tbuckley/cabot-search huggingface dataset:
Abstract 10630: Is Beta3-Adrenergic-Receptor (AR) a Target for Diabetic Cardiomyopathy Therapy? Evidence From Beta3-AR Knockout Mice
Authors: Zhe Chen, Che Ping Cheng, Yixi Liu, Peng Zhou, Zhi Zhang, Tiankai Li, Xiaowei Zhang, Dalane Kitzman, Heng-Jie Cheng
Journal: Circulation (2018)

Background: Diabetes mellitus (DM) increases the risk for the development of diabetic cardiomyopathy (DCM) and leads to heart failure. DM is associated with the upregulation of β3adrenergic recepto...
Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes
Authors: Daniel J. Corsi, Laura Walsh, Deborah Weiss, Helen Hsu, Darine El-Chaar, Steven Hawken, Deshayne B. Fell, Mark Walker
Journal: JAMA (2019)

Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited.To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes.Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017.Self-reported cannabis exposure in pregnancy was ascertained through routine perinatal care.The primary outcome was preterm birth before 37 weeks' gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks' gestation (late preterm), 32 to 33 6/7 weeks' gestation, 28 to 31 6/7 weeks' gestation, and less than 28 weeks' gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding.In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51% of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks' gestation was 6.1% among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95% CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98% (95% CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95% CI, 1.45-1.61]), placental abruption (1.6% vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3% vs 13.8%; RR, 1.40 [95% CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95% CI, 1.13-1.45]).Among pregnant women in Ontario, Canada, reported cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.
Abstract 12052: Myocardial Extracellular Matrix Expansion Detected With Cardiac MRI: A Biomarker of Cardiomyopathic Disease in Duchenne Muscular Dystrophy
Authors: Jonathan H Soslow, Stephen M Damon, Kimberly Crum, Mark Lawson, James C Slaughter, Meng Xu, Andrew E Arai, Douglas B Sawyer, David A Parra, Bruce M Damon, Larry W Markham
Journal: Circulation (2015)

Introduction: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which standard heart failure therapies have limited efficacy. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. Hypothesis: The study hypothesis is that T1 and extracellular volume fraction (ECV) mapping using cardiac magnetic resonance imaging (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without late gadolinium enhancement (LGE). Methods: 28 DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. Results: DMD participants had significantly higher mean native T1 compared with controls (1045ms vs 988ms, p&lt;0.001) (Fig 1A). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1036ms vs 988ms, p&lt;0.001, and 1039ms vs 988ms, p=0.001) (Fig 1C, 1E). Mean post-contrast T1 values were not significantly different between DMD participants and controls. DMD participants had a significantly greater mean ECV than controls (0.31 vs 0.24, p&lt;0.001), even in the settings of normal LVEF (0.29 vs 0.24, p&lt;0.001) and negative LGE (0.30 vs 0.24, p&lt;0.001) (Fig 1B, 1D, 1F). Conclusions: DMD participants have elevated native T1 and ECV in left ventricular myocardium, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.
PS1574 HLA‐DRB1<sup>∗</sup>15 INCREASES THE RISK OF RED BLOOD CELLS ALLOANTIBODIES IN PATIENTS WITH BETA THALASSEMIA MAJOR
Authors: L.A. Al Mashaykhi, M.K. Al‐Khabori, H. Al‐Riyami, B. Al‐Rawahi, Y. Wali, S. Daar
Journal: HemaSphere (2019)

Background: The cornerstone of the management of Beta Thalassemia Major (B‐TM) is lifelong Red Blood Cells (RBC) transfusion. This is associated with the development of RBCs alloantibodies. Human Leukocyte Antigen (HLA) is considered a risk factor for a number of autoimmune disorders. We hypothesized that HLA impacts the rate of alloantibody formation in patients with B‐TM. Aims: To assess the impact of HLA alleles on the risk of RBC alloimmunization in patients with B‐TM. Methods: This is a retrospective cohort study of patients with B‐TM managed at Sultan Qaboos University Hospital (SQUH) between January 1996 till December 2016. All adult and paediatric patients with B‐TM with available HLA typing results were included. Patients with missing data were excluded. Chi‐squared test was used to assess the impact of HLA alleles on alloimmunization and the effect size was estimated using odd ratio (OR). HLA testing was performed using polymerase chain reaction – specific sequence of oligonucleotides (PCR‐SSO). Gel card technique (BIORAD ID‐System; DiaClon, Bio‐Rad, DiaMed GmbH, Switzerland) was used to screen for the RBC alloantibodies. Results: One hundred and sixty‐five patients fulfilled the inclusion criteria without missing information. The median age of all patients was 14 years. Females constituted 48% of the sample and 45% of patients were O RhD positive. The median RBC transfusion was 17 times per year. Patients were first detected to have RBC alloantibody at a median age of 16 years. The commonest RBC alloantibodies found in these patients were anti‐K (50%) and anti‐E (58%). The commonest HLA allele in loci A, B, C, DQ and DRB1 were HLA‐A ∗ 02 (21%), HLA‐B ∗ 51 (14%), HLA‐C ∗ 7 (18%), HLA‐DQ ∗ 05 (47%) and HLA‐DRB1 ∗ 16 (32%) respectively. HLA‐DRB1 ∗ 15 and HLA‐DQ ∗ 6 were associated with a higher risk of RBC alloantibody formation (HLA‐DRB1 ∗ 15: OR 3.57, P = 0.047; HLA‐DQ ∗ 06: OR 4.37, P = 0.025). None of the remaining common alleles (&gt;5%) in Omani population were associated with the risk of alloantibody formation ( p values &gt;0.05). Summary/Conclusion: HLA‐DRB1 ∗ 15 and HLA‐DQ ∗ 06 increases the risk of RBC alloantibody formation in patients with B‐TM. We recommend extended RBC phenotyping and extended antigen matched blood transfusion in patients carrying these two alleles. These findings will need to be confirmed in a larger multicenter study.
AB1083 IN A FAMILIAL MEDITERRANEAN FEVER PREVALENT REGION, ARE FAMILIAL MEDITERRANEAN FEVER AND BEHÇET’S DISEASE ASSOCIATED?
Authors: Ozgur Alparslan, Bugra Han Egeli, Yeltekin Demirel, Serdal Ugurlu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The co-existence of Familial Mediterranean Fever (FMF) and BehÇet's Disease (BD) has been questioned. There have been a variety of claims on a common pathogenesis. <h3>Objectives</h3> We intended to report the prevalence of Familial Mediterranean Fever (FMF) and BehÇet's disease (BD) and comorbidity ratio of these two diseases in Sivas, Turkey, a city where FMF is known to be very high. <h3>Methods</h3> Seventy-two primary schools in the center of Sivas participated in the study. A total of 14881 randomized sample children from 6th, 7th, and 8th grades, and also 985 of them with their parents (n: 978) were interviewed. During these interviews, the family tree up to second degree relatives was drawn. The presence of a diagnosis of FMF or BD was questioned. The ones who have a diagnosis were confirmed by contacting the medical centers. The ones who were suspected of a disease were further investigated at Sivas Cumhuriyet University Medical Faculty, Family Medicine Outpatient unit. For each disease a disease related history, physical examination, eye examination and pathergy test for BD were performed when needed. <h3>Results</h3> 985 students, 978 mothers, 953 fathers and 1876 relatives (4792 in total) were included in the study. Only 30 (0.6%) of the sample was diagnosed with FMF, and 3 (%0.06) was diagnosed with BD. One of them had concomitant FMF diagnosis. <h3>Conclusion</h3> The prevalence of FMF in Sivas is higher than Turkey's prevalence; however, BD prevalence was found very low. According to these findings, it is not easy to conclude that these two diseases share a similar background of pathogenesis. <h3>Disclosure of Interests</h3> None declared
PF598 STEM CELL YIELD AND TRANSPLANTATION IN TRANSPLANT‐ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS RECEIVING DARATUMUMAB + BORTEZOMIB/THALIDOMIDE/DEXAMETHASONE (D‐VTD): PHASE 3 CASSIOPEIA STUDY
Authors: C. Hulin, P. Moreau, M. Attal, K. Belhadj, L. Benboubker, D. Caillot, T. Facon, L. Garderet, F. Kuhnowski, A.‐M. Stoppa, B. Kolb, M. Tiab, P. Sonneveld, K.‐S. Jie, M. Westerman, L. Pei, T. Kampfenkel, C. de Boer, J. Vermeulen, N.W. van de Donk
Journal: HemaSphere (2019)

Background: High‐dose therapy (HDT) followed by autologous stem‐cell transplantation (ASCT) is the standard of care in transplant‐eligible newly diagnosed multiple myeloma (NDMM). In the phase 3 CASSIOPEIA study, daratumumab + standard‐of‐care regimen VTd (D‐VTd) significantly improved stringent complete response (sCR), complete response or better (≥CR), and minimal residual disease (MRD)‐negative rates and reduced the risk of progression or death versus VTd in NDMM patients who were eligible for transplant. Aims: Here, we assessed stem cell yield and transplantation results among patients receiving D‐VTd versus VTd induction prior to HDT and ASCT in Part 1 of the CASSIOPEIA trial. Methods: In Part 1, transplant‐eligible NDMM patients ages 18–65 years were randomized 1:1 to 4 pre‐transplant induction and 2 post‐transplant consolidation cycles of D‐VTd or VTd alone. After induction, patients underwent stem cell mobilization with cyclophosphamide 3 g/m 2 (recommended dose) and granulocyte colony‐stimulating factor (G‐CSF). Peripheral blood stem cells were harvested based on response to mobilization. Plerixafor was administered if stem cell collection failed at first attempt and in accordance with institutional practice. Melphalan 200 mg/m 2 IV was given as HDT prior to ASCT. Results: A total of 1,085 patients were randomized to D‐VTd (n = 543) or VTd (n = 542). Among patients who completed mobilization (D‐VTd, 506; VTd, 492), more patients in the D‐VTd arm received plerixafor during mobilization than in the VTd arm (21.7% vs 7.9%). Patients underwent a median (range) of 2 (1–6) versus 1 (1–4) days of apheresis for D‐VTd versus VTd. The median number of CD34 + cells collected was lower in patients receiving D‐VTd versus VTd (6.3 × 10 6 /kg vs 8.9 × 10 6 /kg). Nevertheless, a similar percentage of intention‐to‐treat patients receiving D‐VTd versus VTd underwent ASCT (90.1% vs 89.3%). The median number of CD34 + cells transplanted for D‐VTd versus VTd was 3.3 × 10 6 /kg versus 4.3 × 10 6 /kg. Hematopoietic reconstitution rates were high and similar in transplanted patients receiving D‐VTd versus VTd (99.8% vs 99.6%). For D‐VTd versus VTd, a median (range) of 13.0 (6–54) versus 13.0 (4–43) days was required to achieve sustained absolute neutrophil counts &gt;500 cells/mm 3 , and a median (range) of 14.0 (2–56) versus 12.0 (1–47) days was required to achieve sustained platelets &gt;20,000 cells/mm 3 without transfusion. Summary/Conclusion: Stem cell mobilization and collection was feasible with D‐VTd induction. Adding daratumumab to VTd allowed successful transplantation in patients with NDMM who were transplant eligible.
Annals Graphic Medicine - Progress Notes: Chess
Authors: Michael Natter
Journal: Annals of Internal Medicine (2019)

Web Exclusives18 June 2019Annals Graphic Medicine - Progress Notes: ChessFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0023 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 June 2019Volume 170, Issue 12Page: W123-W124KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFellowshipsGraduate medical educationResidency ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PB1712 PROGNOSTIC IMPACT OF ABERRANT EXPRESSION IN ACUTE MYELOID LEUKEMIA
Authors: I. Turki, N. Louati, T. Rekik, O. Kassar, H. Mnif, M. Elloumi
Journal: HemaSphere (2019)

Background: Immunophenotyping allows identification of aberrant antigen expression in acute myeloid leukemia (AML). These antigens are related with particular and genetic abnormalities and recognized as factors of poor prognosis in AML. Aims: To assess prognostic impact of aberrant expression in treated AML. Methods: Our study is retrospective (January 2017‐June 2018) concerning 97 cases of AML (AML 3 and mixed phenotype acute leukemia were excluded) of the adult from 18 to 60 years old diagnosed and treated at one institution. The immunophenotyping was performed by flow cytometry (BD Facs Canto II®) after incubation with monoclonal antibodies labeled with different flurochromes. Aberrant expression correspond to the expression of antigens of the lymphoid line B or T in AML. We studied the impact of aberrant expression on complete remission (CR) and relapse in a delay of 1 year. We excluded the cases with missing data. Results: We had collected 33 cases of treated AML. Aberrant lymphoid antigen were seen in 18 cases (54.54%). It is about CD 56 in 6 cases (33%), CD7 in 6 cases (33%), CD4 in one case (5.5%) and CD19 in 2 cases (11%). Association between lymphoid B and T antigens or T and NK antigens was seen in 3 cases (CD19 + CD7, n= 1; CD7 + CD56, n=2). We didn’t find any correlation between expression of lymphoid antigen and lower CR rates (93% vs 54%; r= 0.17, p = 0.42). Analysed individually, no lymphoid antigen was associated with more induction failure. Relapse seems to be associated with aberrancy expression without statistically significant association (p = 0.29); CD7 was the most aberrant antigen expressed in cases of relapses (75%). Summary/Conclusion: The expression of aberrant antigens in AML is correlated with poor prognosis in literature. This result was not statistically prouved in our study and that's can be explained by the reduced size of our sample. Otherwise, our study shows the pejorative impact of the expression of CD7 on cases of relapses. Expression of CD56 (33% of our cases), similar to literature (10‐30% of cases), was not associated with higer relapse's rate in the limit of our sample (12.5% of AML CD56 + ). Despite the limited number of cases, this study allow us to better understand the impact of aberrant antigens expression in prognosis of AML. A study on a larger series is underway.
Abstract 14773: Progressive Malnutrition During Hospitalization Provides the Additional Long-Term Prognostic Information in Patients Admitted With Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamomoto, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Masatake Fukunami
Journal: Circulation (2013)

Backgrounds: Malnutrition is associated with increased mortality risk in patients (pts) with heart failure. Nutritional status tends to worsen during hospitalization for acute decompensated heart f...
Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs
Authors: Christopher R. Rowland, Katherine A. Glass, Adarsh R. Ettyreddy, Catherine C. Gloss, Jared R.L. Matthews, Nguyen P.T. Huynh, Farshid Guilak
Journal: Biomaterials (2018)
Abstract 11263: Impaired Endothelial Glucocalyx is Related With Abnormal Aortic and Coronary Function in Newly Diagnosed Untreated Hypertensives
Authors: Ignatios Ikonomidis, Astrinos Voumvourakis, Helen Triantafyllidi, George Pavlidis, Mary Varoudi, Ioannis Papadakis, Maria Anastasiou-Nana, John Lekakis
Journal: Circulation (2013)

The integrity of endothelial glucocalyx plays a vital role in vascular permeability, inflammation and elasticity. The association between damage of endothelial glucocalyx, impaired arterial elastic...
PB2024 A RARE CAUSE OF NEUTROPHIL FUNCTION DISORDER: THE MUTATION IN IKBKB GENE
Authors: T. Patıroglu, H. Gungor, M. Cansever, E. Unal, C. Klein
Journal: HemaSphere (2019)

Background: Some patients with severe combined immunodeficiency may have normal T-cell counts with a severe immune-cell activation defect in complex signaling that regulates transcriptional programs. The nuclear factor κB (NF-κB) pathway plays a role in inflammatory and immune responses, cell adhesion, and protection against apoptosis. NF-κB pathway activation requires degradation of the NF-κB inhibitor (IκB) proteins initiated by their phosphorylation by the IκB kinase (IKK) complex consisting of two active kinases, IKKα and IKKβ. The IκB kinase (IKK) complex links these transcription factors to immune receptors. Several primary immunodeficiencies in humans are caused by an impaired IKK–IκB axis. The mutation in IKBKB is characterized by viral,fungal,bacterial infections that leads to the life-threatening consequences. The patients have agammaglobulinemia/hypogammaglobulinemia and normal lymphocyte count. Aims: Here, we describe an infant with a severe combined immunodeficiency with homozygous IKBKB mutation because of rarity. Methods: The 40 day-old girl applied to the hospital with perianal and periumbilical abcesses. She was the second child from the first generation consanguineous parents. There was history of sibling death with unknown ethiology at age of 5 th months. Results: The immunological investigations revealed that she had WBC:27190 mm3/L, absolute neutrophil count:6150 mm3/L, absolute lymphocyte count:10740 mm3/L, IgG:287 mg/dl, IgA:6.2 mg/dl, IgM:17.4 mg/dl, IgE:17.7 IU/ml, CD4:55.6%, CD8:29.7%, CD3: 83.8%, CD16+56:6.3%, CD19:7.1%, CD45:99.9%, CD11/CD18:98%. The homozygous missense c.965_967delTCC;p.IIe322_His323delins Asn variant in IKKβ gene was identified. Although she was administrated intensive antibiotic and immunoglobulin therapy, she died at 5 th month of age because of septic shock. Summary/Conclusion: As a result, the case report is first for presentation of SCID with normal lymphocyte count, agammaglobulinemia and homozygous missense mutation in IKBKB gene in the medical literatüre.
Abstract 257: Determining the Potential Role of cTnT Isoform Switching in the Development of Early Childhood Tropomyosin-linked DCM
Authors: Melissa Lynn, Teryn Holeman, Lauren Tal-Grinspan, J.P. Jin, Jil C Tardiff
Journal: Circulation Research (2016)

An oft noted component of sarcomeric DCM is the observation that patients within families carrying the same primary mutation exhibit significant phenotypic variability. This lack of a distinct link between genotype and phenotype has complicated clinical management. Recently two unrelated multigenerational families were identified with the tropomyosin (Tm) mutation Asp230Asn (D230N), exhibiting a striking “bimodal” distribution of severity. In these families, many children (&lt;1 year) with D230N Tm presented with a severe form of DCM that led to sudden, often fatal CHF, while adults developed a mild to moderate DCM in mid-life. Of note, children who survived the initial presentation often recovered significant systolic function into young adulthood. To explain this improvement, despite the persistence of D230N Tm, we hypothesized that the phenotype is modified by other thin filament (TF) isoforms. Thus we propose the age-dependent remodeling seen in children with D230N Tm is a result of temporal isoform switches involving a closely linked Tm binding partner cardiac Troponin T (cTnT). We have shown that D230N Tm leads to a more stable (rigid) filament primarily at the C-terminus of Tm near the Tm overlap, a crucial region for TF regulatory function that cTnT modulates. Myofilaments from D230N Tm mice exhibited a small decrease in calcium sensitivity of force development that was significantly reduced in the presence of cTnT1, supportive of a modulatory role. We assessed cardiac performance in our novel D230N Tm x cTnT1 double transgenic (DTg) mice, % FS was similarly reduced for D230N Tm and DTg mice at 2 months likely due to persistent endogenous expression of cTnT1. Divergent cardiac remodeling occurred at 4 months at which point DTg mice had significantly reduced % FS compared to D230N, indicating that additive exposure to cTnT1 is detrimental to the function of D230N hearts. Additionally, In vitro studies on non-failing and failing human heart tissue found that RNA levels of cTnT1 are significantly higher in failing hearts. Thus modulation by cTnT1 could be a more general mechanism for the progressive remodeling seen in heart failure.