tbuckley/cabot-search huggingface dataset:
Interest of Eosinophil Count in Bacterial Infections to Predict Antimicrobial Therapy Efficacy
Authors: Benjamin Davido, Pierre de Truchis, Aurélien Dinh
Journal: JAMA Surgery (2019)

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Abstract MP018: Performance of 1,5-anhydroglucitol Compared to the Oral Glucose Tolerance Test and Fasting Glucose for Identification of Diabetes in the Community
Authors: Bethany Warren, Alexandra K Lee, Christie Ballantyne, Ron Hoogeveen, James S Pankow, Anna Kottgen, Elizabeth Selvin
Journal: Circulation (2017)

Introduction: The oral glucose tolerance test has been a long-standing gold standard for diabetes diagnosis. The oral glucose tolerance test measures glycemic response to a glucose challenge, but has fallen out of favor due to its high patient burden. There is growing interest in 1,5-anhydroglucitol (1,5-AG), a non-fasting test that does not require a carbohydrate challenge, for use in clinical practice. There is currently no consensus on clinical cut points for 1,5-AG, although low levels of 1,5-AG reflect recent (~2 week) glycemic excursions. Our objective was to evaluate the performance of 1,5-AG to identify cases of undiagnosed diabetes defined by the oral glucose tolerance test or fasting glucose in a community-based population. Methods: We included 7,754 Atherosclerosis Risk in Communities (ARIC) Study participants without diagnosed diabetes who attended visit 4 (1996-98). We calculated ROC curves, Youden’s index, sensitivity, and specificity to investigate the performance of 1,5-AG to identify cases of undiagnosed diabetes defined by an oral glucose tolerance test ≥ 200 mg/dL or fasting glucose ≥ 126 mg/dL. Results: The ROC curve of 1,5-AG compared to the oral glucose tolerance test as the gold standard was 0.658 and 1,5-AG compared to fasting glucose as the gold standard was 0.714. Youden’s index identified “optimal” 1,5-AG cut-points of 16 μg/mL and 17 μg/mL to identify diabetes defined by oral glucose tolerance test and fasting glucose, respectively. Decreasing values of 1,5-AG were more specific and less sensitive for detection of oral glucose tolerance test and fasting glucose-defined diabetes (Table). Conclusion: 1,5-AG is currently approved for clinical use but its utility is unclear. Given its low sensitivity for detection of diabetes, 1,5-AG may not be able to substitute for fasting glucose or the oral glucose tolerance test for screening of diabetes.
An ARC-Regulated IL1β/Cox-2/PGE2/β-Catenin/ARC Circuit Controls Leukemia–Microenvironment Interactions and Confers Drug Resistance in AML
Authors: Bing Z. Carter, Po Yee Mak, Xiangmeng Wang, Wenjing Tao, Vivian Ruvolo, Duncan Mak, Hong Mu, Jared K. Burks, Michael Andreeff
Journal: Cancer Research (2019)

The apoptosis repressor with caspase recruitment domain (ARC) protein is a strong independent adverse prognostic marker in acute myeloid leukemia (AML). We previously reported that ARC regulates leukemia-microenvironment interactions through the NFκB/IL1β signaling network. Malignant cells have been reported to release IL1β, which induces PGE2 synthesis in mesenchymal stromal cells (MSC), in turn activating β-catenin signaling and inducing the cancer stem cell phenotype. Although Cox-2 and its enzymatic product PGE2 play major roles in inflammation and cancer, the regulation and role of PGE2 in AML are largely unknown. Here, we report that AML-MSC cocultures greatly increase Cox-2 expression in MSC and PGE2 production in an ARC/IL1β-dependent manner. PGE2 induced the expression of β-catenin, which regulated ARC and augmented chemoresistance in AML cells; inhibition of β-catenin decreased ARC and sensitized AML cells to chemotherapy. NOD/SCIDIL2RγNull-3/GM/SF mice transplanted with ARC-knockdown AML cells had significantly lower leukemia burden, lower serum levels of IL1β/PGE2, and lower tissue human ARC and β-catenin levels, prolonged survival, and increased sensitivity to chemotherapy than controls. Collectively, we present a new mechanism of action of antiapoptotic ARC by which ARC regulates PGE2 production in the tumor microenvironment and microenvironment-mediated chemoresistance in AML.Significance: The antiapoptotic protein ARC promotes AML aggressiveness by enabling detrimental cross-talk with bone marrow mesenchymal stromal cells.
Blinatumomab for Minimal Residual Disease (MRD) in Adults with B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL): Median Overall Survival (OS) Is Not Reached in Complete MRD Responders at a Median Follow-up of 53.1 Months
Authors: Nicola Goekbuget, Hervé Dombret, Gerhard Zugmaier, Massimiliano Bonifacio, Carlos Graux, Christoph Faul, Max S. Topp, Monika Brüggemann, Kate Taylor, Ralf Bargou
Journal: Blood (2018)
Point-of-Care Manufacturing of CD20.19 Bi-Specific Chimeric Antigen Receptor T (CAR-T) Cells in a Standard Academic Cell Processing Facility for a Phase I Clinical Trial in Relapsed, Refractory NHL
Authors: Fenlu Zhu, Nirav N Shah, Dina Schneider, Huiqing Xu, Katherine Chaney, Lawrence Luib, Carolyn A. Keever-Taylor, Boro Dropulic, Rimas Orentas, Parameswaran Hari, Bryon Johnson
Journal: Blood (2018)
Abstract 17580: Angina Pectoris in Diabetic Patients: Insights From the Duke Databank for Cardiovascular Disease
Authors: Robert J Mentz, Adam Z Banks, Samuel Broderick, Adam D DeVore, Karen Chiswell, Linda K Shaw, Mona Fiuzat, Eric J Velazquez, G. Michael Felker, Christopher M O'Connor
Journal: Circulation (2015)

Background: Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The association between the presence or absence of AP in DM patients with CAD is unknown. Methods: We analyzed DM patients with obstructive CAD who underwent coronary angiography at Duke University Medical Center from 2002 to 2011 and compared patients without AP to those with AP. DM and AP were defined based on physician-obtained past medical history at catheterization. Patients were categorized as no AP, atypical AP or typical AP within the 6 weeks prior. We assessed the association with subsequent cardiovascular (CV) death/CV hospitalization and all-cause mortality in patients with no or atypical AP relative to typical AP using multivariable Cox proportional hazards analysis. Results: In the Duke Databank, 5550 patients met criteria for inclusion and 1732 (31%) had no AP, 1075 (19%) had atypical AP and 2743 (50%) had typical AP. Those without AP more often had a prior MI and lower ejection fraction, but had similar HbA1c values compared to those with atypical AP or typical AP. Over a median follow-up of 5.4 years (IQR: 2.9-8.8), the lack of recent AP was associated with increased risk for outcomes (Table). Following adjustment, the lack of recent AP was independently associated with increased mortality compared to typical AP. Conclusions: In DM patients with CAD, the lack of AP was associated with increased mortality, but similar risk for CV events compared to patients with typical AP. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival.
Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study
Authors: E. Brocchi, G. Caletti, G. Brambilla, L. La Mantia, G. Lupinacci, G. Pisano, G. Puerari, A. Zambelli, S. Barbagli, P. Ciani, L. Manneschi, S. Brunati, R. Curioni, D. Agape, F. Antoniozzi, P. Arcidiacono, E. Ballarin, M. Basilico, P. Bocchia
Journal: New England Journal of Medicine (1988)
Helen Salisbury: Social prescribing and the No 17 bus
Authors: Helen Salisbury
Journal: BMJ (2019)

The link between social isolation and poor health has been widely studied,1 and intuitively it rings true. If you have only yourself to feed, is there really any incentive to cook a healthy meal? Where’s the motivation to go for a walk if you have no one to visit?

In recognition of the fact that the main health problem for many elderly people may be loneliness rather than a statin deficiency, social prescribing is now hugely popular at all levels of the NHS.

We are told that, instead of prescribing yet another pill of dubious marginal benefit, we should …
Abstract P259: Smoking Increases Risks of Death and Stroke in Both Men and Women. Absolute Risk Difference of Stroke is Likely to be Larger in Women
Authors: Masaki Ohsawa, Kuniaki Ogasawara, Shinichi Omama, Kozo Tanno, Kazuyoshi Itai, Yuki Yonekura, Motoyuki Nakamura, Yasuhiro Ishibashi, Toru Kuribayashi, Toshiyuki Onoda, Kiyomi Sakata, Fumitaka Tanaka, Mutsuko Ohta, Hirobumi Seki, Kazuki Konishi, Akira Okayama
Journal: Circulation (2017)

Background: Smoking is an important risk factor for cardiovascular disease, however, to what extent smoking increases excessive deaths and strokes in a general population has not been sufficiently examined especially in women. Methods: A total of 10,382 female and male participants aged 65 years or older were divided into two groups according to smoking status (current smoker; never smoker). Past smokers were excluded. Main outcomes were all-cause death and incident stroke. Age-adjusted mortality and incidence rates were estimated in the groups using Poisson’s regression analysis. Age-adjusted rate ratios (RR) and excess events (EE per 1000 person-years) attributable to smoking were determined using the rate in never smokers as a reference. Results: There were 1410 deaths and 735 strokes during the 9.0-year observation period (90,099 person-years). Smoking contributed to a 2.3-fold higher risk of death in women and 1.8-fold higher risk in men. It contributed to 12 excess deaths per 1000 person-years in both men and women. The rate ratio and excessive events of stroke were likely to be higher in women than those in men (RR: 2.6 vs. 1.6; EE: 9.3 vs 5.0, see table). Conclusion: Smoking significantly increases risks of death and stroke not only in men but also in women. Absolute risk difference of stroke attributable to smoking is likely to be larger in women than in men.
Assessing the association between bronchiolitis in infancy and recurrent wheeze: a whole English birth cohort case–control study
Authors: Robin Marlow, Adam Finn, John Henderson
Journal: Thorax (2019)

The precise association between bronchiolitis and predisposition to childhood wheeze is unclear. We assessed bronchiolitis aetiology and later wheeze phenotypes in the entire 2007 English birth cohort. All infants admitted to hospital in England during their first year of life with bronchiolitis or urinary tract infection (UTI) were followed using Hospital Episode Statistics to determine risk and characteristics of wheeze admission over the subsequent 8 years. In our cohort of 21 272 children compared with UTI, the risk of wheeze admission was higher with previous bronchiolitis (risk ratio (RR) 2.4), even higher in those with non-respiratory syncytial virus bronchiolitis (RR 3.1) and persisted into late-onset wheeze (RR 1.7).
Abstract P5-15-07: Breast surgery – Is routine 'group &amp; save' required? A quality improvement project
Authors: R Burrah, W Chicken, S Sathananthan
Journal: Cancer Research (2019)

Abstract Introduction Breast surgery, especially for malignant disease, is not associated with significant blood loss and therefore rarely requires blood transfusions. Pre-operative protocols in our hospital and in most other centers routinely require a blood group screening process (group and save) for elective breast cancer surgery. The process of group and save (G&amp;S) in our hospital requires two blood samples to be drawn with at least 30 minute interval in-between. It takes at least 40 minutes for the samples to get processed and the cost for each test is £2.12. The test is valid for a period of 5 days after which time it needs to be repeated. This process in busy hospitals is clearly time consuming, results in delays and is inconvenient for patients and medical staff. The aim of this study was to ascertain the number G&amp;S performed and rate of post-operative blood transfusion for patients undergoing surgery for malignant breast disease. This was to establish if mandatory pre-operative G&amp;S is necessary in all cases, and if the number of tests performed can be reduced. The second part of the study was to analyze the outcome after implementation of changes to reduce the number of G&amp;S tests. Method Retrospective review of patient records who had surgeries for malignant breast disease from December 2015 to November 2016. Exclusion criteria included benign disease, flap reconstruction and breast surgery combined with another major procedure. Following the initial analysis, it was proposed that only the operating surgeon will request the test and that it will not be routinely requested by the pre-op assessment team. A re-audit was done prospectively to study the outcome of change in practice and close the audit loop. Results 151 cases were eligible for review. 97.35% (147 patients) had G&amp;S, and the post-operative transfusion rate was 1.32% (2 patients). Following a change in protocol a significant fall in the testing (97.35% to 35.5%) was seen and there were no post-operative blood transfusions in this period. Conclusion This simple yet important audit showed that routine G&amp;S did not contribute to the patient management, increased cost of treatment, caused patient inconvenience and consumed hospital personal time. The changes we implemented significantly reduced the frequency of this test and was cost effective to the trust. This study has now been converted into a Quality Improvement Project and through this we will continue to improve the results further. This project has also stimulated an interest in the General Surgery department, and other units are now considering changing their practice based on our results. Citation Format: Burrah R, Chicken W, Sathananthan S. Breast surgery – Is routine 'group &amp; save' required? A quality improvement project [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 P5-15-07.
A DNA Repair and Cell-Cycle Gene Expression Signature in Primary and Recurrent Glioblastoma: Prognostic Value and Clinical Implications
Authors: Matthieu Gobin, Petr V. Nazarov, Rolf Warta, Marco Timmer, Guido Reifenberger, Joerg Felsberg, Laurent Vallar, Anthony J. Chalmers, Christel C. Herold-Mende, Roland Goldbrunner, Simone P. Niclou, Eric Van Dyck
Journal: Cancer Research (2019)

Inevitable tumor recurrence and a poor median survival are frustrating reminders of the inefficacy of our current standard of care for patients with newly diagnosed glioblastoma (GBM), which includes surgery followed by radiotherapy and chemotherapy with the DNA alkylating agent temozolomide. Because resistance to genotoxic damage is achieved mainly through execution of the DNA damage response (DDR) and DNA repair pathways, knowledge of the changes in DNA repair and cell-cycle gene expression that occur during tumor development might help identify new targets and improve treatment. Here, we performed a gene expression analysis targeting components of the DNA repair and cell-cycle machineries in cohorts of paired tumor samples (i.e., biopsies from the same patient obtained at the time of primary tumor operation and at recurrence) from patients treated with radiotherapy or radiotherapy plus temozolomide. We identified and validated a 27-gene signature that resulted in the classification of GBM specimens into three groups, two of which displayed inverse expression profiles. Each group contained primary and recurrent samples, and the tumor at relapse frequently displayed a gene expression profile different from that of the matched primary biopsy. Within the groups that exhibited opposing gene expression profiles, the expression pattern of the gene signature at relapse was linked to progression-free survival. We provide experimental evidence that our signature exposes group-specific vulnerabilities against genotoxicants and inhibitors of the cell cycle and DDR, with the prospect of personalized therapeutic strategies.Significance: These findings suggest that classification of GBM tumors based on a DNA repair and cell-cycle gene expression signature exposes vulnerabilities to standard-of-care therapies and offers the potential for personalized therapeutic strategies.
Impact of obesity upon the survival of cholangiocarcinoma patients.
Authors: Phani Keerthi Surapaneni, Zhuo Li, Lalitha Padmanabha Vemireddy, Pashtoon Murtaza Kasi, Jason Scott Starr, Ashton Ritter, Jessica McMillan, Natasha Wylie, Kabir Mody
Journal: Journal of Clinical Oncology (2019)

288 Background: Obesity is a risk factor for developing cholangiocarcinoma (CCA). However, the effect of obesity on survival of CCA is unclear. The primary aim of this study was to analyze the impact of obesity upon overall survival of CCA patients. Secondary aims were to analyze impact of obesity upon other disease characteristics such as tumor site, stage, age, sex, BMI and Ca 19-9. Methods: A total of 411 unique pts diagnosed with CCA at Mayo Clinic Florida between 2000 and 2018 were retrieved from our collective SDMS database. Variables evaluated included:demographics, Body Mass Index (BMI), AJCC stage, tumor location and Ca 19-9.A total of 185 pts had all data available pertaining to these variables. We further restricted the analysis to pts with intrahepatic CCA classified BMI as per CDC criteria normal (18.5-25kg/m 2 ), overweight (25-29.9kg/m 2 ) and obese (≥30 kg/m 2 ), thus leaving a total of 152 pts. Continuous and categorical variables were compared across BMI groups using Chi-squared or Fisher’s exact test. Overall survival rates after diagnosis at 1, 2 and 3 years were estimated using Kaplan-Meier method. Results: Among 152 pts included in the study, 28% were normal weight, 40% were overweight and 32% were obese. The overall survival rate at 1, 2 and 3 years for normal weight pts with all stages combined was 54.1%, 35%, and 30.7%, respectively. The overall survival rate at 1, 2 and 3 years for overweight pts with all stages combined was 59.7 %, 32.6%, and 25.4%, respectively. The overall survival rate at 1, 2 and 3 years for obese pts with all stages combined was 63.9%, 37.6%, and 26.7%, respectively(p = 0.8766). Multivariate analysis demonstrated is no significant difference in overall survival for obese pts compared to normal or overweight pts.(Table to be shown) However it showed, gender and Ca19-9 were statistically significant predictors of overall survival, with males and pts with Ca19-9≥100 doing worse (HR1.65 (CI = 1.05, 2.61, p = 0.031) and HR 2.31 (CI = 1.49, 3.59, p = &lt; 0.01), respectively). Conclusions: BMI did not make a significant impact on the overall survival, though there may be a trend toward worse OS for ptswith higher BMI. A larger, stage focused evaluation is warranted for further exploration of this trend.
Abstract 17360: Catheter Ablation of Atrial Flutter Reduces Healthcare Utilization and Incident Atrial Fibrillation
Authors: Thomas A Dewland, David V Glidden, Gregory M Marcus
Journal: Circulation (2012)

Introduction Endocardial catheter ablation is a safe and highly effective treatment for atrial flutter (AFL). Although a single, small clinical trial has demonstrated a reduction in hospitalization and atrial fibrillation among AFL patients treated with ablation versus pharmacologic therapy, it is unknown if catheter ablation improves outcomes in real world populations. Hypothesis AFL catheter ablation is associated with reductions in healthcare utilization, atrial fibrillation, and stroke. Methods We identified patients from the Healthcare Cost and Utilization Project database who received care in a California hospital setting (emergency department, inpatient ward, or ambulatory surgery unit) with a diagnosis of AFL between 2005 and 2009. Patients with a prior or concurrent diagnosis of atrial fibrillation were excluded. AFL ablation procedures, medical diagnoses, and Charlson Comorbidity Index (CCI) scores were determined at each encounter using ICD-9 codes. Individuals were observed for repeat healthca...
Abstract 14882: Change in Serum PCSK9 Does Not Explain the Difference in the LDL-C Response Between EPA and DHA Supplementation: The ComparED Study
Authors: Janie Allaire, Patrick Couture, Amélie Charest, Johanne Marin, Marie-Claude Lépine, André Tchernof, Benoît Lamarche
Journal: Circulation (2016)

Introduction: Supplementation with high dose docosahexaenoic acid (DHA) increases serum LDL-C concentrations more than with eicosapentaenoic acid (EPA). Mechanisms underlying this difference are un...
AERD: PERSPECTIVE OF THE USE OF LICENSED MONOCLONALS FOR TREATMENT BASED ON THEIR PHENOTYPES
Authors: Gabriella M.F.S. Dias, Joao Paulo de Assis, Raisa Borges Castro, Jorge Kalil, Pedro Giavina-Bianchi, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2019)

Currently, the gold standard for treatment of Aspirin-Exacerbated Respiratory Disease (AERD) is desensitization with ASA. Monoclonal therapy would be a promising option for these patients. The objective of the study was to evaluate the possible indications of these licensed biologicals for patients with AERD. Retrospective study of adult patients being followed up at an asthma outpatient clinic with a history of AERD. All patients had nasal polyposis, rhinosinusitis, asthma, NSAID hypersensitivity, and sporadic exacerbation of the clinical condition. The clinical characteristics, asthma severity, peripheral eosinophilia, total and specific IgE for aeroallergens were analyzed, classifying them according to the current criteria in the label for monoclonal therapies. A total of 61 patients were included, 75% female, with age of 55.7 years. Twenty-eight patients (45.9%) were atopic. The IgE was 538.9 IU/mL and eosinophils was 649.8 cells/mm3. According to the on-label use of anti-IgE for asthma, only 20 patients would meet the criteria, 9 patients would be excluded due to IgE values, 16 due to non-severe asthma and 16 non-atopic patients. In relation to Anti-IL5, 35 patients would meet the criteria, and 17 patients were excluded because they presented non-severe asthma and 9 had eosinophils <300 cells/mm3. AERD is characterized by an eosinophilic inflammatory profile. This study showed that, according to the current criteria for monoclonal therapies, more patients would meet the criteria for anti-IL-5 due to the high frequency of peripheral eosinophilia and, on the other hand, the large number of non-atopic patients could restrict the use of anti-IgE.