tbuckley/cabot-search huggingface dataset:
Transverse Arrest of Head
Authors: J. D. Martin
Journal: BMJ (1953)

<b>Background:</b> There is limited epidemiological data for idiopathic pulmonary fibrosis(IPF) in Australia. <b>Aim:</b> Our study aimed to estimate the mortality, incidence, and prevalence rates of IPF in Australia for the period 1997-2015 and projections for 2016-2025. <b>Methods:</b> Our estimates were generated&nbsp;utilising the&nbsp;Mortality Incidence Analysis Model (MIAMOD) method and software. This method is useful in situations where incidence and prevalence data are limited but mortality and registry data are available. Data from the Australian IPF Registry and population and death index data from the Australia Bureau of Statistics were used&nbsp;to generate&nbsp;estimates. Age standardised rates were based on the standard Australian population in 2011. <b>Results:</b> There was an increasing trend in crude and age standardised mortality, incidence, and prevalence over the study period (1997-2015), however age standardised mortality, incidence and prevalence showed a decreasing trend over the projected period from 2017-2025. Highest crude and age standardised estimates were in persons 70 years and above and all estimates were higher in males than in females. Overall crude and age standardised estimates were mortality, 5.9 and 6.2 per 100,000&nbsp;persons respectively; incidence, 10.4 and 11.0 per 100,000 person years, respectively; and prevalence, 32.6 and 34.3 per 100,000&nbsp;persons, respectively. <b>Conclusion:</b> Our study has revealed an increasing trend in mortality, incidence, and prevalence of IPF in Australia. This adds to the current evidence base for policy and planning decisions particularly related to resources for the management of patients with IPF. Moreover, this study serves as a benchmark for future research which will improve the knowledge base on IPF in Australia.
MEK Inhibitors in Lung Cancer—You Can Teach an Old Drug New Tricks
Authors: Jonathan J. Havel
Journal: Cancer Research (2019)

In this issue of Cancer Research, Xie and colleagues reveal an unexpected synergy between MEK inhibitors and immune checkpoint blockade in non-small cell lung cancer (NSCLC). Small-molecule inhibition of MEK led to increased cell surface expression of TNF receptor-1 (TNFR1) and sensitized NSCLC cells to cytokine-induced apoptosis. This study provides preclinical rationale for exploring the combination of MAPK pathway inhibitors with immunotherapy in NSCLC, independent of KRAS mutation status.See related article by Xie et al., p. 5812.
GENE-54. INVESTIGATING THE ROLES OF NCOR1 AND NCOR2 IN METASTATIC INVASION INTO THE SPINE
Authors: Zain Sultan, Sabrina Rocco, Nicholas Szerlip, Alexandra Calinescu
Journal: Neuro-Oncology (2019)

Abstract Anywhere from 30–70% of osseous metastatic disease occurs in the spine across many different tumor types. These metastases lead to debilitating pain and neurologic dysfunction significantly reducing patients’ quality of life. Unfortunately, the cause of preferential metastatic growth to the spine is not understood. The purpose of this study was to identify the role of NCOR1 and NCOR2/SMRT, genes included in Cancer Gene Census (https://cancer.sanger.ac.uk/cosmic), in the promotion of metastatic spread to the spine. NCOR1, located on chromosome 17, and NCOR2, located on chromosome 12, encode for proteins that mediate ligand-independent transcription repression by forming a complex that activates HDAC3. Studies have shown that low expression of NCOR1 and NCOR2 is associated with decreased median survival in some cancers. Our lab collected tumors and blood/bone marrow samples from 9 patients with different primary tumors that metastasized to the spine, and sequenced their DNA. Based on preliminary bioinformatics analysis, we discovered a substitution of thymine to cytosine at chr17:16165160 in the NCOR1 sequence, which results in a nonsense mutation that ends transcription in the second exon. After Sanger sequencing validation, this mutation was found to be present in both the tumor and control samples of all patients, resulting in two possible interpretations: a germline mutation of NCOR1 sequence or the presence of tumors cells in the blood. In addition, by bioinformatics analysis, we identified a substitution of cytosine to thymine at chr12:124341916 in exon 34 of the NCOR2 sequence, resulting in a missense mutation that changes an alanine to threonine. Further experimentation must be done to determine the role of NCOR1 and NCOR2 in metastatic spread to the spine. The hope is to identify targetable molecules and pathways for the design of novel therapies aimed to improve the outcome of these patients.
Cell of Origin and Treatment Impact on the Outcome of Monomorphic Post-Transplant Lymphoproliferative Disorder-Diffuse Large B-Cell Lymphoma Subtype
Authors: Francesca Montanari, Changchun Deng, Ahmed Sawas, Jennifer Kimberly Lue, Enrica Marchi, Dejan Radeski, Bin Cheng, Govind Bhagat, Owen A. O'Connor
Journal: Blood (2019)
Effectiveness of Daratumumab in Combination with Lenalidomide and Dexamethasone (DRd) Vs. Common Standard-of-Care Regimens in Patients with Non-Transplant Newly Diagnosed Multiple Myeloma (NDMM)
Authors: Brian G.M. Durie, Shaji K. Kumar, Saad Z. Usmani, Bareng A.S. Nonyane, Eric A. Ammann, Annette Lam, Rachel Kobos, Eric M Maiese, Thierry Facon
Journal: Blood (2019)
Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells
Authors: Annika Scheffold, Ali H. Baig, Zhiyang Chen, Sarah E. von Löhneysen, Friedrich Becker, Yohei Morita, Alush I. Avila, Marco Groth, André Lechel, Florian Schmid, Johann M. Kraus, Hans A. Kestler, Stephan Stilgenbauer, Melanie Philipp, Martin D. Burkhalter
Journal: Leukemia (2019)

Abstract Accumulation of DNA damage and myeloid-skewed differentiation characterize aging of the hematopoietic system, yet underlying mechanisms remain incompletely understood. Here, we show that aging hematopoietic progenitor cells particularly of the myeloid branch exhibit enhanced resistance to bulky DNA lesions—a relevant type of DNA damage induced by toxins such as cancer drugs or endogenous aldehydes. We identified aging-associated activation of the Hedgehog (Hh) pathway to be connected to this phenotype. Inhibition of Hh signaling reverts DNA damage tolerance and DNA damage-resistant proliferation in aged hematopoietic progenitors. Vice versa, elevating Hh activity in young hematopoietic progenitors is sufficient to impair DNA damage responses. Altogether, these findings provide experimental evidence for aging-associated increases in Hh activity driving DNA damage tolerance in myeloid progenitors and myeloid-skewed differentiation. Modulation of Hh activity could thus be explored as a therapeutic strategy to prevent DNA damage tolerance, myeloid skewing, and disease development in the aging hematopoietic system.
Management Strategies and Satisfaction Levels in Patients with Sickle Cell Disease: Interim Results from the International Sickle Cell World Assessment Survey (SWAY)
Authors: John James, Biree Andemariam, Baba PD Inusa, Fuad El-Rassi, Beverly Francis-Gibson, Alecia C. Nero, Caterina P. Minniti, Cassandra Trimnell, Miguel R. Abboud, Jean-Benoît Arlet, Raffaella Colombatti, Mariane de Montalembert, Suman Jain, Wasil Jastaniah, Erfan Nur, Laurie DeBonnett, Ifeyinwa (ify) Osunkwo
Journal: Blood (2019)
Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma: Final Results from a Prospective Phase II Study
Authors: Solomon A. Graf, Ryan D. Cassaday, Karolyn K. Morris, Sanaz Behnia, Qian Vicky Wu, Jenna M. Voutsinas, Ryan C. Lynch, Elizabeth Krakow, Heather A. Rasmussen, Thomas R. Chauncey, Sandra Kanan, Lorinda A. Soma, Stephen D. Smith, Ajay K. Gopal
Journal: Blood (2019)
Clinical Outcomes Under Hydroxyurea and Impact of ELN Responses in Patients with Polycythemia Vera: A PV-NET Real World Study
Authors: Francesca Palandri, Elena Maria Elli, Giulia Benevolo, Mario Tiribelli, Massimiliano Bonifacio, Alessia Tieghi, Francesco Cavazzini, Giuseppe A. Palumbo, Florian H. Heidel, Monica Crugnola, Gianni Binotto, Alessandra D'Addio, Nicola Polverelli, Micaela Bergamaschi, Giovanni Caocci, Uros Markovic, Giuseppe Auteri, Lucia Catani, Christian Di Pietro, Elisa Diral, Luigi Scaffidi, Davide Griguolo, Katia Codeluppi, Antonio Cuneo, Gianpietro Semenzato, Mauro Krampera, Francesco Lanza, Roberto Massimo Lemoli, Massimo Breccia, Daniela Bartoletti, Michele Cavo, Nicola Vianelli, Roberto Latagliata
Journal: Blood (2019)
Association of Disability With Mortality From Opioid Overdose Among US Medicare Adults
Authors: Yong-Fang Kuo, Mukaila A. Raji, James S. Goodwin
Journal: JAMA Network Open (2019)

Patients qualifying for Medicare disability have the highest rates of opioid use compared with older Medicare beneficiaries and commercial insurance beneficiaries. Research on opioid overdose deaths in this population can help identify appropriate interventions.To assess the rate of opioid overdose death and to identify its associated risk factors.This cohort study included a 20% national sample of Medicare enrollees aged 21 to 64 years whose initial Medicare entitlement was based on disability and who resided in 50 US states and Washington, DC, in 2012 to 2016. Data analyses were performed from March 15, 2019, through September 23, 2019.Fifty-five chronic or potentially disabling conditions were selected from the Centers for Medicare & Medicaid Services Chronic Disease Data Warehouse.Opioid overdose death rate estimated from Medicare National Death Index linkage data.Among 1 766 790 Medicare enrollees younger than 65 years who qualified for Medicare because of disability, the mean (SD) age was 52.2 (10.2) years, and 866 914 (49.1%) were women. These enrollees represent 14.9% (95% CI, 14.9%-15.0%) of the entire Medicare population and accounted for 80.8% (95% CI, 78.9%-82.7%) of opioid overdose deaths among all Medicare enrollees. Opioid overdose mortality in this population increased from 57.4 per 100 000 (95% CI, 53.9-61.0 per 100 000) in 2012 to 77.6 per 100 000 (95% CI, 73.5-81.8 per 100 000) in 2016. Results from the stepwise logistic regression model revealed that 3 categories of conditions are associated with opioid overdose death: substance abuse, psychiatric diseases, and chronic pain. Among the 11.1% (95% CI, 11.0%-11.2%) of adults with disability who had all 3 conditions, the rate of opioid overdose death was 363.7 per 100 000 (95% CI, 326.7-402.6 per 100 000), which is 23.4 times higher than the rate for individuals with none of the conditions (15.5 per 100 000; 95% CI, 11.6-20.1 per 100 000).This study identifies differences in opioid overdose mortality among subgroups of Medicare enrollees younger than 65 years who qualify for Medicare because of disability. Understanding the heterogeneity of medical and psychiatric conditions associated with opioid use and misuse is key to developing specific, data-driven interventions targeted to each subgroup of high-risk populations.
INNV-18. THE AVAILABILITY AND ROLE OF CLINICAL PHARMACISTS IN THE AMBULATORY NEURO-ONCOLOGY SETTING: AN INTERNATIONAL SURVEY
Authors: Mallika Patel, Eric Lipp, Elizabeth Miller Patrick Healy, James Herndon, Katherine Peters
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Outpatient clinics treating neuro-oncology patients are becoming more multidisciplinary. Utilization of all team members is critical for the holistic care of these complex patients. Specifically, the role of a clinical pharmacist in the ambulatory multidisciplinary clinic remains undefined and will likely evolve as more therapeutic options are developed to treat central nervous system malignancies. We queried the Society for Neuro-Oncology (SNO) membership about the availability of a clinical pharmacist in their ambulatory setting and, if present, the role of that clinical pharmacist. METHODS In an IRB exempt study, we surveyed the SNO community (targeting primarily clinicians) and analyzed responses to queries about clinical pharmacists in the ambulatory neuro-oncology setting. RESULTS Of the 65 SNO members who responded, 52 of these were clinical members. Of these 52 clinical members, the majority were physicians (88.5%, n=46). Of these 46 physicians, most were in academic practices (93.5%, n=43). Over half of the 52 clinical respondents (51.9%, n=27) reported that they saw ≥ 30 primary brain tumor patients a month, thus typifying busy clinical neuro-oncology ambulatory clinics. Despite having busy clinics, only 12 (28.6%) of the 42 providers with access to a clinical pharmacist reported that their clinical pharmacist was solely dedicated to neuro-oncology patients. For the respondents who had access to a clinical pharmacist, only 28 (66.7%) of those pharmacists had direct patient interaction in the clinic. The top three roles of the clinical pharmacist included medication review (81%, n=34), chemotherapy dosing and modifications (73.8%, n=31), and practice guideline development (61.9%, n=26), none of which are associated with direct patient interaction. CONCLUSIONS We found that while our surveyed population of SNO clinical members have demanding outpatient neuro-oncology practices, most do not have the support or expertise of dedicated neuro-oncology clinical pharmacists.
HIV Preexposure Prophylaxis—The Role of Primary Care Clinicians in Ending the HIV Epidemic
Authors: Joshua Khalili, Raphael J. Landovitz
Journal: JAMA Internal Medicine (2019)

A global human immunodeficiency virus (HIV) epidemic persists despite data to support multiple effective and safe tools that prevent HIV transmission and acquisition. Human immunodeficiency virus preexposure prophylaxis (PrEP) for HIV-uninfected at-risk populations using tenofovir disoproxil fumarate emtricitabine is highly effective, safe, and recently endorsed by the US Preventive Services Task Force (USPSTF) as a grade A recommendation. In this Special Communication, we summarize current guidelines and expert recommendations in a call for wider adoption of PrEP prescribing activities by frontline primary care clinicians. Key components include the ideal contexts in which PrEP may be prescribed, eligibility criteria, clinical considerations and pitfalls, laboratory monitoring, prescription practices, situations that may warrant expert consultation, and future directions. Given the broad scope, access, and point-of-entry status of primary clinicians in health systems, generalists will need to be at the center of any successful effort to leverage the power of, and destigmatize PrEP to end the HIV epidemic.
Single-Cell RNA-Seq Reveals the Differentiation Hierarchy of Normal Human Bone Marrow and a Distinct Transcriptome Signature of Monosomy 7 Cells
Authors: Xin Zhao, Shouguo Gao, Xingmin Feng, Delong Liu, Sachiko Kajigaya, Zhijie Wu, Qingguo Liu, Keyvan Keyvanfar, Marie J. Desierto, Danielle M. Townsley, Xujing Wang, Neal S. Young
Journal: Blood (2016)
Changes in Liver Stiffness, Measured by Magnetic Resonance Elastography, Associated With Hepatic Decompensation in Patients With Primary Sclerosing Cholangitis
Authors: John E. Eaton, Aditi Sen, Safa Hoodeshenas, Cathy D. Schleck, William S. Harmsen, Gregory J. Gores, Nicholas F. LaRusso, Andrea A. Gossard, Konstantinos N. Lazaridis, Sudhakar K. Venkatesh
Journal: Clinical Gastroenterology and Hepatology (2019)
HOUT-28. FIRST-LINE TEMOZOLOMIDE VS PCV FOR LOW GRADE GLIOMAS: A 11 YEARS REAL-WORLD DATA FROM CHUM, UNIVERSITY CENTER
Authors: Myriam Nait Ajjou, Anis Assad, Laurent Letourneau Guillon, Karl Belanger, Emilie Lemieux Blanchard, Bernard Lemieux, Jean-Paul Bahary, Laura G Masucci, David Roberge, Cynthia Menard, Carole Lambert, Robert Moumdjian, France Berthelet, Meriem Ben-Abdallah, Jacques De Guise, Marie Florescu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Before 2012, Temozolomide (TMZ) was used for low-grade gliomas (LGG) to avoid Lomustine toxicity. After 2012 RTOG data, Procarbazine, Lomustine and Vincristine (PCV) given sequentially with radiotherapy became standard treatment with the side effects burden associated. METHODS We retrospectively reviewed our SARDO clinical database of patients with low-grade glioma LGG grades 2 and 3 between 2006 and 2017 at CHUM University Health Center. Molecular profile for these tumors is reflex and standard in our institution since 2016. RESULTS A total of 123 patients were identified with grade 2 and grade 3 LGG; 37 (30%) treated with PCV and 86 (70%) received TMZ. Median follow up was 11mo for PCV 11mo vs 22mo TMZ. Both groups were balanced in terms of median age, sex, neurologic symptoms and surgery rate. 53% patients had tumor untested for IDH1-2 and codeletion1p19q because of diagnostic before 2016. Disparities were noted with a predominance of grade 3 in the TMZ group (74% vs 27%, p&lt; 0.01). TMZ was the preferred regimen before 2012 (100% vs 43%) and PCV became the standard of care after 2012 (0% vs 57%). Radiation use as first line treatment was 90%. The 4y OS was not significantly longer for PCV 50% compared with TMZ 47% with mOS between both groups (PCV NR vs TMZ 39.9mo, p=0.158). When controlled for tumor grade, the 2y OS was 80% for PCV vs 64% for TMZ,p=0.542. The 4y PFS was trendly longer for PCV group 78% than TMZ group 45%, p=0.148. CONCLUSION As we are still waiting for the prospective ongoing prospective trials comparing these 2 regimens, PCV and radiation are still standard of care regimens for grade 2 and 3 LGG. This retrospective data is not reassuring for a replacement for PCV with TMZ.
All inpatients with learning disabilities or autism to have case review in next 12 months, says health secretary
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The government has announced that all inpatients with learning disabilities or autism in mental health hospitals in England will have their care reviewed over the next 12 months.

Every patient will be given a date for discharge or a clear explanation where this is not appropriate, the health and social care secretary, Matt Hancock, pledged. The review will also provide all 2250 inpatients in England with learning disabilities or autism with a plan to move them closer towards being …
SAT0547 ULTRASONOGRAPHIC FOLLOW UP OF ENTHESOPHYTE GROWTH IN A CONSECUTIVE SERIES OF IBD PATIENTS
Authors: Pierluigi Macchioni, Federica Martinis, Giorgia Citriniti, Carlo Salvarani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Previous studies have found an interconnection between inflammatory intestinal diseases (IBD), particularly Crohn disease (CD) and Ulcerative Colitis (UC), and spondyloarthritis. <h3>Objectives:</h3> <b>We</b> prospectively <b>evaluate</b> the pattern and predictive factors of enthesophyte growth in a cohort of patients with IBD. <h3>Methods:</h3> A total of 68 IBD consecutive patients (31 CD, 36 UC, 1 ID, M/F 37/31, mean age 40.2 ± 13.2 years, mean disease duration 107.5±129 months) were enrolled. Rheumatological examination included 66 peripheral joint count, MASES and Leeds entheseal indexes, BASDAI, BASFI and evaluation of spine mobility. US examination was done at baseline and at 24 months using an Esaote MyLabClass, 18-6 MHz linear multifrequence transducer both in B-mode and PD-mode. The following sites were blindly evaluated bilaterally: lateral epicondyle of the humerus, distal quadricipital insertion at the patella, superior and inferior pole of the patella, Achilles tendon insertion, and plantar aponeurosis insertion. Quadriceps, patellar, Achille and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). The presence of enthesophyte were scored dichotomously as present (=1) or absent (=0) for each site and summed up to generate the ARE score (ARES). Enthesophytes was also scored semiquantitatively in a 0-3 scale (0 = absent, 1 = minimal, 2 = discrete, 3 = massive) for each site and summed up to generate RES score (RESS). <h3>Results:</h3> Eighteen patients showed no increase of the RESS, 13 pts had 1 point increase, 12 pts less than 4 and 25 pts more than 4 points increase of the RESS at the end of follow-up. Baseline factors associated with RESS progression were age &gt; 50 years, male sex, BMI &gt; 25, CRP &gt; 0.50 mg/dl, and alcohol consumption. As far as the number of sites involved only 8 patients showed no increase of ARES, while 25 pts had ARES increased more than 4. Baseline factors predicting ARES increase were pre-existing presence of enthesophytes at quadriceps tendon insertion at superior patellar pole, age &gt; 50 y, male sex, and alcohol consumption. Progression of ARES and RESS was not associated with type of IBD, use of corticosteroid, biological agents or immunosuppressive drugs nor with the concomitant presence of cutaneous psoriasis, smoke habit, diabetes, dyslipidemia. <h3>Conclusion:</h3> US examination of selected entheseal area demontrates the increase of number and size of enthesophytes during a 2 years follow-up of IBD patients. Alcohol consumption and the presence at baseline of enthesophytes are the most important predictive factors for RESS and ARES progression respectively. <h3>Disclosure of Interests:</h3> None declared
Nutritional Risks in Adolescents After Bariatric Surgery
Authors: Stavra A. Xanthakos, Jane C. Khoury, Thomas H. Inge, Todd M. Jenkins, Avani C. Modi, Marc P. Michalsky, Mike K. Chen, Anita P. Courcoulas, Carroll M. Harmon, Mary L. Brandt, Michael A. Helmrath, Heidi J. Kalkwarf
Journal: Clinical Gastroenterology and Hepatology (2019)
CBMT-47. MODULATION OF NAD PATHWAYS AS A THERAPEUTIC STRATEGY FOR TARGETING IDH MUTANT GLIOMA
Authors: Julie Miller, Hiroaki Nagashima, Alexandria Fink, Kensuke Tateishi, Hiroaki Wakimoto, Jack Banagis, Daniel Cahill
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND IDH mutant tumors exhibit an altered metabolic state which may be exploited for use as a novel therapeutic approach. Our previous work has shown the IDH mutant cancer survival is dependent on the biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT), for the production of nicotinamide adenine (NAD). Inhibition of NAMPT activity (NAMPTi) efficiently targets IDH mutant cells. NAD steady-state is also influenced by consumptive processes that utilize NAD as a coenzyme, including Sirtuin (SIRT) signaling. To avoid concerns surrounding NAMPT inhibitor toxicity at high doses, we sought to investigate whether modulation of SIRT activity can effectively target IDH mutant cells. METHODS IDH1 mutant cancer cells and patient-derived glioma lines were engineered for loss of SIRT gene expression using CRISPR/Cas9 gene editing or SIRT1 overexpression using a tetracycline-inducible expression system. The effect of silenced or enhanced SIRT1 activity was then assessed in IDH1 mutant cells alone or in combination with NAMPT inhibitors. RESULTS Loss of SIRT1 expression, but not other SIRT family members, confers resistance to NAMPT inhibition in IDH1 mutant cells. Consistent with the hypothesis that SIRT1 is a major consumer of NAD, we observed a significantly smaller decline in NAD when SIRT1 is deleted. In agreement with these findings, when SIRT1 activity is enhanced from baseline by tetracycline-mediated induction of SIRT1 expression, IDH mutant cell growth is slowed. Further, overexpression of SIRT1 leads to decreased cell viability and enhanced NAD depletion when induced in combination with NAMPTi. CONCLUSIONS IDH mutant tumors are vulnerable to NAD depletion. Our results show that this metabolic liability can be targeted by a combination of enhanced NAD consumption via SIRT1 activation and inhibition of NAD synthesis. Importantly, compounds to enhance SIRT1 activity are relatively non-toxic and in development for aging and neurologic disease, allowing potential for rapid translation to an IDH mutant-directed treatment.
Pentotstatin/TBI Conditioning Is Well-Tolerated and Permits Engraftment of a Second Allogeneic Stem Cell Transplant Following Primary or Secondary Rejection of an Allogeneic Hematopoietic Stem Graft
Authors: Ani Gvajaia, Amelia Langston, Natia Esiashvil, Michael Graiser, Kelly Valla, Edmund K. Waller
Journal: Blood (2019)