tbuckley/cabot-search huggingface dataset:
PS1452 GLI‐1, EFFECTOR OF CANONICAL HEDGEHOG SIGNALING PATHWAY, DOES NOT SEEM TO BE DYSREGULATED IN PATIENTS WITH MYELOFIBROSIS
Authors: M. Lucijanic, A. Livun, T. Stoos‐Veic, V. Pejsa, Z. Jonjic, A. Fazlic Dzankic, M. Ivic, R. Kusec
Journal: HemaSphere (2019)

Background: Although activation of Hedgehog signaling pathway was reported to be present in murine bone marrow transplant model of primary myelofibrosis (PMF) and increased expression of Hedgehog target genes was reported in granulocytes isolated from unselected patients with myeloproliferative neoplasms, therapeutic Hedgehog inhibition showed only limited results in myelofibrosis so far. Also, inconsistent effects of such therapy on Gli1 (effector of hedgehog signaling) were observed. Aims: We aimed to investigate Gli‐1 expression in bone‐marrow tissues of patients with primary and secondary myelofibrosis (SMF) and to assess its clinical correlations. Methods: We retrospectively investigated Gli‐1 mRNA expression in 32 diseased (28 PMF, 4 SMF) and 16 healthy (limited stage agressive Non‐Hodgkin lymphoma) bone marrow samples using real‐time‐polymerase‐chain‐reaction (GLI1 Hs01110766_m1 Thermo Fischer Scientific TaqMan assay). Expression was normalized to Abl and expressed as a ΔCT value. Correlations with clinical parameters were made. Study was approved by the institutional review board. All procedures were in accordance with the Helsinki Declaration. All patients provided written informed consent. Results: Median age of our patients was 70 years, there were 21 (66%) males and 11 (34%) females. Gli‐1 expression did not significantly differ between PMF, SMF and controls (median ΔCT 7.2, 7.3 and 6.9 respectively; P = 0.864). Higher Gli‐1 bone marrow expression was not significantly associated with neither age, gender, JAK2, CALR, MPL mutational status nor degree of bone marrow fibrosis (P&gt;0.05 for all analyses). Only statistically significant associations were present between higher Gli‐1 expression and higher transferrin saturation (P = 0.039; Rho = 0.4) and higher absolute lymphocyte count (P = 0.032; Rho = 0.4). Gli‐1 expression separated at median (ΔCT 7.25) had neutral effect on overall survival in our cohort of patients (P = 0.651) as shown in a Figure. Summary/Conclusion: Our findings indicate Gli‐1 mRNA expression might not be dysregulated in patients with myelofibrosis and has neutral impact on prognosis of these patients. Although limited by small number of patients, retrospective study design and single center experience, our results are in line with previous observations of modest clinical effects of Hedgehog inhibition in patients with myelofibrosis. image
Long term safety of inotropes and/or vasopressors in acute heart failure: results from ESC-HF-LT registry
Authors: Alexandre Mebazaa, Justina Motiejunaite, Etienne Gayat, Eichi Akiyama, María Generosa Crespo-Leiro, Lars H. Lund, Aldo P. Maggioni, Ovidiu Chioncel, Frank Ruschitzka, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2017)
AB1088 HEMOGRAM PARAMETER CHANGES DURING THE ATTACK AND THE REMISSION IN FAMILIAL MEDITERRANEAN FEVER PATIENTS
Authors: Emel Gönüllü, Yunus Emre Özer, ünal Erkorkmaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease. Disease-specific symptoms are fever and polyserositis attacks (1). The most important complication in the long term is amyloidosis (2). Many cytokines and acute phase reactants have been studied in patients with familial Mediterranean fever. Erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen levels increase during attack and return to normal values after the attack (3,4). Biomarkers that are useful on the course of the disease and the development of amyloidosis are still needed. <h3>Objectives</h3> In this study, we aimed to observe the changes reflected in the hemogram parameter values during the remission and attack periods of FMF patients. <h3>Methods</h3> Study included 67 patients who met the FMF Tel-Hashomer criteria. The patients with available results of both remission and attack periods were included in the study.Since the distribution of all continuous variables used in the study as a statistical method was not suitable for normal distribution, Wilcoxon T test was used to investigate the difference in hematological variables during remission and attack periods <h3>Results</h3> 21 of the patients were male and 46 were female. The mean age of the male patients was 41.57 ± 11.08 and the female patients were 35.84 ± 11.75. The mean age of all patients was 38.18 ± 11.20 years. There was a statistically significant difference between neutrophils in the comparisons of hematological variables between remission and episode periods of familial Mediterranean Fever patients (p &lt;0.001). No significant difference was found in terms of other variables (Table 1). <h3>Conclusion</h3> Our study does not support that neutrophil/lymphocyte ratio, MPV and PDW values may be helpful in the attack. Significant differences in neutrophil counts suggest that further studies are needed to show neutrophil cell morphology, number, and function in FMF patients. <h3>References</h3> [1] Özen S, Batu ED, Demir S. Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management.Front Immunol. 2017 23;8:253. [2] Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: current perspectives.J Inflamm Res. 2016 17;9:13-20. [3] Özer S, Yılmaz R, Sönmezgöz E, Karaaslan E, TaŞkın S, Bütün İ, Demir O. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever.Med Sci Monit. 2015 23;21:298-303. [4] Tunca M, Kirkali G, Soyturk M, et al. Acute phase response and evolution of familial Mediterranean fever. Lancet. 1999;353:1415. <h3>Disclosure of Interests</h3> None declared
San Francisco Voters End the Sale of Flavored Tobacco Products
Authors: Alain Braillon
Journal: Annals of Internal Medicine (2019)

Letters18 June 2019San Francisco Voters End the Sale of Flavored Tobacco ProductsAlain Braillon, MD, PhDAlain Braillon, MD, PhDUniversity Hospital, Amiens, France (A.B.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0153 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Yang and Glantz (1) commend San Francisco voters' 5 June 2018 decision to ban the sale of flavored tobacco products, including menthol cigarettes and vaping liquids, despite a $12 million campaign funded by the R.J. Reynolds Tobacco Company. However, readers outside the United States may require a further explanation. This policy is a bylaw, as is the genuinely successful Berkeley, California, excise tax on sugar-sweetened beverages of $0.01 per ounce (2). Bylaws are unusual in many countries, particularly in Europe. Local governments could be a key to instituting public policy. The foundation of democracy depends on the ...References1. Yang YT, Glantz S. San Francisco voters end the sale of flavored tobacco products despite strong industry opposition. Ann Intern Med. 2018;169:708-9. [PMID: 30304334]. doi:10.7326/M18-2317 LinkGoogle Scholar2. Falbe J, Thompson HR, Becker CM, et al. Impact of the Berkeley excise tax on sugar-sweetened beverage consumption. Am J Public Health. 2016;106:1865-71. [PMID: 27552267] doi:10.2105/AJPH.2016.303362 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University Hospital, Amiens, France (A.B.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0153. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSan Francisco Voters End the Sale of Flavored Tobacco Products Despite Strong Industry Opposition Y. Tony Yang and Stanton Glantz San Francisco Voters End the Sale of Flavored Tobacco Products Y. Tony Yang and Stanton Glantz Metrics Cited byMental health of electronic cigarette advocates: Over both sides of the Atlantic 18 June 2019Volume 170, Issue 12Page: 907KeywordsBeveragesConflicts of interestDisclosureFood and Drug AdministrationPublic policySmoking preventionTaxesTobacco control ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Human Genome Project—An Overview
Authors: David R. Bentley
Journal: Medicinal Research Reviews (2000)

The human genome sequence will underpin human biology and medicine in the next century, providing a single, essential reference to all genetic information. The international program to determine the complete DNA sequence (3,000 million bases) is well underway. As of January 2000, 50% of the sequence is available in the public domain. A comprehensive working draft is expected this year, and the entire sequence is projected to be finished in 2003. DNA sequencing is carried out on mapped, overlapping bacterial clones of 150-200 kb. The working draft comprises assembled unfinished sequence and is released immediately in the public domain. The draft sequence of each clone is then completed, by closing any remaining gaps and resolving any ambiguities, before the entire sequence is checked, annotated, and submitted to the public databases. The sequence of each clone is finished to an accuracy of >99.99%. The availability of a reference sequence of the genome provides the basis for studying the nature of sequence variation, particularly single nucleotide polymorphisms (SNPs), in human populations. SNP typing is a powerful tool for genetic analysis, and will enable us to uncover the association of loci at specific sites in the genome with many disease traits. SNPs occur at a frequency of approximately 1 SNP/kb throughout the genome when the sequence of any two individuals is compared. Programs to detect and map SNPs in the human genome are underway with the aim of establishing a SNP map of the genome during the next two years. The human genome sequence will provide a complete description of all the genes. Annotation of the sequence with the gene structures is achieved by a combination of computational analysis (predictive and homology-based) and experimental confirmation by cDNA sequencing. Detecting homologies between newly defined gene products and proteins of known function helps to postulate biochemical functions for them, which can then be tested. Establishing the association of specific genes with disease phenotypes by mutation screening, particularly for monogenic disorders, provides further assistance in defining the functions of some gene products, as well as helping to establish the cause of the disease. As our knowledge of gene sequences and sequence variation in populations increases, we will pinpoint more and more of the genes and proteins that are important in common, complex diseases. A more detailed understanding of the function of the human genome will be achieved as we identify sequences that control gene expression. Given the availability of gene sequences, the expression status of genes in particular tissues can be monitored in parallel. By comparing corresponding genomic sequences in different species (for example: man, mouse, chicken, and zebrafish), regions that have been highly conserved during evolution can be identified, many of which reflect conserved functions such as gene regulation. These approaches promise to greatly accelerate our interpretation of the human genome sequence.
The discordance of the ER, PR, and HER2 status after neoadjuvant chemotherapy in breast cancer.
Authors: Basak Oven Ustaalioglu, Ahmet Bilici, Fugen Vardar Aker, Burcak Erkol, Mehmet Aliustaoglu, Gunay Gurleyik
Journal: Journal of Clinical Oncology (2013)

e12037 Background: Neoadjuvant chemotherapy(NAC) is the accepted approach for women with locally advanced breast cancer with technically inoperable disease. Systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and HER2 status on the core needle biopsy prior to treatment. Previously, discordance of the hormone receptor (HR) status was reported as 8-33% in the breast cancer patients after NAC. In here, we evaluated the HR and HER2 discordance after NAC in locally advanced breast cancer patients. Methods: We reviewed the data of 849 breast cancer patients retrospectively. The pathological specimens of core needle biopsy and operation specimens were re-evaluated for HR and HER2 status in 38 patients who had been treated with NAC. The changing of HR and HER2 status after chemotherapy was defined as discordance. The relationship between clinicopathological parameters and discordance and significance of them for disease-free survival (DFS) was analyzed by chi-square and univariaty test. Results: Over 80% of patients were clinically stage III breast cancer. Out of 24 patients were premenapouse and median age was 44.5(30-94). The patients were received median 4(1-6) cycles of NAC as 2 of them were only hormonotherapy, 8 were only antracycline and others were both antracycline and taxanes. Nearly 80% of patients were performed modified radical mastectomy(MRM).Postoperatively median tumor size was 1.6cm(0-10) and median dissected lymph nodes was 14(0-28). After operation, 4(10.5%), 8(21.1%) and 8(21.1%) discordance were detected for ER, PR and HER2 respectively. While HER2 discordance were related with recurrence(p=0.01) and PR discordance(p=0.04), ER discordance was related with only patological stage(p=0.03). At the median follow-up of 15.7 months, 5 year DFS rate and time were 30% and 30.4 months(18.7-42.2), respectively. Operation type, stage, lymphovascular invasion, perineural invasion were found to be significant for DFS, HR and HER2 discordance was not related with DFS. Conclusions: Until more definitive results will be obtained from future studies, receptor status of the residual tumor after NAC should be retested.
PS1513 ESTIMATING LIFE‐YEAR LOSS OF PRIMARY MYELOFIBROSIS IN EUROPE
Authors: Z. Li, D. Tang, J. Tang, L. Cavalli, E. Oliva
Journal: HemaSphere (2019)

Background: Primary myelofibrosis (PMF) is a myeloid neoplasm impacting patient survival and quality of life. Although JAK2 inhibitors were recently approved for the treatment of patients with PMF, there is still a lack of strong evidence supporting a survival benefit in this patient population. 1 Existing published survival data focus on describing duration of survival, however as there is no general population comparator for this outcome, interpretations are often subjective. Aims: This study aimed to quantify the real‐world mortality caused by PMF in comparison with the general population in Germany, France, Italy, Spain, and the UK (EU5). Methods: A simulation model was developed in Microsoft Excel, using parameters sourced from a large‐scale European‐based real‐world retrospective MF study by the International Working Group for Myeloproliferative Neoplasm Research and Treatment. 2 Baseline demographics predictive of survival, including age, sex, and International Prognostic Scoring System (IPSS) risk level, were simulated using the patient characteristics statistics published by Cervantes et al. in 2012. 2 The survival of patients with PMF was simulated using the exponential survival function. To examine the rate of mortality, the exponential distribution parameter (modeled as a function of age, sex, and IPSS risk level) was estimated using published median survival times and derived hazard ratios. Patient characteristics and survival statistics from the simulation sample were verified with the published data. 2 Real‐world life‐year loss was calculated as the difference between simulated survival time and the population‐level life expectancy specific to the patient's age, sex, and country. Results: A total of 5,000 patients were simulated (Table), with 1,000 from each EU5 country. The simulated sample generated similar patient characteristics statistics and median survival years as found by Cervantes et al. 2 The additional mean life‐year loss of PMF was estimated at 9.6 years (median 10.7 years; 5 and 95 percentile [−18.7, 33.4]), with a 45% relative survival loss, compared with the general population. Overall, 81% of patients with PMF were estimated to experience life‐year loss. More pronounced life‐year loss was found to be associated with being male (mean 11.3 years; 57% relative survival loss; 86% with life‐year loss), age &lt;65 years (mean 14.3 years; 48% relative survival loss; 84% with life‐year loss), and IPSS Intermediate‐2 to High risk classification (mean 15.4 years; 73% relative survival loss; 95% with life‐year loss). The results were consistent among the EU5 countries modeled. Summary/Conclusion: PMF patients experience significant real‐world life‐year loss when compared with the general population in Europe. image
Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn’s Disease
Authors: Kirstin M. Taylor, Ken B. Hanscombe, Natalie J. Prescott, Raquel Iniesta, Matthew Traylor, Nicola S. Taylor, Steven Fong, Nicholas Powell, Peter M. Irving, Simon H. Anderson, Christopher G. Mathew, Cathryn M. Lewis, Jeremy D. Sanderson
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract 443: Class I Histone Deacetylases Mediate Cardiac I/R Injury and Modify the Mitochondrial Acetylome
Authors: Daniel J Herr, Sverre E Aune, Jennifer R Bethard, Lauren E Ball, Donald R Menick
Journal: Circulation Research (2016)

Although rapid reperfusion of ischemic tissue is the treatment of choice for myocardial infarction, a significant amount of damage occurs as a result of reperfusion itself. The role of epigenetic enzymes in modulating this damage has become an area of interest in basic cardiac research. Previously, we have shown that pharmacological inhibition of the class I histone deacetylases (HDACs) with MS-275 (entinostat) preserves left-ventricular (LV) function and substantially reduces the area of infarcted tissue in isolated rat hearts subjected to ischemia-reperfusion (IR) injury. Interestingly, we have also observed that class I HDAC inhibition during 60 minutes of reperfusion alone is sufficient to protect cardiac tissue viability following I/R injury. Therefore, we hypothesized that class I HDACs mediate reperfusion injury by modulating acetylation of non-canonical pathways. To examine this, hearts from male Sprague-Dawley rats were subjected to I/R injury +/- class I HDAC inhibition during reperfusion. We then performed mass spectrometry to analyze the changes in the acetylome between sham and I/R groups with and without class I HDAC inhibition. Unexpectedly, mass spectrometry analysis revealed significant changes in the acetylation state of multiple mitochondrial enzymes. Further biochemical studies show that class I HDACs localize to the mitochondrial fraction of cardiac tissue homogenates and may modulate mitochondrial acetylation by direct or indirect mechanisms. This study emphasizes the importance of exploring class I HDAC inhibitors for protection against ischemia-reperfusion injury.
Abstract 11004: Coronary Microvascular Dysfunction and Wall Stress Correlate with Cardiac Troponin T Release Measured by a Highly Sensitive Assay in Patients with Nonischemic Heart Failure
Authors: Seiji Takashio, Megumi Yamamuro, Yasuhiro Izumiya, Sunao Kojima, Eiichiro Yamamoto, Kenichi Tsujita, Tomoko Tanaka, Shinji Tayama, Koichi Kaikita, Seiji Hokimoto, Seigo Sugiyama, Hisao Ogawa
Journal: Circulation (2012)

Background: Persistent and modest elevation of serum cardiac troponin T (cTnT) is frequently observed in heart failure (HF) patients without coronary artery disease, although the mechanisms underly...
PB1665 TREATMENT OF FAVORABLE RISK YOUNG PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) USING A LOW‐DENSE/ LOW‐INTENSE CHEMOTHERAPY PROTOCOL
Authors: M. Salamoon, M. balti, K. ghanem, M. kenj
Journal: HemaSphere (2019)

Background: ALL is a disease affecting the lifespan from neonates to elderly, however, overall survival reaches 90% using pediatric protocols. In older patients, survival is still very poor reaching only 45% which can be attributed to several reasons including heterogeneity of biology, physiologic status of patients as well as therapeutic approach. Another factor justifying the poor outcome is the low rate of enrollment in clinical trials of this population aged between 15‐39 years as defined by the National Cancer Institute (NCI). Aims: the study evaluates the response rate, progression free survival (PFS) and overall survival at % years (OS) as well as the safety profile. Methods: this is a multicenter study performed in part at Al Bairouni university cancer center, Al Mwasat charity and Ospedale Italiano in Damascus, Syria between 2008 and 2013 where we recruited 224 patients having a favorable risk ALL confirmed by Bone Marrow aspiration (morphologic study, Flocytometeric study and Karyotype) was performed in all patients. Induction with (Dxorubicin 45 mg/m 2 + Cyclophosphamide 75 mg/m 2 + Vincristin 1.4 mg/m 2 ) every weeks X 4 weeks and prednisolone 1 mg/kg for 4 weeks. Complete responders consolidated with 1 st block: Cyclophosphamide 75 mg/m2+ Cytarabine 30 mg/m 2 BID/SC for 5 days+ 6‐Mercaptopurine 75 mg/m 2 every day repeated every 14 days 4 times followed by a 2 nd block: Methotrexate 3 gram/m 2 + Kidrolase 10000IU repeated every 14 days for 4 times. Maintenance with cyclophosphamide 750 mg/m 2 + Vincristin 1.4 mg/m 2 + oral Methotrexate 15 mg + 6‐Mercaptopurine daily, repeated every month for 24 times. Intralthecal prophylaxis with Methotrexate as performed 2 times in the induction, with every consoloidation and every 3 month during maintenance. Results: complete remission in the first induction was seen in 185 patients (82.5%) with other 32 joined them after an extra induction round (96.8%). Only 8 patients progressed in the consolidation period versus 10 in the maintenance with a PFS of 88.9% at 5 years and 202 patients still surviving after 5 years with an overall survival rate of (90.17%). We have lost 4 patients in the induction and 2 in the consolidation due to unusual toxicity profile of Methotrexate, however, other toxicities were manageable. Response was more prominent in younger population (those younger than 22) (p value 0.003) and late in those with Philadelphia positive disease (p value 0.02). Summary/Conclusion: ALL is still a lethal disease especially in those who do not respond well to induction protocols. Progress was made during the last decade in both understanding the biology and employment of new treatment approach especially in pediatric population, however, results are still poor in elderly patients. Our study shows good results compared with published data which could be adopted in the light of other trials conducted to test our results.