tbuckley/cabot-search huggingface dataset:
Abstract 347: End-Stage Renal Disease (ESRD) Patients Undergoing Hemodialysis Have Higher Possibility of Return of Spontaneous Circulation (ROSC) During Out-Hospital Cardiac Arrest (OHCA) and Non-Inferior Short-Term Survival: A Nationwide Population Cohort Study in Taiwan
Authors: Ming-Shun Hsieh, Chorng-Kuang How, Pau-Chung Chen
Journal: Circulation (2018)

Objective: To compare the incidence rate of return of spontaneous circulation (ROSC) between end-stage renal disease (ESRD) patients undergoing hemodialysis and non-ESRD patients after out-hospital cardiac arrest (OHCA) and subsequent hospital outcomes. Participants and Methods: We enrolled a cohort of 101,876 ESRD patients undergoing hemodialysis between 2000 and 2010 years. After matching for age and gender, an equal number of non-ESRD patients were enrolled to serve as the comparison cohort. We compared the incidence rate of OHCA and subsequent ROSC between the two cohorts. Hazard ratios (HRs) with 95% confidence interval (CI) of OHCA incidence rate were calculated using the Cox proportional hazards regression model. Chi-square test was conducted to compare the incidence rate of ROSC between the two cohorts. Multi-variate analysis with logistic regression was conducted to calculate the odds ratio (OR) of ROSC for different variables. Kaplan-Meier analysis with log-rank test was conducted to determine the difference of survival rate after ROSC between the two cohorts. Results: During the median follow-up of 3.71 and 5.65 years for ESRD and non-ESRD patients, there were 2563 (2.51%) and 1125 (1.10%) OHCA events, respectively. The condition of ESRD undergoing hemodialysis presented as an risk factor to develop OHCA compared with non-ESRD patients (adjusted HR = 2.11, 95% CI 1.89-2.36, P &lt;0.0001 ). Within these OHCA patients with ESRD and non-ESRD, 1085 of 2563 (42.33%) and 202 of 1125 (17.96%) patients got ROSC. In the multivariate analysis with logistic regression, ESRD under hemodialysis presented to be a protective factor for ROSC (adjusted OR = 2.47, 95% CI 1.90-3.21, P &lt;0.0001). In the further Kaplain-Meier analysis with log-rank test, the ESRD patients with OHCA and subsequent ROSC had a better 30-day hospital survival rate compared with the non-ESRD patients. Conclusion: Although, ESRD patients undergoing hemodialysis had a higher incidence rate of OHCA compared with non-ESRD patients. They had a higher possibility to get ROSC and had a better short-term hospital outcome. This observation may be explained by the training of vascular compliance during regular hemodialysis.
A Phase 1b/2 Study of Selinexor, Carfilzomib, and Dexamethasone (SKd) in Relapsed/ Refractory Multiple Myeloma (RRMM)
Authors: Cristina Gasparetto, Gary J. Schiller, Natalie Scott Callander, Suzanne Lentzsch, Sascha A Tuchman, Nizar Bahlis, Darrell J White, Christine I Chen, Heather J. Sutherland, Muhamed Baljevic, Rami Kotb, Richard Leblanc, Michael Sebag, Christopher P Venner, William I. Bensinger, Heidi Sheehan, Yi Chai, Kazuharu Kai, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Brea C. Lipe
Journal: Blood (2019)
PB1778 ESTIMATION OF PROTEIN Z LEVEL IN ADULT NAÏVE ACUTE MYELOID LEUKEMIA PATIENTS
Authors: H. Mohamed, H. Hegab, M. El Razazz
Journal: HemaSphere (2019)

Background: The occurrence of various coagulation abnormalities in acute leukemia is well established, but there are no data assessing the role of protein Z (PZ), a vitamin K‐dependent plasma protein in hemostatic disorder in hematology cancers, including acute leukemia, The potential role of alterations of PZ levels in the pathogenesis of disorders of coagulation has been investigated and revealed conflicting results as Protein Z (PZ) deficiency may induce bleeding as well as thrombosis. Aims: to estimate the level of protein Z in Acute Myeloid Leukemia (AML) patients and its correlation with bleeding tendency or thrombosis Methods: PZ level was measured by ELISA kits in 60 adult naïve (AML) patients aged above 16 years old and 30 healthy controls after informed consent from Clinical Hematology Unit, Ain‐Shams University Hospital and correlated it with bleeding and thrombotic episodes. Patient on oral anti‐coagulant regularly, Inherited bleeding disorder, Inherited thrombophilia were excluded. Results: The median PZ level was lower in AML Patients in comparison to healthy controls{205ng/L (150 – 340) vs 349.5ng/L (274 – 400) with p value &lt; 0.001 }. No statistically significance correlation between protein Z level with initial platelet count (P value 0.323). A statistically significant correlation was detected between episodes of bleeding and PZ level (P value 0.008) . By utilizing ROC curve, the best cutoff value for protein Z as a predictor for bleeding episodes during induction was found &gt;350ng/L. Summary/Conclusion: Conclusion: The results suggest that PZ level was lower in AML patients than healthy control and it was correlated with bleeding episodes. can be a cofactor associated with an increased bleeding tendency in AML patients. Summary: PZ can be a cofactor associated with an increased bleeding tendency in AML patients.
PS1541 OUTCOMES OF AUTOLOGOUS AND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR BPDCN
Authors: M. Qazilbash, Q. Bashir, D. Milton, R. Patel, U. Popat, C. Hosing, P. Kebriaei, S. Ciurea, M. Konopleva, R. Champlin, N. Pammaraju
Journal: HemaSphere (2019)

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy arising from plasmacytoid dendritic cells. It commonly presents as skin lesions with or without bone marrow and soft tissue involvement. Limited retrospective data have shown durable remissions after both autologous (auto) or allogeneic (allo) hematopoietic cell transplantation (HCT). Aims: To evaluate progression-free survival (PFS) and overall survival (OS) after and auto or allo-HCT. Methods: In this retrospective single-center analysis, we evaluated the outcomes of BPDCN patients who received either an auto- or allo-HCT between September 2000 and January 2019 at our institution. Results: We identified 24 consecutive patients who received an auto-HCT (n = 10) or allo-HCT (n = 14) for BPDCN. Skin involvement, with or without other organs, was seen in 16 (67%), BM involvement, with or without soft tissue, in 5 (21%), and other organs in 3 (13%) patients. Patient characteristics are summarized in the attached table. In general, we used auto-HCT for older patients and those with skin-only involvement. Median age at HCT was 52 (range: 18–79) years for all patients. Median (range) follow up in auto-HCT and allo-HCT patients was 6.2 (0.2–37.6) and 8.4 (1.1–76.1) months, respectively (p = 0.52). One-hundred day and 1-year non-relapse mortality (NRM) in auto-HCT was 21% and 35%, and in allo-HCT was 7% and 32%, respectively (p = 0.58). Two of the 14 (14%) allo patients and 2 of the 10 (20%) auto patients progressed after HCT (p = 1.00). Two-year PFS was 28% (4%, 60%) and 47% (95% confidence interval = 17%, 73%) in auto and allo-HCT, respectively (p = 0.34). Two-year OS was 26% (4%, 57%) and 56% (24%, 80%) in auto and allo-HCT, respectively (p = 0.33). In patients transplanted <2015 vs. ≥ 2015, 2-year PFS was 13% vs. 54% (p = 0.009) and 2 year OS was 13% and 68% (p = 0.017).Summary/Conclusion: These results demonstrate the efficacy of both auto and allo-HCT in BPDCN, with a significant improvement in the outcome since 2015. Prospective studies are needed to better define the role of HCT in BPDCN.
Merkel cell carcinoma in kidney transplant recipients in Ireland 1964–2018
Authors: E. Keeling, S.L. Murray, Y. Williams, D.J. Sexton, P. O'Kelly, S. Deady, E. O'Leary, A. Dorman, M. Roche, S. Ni Raghallaigh, A. McCormick, F.J. Moloney, J.P. O'Neill, P.J. Conlon
Journal: British Journal of Dermatology (2019)
Abstract P009: Break the Myth and Revisit Non-Obese Asian American’s Cardiometabolic Risk
Authors: Kyungeh An, Cha-Nam Shin, Mikyung Lee, Kyeung Mi Oh
Journal: Circulation (2017)

Asian Americans (AA) have been excluded in major research addressing cardiometabolic health mainly due to their low rate of obesity. However, CVD morbidity and mortality are rapidly increasing among AA population and that warrants revisiting their cardiometabolic risks. The recent National Health and Nutrition Examination Survey (NHANES) conducted between 2011-14 included non-Hispanic Asian Americans as the first time ever since the survey started in 1960’s, and that will advance our understanding of the AA population by characterizing their cardiometabolic risk. We aimed to compare AA with other ethnic groups in terms of obesity indices, such as body mass Index (BMI), waist circumference (WC), and sagittal abdominal diameter (SAD): and clinical markers of CVD risks, such as level of cholesterol, triglyceride, and glucose, systolic- and diastolic blood pressure, whether being treated with medication for blood pressure, smoking, and having diabetes. Method: From NHANES 2013-2014 data with total 6553 participants, 5992 were selected by age≥19 for analysis. Demographics, obesity indices, CVD risk factors were extracted in six ethnic groups for comparisons using univariate analysis, ANOVA and Chi-square tests. Results: AA, compared to all ethnic groups, was the leanest in terms of the BMI (24.86±4.32 vs. 29.05±7.18, p&lt;0.001), WC (88.55±11.26 vs. 98.93±16.70 cm, p&lt;0.001), and SAD (19.80±3.20 vs. 22.76±4.89 cm, p&lt;0.001). However, the plasma levels of cholesterol (195.11±40.73 vs. 190.11±42.37 mg/dL, p&lt;0.005), triglyceride (162.85±106.12 vs. 111.13±76.60 mg/dL, p&lt;0.001), and glucose (106.54±42.10 vs. 102.25±40.81 mg/dL, p&lt;0.05) were all higher in AA than in non-Hispanic Black. AA had the highest diastolic blood pressure among all ethnic groups (71.37±11.55 vs. 69.00-69.28mmHg in other groups, p&lt;0.001), but lower in systolic blood pressure compared to non-Hispanic White and non-Hispanic Black (120.60±17.56 vs. 122.30± 17.82, p&lt;0.05, and 126.60±17.56 mmHg, respectively, both p&lt;0.001). In AA, 7.7% were taking prescription for blood pressure, 24.6% smoked everyday which was the lowest among ethnic groups (p&lt;0.001), however AA started smoking at younger age than all other ethnic groups (18.50 vs. 21.40 years, p&lt;0.05). Morbidity of diabetes was 10.2% in AA, lower than other ethnic groups except other-Hispanics (p&lt;0.001). We conclude that unlike the longtime-believed myth, Asian Americans are at high risk as other ethnic groups. Our findings warrants further studies for the mechanisms of non-obese-related CVD that will advance the precision of intervention for AA and the larger population in the world.
AB1360-HPR PREVALENCE OF TOBACCO AND ALCOHOL COMSUMPTION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Laura Villarreal, Michael Cabrera, Pedro Santos-Moreno, Diana Buitrago-Garcia
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis leading to progressive joint and organ system damage and disability. It has been demonstrated that smoking and alcohol consumption is a risk factor for poor response to RA treatment. <h3>Objectives</h3> To describe the prevalence of smoking and alcohol consumption in patients with rheumatoid arthritis. <h3>Methods</h3> We conducted a retrospective study, patients were followed during 12 months. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured annually by the DAS28. We calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We estimated the prevalence smoking and alcohol consumption and explored if there was an association between DAS28 and smoking or alcohol consumption. <h3>Results</h3> We included 6491 patients. patients, 82% were female and 18% male; median age was 60 years RIQ (50-67), regarding disease activity, mean DAS28 was 2.59 1.08. The prevalence of alcohol consumptions was 2.26% while smoking 7.83%. We did no find an statistical association between smoking alcohol consumption and DAS28. <h3>Conclusion</h3> Our study showed a small prevalence of patients with rheumatoid arthritis who smoke or consume alcohol without any associations between smoking or alcohol consumption with disease activity. This could be attributed to a low prevalence in our study. Further research is needed in order to propose other methodological approaches to explore this association. <h3>Disclosure of Interests</h3> Laura Villarreal: None declared, Michael Cabrera: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Diana Buitrago-Garcia: None declared
PB1956 COEXISTENCE OF BCR/ABL1 AND JAK2 MUTATION IN MYELOPROLIFERATIVE NEOPLASMS
Authors: L. Luciano, S. Crisci, F. Trastulli, M. Fatigati, B. Izzo, F. Pane, F. Frigeri
Journal: HemaSphere (2019)

Background: Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive. However some recent reports have described the co‐occurrence of BCR/ABL1 and JAK2 mutation in patients with CML phenotype. Generally, in the few reported cases, clinical and laboratory data suggest the presence of two different clones. Aims: Here we describe the clinical and molecular data of 3 patients showing the presence of BCR/ABL1 and JAK 2 mutation, with CML phenotype in 1 and myeloproliferative phenotype evolving in CML in the others. Methods: BCR/ABL1 transcript were identified and quantified by Rq‐PCR according to ELN recommendations; JAK2 mutation were evidenced by PNA clamping PCR in one patient and by ASO‐PCR in the others. Results: Patient clinical characteristics are summarized in table 1. Patient 1 showed CML phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. He started Dasatinib treatment at standard dose (100 mg/die) but after 6 months because of intolerance, he switched to Ponatinib obtaining a major molecular response. Patient 2 was diagnosed Thrombocytemia carrying V617F JAK2 mutation, after a portal vein thrombosis and started anticoagulant therapy combined to Hydroxiurea treatment. After 2 years, he switched to IFN therapy and in 2011 (after 2 more years) he showed CML feature with the appearance of BCR/ABL1 hybrid transcript. Imatinib treatment was added to Interferon and combination therapy was sustained for 7 years. Because of intolerance to IFN, in 2018 patient switched to Ruxolitinib at the dose of 30 mg BID, while also maintaining Imatinib. Patient 3 was diagnosed Thrombocytemia carrying V617F JAK2 mutation in 2009 and received IFN treatment. In 2017 he developed leukocytosis with the appearance of e1a2 BCR/ABL1 hybrid transcript. At that time, he stopped IFN therapy and started Imatinib at the standard dose of 400 mg per day with control of both diseases. Molecular monitoring showed a simultaneous decrease of both abnormalities in patient 1 who got a deep molecular response (MR 4). Patient 2 reached a deep molecular response (MR 4.5) but still needs of Ruxolitinib treatment for thrombocytemia, suggesting the presence of two different clones. Patient 3 got a deep molecular response (MR 5) and it is ongoing the evaluation of JAK2 mutation. Summary/Conclusion: Coexistence of BCR/ABL1 and JAK2 mutation is rarely reported so far but a widely use of molecular techniques could increase the number of patients with both abnormalities. At least in patient 3 of our series, clinical and molecular data suggest that both abnormalities are present in the same clone and V617F JAK2 mutation is the first occurred one. Digital PCR experiments could clarify if a single cell express both molecular abnormalities. Such cases are relevant to better understand the pathogenesis of myeloproliferative neoplasms.
Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts
Authors: Sandra Sanchez-Roige, Abraham A. Palmer, Pierre Fontanillas, Sarah L. Elson, Mark J. Adams, David M. Howard, Howard J. Edenberg, Gail Davies, Richard C. Crist, Ian J. Deary, Andrew M. McIntosh, Toni-Kim Clarke
Journal: American Journal of Psychiatry (2018)

Objective: Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits. Method: This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) from two population-based cohorts of European ancestry (UK Biobank [N=121,604] and 23andMe [N=20,328]) and performed a genome-wide association study (GWAS) meta-analysis. Two additional GWAS analyses were performed, a GWAS for AUDIT scores on items 1–3, which focus on consumption (AUDIT-C), and for scores on items 4–10, which focus on the problematic consequences of drinking (AUDIT-P). Results: The GWAS meta-analysis of AUDIT total score identified 10 associated risk loci. Novel associations localized to genes including JCAD and SLC39A13; this study also replicated previously identified signals in the genes ADH1B, ADH1C, KLB, and GCKR. The dimensions of AUDIT showed positive genetic correlations with alcohol consumption (rg=0.76–0.92) and DSM-IV alcohol dependence (rg=0.33–0.63). AUDIT-P and AUDIT-C scores showed significantly different patterns of association across a number of traits, including psychiatric disorders. AUDIT-P score was significantly positively genetically correlated with schizophrenia (rg=0.22), major depressive disorder (rg=0.26), and attention deficit hyperactivity disorder (rg=0.23), whereas AUDIT-C score was significantly negatively genetically correlated with major depressive disorder (rg=−0.24) and ADHD (rg=−0.10). This study also used the AUDIT data in the UK Biobank to identify thresholds for dichotomizing AUDIT total score that optimize genetic correlations with DSM-IV alcohol dependence. Coding individuals with AUDIT total scores ≤4 as control subjects and those with scores ≥12 as case subjects produced a significant high genetic correlation with DSM-IV alcohol dependence (rg=0.82) while retaining most subjects. Conclusions: AUDIT scores ascertained in population-based cohorts can be used to explore the genetic basis of both alcohol consumption and alcohol use disorders.
CXCR4 regulates <i>Plasmodium</i> development in mouse and human hepatocytes
Authors: Hironori Bando, Ariel Pradipta, Shiroh Iwanaga, Toru Okamoto, Daisuke Okuzaki, Shun Tanaka, Joel Vega-Rodríguez, Youngae Lee, Ji Su Ma, Naoya Sakaguchi, Akira Soga, Shinya Fukumoto, Miwa Sasai, Yoshiharu Matsuura, Masao Yuda, Marcelo Jacobs-Lorena, Masahiro Yamamoto
Journal: The Journal of Experimental Medicine (2019)

The liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase C ζ–mediated NF-κB activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca2+ levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver-stage development of the Plasmodium berghei rodent malaria parasite and the human Plasmodium falciparum parasite. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis.
FRI0072 PREDICTING SARCOPENIA AND OBESITY BY MEASURING THIGH MUSCLE AND FAT THICKNESS BY ULTRASOUND IN PATIENTS WITH RHEUMATOID ARTHRITIS: FROM THE CHIKARA STUDY
Authors: Yutaro Yamada, Masahiro Tada, Koji Mandai, Noriaki Hidaka, Kentaro Inui, Hiroaki Nakamura
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) patients often have sarcopenia. The thickness of the quadriceps muscle, easily measurable by ultrasound (US), is known to be related to skeletal muscle mass, and its decreased thickness may suggest sarcopenia. <h3>Objectives</h3> To investigate the utility of US for predicting sarcopenia by examining the anterior thigh in RA patients. <h3>Methods</h3> Ninety-four patients (66 female) enrolled in the prospective CHIKARA study (UMIN000023744) underwent US muscle (MT) and fat thickness (FT) examinations of the anterior thigh. Muscle and body fat mass were also examined by a body composition analyzer (MC-780A; TANITA, Tokyo, Japan). Whether MT and FT can predict sarcopenia and obesity was also examined. Sarcopenia was diagnosed based on the Asian Working Group on Sarcopenia definition, and obesity was diagnosed by% body fat (%BF). <h3>Results</h3> MT was significantly lower in RA patients with sarcopenia than in those without (24.8 ± 3.5 mm vs. 29.6 ± 3.8 mm, p=0.01). MT was related to sarcopenia (males r=0.56, p=0.02; females r=0.32, p=0.01). The MT cut-off value for sarcopenia was 24.7 mm in males and 19.7 mm in females on receiver operating curve (ROC) analysis. FT was correlated with%BF (males r=0.66, p&lt;0.01; females r=0.62, p&lt;0.001).%BF was estimated by 2.21FT+7.28 in males and 1.45FT+14.46 in females by a simple linear regression model. This means that FT&gt;8.0 mm in males and FT&gt;10.7 mm in females indicate obesity (Table 1). When assessing the accuracy of these cut-off values, the kappa values were 0.541 and 0.469, respectively <h3>Conclusion</h3> Sarcopenia and obesity can be predicted by US examination of the anterior thigh in RA patients. <h3>Reference</h3> [1] Kawai H., Kera T., Obuchi S., et al. Morphological and qualitative characteristics of the quadriceps muscle of community-dwelling older adults based on ultrasound imaging: classification using latent class analysis. Aging Clin Exp Res. 2018; 30:283–29. <h3>Acknowledgement</h3> Yutaro Yamada <h3>Disclosure of Interests</h3> Yutaro Yamada Speakers bureau: Abbvie, Chugai, Mitsubishi Tanabe, Masahiro Tada Speakers bureau: Abbvie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical, Pfizer Japan, Takeda Pharmaceutical, Koji Mandai: None declared, Noriaki Hidaka: None declared, Kentaro Inui Speakers bureau: Takeda Pharmaceutical, Pfizer Japan, Daiichi-Sankyo Co.Ltd., Abbvie, Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Eisai Co.Ltd., Eli-Lilly, Nippon Kayaku Co.,Ltd., Maruho Co.,Ltd, Kaken Pharmaceutical Co.,Ltd., Hiroaki Nakamura: None declared
Multiplex assessment of protein variant abundance by massively parallel sequencing
Authors: Kenneth A. Matreyek, Lea M. Starita, Jason J. Stephany, Beth Martin, Melissa A. Chiasson, Vanessa E. Gray, Martin Kircher, Arineh Khechaduri, Jennifer N. Dines, Ronald J. Hause, Smita Bhatia, William E. Evans, Mary V. Relling, Wenjian Yang, Jay Shendure, Douglas M. Fowler
Journal: Nature Genetics (2018)