tbuckley/cabot-search huggingface dataset:
Abstract P353: Health-Related Quality of Life and Risk of All-cause and Cardiovascular Hospitalization in a Healthy General Population: Prospective Findings From the Moli-Sani Study
Authors: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia De Curtis, Mariarosaria Persichillo, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2019)

Introduction: There is paucity of data on the longitudinal association of health-related quality of life (HRQL) with health outcomes from the general population, and little is known on the pathways of such associations. Hypothesis: We assessed the hypothesis that HRQL would predict risk of total and cardiovascular (CVD) hospitalization in a population-based cohort of healthy subjects, and tested four pathways possibly accounting for such associations. Methods: Longitudinal analysis on 16,097 subjects from the general population of the Moli-sani study, Italy (2005-2010), free from CVD, cancer and diabetes. HRQL was assessed by the 36-Item Short Form Health Survey including both mental and physical domains. Behavioural, traditional, inflammatory and novel markers of CVD risk (listed in table) were tested as explanatory factors. First hospital admissions were recorded by direct linkage with hospital discharge forms. Hazard ratios (HR) with 95% confidence interval (95%CI) were calculated by multivariable Cox-regression. Results: Over a median follow-up of 7.4 years, 5644 all-cause and 1724 CVD hospital admissions were ascertained. The highest quintile of mental HRQL was associated with 23% (95%CI: 17% to 29%) and 27% (15% to 37%; Table) lower risk of total and CVD hospitalization, respectively, as compared to the lowest. Risk estimates for physical health were 0.59 (0.54-0.63 for Q5 vs Q1) and 0.56 (0.48-0.64) for total and CVD risk of hospital admissions, respectively. Novel biomarkers (listed in table) accounted for the largest, although modest, proportion of the association of HRQL with risk of CVD hospitalization. Conclusions: In a large sample of disease-free subjects, not only higher physical, but also higher mental HRQL is associated with lower risk of total and CVD hospitalizations. Differences in baseline novel biomarkers slightly explain such associations. Our results suggest that HRQL assessment may be useful in stratifying hospitalization risk among a general population of adults.
Demographic factors associated with a high 30 day readmission rate after bone marrow transplant.
Authors: Abhishek Seth, Colleen MacCallum, Sourabh Aggarwal, Sreenivasa Rao Chandana, Akshay Amaraneni
Journal: Journal of Clinical Oncology (2015)

e18006 Background: Patient readmission within 30 days from discharge has been perceived to be an indicator of poor healthcare quality for high-cost medical conditions. Patient’s who undergo bone marrow transplant are often readmitted. In order to understand the population risk factors for readmission after a bone marrow transplant, our we studied the Nationwide Inpatient Sample Database. Our study identifies the demographic risk factors associated with a high 30-day readmission among recipients of bone marrow transplant Methods: Nationwide Inpatient Sample Database was used to extract the data for patients who were discharged after a Bone Marrow Transplant, (both autologus as well as allogenic) for the years 2009-2012, using clinical classification software. We collected data variables including age, gender, the type of insurance on all the patients, who were readmitted with in 30 days after index hospitalization for bone marrow transplant. Statistical analysis was done using SAS software. We used chi-square analysis to determine group differences. Results: We identified 65,699 index hospitalizations, with a 30 day readmission rate of 24%. Readmission rate was highest among younger patient (less than 17 years), with a readmission rate of 45% as compared to older patients (18-44yrs, 27.4%; 45-64 yrs, 19.8% and > 65 yrs, 19.9%). Chi square analysis was statistically significant (p < 0.0001). The readmission of female patients was higher than male patients (25.2% vs 23.3%, p < .0001). Statistically significant difference was seen among patients with medicaid(32.6%) vs medicare (22%) vs private insurance(22.1%) Conclusions: In the retrospective study involving 65,699 patients with bone marrow transplant, we identified several risk factors, which could explain their 30 day readmission. Strategies to reduce 30-day readmissions after bone marrow transplant should be focused on more susceptible population including females, age less than 17 years and those with Medicaid insurance.
miR-196b and miR-486 as predictive biomarkers for the efficacy of the vaccine treatment: From the results of phase I and II studies for metastatic colorectal cancer.
Authors: Hiroaki Ozasa, Shoichi Hazama, Ryoichi Shimizu, Ryuichi Etoh, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Nobuaki Suzuki, Hiroko Takenouchi, Ryouichi Tsunedomi, Norio Iizuka, Shigefumi Yoshino, Kiyotaka Okuno, Fumiaki Sugiura, Yusuke Fujita, Yoshihiko Hamamoto, Tomonobu Fujita, Yutaka Kawakami, Yusuke Nakamura, Masaaki Oka
Journal: Journal of Clinical Oncology (2015)

e14001 Background: microRNAs (miRNAs) are endogenous single-stranded RNA molecules of 18-24 nucleotides that regulate the levels of transcripts and have a critical role in regulation of tumor microenvironments including the activity of anti-tumor T cells. Hence, miRNA levels in cancer tissues are thought to be possible biomarkers for immunotherapy. Methods: Among 18 patients who were treated with a phase I trial of the vaccine treatment using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, we obtained colorectal cancer tissues from 8 cases and normal colorectal tissues from 5 cases through surgical operation; among 96 patients who were enrolled in the phase II trial of the same vaccine regimen in combination with oxaliplatin-containing chemotherapy, colorectal cancer tissues were obtained from 16 cases with HLA-A*2402. We have used these tissues for miRNA microarray analysis. Results: As the first step, we used cancer tissues in the phase I study and selected ten candidate miRNAs that might predict the efficacy of immunotherapy by comparison of miRNA expression levels in two groups, patients with better prognosis and those with poorer prognosis. We then validated these miRNAs using the cases enrolled in the phase II study and confirmed the significantly better prognoses in patients with cancer tissues having expressions of miR-196b-5p of > 410 (hazard ratio = 0.104, p = 0.007; log-rank test, p = 0.001) and a miR-486-5p of < 340 (hazard ratio = 0.246, p = 0.032; log-rank test, p = 0.022), respectively, indicating that these two miRNAs might be predictive biomarkers for the efficacy of immunotherapy coupled with chemotherapy for patients with an unresectable colorectal cancer. Conclusions: A high miR-196b-5p and a low miR-486-5p expression might be considered as novel biomarkers for good immune response to cancer vaccine treatment. In a planned phase III study, expression levels of these two miRNAs might be useful biomarkers for assessing patients who are likely to have a better outcome with the vaccination. Clinical trial information: UMIN000004948 and UMIN000001791.
Abstract P351: Psychological Resilience is Associated With Higher Subjective Well-being Among Adults Living With Chronic Disease
Authors: Kristen M Tecson, Lindsay R Wilkinson, Bethany Smith, Jong M Ko
Journal: Circulation (2019)

Introduction: While living with a chronic disease can be challenging, some studies have shown that psychological resilience is associated with better outcomes. In this study, we aimed to determine the impact of resilience on well-being among adults living with chronic disease. Hypothesis: We hypothesized that resilient participants would have higher quality of life, life satisfaction, happiness, and less psychological distress than those with low resilience. Methods: Patients who received treatment for a chronic disease within Baylor Scott &amp; White Health (Dallas, TX) and self-identified an informal caregiver, i.e., a nonpaid friend/family member who provides regular care, were eligible for this study. A phone survey was administered from February-May 2017 by the Center for Community Research and Development at Baylor University. We built linear and ordinal logistic regression models to assess the effect of psychological resilience on well-being while adjusting for sociodemographic and health covariates. Results: Forty-one participants completed the study. The average age was 66.5 ± 9.5 years and the most common disease was heart failure (16; 39%). Overall, participants had high resilience (median: 4 [quartile 1=3.3, quartile 3=4.7], scale: 1-5), low psychological distress (4 [2, 7], scale: 0-24), good quality of life (8 [5, 9], scale: 0-10), and high life satisfaction (5 ± 1.6, scale: 1-7). In addition, 33 (81%) respondents were pretty/very happy. The effect of resilience was significant in the expected direction in unadjusted analyses. After accounting for potential confounders, the resilience effect lost significance in the model for life satisfaction (b=0.37, p=0.195), trended toward significance for quality of life (b=0.63, p=0.117), and remained highly significant for psychological distress and happiness (b=-1.91, p=0.003, odds ratio=4.71, p=0.004, respectively). Conclusion: In conclusion, psychological resilience may be a resource to preserve well-being for those living with chronic disease.
Immunogenomic landscape of neuroendocrine small cell prostate cancer.
Authors: Lucia Nappi, Claudia Kesch, Sepideh Vahid, Ladan Fazli, Bernhard J. Eigl, Christian K. Kollmannsberger, Martin Gleave, Amina Zoubeidi, Alexander William Wyatt, Kim N. Chi
Journal: Journal of Clinical Oncology (2019)

217 Background: Neuroendocrine small cell prostate cancer (NEPC) is a lethal variant of prostate cancer (PCa) unresponsive to hormone therapy and associated with poor prognosis. Cisplatin induces short-lived responses and therefore alternative novel therapeutic options are urgently needed. Methods: Prostate specimens from radical prostatectomy or transurethral resection (benign prostate specimens n = 4, primary untreated or neoadjuvant hormone-treated adenocarcinoma n = 30, castrate-resistant prostate cancer-CRPC n = 38 and NEPC n = 16) were evaluated for PD-L1 (SpringBio, M4420), AR, chromogranin A, synaptophysin, NSE and CD56 expression by immunohistochemistry (IHC). Archival tissue from liver, lymph nodes and prostate from 30 additional patients with de novo and treatment emergent NEPC were analyzed for PD-L1 expression by IHC. The intensity was assessed as percentage of positive cells / mm2 of tissue. Targeted and whole exome sequencing of the high-density tumor areas were performed and correlated to the PD-L1 status (PD-L1+ve: &gt; 1% of positive cells). OS was calculated from the date of diagnosis of NEPC to death. We set out to define PD-L1 expression and immunogenomic characteristics of NEPC. Results: PD-L1 was expressed in 0%, 5%, 10% and 41% of benign, adenocarcinoma, CRPC and NEPC specimens, respectively. The PD-L1 expression intensity was significantly higher in patients with NEPC (mean: 40%, range: 5-100%) compared to benign, adenocarcinoma and CRPC samples (mean: 0%, 2% and 8%, respectively, P &lt; 0.0001). There was a higher prevalence of biallelic DNA Repair Defects (DRD) in the PD-L1+ve vs PD-L1-ve patients (65% vs 0%, P = 0.005). The median OS of the NEPC patients was 8.5 months vs 10.5 months in PD-L1+ve vs PD-L1-ve tumors (HR 1.24, 95% CI: 0.59-2.75, p = 0.55). Conclusions: NEPC have greater PD-L1 expression than adenoCa and CRPC. Biallelic DRD was exclusively observed in PD-L1+ve patients. Since PD-L1 expression and DRD have been associated to response to PARP and PD1/PD-L1 inhibitors in prostate and other cancers, further studies evaluating the activity of those agents in NEPC patients are warranted.
Effects of antibiotics on CNS radiation necrosis.
Authors: Yanqing Feng, Xi Chen, Ning Guo, Zhenhua Gao
Journal: Journal of Clinical Oncology (2015)

e17008 Background: The mechanism of radiation-induced delayed brain injuries remains poorly understood, and few treatment options are available. The aim of this study was to investigate whether temporal lobe necrosis can be reversed by anti-mycobacterium therapy (AMT). Methods: We conducted this prospective, controlled study in southern China. Ten patients with symptomatic delayed radiation injury were monitored during AMT and compared with a control group of 11 patients who received current standard therapies. Activities of daily living were assessed by the Barthel Index (BI) at study entry and after 2 years of therapy. Magnetic resonance imaging (MRI) was performed before treatment, and changes were monitored during the study. Kaplan–Meier analysis was employed to delineate time-related mortality. Results: A significant treatment effect was observed in the AMT group. The patients’ headaches, seizures, dizziness, and cognitive deterioration rapidly improved. BI improved in the AMT treatment group compared with the control group after 2 years (Mann–Whitney U test; P= 0·001). Abnormalities of the temporal lobes, observed by MRI, markedly decreased over time in eight patients, whereas in the control group significant BI deterioration was observed (Wilcoxon signed-rank test; P= 0·003) and the patients did not show favorable MRI changes. By 24 months, there was a significant difference between the AMT and control groups with respect to survival time (log-rank test; P= 0·011). Conclusions: The results of present study revealed that AMT can effectively treat DRI, and indicates skull-base irradiation may disrupt the local immune function, and predisposes to chronic mycobacterial infection. Clinical trial information: ISRCTN04023349.
Trends in the Utilization of Radiation Therapy (XRT) Among Patients with Non-Hodgkin's Lymphoma (NHL) in the United States (US)
Authors: Vivek Kumar, Taimur Sher, Prakash Vishnu, Vivek Roy, Anne M Hazen, Victoria R. Alegria, Meghna Ailawadhi, Salman Ahmed, Prachi Jani, Zan Tahir Shareef, Sri Lekha Bodepudi, Aneel Paulus, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2018)
The IL-1/IL-1 receptor axis and tumor cell released inflammasome adaptor ASC are key regulators of TSLP secretion by cancer associated fibroblasts in pancreatic cancer
Authors: Emanuela Brunetto, Lucia De Monte, Gianpaolo Balzano, Barbara Camisa, Vincenzo Laino, Michela Riba, Silvia Heltai, Marco Bianchi, Claudio Bordignon, Massimo Falconi, Attilio Bondanza, Claudio Doglioni, Maria Pia Protti
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The thymic stromal lymphopoietin (TSLP), a key cytokine for development of Th2 immunity, is produced by cancer associated fibroblasts (CAFs) in pancreatic cancer where predominant tumor infiltrating Th2 over Th1 cells correlates with reduced patients' survival. Which cells and molecules are mostly relevant in driving TSLP secretion by CAFs in pancreatic cancer is not defined. <h3>Methods</h3> We performed in vitro, in vivo and ex-vivo analyses. For in vitro studies we used pancreatic cancer cell lines, primary CAFs cultures, and THP1 cells. TSLP secretion by CAFs was used as a read-out system to identify in vitro relevant tumor-derived inflammatory cytokines and molecules. For in vivo studies human pancreatic cancer cells and CAFs were orthotopically injected in immunodeficient mice. For ex-vivo studies immunohistochemistry was performed to detect ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression in surgical samples. Bioinformatics was applied to interrogate published data sets. <h3>Results</h3> We show in vitro that IL-1α and IL-1β released by pancreatic cancer cells and tumor cell-conditioned macrophages are crucial for TSLP secretion by CAFs. Treatment of immunodeficient mice orthotopically injected with human IL-1 positive pancreatic cancer cells plus CAFs using the IL-1R antagonist anakinra significantly reduced TSLP expression in the tumor. Importantly, we found that pancreatic cancer cells release alarmins, among which ASC, able to induce IL-1β secretion in macrophages. The relevance of ASC was confirmed ex-vivo by its expression in both tumor cells and tumor associated macrophages in pancreatic cancer surgical samples and survival data analyses showing statistically significant inverse correlation between ASC expression and survival in pancreatic cancer patients. <h3>Conclusions</h3> Our findings indicate that tumor released IL-1α and IL-1β and ASC are key regulators of TSLP secretion by CAFs and their targeting should ultimately dampen Th2 inflammation and improve overall survival in pancreatic cancer.
Dust mite induces leukocyte exosomes with proinflammatory effects toward airway epithelial cells
Authors: Kristin A. Lambert, Man-Hsun Hsu, Zoe C. Laryea, Yuanjun Zhao, Alanna N. Roff, Jeffrey M. Sundstrom, Faoud T. Ishmael
Journal: Journal of Allergy and Clinical Immunology (2019)
Regulation of stem cell-like phenotype and response to chemotherapy in bladder cancer by beta-arrestins.
Authors: Martin Jp Hennig, Georgios Kallifatidis, Diandra K Smith, Dailey S Morera, Marie C Hupe, Markus A Kuczyk, Axel S. Merseburger, Vinata B Lokeshwar
Journal: Journal of Clinical Oncology (2019)

461 Background: Identification of molecular drivers that promote a muscle invasive phenotype and chemoresistance in bladder cancer, as well as an understanding of their mechanism of action should help in designing potential prognostic markers and effective targeted treatments for patients with advanced bladder cancer. β-arrestins (ARRBs) are classic attenuators of G-Protein coupled receptor signaling. However, they have multiple roles in cellular physiology, including carcinogenesis. Methods: β-arrestin-1 (ARRB1) and β-arrestin-2 (ARRB2) mRNA levels were measured by quantitative RT-PCR in two clinical specimen cohorts (n = 63; n = 43). The role of ARRBs in regulating a stem cell-like phenotype and response to chemotherapy treatments was investigated using CRISPR-Cas9 mediated gene-knockout of ARRB1. The consequence of forced expression of ARRBs on tumor growth and response to gemcitabine in vivo were investigated using bladder tumor xenografts in nude mice. Results: ARRB1 levels were significantly elevated and ARRB2 levels downregulated in cancer tissues compared to normal tissues. In multivariate analysis only ARRB2 was an independent predictor of metastasis, disease-specific-mortality and failure to Gemcitabine + Cisplatin (G+C) chemotherapy; ~ 80% sensitivity and specificity to predict clinical outcome. ARRBs were found to regulate stem cell characteristics in bladder cancer cells. Depletion of ARRB2 resulted in increased cancer stem cell markers but ARRB2 overexpression reduced expression of stem cell markers (CD44, ALDH2, and BMI-1), and increased sensitivity towards gemcitabine. Overexpression of ARRB2 resulted in reduced tumor growth and increased response to Gemcitabine in tumor xenografts. Conclusions: β-Arrestins regulate response towards gemcitabine and are therefore potential targets and predictive markers for chemotherapy failure in bladder cancer. The present work shows for the first time that β-arrestins have prognostic significance for predicting metastasis and response to chemotherapy in bladder cancer.
Abstract 238: Substantial Incomplete Chest Recoil Occurs During CPR in a Pig Model
Authors: Paul Aelen, Simone Ordelman, Igor Paulussen, Gerrit-Jan Noordergraaf, Pierre Woerlee
Journal: Circulation (2012)

INTRODUCTION The 2010 AHA / ERC Guidelines recommend compression depths of 5-6 cm. However, the neutral sternal position is assumed to remain unchanged. Changes in chest wall or lungs might cause incomplete chest recoil, altering the effect of 5-6 cm as a percentage of chest diameter. This could induce injury and affect the optimal compression depth. We investigated the hypothesis that incomplete chest recoil occurs during CPR in a pig model and that the speed at which this occurs changes with prolonged CPR. The incomplete chest recoil, or chest molding is a process of change, not a limitation to re-expansion caused by “leaning” or partial compression relaxation. MATERIAL AND METHODS Fourteen Yorkshire pigs with an average AP diameter of 20 cm were anesthetized, placed in dorsal recumbency, and ventricular fibrillation (VF) induced. After 90 s of VF, a specially made, proprietary servo controlled automated CPR device was used to deliver compressions of 5 cm depth at various frequencies (80-120 cpm) and duty cycles (40-60%). The plunger position (and unstressed sternal position) was determined at the start of each compression by the servo system. The position of the compression plunger (and thorax) was measured at a sample frequency of 250 Hz. An altered position at the start of a new compression is called the molded position. RESULTS In the 14 animals, chest molding occurred with an average initial rate of 0.34 ± 0.12 mm per compression. The average chest molding after 100 compressions was 17.4 ± 3.6 mm. After 21 minutes the average molding was 29.2 ± 10.3 mm with an average molding rate of -0.02 ± 0.04 mm/compression. The moulding curve shape was logarithmic. Initial compression depth was approximately 25% of AP diameter, increasing to 30% after 21 minutes CPR due to chest molding. CONCLUSION In conclusion, the molding magnitude was substantial. After initiation of CPR, chest molding occurs quickly, the rate slowing but never stopping, until compressions are stopped. The results could be extrapolated to humans but may be less pronounced due to a more vertical rib construction. Implications on CPR quality and injury need further investigation. Nevertheless, chest molding should be considered in the instructions for compression depth.
Hypertrabeculation as a Noncompaction Phenotype in Dilated Cardiomyopathy Defined by Contrast Echocardiography
Authors: Marin Nishimura, Sachiyo Igata, Darrin J. Wong, Nicholas Wettersten, Andrew M. Kahn, Ajit Raisinghani, Daniel G. Blanchard, Monet Strachan, Anthony N. DeMaria
Journal: JACC. Cardiovascular imaging (2019)
Low incidence of microsurges with biodegradable polymer-delivered, subcutaneously-administered leuprolide acetate in prostate cancer patients.
Authors: Eleni Efstathiou, John A. McLane, Stuart Atkinson, Debbie Boldt-Houle, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2019)

158 Background: Androgen deprivation therapy is a foundational treatment of advanced prostate cancer (PCa) with the primary objective of suppressing circulating androgens.Consistent drug delivery with long-acting leuprolide acetate (LA) formulations is important in providing continuous testosterone (T) suppression throughout the course of treatment without T rising above castrate level (T breakthrough). To assess subcutaneously-administered LA (SC-LA) maintenance of T levels in PCa patients, the incidence of microsurges was evaluated in 4 pivotal trials. Methods: In 4 open-label, fixed-dose, pivotal trials, 424 eugonadal prostate cancer patients (age 40-86) who achieved medical castration (T&lt;50 ng/dL) while on the first administration of SC-LA 7.5, 22.5, 30, or 45 mg, lasting 1, 3, 4, or 6 months, respectively, were evaluated for microsurges. A microsurge was defined as an absolute increase in T level of at least 25 ng/dL during the 4 week period after the second study dose was administered. T was measured 2-4 times on day 0 and once on days 1, 2, 3, 7, and every week until the next dose through the end of the studies. Results: Across the individual studies, 8 patients out of 424 (range 0.9-3.4% by dose, pooled 1.9%) experienced a microsurge during the acute period after the second SC-LA dose (Table). 6 of these 8 patients remained below castrate level at the peak of the surge. Conclusions: SC-LA demonstrated a very low incidence of T breakthroughs and microsurges in PCa patients and only 2 of 424 patients experienced a T microsurge above castrate levels. Limiting the occurrence of T levels above castrate levels may have clinical implications with respect to prolonged progression-free survival. [Table: see text]