tbuckley/cabot-search huggingface dataset:
Abstract 19805: Characteristics and Disparity of Care Among Heart Failure Patients in the Midwest Participating in Get With the Guidelines-Heart Failure
Authors: Carolyn Dickens, Kathie Thomas
Journal: Circulation (2016)

Background:  Heart failure places a burden on the healthcare system and affects African Americans (AA) disproportionately. AA have greater fatality rates, and prior to age 50, AA have a heart failure incidence rate 20 times higher than Caucasians. There are several predictive risk factors associated with heart failure incidence including hypertension, obesity, and diabetes, all of which are more common in the AA population. The same evidence-based treatment guidelines apply to both AA and Caucasians with heart failure, with the exception of the recommendation of hydralazine plus isosorbide dinitrate for AA. The objective of this study was to examine the quality of care and characteristics of AA heart failure patients compared to Caucasians.   Methods:  There were 28642 heart failure patients analyzed from January 1 to December 31, 2015 from 11 Midwest states using Get With The Guidelines-Heart Failure (GWTG-HF). GWTG-HF is an in-hospital quality initiative that improves care by promoting adherence to scientific treatment guidelines in heart failure patients. Of the heart failure patients analyzed, 52% were male and 48% were female, while 18.8% were AA and 81.2% were Caucasian. Achievement and quality measures, characteristics, and defect-free care were examined.   Results:  AA heart failure patients had a median age of 62, while Caucasian heart failure patients had a median age of 77. AA heart failure patients had a higher prevalence of diabetes and hypertension. Overall, AA and Caucasians had similar quality of care, though AA were more likely to receive an aldosterone antagonist at discharge and DVT prophylaxis during hospitalization. For both AA and Caucasians, defect free care was provided 82.1% of the time.   Conclusions:  AA and Caucasian heart failure patients receive similar quality of care but differed in age, DVT prophylaxis and use of an aldosterone antagonist. Further research should examine the causes of these differences of aldosterone use and DVT prophylaxis.
DIPG-28. BURDEN OF DIFFUSE INTRINSIC PONTINE GLIOMA DIAGNOSIS IN A DEVELOPING COUNTRY
Authors: Zebin Al Zebin, Maisa Sawidan, Ahmed Ibrahimi, Hadeel Halalsheh, Kawther Khalifeh, Raed Ramlawi, Nisreen Amayiri
Journal: Neuro-Oncology (2018)

Diffuse Intrinsic Pontine Glioma (DIPG) is a universally fatal tumor with significant burden on families. Experiences from a developing country are rarely reported. We reviewed the medical charts of children treated for DIPG at KHCC/Jordan between 1/2008 and 9/2015 and fulfilled the radiological diagnostic criteria. We evaluated their clinical characteristics and disease burden. Twenty-eight patients were identified (50% females, 20 Jordanians). Median age 7.9years (3.1–17.6years). Twenty-three patients (82%) had 2/3 symptoms of long tracts, ataxia and cranial nerve deficits at median duration 7weeks (2-24weeks). Two patients had initial spinal metastasis; one was paralyzed. Five (19%) had attempted tumor biopsy. Three patients didn’t receive radiotherapy; two refused and one intubated earlier. Median time to begin radiation was 15days (2-35days) with median duration 42days (35-64days). All patients except 3 received dexamethasone at diagnosis, mostly high dose >8mg/day for > 60days. Fifteen patients (63%) improved with radiation and 4 stabilized. Seventeen follow-up MRIs showed tumor shrinkage (5), stability (8) and progression (4). Seventeen patients required 1–5 hospitalizations (median 4 total days/ patient, 1-150days) most due to respiratory distress, altered-consciousness and near-death. All patients had DNR code except two died intubated (parental refusal). Median duration between DNR code and death was 127days (25-478days). While ten patients lost follow up, eighteen died at median 7.9months (1.3-16months); sixteen died hospitalized. With the disease rapid course and dismal prognosis, oncologists in developing countries should avoid unnecessary interventions (biopsy, follow-up MRIs, intubation) and advocate for palliative home care.
Interval Since Last HIV Test for Men and Women with Recent Risk for HIV Infection — United States, 2006–2016
Authors: Marc A. Pitasi, Kevin P. Delaney, Emeka Oraka, Heather Bradley, Elizabeth A. DiNenno, John T. Brooks, Joseph Prejean
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Since 2006, CDC has recommended routine screening of all persons aged 13-64 years for human immunodeficiency virus (HIV) and at least annual rescreening of persons at higher risk (1). However, national surveillance data indicate that many persons at higher risk for HIV infection are not screened annually, and delays in diagnosis persist (2). CDC analyzed 2006-2016 data from the General Social Survey (GSS)* and estimated that only 39.6% of noninstitutionalized U.S. adults had ever tested for HIV. Among persons ever tested, the estimated median interval since last test was 1,080 days or almost 3 years. Only 62.2% of persons who reported HIV-related risk behaviors in the past 12 months were ever tested for HIV, and the median interval since last test in this group was 512 days (1.4 years). The percentage of persons ever tested and the interval since last test remained largely unchanged during 2006-2016. More frequent screening of persons with ongoing HIV risk is needed to achieve full implementation of CDC's screening recommendations and to prevent new infections. Integration of routine screening as standard clinical practice through existing strategies, such as electronic medical record prompts (3), or through new, innovative strategies might be needed to increase repeat screening of persons with ongoing risk.
NURS-01. CRITICAL BRAIN CONTINGENCY: A TOOL TO IMPROVE PATIENT SAFETY AND OUTCOMES
Authors: Caroline Fitzgerald, Kathryn Matson, Deborah Shiers
Journal: Neuro-Oncology (2018)

Early detection of a neurologic emergency such as brain herniation can prevent permanent neurologic sequelae and death. To improve early recognition of deterioration in hospitalized patients, a modified Pediatric Early Warning System, known as Children’s Hospital Early Warning Score (CHEWS), was adopted. The components of CHEWS are neuro/behavior, cardiovascular, respiratory, family concern and staff concern. Following case reviews of children with unexpected neurological deterioration, there was concern CHEWS may not perform well in the high risk pediatric neuroscience population. A multidisciplinary group convened to consider revision to CHEWS that would provide early warning of neurological deterioration through risk stratification to prevent catastrophic outcomes. A qualitative assessment identifying pediatric patients at risk for neurological deterioration was developed via literature review and multidisciplinary expert panel discussion with iterative revisions. A “Critical Brain Contingency” tool was created to identify admitted patients who are at risk for acute neurologic emergencies. Each neuroscience service (neurology, neurosurgery, and neuro oncology) created a list of inclusion criteria tailored to its population. If a patient meets criteria, a “Critical Brain Contingency” banner will be located at the top of the patient’s chart and a sign will be placed at the bedside. The tool is to be completed on admission and criteria for continuing the contingency should be reevaluated every 24 hours. The purpose of this intervention is to achieve clear and effective communication with all team members across the continuum of care and improve patient safety and outcomes.
Phylogenomic Evidence Overturns Current Conceptions of Social Evolution in Wasps (Vespidae)
Authors: Patrick K Piekarski, James M Carpenter, Alan R Lemmon, Emily Moriarty Lemmon, Barbara J Sharanowski
Journal: Molecular Biology and Evolution (2018)

The hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral castes → eusociality with preimaginal caste-biasing (PCB) → morphologically differentiated castes). Here, we infer the phylogeny of Vespidae using sequence data generated via anchored hybrid enrichment from 378 loci across 136 vespid species and perform ancestral state reconstructions to test whether rudimentary and monomorphic castes characterized the initial stages of eusocial evolution. Our results reject the single origin of eusociality hypothesis, contest the supposition that eusociality emerged from a casteless nest-sharing ancestor, and suggest that eusociality in Polistinae + Vespinae began with castes having morphological differences. An abrupt appearance of castes with ontogenetically established morphophysiological differences conflicts with the current conception of stepwise social evolution and suggests that the climb up the ladder of sociality does not occur through sequential mutation. Phenotypic plasticity and standing genetic variation could explain how cooperative brood care evolved in concert with nest-sharing and how morphologically dissimilar castes arose without a rudimentary intermediate. Furthermore, PCB at the outset of eusociality implicates a subsocial route to eusociality in Polistinae + Vespinae, emphasizing the role of mother-daughter interactions and subfertility (i.e. the cost component of kin selection) in the origin of workers.
Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
Authors: Jeanne E. Savage, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A. de Leeuw, Mats Nagel, Swapnil Awasthi, Peter B. Barr, Jonathan R. I. Coleman, Katrina L. Grasby, Anke R. Hammerschlag, Jakob A. Kaminski, Robert Karlsson, Eva Krapohl, Max Lam, Marianne Nygaard, Chandra A. Reynolds, Joey W. Trampush, Hannah Young, Delilah Zabaneh, Sara Hägg, Narelle K. Hansell, Ida K. Karlsson, Sten Linnarsson, Grant W. Montgomery, Ana B. Muñoz-Manchado, Erin B. Quinlan, Gunter Schumann, Nathan G. Skene, Bradley T. Webb, Tonya White, Dan E. Arking, Dimitrios Avramopoulos, Robert M. Bilder, Panos Bitsios, Katherine E. Burdick, Tyrone D. Cannon, Ornit Chiba-Falek, Andrea Christoforou, Elizabeth T. Cirulli, Eliza Congdon, Aiden Corvin, Gail Davies, Ian J. Deary, Pamela DeRosse, Dwight Dickinson, Srdjan Djurovic, Gary Donohoe, Emily Drabant Conley, Johan G. Eriksson, Thomas Espeseth, Nelson A. Freimer, Stella Giakoumaki, Ina Giegling, Michael Gill, David C. Glahn, Ahmad R. Hariri, Alex Hatzimanolis, Matthew C. Keller, Emma Knowles, Deborah Koltai, Bettina Konte, Jari Lahti, Stephanie Le Hellard, Todd Lencz, David C. Liewald, Edythe London, Astri J. Lundervold, Anil K. Malhotra, Ingrid Melle, Derek Morris, Anna C. Need, William Ollier, Aarno Palotie, Antony Payton, Neil Pendleton, Russell A. Poldrack, Katri Räikkönen, Ivar Reinvang, Panos Roussos, Dan Rujescu, Fred W. Sabb, Matthew A. Scult, Olav B. Smeland, Nikolaos Smyrnis, John M. Starr, Vidar M. Steen, Nikos C. Stefanis, Richard E. Straub, Kjetil Sundet, Henning Tiemeier, Aristotle N. Voineskos, Daniel R. Weinberger, Elisabeth Widen, Jin Yu, Goncalo Abecasis, Ole A. Andreassen, Gerome Breen, Lene Christiansen, Birgit Debrabant, Danielle M. Dick, Andreas Heinz, Jens Hjerling-Leffler, M. Arfan Ikram, Kenneth S. Kendler, Nicholas G. Martin, Sarah E. Medland, Nancy L. Pedersen, Robert Plomin, Tinca J. C. Polderman, Stephan Ripke, Sophie van der Sluis, Patrick F. Sullivan, Scott I. Vrieze, Margaret J. Wright, Danielle Posthuma
Journal: Nature Genetics (2018)
MBRS-63. CCR2+ HEMATOPOIETIC STEM CELLS OVERCOME TREATMENT RESISTANCE TO PD-1 IN MEDULLOBLASTOMA
Authors: Catherine Flores, Tyler Wildes, Jeffrey Drake, Rebecca Abraham, Duane Mitchell
Journal: Neuro-Oncology (2018)

We have previously reported that different medulloblastoma models have different responsiveness to checkpoint blockade including anti-PD-1. In a preclinical model of molecular subtype sonic hedgehog (Shh) medulloblastoma (Ptc) that is completely resistant to PD-1 blockade alone, we have found that bone marrow-derived, lineage-negative hematopoietic stem and progenitor cells (HSCs) that express CCR2+ reverses treatment resistance and sensitizes mice to curative immunotherapy. Shh molecular subtype medulloblastoma tumor cells were implanted into the cerebellum of C57BL/6 mice. Experimental groups were treated with anti-PD-1 blocking antibody (10mg/kg x 5) with or without co-transfer of syngeneic bone marrow derived HSCs. HSC transfer with concomitant PD-1 checkpoint blockade leads to increased intratumoral T cell frequency and activation in preclinical models of glioblastoma and medulloblastoma. Of significance, HSC transfer significantly downregulates expression of immunosuppressive markers within tumors and leads to increased gene expression of immune activation markers, but these findings are restricted to occur only within intracranial brain tumors. We have identified that CCR2+ HSCs preferentially migrate to intracranial brain tumors and differentiate into antigen presenting cells within the tumor microenvironment that cross-present tumor-derived antigens to CD8+ T cells and lead to increased antitumor immunity. In addition, HSC transfer also rescues brain tumor resistance to adoptive T cell therapy in medulloblastoma, glioblastoma, and brain stem glioma models. Our studies demonstrate a novel role for CCR2+ HSCs in overcoming brain tumor resistance to PD-1 checkpoint blockade and adoptive cellular therapy in multiple invasive brain tumor models.
EMBR-17. PINEOBLASTOMA SEGREGATES INTO MOLECULAR SUBTYPES WITH DISTINCT CLINICOPATHOLOGIC FEATURES: REPORT FROM THE RARE BRAIN TUMOR CONSORTIUM
Authors: Bryan Li, Alexandre Vasiljevic, Ben Ho, Joseph Norman, Mei Lu, Eugene Hwang, Jordan Hansford, Anne Jouvet, Annie Laquerriere, Marie-Bernadette Delisle, Sridharan Gururangan, Jason Fangusaro, Fabien Forest, Nobusawa Sumihito, Helen Toledano, Diane Birks, Xing Fan, Maryam Fouladi, Amar Gajjar, Guillaume Gauchotte, Lindsey Hoffman, Chris Jones, Delphine Loussouarn, Karima Mokhtari, Scott Pomeroy, Audrey Rousseau, Gino Somers, Michael Taylor, David Ziegler, Cynthia Hawkins, Eric Bouffet, Richard Grundy, Christelle Dufour, Annie Huang
Journal: Neuro-Oncology (2018)

Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Outcomes remain dismal with long-term survival rates between 10–40% despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of PB, the clinical significance of such alterations and the biology of sporadic cases remains unknown. We undertook global methylation profiling of 75 PB cases, and discovered that PBs comprise four molecular sub-types, designated groups 1 to 4 with characteristic copy number alterations and mutational patterns. Molecular sub-groups of PB also exhibited distinct clinical features and survival outcomes. While PBs group 1–3 arose in older children (median ages 5.2–12.6 years), group 4 PB was restricted to much younger children (median age 1.4 years). Group 4 PB exhibited the highest incidence of metastases (53%) and had the worst 5-year event-free survival (EFS) and overall survival (OS), respectively 7.7% and 16.7%. In contrast, group 2 patients had a 5-year EFS and OS of 100%, while group 1 and 3 had intermediate outcomes (68.1%, 53.3% respectively). These findings demonstrate significant clinical and molecular heterogeneity in PB and underscore the critical need to define mechanisms underlying PB, so that precise patient stratification and selection of biology-informed therapies can be undertaken in future clinical trials.
MBRS-61. IN VIVO METABOLOMICS REVEALS A POTENT COMBINATION THERAPY FOR MYC-DRIVEN MEDULLOBLASTOMA
Authors: Allison Hanaford, Brad Poore, Jesse Alt, Barbara Slusher, Charles Eberhart, Eric Raabe
Journal: Neuro-Oncology (2018)

The MYC oncogene is associated with aggressive forms of medulloblastoma. MYC promotes oncogenesis partly by altering cellular metabolism. We hypothesized that MYC-driven medulloblastoma would be sensitive to the glutamine metabolic inhibitor 6-diazo-5-oxo-l-norleucine (DON). We found that 10uM DON treatment increases apoptosis by up to 280% (p<0.04) as compared to vehicle control in four MYC-driven medulloblastoma cell lines. Once-weekly DON therapy increased median survival by up to 246% (p<0.004) in three different MYC-driven medulloblastoma orthotopic xenograft models. We performed in vivo stable isotope resolved metabolomics (SIRM) on two MYC-driven medulloblastoma tumor models and found that tumors from DON treated animals had decreased production of asparagine (p<0.016), leading us to hypothesize that treatment with asparaginase would enhance DON efficacy. Asparaginase breaks down asparagine into aspartate and ammonia and is a commonly used therapy for pediatric leukemia and lymphoma. In MYC-driven medulloblastoma cell lines, treatment with 4uM DON or asparaginase alone did not significantly increase apoptosis by cleaved caspase-3 immunofluorescence or cleaved-PARP western blot. The combination of low-dose DON and asparaginase increased apoptosis by up to 577%, more than observed with 10uM DON alone (p<0.0001). We hypothesized that asparagine depletion would induce apoptosis via the uncharged tRNA/endoplasmic reticulum stress response. Western blotting revealed that the combination of DON and asparaginase increased expression of the transcription factor ATF4 and the pro-apoptotic protein CHOP, which are critical components of the uncharged tRNA response. These data suggest that DON and asparaginase could be a powerful therapeutic combination for treating MYC-driven medulloblastoma and possibly other MYC-driven malignancies.
Gemcitabine induced hemolytic uremic syndrome: Underestimated?
Authors: E Una Cidon, P. Alonso
Journal: Annals of Oncology (2018)

Introduction: Thrombotic microangiopathy (TMA) is characterized by inflammation of the arterioles and capillaries wall, detachment of endothelial cells, accumulation of proteins, cellular debris and platelet thrombi that occlude the vessels. It mainly affects the kidney. The clinical signs are called hemolytic-uremic syndrome (HUS). This includes non-immune hemolytic anemia, thrombocytopenia and acute kidney injury. Gemcitabine is an antineoplastic agent with many uses in oncology. HUS is an infrequent toxicity although it could be easily underdiagnosed as many cases may go unrecognized due to difficulties in diagnosis. The true incidence is difficult to estimate. It varies from 0.078% in clinical trials to 0.008% in standard practice. However, some authors have documented 2.2%. We carried out a retrospective review to know the incidence of gemcitabine induced HUS in our population of pancreatic cancer patients receiving adjuvant treatment and to ascertain potential risk factors. Methods: We reviewed 187 patients on adjuvant gemcitabine for pancreatic carcinoma. We collected data about haemoglobin, platelets, white cells count, creatinine clearance before each cycle. We calculated the maximum drop between baseline and minimum level of haemoglobin and creatinine clearance for all these patients. Results: We found that two patients developed HUS (1.06%). 185 patients developed a maximum drop in haemoglobin of 22% (18-27%) and around 19% in creatinine clearance (10-45%). The HUS patients had a drop in haemoglobin of 37% and 34% and a drop in creatinine clearance of 41% and 31%. We carried out a logistic regression analysis. This showed that a drop in haemoglobin >25% and in creatinine clearance >30% from baseline, increased significantly the chances of developing HUS (p 0.0001). Conclusion: Our data point to a significant drop in hemoglobin and creatinine clearance as two significant risk factors to develop HUS induced by gemcitabine. We recommended that in cases with high index of suspicion, gemcitabine should be stopped or delayed until we receive the results of extra tests such as haptoglobin, lactate dehydrogenase, test de Coombs, to confirm or rule out this diagnosis.
MBRS-38. IDENTIFYING THE MOST FREQUENT VARIANTS IN PEDIATRIC MEDULLOBLASTOMA DRIVER GENES: A SINGLE INSTITUTION STUDY
Authors: Bruna Mascaro-Cordeiro, Indhira Oliveira, Leonardo Santos, Renan Martin, Rafael Silva, Maria Teresa Alves, Nasjla Saba-Silva, Patricia Dastoli, Sergio Cavalheiro, Silvia Toledo
Journal: Neuro-Oncology (2018)

Medulloblastoma (MB) is a malignant childhood brain tumor from cerebellum. Four principal MB molecular subgroups were established: Sonic Hedgehog (SHH), Wingless (WNT), group 3 and group 4. The present study reports the results of the first Brazilian single-institution investigation of pediatric MB subgroups-related genes. We developed an AmpliSeqTM custom panel for DNA sequencing, comprising CTNNB1, PTCH1, DDX3X, TERT and TP53 genes. We selected 28 MB treatment-naïve tumor samples. We observed two variants in exon 3 of CTNNB1, and two non-described variants in DDX3X gene. PTCH1 gene presented the highest number of variants observed (74% of samples). TP53 variants were present in 15% of samples, occurring concomitantly with PTCH1 mutations, and was related to worst overall survival (p=0.0005). Previous studies about pediatric MB genome were carried out from cohorts of North American and European populations, resulting in the identification of several genes variants. However, these variants might not be representative for other populations, mainly Brazilian population, due to the history of the current Brazilian population formation. This particularity might contribute to a very specific combination of rare and common variation, making this population interesting and enhancing the importance of the present screening study. MB occurring in pediatric patients requires deregulation of a minimal number of driver genes, and, variants that leads to deregulation of these genes may not be the same between different populations. Finally, we reinforce that new molecular diagnostic approaches involving PTCH1 and TP53 genes screening, concomitantly, can collaborate for the better clinical management of infancy and childhood MB.
Pharmacists and medication adherence in asthma: a systematic review and meta-analysis
Authors: Marissa Ayano Mes, Caroline Brigitte Katzer, Amy Hai Yan Chan, Vari Wileman, Stephanie Jane Caroline Taylor, Rob Horne
Journal: European Respiratory Journal (2018)

The Lancet Asthma Commission highlighted that non-adherence remains a persistent barrier within asthma care. Medical consultations remain pivotal in addressing non-adherence, but interest in additional adherence support from pharmacists is increasing. This systematic review and meta-analysis aims to evaluate how effective pharmacist-led interventions are in improving medication adherence in adults with asthma. Studies were included if they had adult participants with asthma, pharmacist-led or collaborative care interventions, randomised controlled trial designs comparing interventions with usual pharmacist care, and a medication adherence outcome. We analysed adherence data using the standardised mean difference ( d ) and the remaining data were synthesised narratively. From 1159 records, 11 were included in the narrative synthesis and nine in the meta-analysis. The meta-analysis for adherence produced a medium effect size of d =0.49 ( se =0.08, 95% CI 0.35–0.64, p&lt;0.0001) with low statistical heterogeneity. In line with the Perceptions and Practicalities Approach, interventions targeted to address both the perceptions and practicalities that influence individual motivation and ability to adhere were more effective. Contextual factors (country and healthcare setting) were also influential. Our findings suggest that with adequate remuneration and integration into asthma care, pharmacists can help improve adherence in asthma.