tbuckley/cabot-search huggingface dataset:
Daratumumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (GEN503): Final Results of an Open-Label, Phase 1/2 Study
Authors: Torben Plesner, Hendrik-Tobias Arkenau, Monique C Minnema, Mario Boccadoro, Philippe Moreau, James D Cavenagh, Aurore Perrot, Jacob Laubach, Tahamtan Ahmadi, Carla de Boer, Diana Chen, Christopher Chiu, Jordan Schecter, Paul G Richardson
Journal: Blood (2017)
GATA/Heme Multi-Omics Reveals a Trace Metal-Dependent Erythrocyte Developmental Mechanism
Authors: Nobuyuki Tanimura, Ruiqi Liao, Gary M Wilson, Matthew R Dent, Miao Cao, Judith N Burstyn, Peiman Hematti, Xin Liu, Yuannyu Zhang, Ye Zheng, Sunduz Keles, Jian Xu, Joshua J Coon, Emery H Bresnick
Journal: Blood (2018)
A reliability study using Network Oriented Research Assistant (NORA <sup>®</sup> ) examining the use of digital photographs in the assessment of psoriasis
Authors: D. Jeong, H. Aralis, K.W. Bruhn, J. Cotliar, N. Craft, I.J. DeLuca, R. Hamidi, K. Nguyen, V.A. Patel, H. Sofen, B.H. Tan, C.V. David
Journal: British Journal of Dermatology (2019)
Younger Age Is A Predictor For HSV Viremia In Eczema Herpeticum
Authors: Vivian Wang, Matthew Keefer, Peck Y. Ong
Journal: Journal of Allergy and Clinical Immunology (2019)

RATIONALE: Family history of allergy and asthma and early onset of eczema are known risk factors for early life sensitization.Whether these risk factors result in different sensitization patterns is unknown.METHODS: Participants were identified from the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort).Infants (n5118) with AD underwent skin prick testing (SPT) to 11 aeroallergens and 6 foods including milk and egg.The MPAACH SPT profiles were compared to published SPT data (15 aeroallergens, milk and egg) from infants (n5680) in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a high-risk birth cohort with at least one atopic parent. RESULTS:The overall rate of sensitization to any allergen was 47.1% in MPAACH compared to 28.4% in CCAAPS (p<0.001).The most prevalent allergen sensitization in both cohorts was egg, but it was over double in the MPAACH cohort compared to CCAAPS (28.8% vs. 12.2%, p<0.001).MPAACH participants had a significantly higher rate of sensitization to dog (11.9% vs. 1.3%, P<0.001) and cockroach (5.9% vs. 1.8%, p50.014), and were almost 4 times more likely to be co-sensitized to food and aeroallergens (16.0% vs. 4.3%, p<0.001).The rate of dog ownership was similar between MPAACH and CCAAPS (35.2% vs. 37.8%).CONCLUSIONS: Allergen sensitization prevalence and pattern differ between the two high-risk groups.Infants with AD are more likely than infants from atopic parents to be co-sensitized to a food and aeroallergen.This suggests that environmental control measures, specifically for dog and cockroach, may have differential effects in children with AD.
Abstract 20389: Heterogeneity of Heart Failure Management Program Components May Affect Delivery of Care for Heart Failure: The Results of a Multicenter Survey Study (CLIMB-HF Study)
Authors: Edimar A Bocchi, Renata Chinen, Marcus V Simões
Journal: Circulation (2017)

Introduction: Guidelines have been recommended heart failure (HF) disease management programs (DMP) for HF, despite conflicting results attributed to variations in interventions. Also, there is not...
Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency
Authors: Oscar Correa-Jimenez, Sonia Restrepo-Gualteros, Milena Villamil-Osorio, Charlotte Cunningham-Rundles, Kathleen E. Sullivan, Ramsay L. Fuleihan, Maria J. Gutierrez
Journal: Journal of Allergy and Clinical Immunology (2019)
Effects of a Personalized Web-Based Decision Aid for Surrogate Decision Makers of Patients With Prolonged Mechanical Ventilation
Authors: Christopher E. Cox, Douglas B. White, Catherine L. Hough, Derek M. Jones, Jeremy M. Kahn, Maren K. Olsen, Carmen L. Lewis, Laura C. Hanson, Shannon S. Carson
Journal: Annals of Internal Medicine (2019)

Treatment decisions commonly have to be made in intensive care units (ICUs). These decisions are difficult for surrogate decision makers and often lead to decisional conflict, psychological distress, and treatments misaligned with patient preferences.
Identifying Factors in Multiple Myeloma Controlling Response to B-Cell Maturation Antigen (BCMA)-Targeted Immunotherapy Using CRISPR-Based Functional Genomics
Authors: Poornima Ramkumar, Jaime Leong, Meghan Seyler, Stratton J Georgoulis, Axel Hyrenius Wittsten, Priya Choudhry, Kole Roybal, Arun P Wiita, Martin Kampmann
Journal: Blood (2018)
Analysis of UGT1A’s polymorphisms and RAS: RAF mutations based on phase II study of biweekly XELIRI plus bevacizumab as a second-line therapy in patients with metastatic colorectal cancer.
Authors: Hiroaki Tanioka, Nobuaki Suzuki, Shoichi Hazama, Takeshi Nagasaka, Yasuo Iwamoto, Yuji Negoro, Yuki Nakagami, Ryouichi Tsunedomi, Hiroaki Nagano, Masazumi Okajima
Journal: Journal of Clinical Oncology (2019)

565 Background: We have previously reported biweekly XELIRI + bevacizumab 10 mg/kg as second-line chemotherapy in metastatic colorectal cancer (mCRC). In this study, we investigated relationships between efficacy/toxicity and biomarkers (polymorphisms of UGT1A’s, somatic mutations of RAS, BRAF and PIK3CA). Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin based regimen were eligible for this study. Treatment protocol administrated capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan 150mg/m2 on day 1, and bevacizumab 10 mg/kg on day 1 every 2 weeks. Results: Between January 2013 and July 2015, 51 patients were enrolled in this study. The patients’ characteristics were as follows (N=51): median age, 66 years (range 41–82); male/female, 29/22; the median PFS was 5.47 months (95% CI, 4.23–7.40 months), the median OS was 13.5months (95%CI, 11.57– 20.23months), and the median TTF was 4.5 months (95%CI, 3.97–6.93 months). The response rate was 16% (95%CI, 7.2–29.1), and the disease control rate was 76% (95%CI, 61.8-86.9). Grade 3 or higher adverse events were mainly febrile neutropenia in two patients and hypertension in 14 patients (28.6%). The patients with UGT1A7 (387G&lt;T) genotype had a trend to suffer from diarrhea ( p=0.089 by Fisher’s exact test). The summary of somatic mutations of cancer was RAS (wild/mutant = 21/23), BRAF (wild/mutant = 39/5), PIK3CA (wild/mutant = 42/0), and MSI (MSS/MSI-H = 42/2). There was no statistical association between efficacy and somatic mutations. The sample size might influenced such the results. Conclusions: In mCRC patients, biweekly XELIRI + bevacizumab 10 mg/kg is effective and feasible as second-line chemotherapy. We found several biomarkers that predict toxicities in this study. Further study is required for predicting the efficacy based on biomarkers using somatic mutations of cancer and germline polymorphisms. Clinical trial information: UMIN000009280.
Abstract 20579: Event-Free Survival in Central Appalachian Implantable Cardioverter Defibrillator Recipients
Authors: Jennifer L Miller, Misook L Chung, Muna Hammash, Jessica L Harman, Christine Haedtke, Samy Claude Elayi, Mary M Czarapata, Martha J Biddle, Debra K Moser
Journal: Circulation (2017)

Introduction: Social determinants of health affect event-free survival in individuals with cardiovascular disease (CVD). Social and economic disparities are well documented in Central Appalachia. T...
EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation
Authors: Laurie Herviou, Michel Jourdan, Anne-Marie Martinez, Giacomo Cavalli, Jerome Moreaux
Journal: Leukemia (2019)

Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Using this unique model, we investigated the role of EZH2 during PC differentiation (PCD) using H3K27me3 and EZH2 ChIP-binding profiles. We then studied the effect of the inhibition of EZH2 enzymatic activity to understand how EZH2 regulates the key functions involved in PCD. EZH2 expression significantly increases in preplasmablasts with H3K27me3 mediated repression of genes involved in B cell and plasma cell identity. EZH2 was also found to be recruited to H3K27me3-free promoters of transcriptionally active genes known to regulate cell proliferation. Inhibition the catalytic activity of EZH2 resulted in B to PC transcriptional changes associated with PC maturation induction, as well as higher immunoglobulin secretion. Altogether, our data suggest that EZH2 is involved in the maintenance of preplasmablast transitory immature proliferative state that supports their amplification.
Prevalence and molecular etiology of mismatch repair deficiency among gastrointestinal cancers.
Authors: Navika Shukla, Aser Abrha, Teri A. Longacre, Rachel Koff, James M. Ford, George A. Fisher, Sigurdis Haraldsdottir
Journal: Journal of Clinical Oncology (2019)

215 Background: In light of recent FDA approval of anti-PD-1 therapy for microsatellite unstable (MSI-H) or mismatch repair deficient (dMMR) solid tumors, identifying patients with dMMR tumors has become increasingly important. While screening for dMMR and MSI-H in colorectal cancer (CRC) is recommended, this screening is less commonly done for extracolonic gastrointestinal (GI) tumors. At Stanford Comprehensive Cancer Institute (SCCI), all GI cancer patients have been universally screened for dMMR via immunohistochemistry since January 2016. Methods: In this study, we undertook a retrospective review of all GI cancer patients screened for dMMR between January 2016 to December 2017. Data on patient characteristics, germline and tumor sequencing, and tumor characteristics were collected and reported. Results: A total of 1543 GI malignancies were screened for dMMR at SCCI during the study period. Colorectal (n = 711), pancreatic (n = 264), gastric (n = 159), and gastro-esophageal (n = 137) cancer were amongst the most frequently screened tumors. dMMR was detected in 7.1% of all GI malignancies. We detected the highest prevalence of dMMR in colorectal (69/711, 9.7%), followed by gastric (15/159, 9.4%), pancreatic (18/264, 6.8%), and gastro-esophageal cancer (6/137, 4.4%). Lynch syndrome was the most common etiology for dMMR in CRC patients (39.4%), double somatic (confirmed or possibly) mutations were most common in pancreatic cancer (44.4%), and somatic MLH1 hypermethylation was the most common etiology in gastric (73.3%) and gastro-esophageal cancer (100%). Conclusions: Given the relatively high incidence of dMMR in GI malignancies, we strongly recommend screening all GI malignancies. Of note, we found higher than previously reported rates of dMMR within pancreatic cancer. Our results also suggest that while rare, double somatic mismatch repair mutations may be a significant pathway causing dMMR in pancreatic cancer.
Prognostic significance of malnutrition in metastatic esophageal squamous cell carcinoma.
Authors: Kirsty Taylor, Osvaldo Espin-Garcia, Di Maria Jiang, Daniel Yokom, Lucy Xiaolu Ma, Charles Henry Lim, Bryan Anthony Chan, Peiran Sun, Hao-Wen Sim, Akina Natori, Geoffrey Liu, Gail Elizabeth Darling, Rebecca Wong, Eric Xueyu Chen, Raymond Woo-Jun Jang, Patrick Veit-Haibach, Dmitry Rozenberg, Elena Elimova
Journal: Journal of Clinical Oncology (2019)

171 Background: Disease related symptoms including anorexia, nausea and dysphagia lead patients with esophageal cancer to become malnourished. Malnourishment can result in systemic inflammation, reduced treatment tolerance, poorer quality of life and decreased overall survival. Currently weight loss is the main clinical measure of malnutrition, and thus we set out to evaluate the prognostic utility of alternative screening tools of malnutrition. Methods: Patients with metastatic esophageal squamous cell cancer (MESCC) attending the Princess Margaret Cancer Centre, between January 2011 and December 2016, were identified from the institutional gastroesophageal database. Nutritional Risk Score (NRS), Nutritional Risk Index (NRI) and Neutrophil Lymphocyte Ratio (NLR) were calculated and correlated with clinical-pathological variables and survival. Malnutrition was defined as NRS ≥ 3, NRI &lt; 97.5 and NLR ≥ 3. Results: Of the 64 consecutive patients, 30 (47%) presented with de novo metastatic disease and 34 (53%) with recurrence. The median age was 62 years (range 40-85), 47 patients were ECOG PS ≤ 2 and 29 (45%) received systemic chemotherapy. 90% of patients experienced weight loss &gt; 5% prior to diagnosis and median BMI was 20.1 (range 14.3-34.9). NRI identified 37 (58%) and NRS 45 (70%) patients as malnourished. Both were associated with poorer ECOG PS (p = 0.012 and p = 0.027 respectively). No difference was identified with sex, smoking status or albumin with univariate analysis. NRI did not associate significantly with age. Median overall survival was 5months; 8.1-9 months with normal nutrition and 2.8-3.2 months in malnourished patients. Kaplan Meier analysis revealed significant difference in overall survival (malnutrition vs. normal nutrition) using NRS (p = 0.029) and NRI (p = 0.001) but not weight (p = 0.509) or NLR (p = 0.69). Conclusions: Patients with MESCC identified as malnourished at the time of diagnosis have inferior survival outcomes. Malnutrition tools are superior to weight alone with respect to discriminating outcomes in this patient population. Further investigation is needed in larger patient cohorts; to identify those at risk, initiate early supportive interventions and improve patient outcomes.
Abstract 14299: MicroRNAs are Released During Myocardial Ischemia Reperfusion Injury and Induce Inflammation via Toll-like Receptor 7 in vitro
Authors: Yan Feng, Lin Zou, Dan Yan, Hongliang Chen, Ganqiong Xu, Wei Chao
Journal: Circulation (2016)

Introduction: We have reported that cardiac RNA elicits a robust cytokine response in both cardiomyocyte (CM) and immune cells and promotes leukocyte peritoneal recruitment, but the type of RNA res...
Feasibility of SM-88 in PC after multiple prior lines and ECOG < 2.
Authors: Marcus Smith Noel, Andrea Wang-Gillam, Allyson J. Ocean, Giuseppe Del Priore, Vincent J. Picozzi
Journal: Journal of Clinical Oncology (2019)

310 Background: Advanced PC patients with ≥ 3Ls of chemo or ECOG PS 2 are generally excluded from clinical trials. SM88 demonstrated no drug related AEs &gt; grade 2 in an interim prostate phase 2 (JCO 2018 36:6S P 175). We sought to determine the feasibility of a trial in this vulnerable population using SM88. Methods: Prospective randomized phase 2 of SM-88 (tyrosine derivative, CYP3a4 inducer, mTOR and oxidative stress catalyst) in patients with locally PD or mPC, ECOG PS &lt; 2 and ≥ 2 weeks from prior therapy. Results: Mean age = 64.9 (range 45.6-84.1); 45.5% female, 93.1% white, 6.9% other; median prior lines = 3 (range 1-6); 12% had prior RT and 17% surgery. Median ECOG PS was 1 with 36.6% 0, 63.3% 1 and 0% ECOG PS 2. From April 2018 to this abstract deadline, 72 patients at 24 sites have consented; 36 patients initiated therapy, 19 failed screening and 17 remained in screening. Time from opening trial to first patient consented = 5.1 wks; median time last regimen to consent = 6.7 wks; from consent to drug administration (C1D1) = 1.7 wks. Subjects traveled up to 2600 miles to enroll at a site with an open slot. Median number of subjects/site = 3 (1-15). Median time on trial is 52 days (1-22 wks). There were 15 unrelated SAEs among 36 randomized subjects; three subjects died after consenting but before receiving study drug (table). Grade 4 and 5 SAEs∗ were more common before receiving drug or unrelated to drug (26/94) than at least possibly drug related (0/17) (Fisher p &lt; 0.05). Efficacy using RECIST, PERCIST and BICR along with CTCs, 19.9, NLR, PROs and other outcomes are being collected with high compliance. Conclusions: This prospective SM88 trial suggests that heavily pretreated PC patients with criteria that includes less than ideal ECOG can participate and gain access to novel therapies. This trial plans to enroll 99 additional subjects in under a year. Although ECOG 2 was allowed none have been consented to date and may reflect investigator bias on enrollment or PS assessment. Investigators can meet the needs of this patient population by considering them for inclusion in future drug development trials. Clinical trial information: NCT03512756. [Table: see text]
Formula milk: RCPCH promises to review funding arrangements with industry
Authors: Susan Mayor
Journal: BMJ (2019)

The Royal College of Paediatrics and Child Health has said that it has suspended “future funding agreements” with the infant formula milk industry while it conducts a review.

The decision came after growing pressure from doctors and campaigners who have been calling for the college to sever its ties with the industry, saying that such relations are incompatible with the healthy promotion of breastfeeding, especially in low and middle income countries, which are vulnerable to predatory advertising.

The BMJ recently reported that 12 organisations and 84 individuals, mostly clinicians, had accused the college of acting against WHO’s code on marketing breastmilk substitutes and associated World Health Assembly resolutions, at a conference the college held in Cairo on 29 January.1 Conference sponsors included Nutricia, Danone, and Nestle, all of which make formula milk products.

The WHO rules state that breastmilk substitutes and infant formula manufacturers “should not . . . …
Superiority of Triple Combination Bortezomib + Cyclophosphamide and Dexamethasone (VCD) Versus Thalidomide + Cyclophosphamide and Dexamethasone (CTD) in Newly Diagnosed Multiple Myeloma Transplant-Eligible Patients
Authors: Edvan De Queiroz Crusoe, Fabiana Higashi, Gracia Martinez, Rosane Bittencourt, Angelo Maiolino, Lais Sousa, Renata Ferreira Marques Nunes, Glaciano Ribeiro, Jandir Nicacio, Karla Richter Zanella, Andre Magalhaes, Danielle Leao, Jorge Vaz Pinto Neto, Abrahão Elias Hallack Neto, Walter Braga, Emmanuella G Souza, Antonio Julio A.M. Guimaraes, Giovanna Steffenello Durigon, Dani Laks, Jose Mauro Kutner, Gilberto Colli, Rodrigo Santucci, Roberto José Pessoa Magalhães, Vania T M Hungria
Journal: Blood (2017)
Gastrin vaccine and immune checkpoint antibody therapy for pancreatic cancer.
Authors: Jill P Smith, Nicholas Osborne, Rebecca Sundseth, Julian Burks, Hong Cao, Xunxian H Liu, Alexander H Kroemer, Lynda Youngpeter Sutton, Allen Cato
Journal: Journal of Clinical Oncology (2019)

259 Background: Pancreatic cancer is poorly responsive to therapy due to fibrosis in the tumor microenvironment and nonspecificity of treatments. The peptide gastrin stimulates growth of pancreatic cancer in an autocrine fashion. Polyclonal Antibody Stimulator (PAS) is a gastrin vaccine that in clinical trials prolongs survival of patients who develop neutralizing gastrin antibodies. We hypothesized that PAS also elicits a memory and T-cell response that would improve effectiveness of immune checkpoint antibodies. Methods: C57BL/6 mice were injected sc with syngeneic mT3 murine pancreatic cancer cells. After 1 week (tumors evident), groups were treated with PBS (control); PAS (100 μg or 250 μg); PD-1 antibody (150 μg); or combined therapy with PAS100/PD-1. PAS was given ip at weeks 0, 1 and 3. Anti-PD-1 was given on days 0, 4, 8, 15 and 21. On day 31 spleens were collected for T-cell surface analysis and cytokine activation by flow cytometry. Tumors were stained for fibrosis and with immunohistochemical stains for CD8+ and FoxP3+ tumor infiltrating lymphocytes (TILs). Results: PAS resulted in T-cell activation; however, the portion of terminally differentiated effector memory double negative T-cells (CD4- CD8-) in CD3+cells from mice treated with the combination PAS100/PD-1 was two-fold higher than those portions from mice treated with PBS, PD-1 or PAS100. Lymphocytes from PAS-treated mice elicited cytokine release (Interferon-γ, granzyme, perforin, and TNF-α) upon re-stimulation with gastrin in vitro, whereas PAS100/PD-1-treated mice show the highest endogenous cytokines levels. PAS250 monotherapy decreased tumor growth. Neither PAS100 nor anti-PD-1 monotherapy decreased tumor size, but combination PAS100/PD-1 antibody tumors were smaller, had less fibrosis, fewer T-regulatory lymphocytes, and increased CD8+ TILs. Conclusions: In addition to eliciting a B-cell response, PAS activates T-lymphocytes rendering tumors susceptible to immune checkpoint antibody treatment. Smaller tumors with combined therapy may be due to the anti-fibrotic effect of PAS on the tumor microenvironment and changes in CD8+ TILs. This study supports that PAS is an important immunotherapy that elicits both B- and T-cell anti-cancer responses.
Abstract P212: Combined Analysis of Longitudinal Cohorts With Case-only Sample Sets for Detecting Genetic Effects on Venous Thromboembolism in Topmed
Authors: Amanda A Seyerle, Brandon Coombes, Cecelia A Laurie, Tamar Sofer, Nicholas L Smith, Weihong Tang, Mariza de Andrade, Charles Kooperberg, James Pankow, Ken Rice, Barbara McKnight, Cathy C Laurie
Journal: Circulation (2018)

Background: The Trans-Omics for Precision Medicine (TOPMed) program is performing whole-genome sequencing across multiple studies, including longitudinal cohorts, case-control, and case-only sample sets. Detecting the effects of low frequency variants requires large sample sizes, which can only be achieved by combining data across diverse study designs, including matching of case-only sample sets with controls from other studies. Here we present a strategy for combined analysis of venous thromboembolism (VTE) case status in 3 longitudinal cohorts and 3 case-only sample sets, in the context of whole-genome association studies. Methods: For each cohort study, we sampled ‘pure’ controls (without replacement) from the risk set of each incident case, within strata defined by sex, ancestry and birth-cohort. Pure controls had no event throughout their period of observation. A case’s risk set was defined as controls with no prior VTE history and under observation through an age at least as old as the case. For case-only sample sets, controls for each case were sampled from a cohort study, using the same risk set definition. Because of limited overlap in birth years between the cohort studies and the case-only sample sets, this matching was done within strata defined only by sex and ancestry group. Mixed model logistic regression will be used to account for relatedness as a random effect. Although conditional logistic regression is not practical for whole-genome association studies, case-control matching is implicitly recognized by a fixed effect for age-at-event for each matched set (1 case and &gt;=1 matched controls). Additional fixed effects will include sample set and sex. We will also adjust for variations in case-control ratio among the matched sets. Results: In two cohort studies, we matched 1,231 cases to 4,820 controls (overall ratio = 1:3.9); only 500 controls and 5 cases could not be matched. For the case-only sample sets we matched 2,141 cases to 2,780 controls from one cohort study (overall ratio = 1:1.3); zero controls and only 14 cases could not be matched. Conclusions: We were successfully able to match nearly all cases to controls, and more than 90% of controls were also matched. By matching controls to cases based on age at event, we can account for the different risk of VTE by age clusters. Although this strategy does not provide an asymptotically unbiased estimated of the hazard ratio, compared to classical risk set sampling, it uses a large portion of the available data, it provides odds ratio estimates yielding the correct sign of association, and it reduces the potential influence of resampling subjects with rare variants. This strategy also enables combined analysis of multiple studies with different designs.