tbuckley/cabot-search huggingface dataset:
Abstract 12681: Determinants of Prolonged Hospital Stay for Patients Undergoing Revascularization: The ASCERT Study
Authors: Zugui Zhang, Fred Edwards, Paul Kolm, Maria Grau-Sepulveda Maria Grau-Sepulveda, Sean O'Brien, David Shahian, Angelo Ponirakis, Lloyd W Klein, Frederick L Grover, Kirk N Garratt, Charles Mckay, William S Weintraub
Journal: Circulation (2015)

Background: Prolonged hospital stay (PHS) has been a costly health care issue. Using data from the Society of Thoracic Surgeons (STS) Database and the American College of Cardiology Foundation (ACCF) National Cardiovascular Data Registry (NCDR) in ASCERT, we examined the determinants of PHS in a 30-day period after the index hospitalization for patients undergoing coronary-artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI). Methods: The STS Database and ACCF NCDR were linked to the Centers for Medicare and Medicaid Services claims data from years 2004 to 2008 for patients who were age ≥65 years with stable 2 and 3-vessel disease undergoing revascularization. The length of stay &gt;7 days in CABG and &gt;2 days in PCI patients was defined as PHS, respectively; the determinants of PHS in a 30-day period after the index hospitalization for CABG and PCI patients were examined. Results: By 30 days, 40,694 (47.18%) of 86,244 in CABG group and 32,789 (31.67%) of 103,549 in PCI group had PHS. Of those, 7,000(17.2%) and 13,721(33.72%) were diagnosed with congestive heart failure (CHF) and unstable angina in CABG, respectively; among PCI patients, 6491 (19.8%) and 18,397 (56.11%) were diagnosed with CHF and unstable angina, respectively. We found that advanced age, gender, race, body mass index, smoking status, stroke, angina status, left ventricular ejection fraction, number of diseased vessels (2 vs 3 or more), CHF, chronic lung disease, CVD, peripheral vascular disease, diabetes, GFR, renal failure, and procedure status were significantly associated with PHS for both groups; previous MI and family CAD history were associated with PHS in CABG group (c-index=0.70) but not in PCI group; AMI, previous PCI, and discharge medication were associated with PHS in PCI group (c-index=0.75) but not in CABG group. Adjusted by other risk factors, PHS was less likely after PCI (odds ratio: 0.46, 95% CI: 0.44 to 0.49, c-index=0.76). Conclusions: Determinants of PHS were significantly related to specified pre-, intra- and postoperative risk factors for CABG and PCI patients in 30 days after index-hospitalization. This analysis that linked large clinical and administrative databases can be applied to inform shared decision making between providers and patients.
Abstract 19821: Integrin αDβ2 (CD11d/CD18) Promotes Atherogenesis by Supporting Macrophage Retention in Atherosclerotic Lesions
Authors: Moammir Aziz, Kathleen Brown, Kui Cui, Juying Han, Jonathan D Smith, Valentin P Yakubenko
Journal: Circulation (2016)

Understanding the mechanism of macrophage retention in atherosclerotic lesions is a key question in the control of atherogenesis. Integrin α D β 2  (CD11d/CD18) is a multiligand leukocyte adhesive receptor with unidentified functions. Previously we found that CD11d overexpression on cell surface inhibits cell migration due to excessive adhesive force. Currently, we found that CD11d expression is dramatically upregulated on macrophages in atherosclerotic lesions and on pro-inflammatory M1 macrophages  in vitro . Hence, we hypothesized that high expression of CD11d promotes atherogenesis and serves for the retention of pro-inflammatory macrophages in atherosclerotic lesions.  To test our hypothesis we generated CD11d -/- /ApoE -/-  mice and evaluated atherogenesis after 16 weeks on a Western diet. CD11d-deficiency markedly reduced lipid deposition in the entire aorta (2.12-fold) and aorta sinuses (1.53-fold). Macrophage number in aorta sinuses of CD11d -/-  mice was also significantly reduced without affecting their apoptosis and proliferation, which indicates a potential role of CD11d in migration-related macrophage accumulation. The effect of CD11d on macrophage migration/retention was tested using adoptive transfer of wild type (WT) and CD11d -/-  monocytes labeled with two non-overlapping near-infrared fluorescent dyes. Equal numbers of WT and CD11d -/-  monocytes were injected into the tail vein of ApoE -/-  mice and their accumulation in atherosclerotic lesions was assessed at 72 hrs. The result showed a similar monocyte emigration from the circulation, but significantly reduced number of labeled CD11d -/-  macrophages in the aortas (2.4-fold). The contribution of CD11d to macrophage retention was further verified in the model of resolution of peritoneal inflammation. Fluorescently-labeled WT and CD11d -/-  M1 macrophages were injected intraperitoneally to WT mice with pre-conditioned thioglycollate-induced peritoneal inflammation. The efflux of CD11d-deficient macrophages was 1.8-fold faster from the peritoneal cavity which confirms improved migratory properties of CD11d -/-  macrophages. In summary, macrophage CD11d is involved in atherogenesis by the contribution to the retention of M1 macrophages in the atherosclerotic lesions.
PHRM-02. DELIVERY OF CHEMOTHERAPEUTICS TO PEDIATRIC BRAIN TUMORS USING CITRATE-CAPPED GOLD NANOPARTICLES
Authors: Krishna Madhavan, Ilango Balakrishnan, Angela Pierce, Sujatha Venkataraman, Rajeev Vibhakar
Journal: Neuro-Oncology (2018)

Medulloblastomas and gliomas account for nearly 28% of primary tumors and about 80% of malignant tumors in children. Many of the chemo-drugs that are found effective in killing tumor cells perform well in laboratory settings but fail to cross the blood-brain barrier in humans in direct clinical applications. This problem is overcome by using carriers which could deliver the drugs across the blood-brain barrier. To increase the efficacy of drugs in targeting different tumors, different nanoparticles have been used as carriers in the recent past. Some drugs, including AZD-1775 and Gemcitabine, have been shown by researchers to be effective in multiple brain tumors but have not been adequately utilized alone and/or in combination in pediatric brain tumor patients. In our study, we have conjugated AZD-1775 and Gemcitabine to citrate-capped gold nanoparticles (AuNPs). Cells have been treated with a drug alone, or AuNP alone and AuNP conjugated with drugs for 72 hours. Cell viability assays, cell cycle analysis and western blotting have been used to evaluate the delivery of drug to cells. Both the drugs and their AuNP-conjugates inhibited the growth of cells tested. AuNPs conjugated with the drugs showed more effective delivery of the drugs to cells than drugs alone at the same concentrations, as measured by tumor cell growth. Also, our initial in vivo study shows prolonged survival of mice bearing brain tumors treated with AuNP-conjugated AZD-1775 than those treated with AZD-1775 alone. These results confirm that AuNPs are a suitable platform to deliver chemotherapeutics to brain tumors.
EPEN-11. ANALYSIS OF EXPRESSION OF YAP1, RELA, MAMLD1 AND FAM118B GENES IN PEDIATRIC EPENDYMOMA
Authors: Bruna Mascaro-Cordeiro, Indhira Oliveira, Maria Teresa Alves, Frederico Adolfo Silva, Nasjla Saba-Silva, Andrea Capellano, Sergio Cavalheiro, Patricia Dastoli, Silvia Toledo
Journal: Neuro-Oncology (2018)

Ependymomas (EPN) are primary tumors in the central nervous system (CNS). In children, 90% of EPNs occur intracranial, with two-thirds being located in the posterior fossa (PF) and one-third within the supratentorial (ST) compartment. Despite the development of new molecular classifications and increasing understanding of the underlying EPN mechanisms, management and treatment remain challenging. We investigated the expression of genes involved in EPN molecular rearrangements (YAP1, RELA, MAMLD1 and FAM118B), in 27 EPN patients from Pediatric Oncology Institute - GRAACC, Brazil. Gene expression levels were quantified using qPCR. Molecular findings were correlated to clinicopathological characteristics of patients. Significant results were considered when p<0.005. Overall survival was significantly lower in patients with PF tumors than ST tumors (p=0.0109), and high YAP1 expression was related to worst overall survival (p=0.0488). ST tumors presented higher RELA expression than PF tumors (p=0.0089). Expression of YAP1 and FAM118B genes significantly correlated (r=0.917, p<0.0001). All investigated genes are partners in fusion genes recently described for EPN and the levels of expression observed were in agreement with findings in the literature. Additional studies are in progress to collaborate with the characterization of EPN genetics, once development of targeted therapies will require the understanding of tumor biology and its effect in the clinical outcomes. Based on recent molecular findings, and after the actualization of WHO classification of tumors of the CNS in 2016, it is becoming evident that, in the near future, histologic criteria alone might be insufficient to direct treatment, to predict outcomes and refine EPN treatment.
Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond–like syndrome
Authors: Christine Bellanné-Chantelot, Barbara Schmaltz-Panneau, Caroline Marty, Odile Fenneteau, Isabelle Callebaut, Séverine Clauin, Aurélie Docet, Gandhi-Laurent Damaj, Thierry Leblanc, Isabelle Pellier, Cécile Stoven, Sylvie Souquere, Iléana Antony-Debré, Blandine Beaupain, Nathalie Aladjidi, Vincent Barlogis, Frédéric Bauduer, Philippe Bensaid, Odile Boespflug-Tanguy, Claire Berger, Yves Bertrand, Liana Carausu, Claire Fieschi, Claire Galambrun, Aline Schmidt, Hubert Journel, Françoise Mazingue, Brigitte Nelken, Thuan Chong Quah, Eric Oksenhendler, Marie Ouachée, Marlène Pasquet, Véronique Saada, Felipe Suarez, Gérard Pierron, William Vainchenker, Isabelle Plo, Jean Donadieu
Journal: Blood (2018)
Correction: Diffusion-Weighted Imaging in Cancer: Physical Foundations and Applications of Restriction Spectrum Imaging
Journal: Cancer Research (2014)

Author(s): White, NS; McDonald, C; Farid, N; Kuperman, J; Karow, D; Schenker-Ahmed, NM; Bartsch, H; Rakow-Penner, R; Holland, D; Shabaik, A; Bjornerud, A; Hope, T; Hattangadi-Gluth, J; Liss, M; Parsons, JK; Chen, CC; Raman, S; Margolis, D; Reiter, RE; Marks, L; Kesari, S; Mundt, AJ; Kane, CJ; Carter, BS; Bradley, WG; Dale, AM
RADI-09. CLASSIC RADIOLOGIC FINDINGS ASSOCIATED WITH BLASTIC HYPERLEUKOCYTIC CRISIS
Authors: Nidhi Shah, Vinay Kandula
Journal: Neuro-Oncology (2018)

Extreme leukocytosis, characterized by white blood cell count greater than 100 x 109/L, is more common in patients with T-cell acute lymphoblastic leukemia or those with massive splenomegaly. There is an increased risk of central nervous system complications, such as leukostasis and tumor lysis syndrome. Severe leukostasis leads to vascular occlusion, which causes ischemic tissue injury subsequently leading to intracranial hemorrhages and respiratory failure. Significant morbidity and mortality can result due to myocardial infarction and ischemia, as well as retinal hemorrhages and cerebral thromboses. Imaging done around the time of blastic hyperleukocytosis reveals unique findings of diffuse petechial hemorrhages in the brain secondary to vaso-occlusion. Here we discuss a 13-year-old male with T-cell ALL, who initially presented with white blood cell count of 350x 109/L, mental status changes as well as respiratory symptoms. Neuroimaging was negative for focal hemorrhages or herniation. He immediately underwent therapeutic leukapheresis with improvement in his symptoms. Imaging done 40 days later showed diffuse petechial hemorrhages in bilateral posterior frontal lobes, bilateral temporal and parietal lobes, as well as within the body and splenium of the corpus callosum, and limbs of internal capsule. No abnormal enhancement was observed, likely representing chronic nature of these foci of hemorrhages. A repeat MRI scan 60 days after admission demonstrated evolving changes of hemorrhage, with no new foci of hemorrhages. During this time, patient had no clinically significant central nervous system abnormalities. In conclusion, hyperkeukocytic blastic crisis can present with diffuse acute microhemorrhages on neuroimaging without significant clinical neurologic deficits.
SIRT therapy with Yttrium-90 resin microspheres in patients with liver cirrhosis Child Pugh B7-9 and unresectable nonmetastatic hepatocellular cancer
Authors: J. Eick, M. Burbelko, M. Plotkin, J. Steinberg, W. Ring, C. Schwertner
Journal: Annals of Oncology (2018)

Introduction: Treatment options of unresectable hepatocellular cancer (HCC) are limited. Drug therapy with sorafenib, regorafenib or lenvatinib was approved only for HCC-patients with good liver function, i.e. liver cirrhosis Child Pugh A. Sorafenib therapy in HCC-patients with Child Pugh B-cirrhosis results in a median overall survival of 5.2 months (GIDEON trial: Marrero J et al., J Hepatology 2016, 65: 1140–47). Yttrium-90 (Y-90) resin microspheres are effective in nonmetastatic HCC but have not been studied in advanced cirrhosis. We evaluated the safety and efficacy of Y-90 microspheres in HCC-patients with liver cirrhosis B7-9. Methods: 12 patients (8 men, 4 women) with a median age of 64.5 years [range 44-83] suffering from both liver cirrhosis B7-B9 and unresectable nonmetastatic HCC were treated once or twice with Y-90 resin microspheres in our hospital in the years 2013-2017. In most patients alcohol abuse was the cause of liver cirrhosis. TACE was considered not to be effective in these patients. Our exclusion criteria for selective internal radiotherapy (SIRT) were either serum bilirubin >2.4 mg%, infiltration of the portal vein by tumor, portal vein thrombosis, extrahepatic metastasis, significant ascites, renal insufficiency, concurrent infection, uncontrolled bleeding or significant encephalopathy. Patients with bilobar HCC were scheduled for 2 separate unilobar SIRT sessions (1 right-sided, 1 left-sided, 4-6 weeks apart). Results: All patients adhered well to therapy and follow-up. Y-90 resin microspheres were well tolerated by the patients. In 2 patients transient flares of AST and/or ALT and/or bilirubin were noted. Epigastric discomfort for 1-2 days was reported by 5 patients. 10 patients died due to progressive disease, 2 patients are still alive. At 3 months after 1st SIRT the disease control rate was 50%. A median overall survival of 10.0 [range 4-16] months as calculated from 1st unilobar application of Y-90 microspheres was observed at this interim analysis; mean overall survival (after SIRT) amounts now to 9.3 + 3.7 months (11.8 months for B7 and 7.5 months for B9 patients). Due to angiographic evaluation and ordering of Y-90 microspheres from overseas 4-6 weeks (without specific treatment) passed by between decision making and the first SIRT. Conclusion: SIRT therapy is safe in patients with unresectable nonmetastatic HCC and liver cirrhosis Child Pugh B7-9, as the chosen exclusion criteria are respected. Overall survival of our patients is better than the one reported for sorafenib treatment in HCC-patients with liver cirrhosis B7-9 of the GIDEON trial. Thus, SIRT with Y-90 resin microspheres should be considered for patients with unresectable nonmetastatic HCC and liver cirrhosis B7-9, if our exclusion criteria are observed.
ESMO Consensus Conference on malignant lymphoma: management of ‘ultra-high-risk’ patients
Authors: M. Hutchings, M. Ladetto, C. Buske, P. de Nully Brown, A.J.M. Ferreri, M. Pfreundschuh, N. Schmitz, A. Sureda Balari, G. van Imhoff, J. Walewski
Journal: Annals of Oncology (2018)

The European Society for Medical Oncology (ESMO) consensus conference on malignant lymphoma was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (1) the elderly patient, (2) prognostic factors suitable for clinical use and (3) the 'ultra-high-risk' group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address clinically relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the questions devised by their group. These recommendations were then presented to the entire multidisciplinary panel and a consensus was reached. This manuscript presents recommendations regarding the management of the following 'ultra-high-risk' situations: (1) early central nervous system relapse of diffuse large B-cell lymphoma, (2) primary refractory Hodgkin lymphoma and (3) plasmablastic lymphoma. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript. All expert panel members approved this final article.
Predicting survival benefit of capecitabine plus cisplatin in patients with metastatic gastric cancer patients using quantitative proteomics
Authors: E. An, M. Ryu, D. Yan, Y. Park, H. Na, J. Ma, Y. Tian, F. Cecchi, T. Hembrough, Y. Kang
Journal: Annals of Oncology (2018)

Introduction: Capecitabine plus cisplatin (XP) is a standard treatment for metastatic gastric cancer (mGC). Capecitabine activation requires the enzymes uridine-cytidine kinase 2 (UCK2) and orotate phosphoribosyl transferase (OPRT). We previously used mass spectrometry to quantitate UCK2 in tumor samples from 5-FUtreated patients with stage II/III colorectal cancer; UCK2 protein expression > 319 amol/ug of tumor protein was associated with improved survival. Here, we assessed whether these biomarkers would predict survival among mGC patients treated with XP. Methods: Formalin-fixed, paraffin-embedded tumor samples from patients with mGC were microdissected and solubilized for mass spectrometric quantitation of 16 protein biomarkers. Kaplan-Meier survival curves were compared using a log-rank test. Multivariate Cox models of survival included clinical covariates and protein biomarkers. Results: mGC tumor samples from 116 XP-treated patients were analyzed (males: 64%; median age: 55 years). All samples expressed OPRT protein (range: 202 – 1719 amol/ug), and 114 of 116 expressed UCK2 (range: 119 – 933 amol/ug). Patients with UCK2 expression above the pre-defined cutoff of 319 amol/μg (n = 30) had longer time to progression (TTP) (HR: 0.60; p = 0.020) than patients below the cutoff. Results for overall survival (OS) were similar (HR: 0.59; p = 0.015). OPRT protein expression > 790 amol/ug (n = 24) was associated with longer TTP (HR: 0.58; p = 0.019) and longer OS (HR: 0.60; p = 0.029). In multivariate analysis, UCK2 and OPRT remained independent predictors of survival after adjustment for age, gender, ECOG performance status, metastatic sites, and other clinical covariates. Conclusion: XP-treated mGC patients with tumor expression of UCK2 and OPRT proteins above quantified thresholds survived longer than patients with lower expression. Mass spectrometric quantitation of these common tumor proteins at diagnosis may improve patient selection for XP. Studies to validate these and other chemopredictive biomarkers are ongoing.
LGG-25. NOVEL FGFR2 FUSIONS DRIVE ONCOGENESIS VIA MAPK AND PI3K/mTOR PATHWAY ACTIVATION IN DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS
Authors: Payal Jain, Lea Surrey, Joshua Straka, Minjie Luo, Adam C Resnick, Phillip B Storm, Mariarita Santi, Marilyn Li, Angela J Waanders
Journal: Neuro-Oncology (2018)

Dysembryoplastic neuroepithelial tumor (DNT) is a benign glioneuronal neoplasm classified by the 2016 WHO under the mixed neuronal-glial tumors. Compared to other low-grade neuroepithelial tumors (LGNTs) in this category, the genetic profile of DNTs is poorly understood. DNTs have been shown to exhibit mutational variability, ranging from stable genomes to occurrence of BRAF V600E (30% of cases), whole chromosome gains and FGFR1 mutations. To further expand our understanding of genetic drivers of DNTs, we performed clinical integrated genomic profiling and identified two novel FGFR2-associated gene fusions, FGFR2-INA and FGFR2-CTNNA3, in three patients with the histologic diagnosis of DNT. All three DNT cases harbored novel in-frame fusions between the kinase domain of FGFR2 and INA or CTNNA3. To functionally characterize the novel FGFR2 fusions, we cloned FGFR2-INA and stably expressed it in heterologous cell models. Soft agar proliferation assays showed significant increase in colony count in FGFR2-INA expressing cells over control (p<0.0005). In western blot assays, increased protein phosphorylation of both the MAPK and PI3K/mTOR pathways was observed in FGFR2-INA cells. Mechanistically, we found that FGFR2-INA dimerizes in co-immunoprecipitation assays suggesting dimerization induced activation of FGFR2 fusion proteins. We thereby identify and describe two novel FGFR2 fusions associated with DNT that aberrantly activate the MAPK and PI3K/mTOR signaling pathways. This oncogenic mechanism is similar to that of BRAF V600E mutations and may explain tumorigenesis in at least a subset of DNTs. In FGFR2 fusion positive DNTs, this genetic event is the likely driver of tumorigenesis and suggests a potential therapeutic target.
ATRT-13. CANCER PREDISPOSITION AMONG CHILDREN WITH RHABDOID TUMORS: A SINGLE-CENTRE RETROSPECTIVE REVIEW
Authors: Hallie Coltin, Anna Pan, David Malkin, Annie Huang, Catherine Goudie
Journal: Neuro-Oncology (2018)

Rhabdoid tumor predisposition syndrome (RTPS) from SMARCB1 germline mutations must be ruled out in children with rhabdoid tumors (RT). The aim was to describe the diagnostic details of children with RT, genetic referral practices, and rates of SMARCB1 germline pathogenic mutations, and to compare clinical features of children with and without RTPS. The medical charts of sequential children diagnosed with RT at the Hospital for Sick Children from 1995–2016 were reviewed for the diagnostic details, family histories, and genetic testing results. Fifty-nine children diagnosed with RT at a mean age of 37.6 months were included. Atypical teratoid rhabdoid tumors represented 73% of the tumors. Of the patients with family histories documented, 17% were suspicious for cancer predisposition. Of the 31 patients with genetic testing results, 12 had SMARCB1 pathogenic mutations. The mean age of diagnosis was 12.0 months for children with RTPS compared to 37.6 months in those without RTPS. In children presenting at ≤ 12 months of age, 64% were subsequently diagnosed with germline SMARCB1 mutations. When the age limit was increased to ≤ 36 months, the rate of SMARCB1 mutations was 42%, while this rate was 25% in those aged > 36 months. Rates of SMARCB1 germline mutations increase with younger age, but the elevated rates of RTPS detection in this cohort for all ages support the practice that all children diagnosed with RT should undergo genetic testing to investigate for RTPS, even if the family history is not suggestive of inherited cancer.