, Jenny Häggkvist, Lenke Tari, Miklós Tóth, Andrea Varrone, Christer Halldin, Andrea E Kudwa, Sylvie Ramboz, Michelle Day, Jyothisri Kondapalli, D James Surmeier, Fyodor D Urnov, Philip D Gregory, Edward J Rebar, Ignacio Muñoz-Sanjuán, H Steve Zhang
Journal: Nature Medicine (2019)
Abstract 4887: Recurrent <i>NRG1</i> rearrangements in Caucasian pulmonary mucinous adenocarcinoma: results from an Italian multi-center cohort
Authors: Domenico Trombetta, Paolo Graziano, Angelo Sparaneo, Giulio Rossi, Antonio Rossi, Marcello Tiseo, Massimo Di Maio, Federico P. Fabrizio, Maria C. Manzorra, Flavia Centra, Leonarda Di Candia, Marco Audisio, Evaristo Maiello, Vito M. Fazio, Lucia A. Muscarella
Journal: Cancer Research (2019)

Abstract Invasive Mucinous Adenocarcinoma (IMA) is a rare histotype of lung adenocarcinoma associated with an unfavorable prognosis due to the lack of effective treatment. The NRG1 rearrangement is a new subtype-specific molecular feature of IMA and acts as a strong oncogenic inductor of the aberrant tyrosine kinase activity of ErbB2/ErbB3 heterodimers through PI3K-AKT/MAPK cellular cascades. We recently described for the first time the occurrence of NRG1 rearrangements in 31% of Caucasian lung IMAs and highlighted a strong association between NRG1 rearrangements and ErbB3 activation. Here we extended our lung IMA samples cohort by enrolling a total of 71 patients from three different Italian Centers and collected clinical-pathological information and molecular profile, included the mutational status of KRAS, EGFR and ALK genes. We screened all samples by fluorescent in situ hybridization (FISH) for the detection of putative NRG1 rearrangements and by immunohistochemistry (IHC) for the expression of phosphorylated-ErbB3 (pErbB3) receptor. Finally, we customized a new targeted RNA Custom Panel to detect all 9 NRG1-fusion variants published to date to molecular characterize the NRG1 fusion variants in NRG1 rearranged IMAs. Results showed NRG1 rearrangements in 32% of lung IMAs, displaying both NRG1 FISH split signals and deletions of the 5' portion of the gene. IHC confirmed our previous findings of association between pErbB3 immunoreactivity and NRG1 rearrangements, and the heterogeneity of fluorescent signal distribution and immunostaining along the tissue sections. The CD74-NRG1 remains the most common fusion variant identified in lung IMA samples. Correlation analysis among clinical-pathological data, pErbB3 expression and NRG1 rearrangements are ongoing. Our results confirm the usefulness of IHC/FISH combined approach for NRG1 broken tumors identification and highlight the role of NRG1 rearrangement as master molecular marker of lung IMAs, potentially useful to select patients for the emerging target therapies. Citation Format: Domenico Trombetta, Paolo Graziano, Angelo Sparaneo, Giulio Rossi, Antonio Rossi, Marcello Tiseo, Massimo Di Maio, Federico P. Fabrizio, Maria C. Manzorra, Flavia Centra, Leonarda Di Candia, Marco Audisio, Evaristo Maiello, Vito M. Fazio, Lucia A. Muscarella. Recurrent NRG1 rearrangements in Caucasian pulmonary mucinous adenocarcinoma: results from an Italian multi-center cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4887.
Abstract 3407: Atherosclerotic Plaque Imaging using Phase-contrast X-ray Computed Tomography
Authors: Masakazu Shinohara, Tomoya Yamashita, Hideto Tawa, Masafumi Takeda, Naoto Sasaki, Akihisa Takeuchi, Takuji Ohigashi, Kunio Shinohara, Kenichi Hirata, Seinosuke Kawashima, Mitsuhiro Yokoyama, Atsushi Momose
Journal: Circulation (2007)

Background: Reliable non-invasive imaging modalities to characterize atherosclerotic plaque components are clinically desirable for detecting unstable coronary plaques, which cause acute coronary syndrome or sudden death. Although recent clinical developments in computed tomography (CT) have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries, the evaluation of non-calcified plaque components remains difficult. Phase-contrast X-ray CT imaging has great potential to reveal the structures inside soft tissues because its sensitivity to light elements is almost 1000 times greater than that of absorption-contrast clinical X-ray imaging. We for the first time examined mouse atherosclerotic plaques using phase-contrast X-ray CT and found promising results. Methods and Results: Ex vivo phase-contrast X-ray CT was performed using a synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic plaque components in mice. Samples were also histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10 –20 μm revealed atherosclerotic plaque components, and thin fibrous caps could be easily detected. The specific mass densities of these components were estimated using dδ (differences in the refractive indexes relative to water). While lipid-rich areas showed low dδ (0.79 ± 0.13 × 10 −8 ) and mass density (1.011 ± 0.001 g/ml), the smooth muscle- and collagen-rich areas showed high dδ (4.18 ± 0.10 × 10 −8 and 5.93 ± 0.13 × 10 −8 , respectively) and mass density (1.057 ± 0.001 g/ml and 1.08 ± 0.002 g/ml, respectively). It was rather easy to evaluate or differentiate the atherosclerotic plaque components using this novel phase-contrast X-ray CT imaging. Moreover, the three-dimensional assessment of plaques was possible, and it enabled the imaging of their anatomical information. Conclusions: Phase-contrast X-ray CT can estimate the tissue-mass density of atherosclerotic plaques and distinguish the lipid-rich areas from the collagen-rich areas. This is a promising non-invasive technique for the investigation of plaque components and detection of unstable coronary plaques.
Abstract 73: A Case Of Fatal Kawasaki Disease Associated With Fulminant Myocarditis
Authors: Kohji Azumagawa, Hiroshi Katayama, Tsuyoshi Horiuchi, Shinji Yamamoto, Keiko Tanaka, Wakaba Morinobu, Yoshio Ohta
Journal: Circulation (2015)

Introduction: Acute phase Kawasaki disease (KD) is often associated with myocarditis. In most cases, such myocarditis is self-limiting. Fulminant myocarditis is rare as a cause of death for acute KD. We report a case of fatal KD associated with fulminant myocarditis. Case: A 4-year-old boy presented high fever and consulted family doctors for the second successive day. Although he received antibiotics, high fever persisted. He consulted to our hospital on the 4th day of illness. At the initial visit, conjunctival congestion, redness of pharyngeal and lip, bilateral cervical lymphadenitis and erythema on neck, palms and abdomen were observed. Initial laboratory data were shown as follows: WBC count 20,800 / μL, CRP 14.18 mg / dL. He was hospitalized with the diagnosis of acute febrile disease including KD. At first he was prescribed acetylsalicyclic acid and intravenous infusion of antibiotics, however high fever still persisted. On the 6th day of illness, immunoglobulin (IG) and prednisolone were administered intravenously because he was anticipated to be refractory to IG. On echocardiography, left ventricular contraction was normal. There were no findings of coronary artery abnormalities or pericardial effusion. After the first administration of IVIG, high fever persisted. Inflammatory markers on blood examination exacerbated. Laboratory data on the 8th day of illness were as follows: WBC 23,500 / μL, CRP 27.35 mg / dL, CPK 1,451 IU / L (MB 2%). Therefore, we added the second IVIG, steroid pulse therapy and urinastatine. On the next day (9th day), however, he suddenly suffered from cardiopulmonary arrest and deceased. Pathological findings revealed scattered myocardial necrosis on both ventricles. The CD 3, CD 8 positive T lymphocytes were infiltrated around myocytes. There were no findings of coronary artery aneurysms or thromboembolisms. These findings were compatible with fulminant myocarditis. Discussion: Recent advances in therapy for acute KD significantly reduce coronary artery lesions and subsequent mortality. However, clinical feature of KD has a lot of variety. Although fulminant myocarditis associated with KD in early acute phase is extremely rare, we should prepare for refractory KD and its abrupt change.
Beta-catenin and p53 expression in ampullary and small intestinal adenocarcinoma.
Authors: Susan Jean Hsiao, Helen Elaine Remotti
Journal: Journal of Clinical Oncology (2013)

e14659 Background: Small intestinal adenocarcinomas are rare tumors with a worse prognosis than tumors arising from the large intestine. The majority of small intestinal adenocarcinomas arise in duodenum, most commonly around the ampulla of Vater; a smaller subset arises from the jejunum and ileum. Small intestinal adenocarcinomas remain poorly characterized due to their rarity, and limited options exist for adjuvant chemotherapy. Characterization of accumulation of the p53 tumor suppressor and aberrant expression of beta-catenin, suggestive of activation of the Wnt signaling pathway, could have important clinical implications and provide therapeutic targets. Methods: Tissue microarrays of ampullary and small intestinal adenocarcinomas were created using 2 cores of formalin-fixed tissues from 57 patients who had undergone surgical resection. Primary tumors involved the ampulla of Vater in 49% of cases, peri-ampullary duodenum in 39% of cases, and jejunum/ileum in 12% of cases.Immunohistochemical stains were performed for beta-catenin and p53. Cases with accumulation of p53 were scored as positive. Normal localization of beta-catenin is membranous; nuclear (or nuclear and cytoplasmic) accumulation of beta-catenin was scored as positive. Results: Accumulation of the p53 tumor suppressor protein was observed in 67.9% of ampullary adenocarcinomas, 86.4% of peri-ampullary/duodenal adenocarcinomas, and 57.1% of jejunal/ileal adenocarcinomas. Aberrant localization of beta-catenin was observed in 10.7% of ampullary adenocarcinomas, 0% of peri-ampullary/duodenal adenocarcinomas, and 42.9% of jejunal/ileal adenocarcinomas. Conclusions: Our initial results show accumulation of p53 in a substantial proportion of cases, similar to that which has been observed in other tumors. Abnormalities in p53 is one of the most common mutations observed in tumors. This is a clinically important result, as these tumors may respond to specific therapies targeting p53. In addition, our results implicate the Wnt signaling pathway in a subset of jejunal/ileal and ampullary adenocarcinomas offering another possible avenue for targeted therapies.
Hepatic sinusoidal obstruction syndrome (HSOS) in cStage III gastric cancer patients undergoing neoadjuvant chemotherapy with oxaliplatin: a retrospective cohort study
Authors: K. Kawaguchi, D. Manaka, S. Konishi, Y. Ikeda, T. Ota, R. Kudo, N. Sasaki, S. Hamasu, R. Nishitai
Journal: Annals of Oncology (2019)
Abstract 19091: Prognosis of Patients With Out-of-hospital Refractory Cardiac Arrest Referred for Extracorporeal Life Support: An Observational Study
Authors: Cecile Ursat, Marie-Ange Tilliette, Charles Groizard, Margot Cassuto, Anna Ozguler, Michel Baer, Thomas Loeb
Journal: Circulation (2015)

Introduction: In case of no return of spontaneous circulation (ROSC) after conventional cardio-pulmonary resuscitation (CPR), out-of-hospital cardiac arrest (OHCA) patients could be referred for extracorporeal life support (ECLS). Guidelines have been published concerning this specific situation (1). The aim of our study was to describe the prognosis of OHCA patients and verify if referral to ECLS was compliant with these recommendations mainly studying time intervals (no-flow &lt; 5 min, low-flow &lt; 100 min). Methods: A prospective survey on OHCA referred to ECLS was implemented from 03/01/12 until 06/11/15 in an Emergency Medical Service (EMS) located in Paris area (France). This survey included 43 patients referred to hospital for ECLS. Variables were given as means and percentages. Results: Patients referred to ECLS were more often men (77%), with a mean age of 51 years old. Most of 43 OHCA occurred at home (51%), although 26% occurred on public area and 16% at workplace. In 40% of cases, CPR was performed by a witness and in 33% by a health professional. A first Basic Life Support ambulance arrived on scene within 7 min 50 sec, whereas EMS ambulance arrived on scene within 18 min 27 sec after OHCA. At EMS arrival on scene, patients were on asystole (44%), ventricular fibrillation (37%), and on spontaneous circulation (12%). The no-flow time interval was 4 min 10 sec on average (6 patients had a no-flow over 5 min) with 43% of patients with no no-flow. Low-flow time-interval was 44 min. External electric shock was delivered before EMS arrival on 21% of cases, and EMS itself delivered a shock in 40% of cases. Epinephrine was used for all patients, 10.35 mg on average. No patient survived OHCA after referral to ECLS. Discussion: Although this is a small series of 43 patients, no OHCA patient referred to ECLS survived. These results are mainly due to a non-shockable initial condition or too long no-flow time intervals. In order to improve the outcome and bring benefit to the proper expected patients through a cost-effective pathway, we released a reminder of the right recommendations in our EMS. (1) Riou B., Adnet F., Baud F et al. A. Recommandation sur les indications de l’assistance circulatoire dans le traitement des arrêts cardiaques réfractaires. Ann Fr Anesth Réanim 2009 ; 28 : 182-6.
Disease characteristics of diffuse large B-cell lymphoma predicting relapse after autologous stem cell transplantation.
Authors: Daria Gaut, David Oveisi, Grant Howell, Tahmineh Romero, Gary J. Schiller
Journal: Journal of Clinical Oncology (2019)

e19030 Background: High-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is standard of care for patients with diffuse large B-cell lymphoma (DLBCL) whose diseases relapse after, or are refractory to, first-line therapy. However, there are still high rates of relapse following ASCT, and non-relapse mortality also affects survival rates. Prognostic indicators are therefore needed to identify the best candidates for HDC/ASCT. Methods: We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed, 33 refractory) who underwent HDC/ASCT at the University of California Los Angeles from 2010-2015. Results: The median age at the time of ASCT was 61 years (IQR 51.5-68.0). 80 patients (72%) had DLBCL in a complete response at the time of ASCT, and the majority (98 patients, 88%) had ECOG performance status of 0-1. After a median follow-up of 4.6 years (IQR 2.2-8.1), the 1-year progression-free survival (PFS) rate was 77.3% (95% CI 69.7%-85.7%) and the 1-year overall survival (OS) rate was 84.7% (95% CI 78.2%-91.7%). 41 patients (37%) relapsed after ASCT with a median PFS of 11 months (IQR 5.0-20.0). 37 patients (33%) died, 23 (21%) from relapse mortality, 11 (10%) from non-relapse mortality, and 3 (3%) from unknown cause of death. In univariate analysis, 2 variables were significantly associated with curtailed PFS and OS: higher number (≥ 3 vs &lt; 3) of chemotherapy regimens prior to ASCT (HR 2.20, 95% CI 1.19-4.06, p = 0.013 for PFS; HR 2.01, 95% CI 1.06-3.84, p = 0.036 for OS) and higher International Prognostic Index (IPI) score at time of ASCT (trend HR 1.61, 95% CI 1.10-2.35, p = 0.018 for PFS; trend HR 2.02, 95% CI 1.37-2.98, p = 0.001 for OS). Higher National Comprehensive Cancer Network (NCCN) IPI score at time of ASCT (trend HR 2.29, 95% CI 1.34-3.90, p = 0.002) and refractory versus relapsed disease (HR 1.99, 95% CI 1.04-3.82, p = 0.038) were also significantly associated with curtailed OS. Conclusions: Our study suggests that IPI, while a validated prognostic tool at diagnosis, is also a prognostic indicator at time of ASCT for PFS and OS. NCCN IPI at time of ASCT was also found to be predictive of OS. Age-adjusted IPI was not associated with outcome following ASCT.
Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction
Authors: Li Shen, Rasmus Rørth, Deborah Cosmi, Søren Lund Kristensen, Mark C. Petrie, Franco Cosmi, Roberto Latini, Lars Køber, Inder S. Anand, Peter E. Carson, Christopher B. Granger, Michel Komajda, Robert S. McKelvie, Scott D. Solomon, Lidia Staszewsky, Karl Swedberg, Thao Huynh, Michael R. Zile, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2019)

Abstract Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM‐Preserved (left ventricular ejection fraction ≥ 45%), I‐Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N‐terminal pro‐B‐type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end‐diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient‐years in patients without diabetes, and 10.2 and 17.1 per 100 patient‐years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin‐treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23–1.63, P &lt; 0.001]. The adjusted HR is 1.67 (95% CI 1.20–2.32, p = 0.002) for sudden death (insulin‐treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose‐lowering treatments in HF needs to be evaluated in clinical trials.