tbuckley/cabot-search huggingface dataset:
Glucose Variables in Type 1 Diabetes Studies With Dapagliflozin: Pooled Analysis of Continuous Glucose Monitoring Data From DEPICT-1 and -2
Authors: Chantal Mathieu, Paresh Dandona, Moshe Phillip, Tal Oron, Marcus Lind, Lars Hansen, Fredrik Thorén, John Xu, Anna Maria Langkilde
Journal: Diabetes Care (2019)

OBJECTIVE This pooled analysis assessed continuous glucose monitoring (CGM) in patients with inadequately controlled type 1 diabetes (HbA1c ≥7.7 to ≤11.0% [≥61 to ≤97 mmol/mol]) who received dapagliflozin as an adjunct to adjustable insulin. RESEARCH DESIGN AND METHODS CGM data were pooled from two 24-week, double-blind, randomized, phase 3 studies: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-1 and DEPICT-2). These studies comprised 1,591 patients receiving dapagliflozin 5 mg (n = 530), dapagliflozin 10 mg (n = 529), or placebo (n = 532). RESULTS Baseline characteristics were balanced between treatment groups. Patients receiving dapagliflozin 5 mg or 10 mg both spent more time with blood glucose in the range &amp;gt;3.9 to ≤10.0 mmol/L (&amp;gt;70 to ≤180 mg/dL) over 24 h than those receiving the placebo. The adjusted mean (SE) change from baseline at week 24 was 6.48% (0.60) with dapagliflozin 5 mg, 8.08% (0.60) with dapagliflozin 10 mg, and −2.59% (0.61) with placebo. At week 24, the mean amplitude of glucose excursion over 24 h, mean 24-h glucose values, and postprandial glucose values were also improved in patients receiving dapagliflozin over those receiving placebo. No marked differences were found at week 24 between dapagliflozin 5 or 10 mg and placebo in the percentage of glucose values ≤3.9 mmol/L (≤70 mg/dL) or ≤3.0 mmol/L (≤54 mg/dL) over 24 h, or in nocturnal (0000–0559 h) glucose values ≤3.9 mmol/L (≤70 mg/dL). CONCLUSIONS In patients with type 1 diabetes, treatment with dapagliflozin over 24 weeks improved time in range, mean glucose, and glycemic variability without increasing the time spent in the range indicating hypoglycemia.
PS-089-Development of advanced alcoholic liver fibrosis involves intensive remodelling of a wide range of extracellular matrix proteins and is characterised by imbalance between collagen formation and -degradation and dysfunctional wound-healing
Authors: Stine Johansen, Natasja Gudmann, Bjørn Stæhr Madsen, Maria Kjærgaard, Mette Juul Nielsen, Diana Leeming, Suganya Jacobsen, Sönke Detlefsen, Aleksander Krag, Morten Karsdal, Maja Thiele
Journal: Journal of Hepatology (2019)
FRI-333-ATG7 genetic variant and defective autophagy: A novel risk factor for non-alcoholic fatty liver disease progression in patients with type 2 diabetes mellitus
Authors: Serena Pelusi, Guido Alessandro Baselli, Annalisa Cespiati, Paola Dongiovanni, Misti McCain, Marica Meroni, Anna Ludovica Fracanzani, Renato Romagnoli, Salvatore Petta, Antonio Grieco, Luca Miele, Giorgio Soardo, Elisabetta Bugianesi, Silvia Fargion, Riccardo De Francesco, Stefano Romeo, Helen Reeves, Luca Valenti
Journal: Journal of Hepatology (2019)
Diabetes-Related Complications and Mortality in Patients With Young-Onset Latent Autoimmune Diabetes: A 14-Year Analysis of the Prospective Hong Kong Diabetes Register
Authors: Andrea O.Y. Luk, Eric S.H. Lau, Cadmon Lim, Alice P.S. Kong, Elaine Chow, Ronald C.W. Ma, Juliana C.N. Chan
Journal: Diabetes Care (2019)

OBJECTIVE Young-onset diabetes is heterogeneous in etiology and disease progression. We compared the incidence of diabetes-related complications and mortality in patients with young-onset type 2 diabetes with or without anti-GAD antibodies and patients with type 1 diabetes. We determined changes in glycemic control before and after commencement of insulin therapy stratified by antibody status. RESEARCH DESIGN AND METHODS Between 1994 and 2012, 1,504 consecutively enrolled patients with type 2 diabetes who had received a diagnosis at &amp;lt;40 years of age and had available anti-GAD antibody status and 251 patients with type 1 diabetes from the Hong Kong Diabetes Register were followed for incident cardiovascular disease (CVD), end-stage renal disease (ESRD), severe hypoglycemia, and all-cause mortality until June 2015. Information on insulin use and HbA1c levels during follow-up was obtained. RESULTS Anti-GAD antibodies were positive in 8.1% of patients with type 2 diabetes (GAD+). By multivariate Cox regression, patients with GAD+ had a lower hazard of CVD (hazard ratio [HR] 0.43, P = 0.048), a higher hazard of severe hypoglycemia (HR 1.63, P = 0.032), and a similar hazard of ESRD and mortality compared with counterparts without anti-GAD antibodies (GAD−). Compared with patients with type 1 diabetes, ESRD was more likely to develop (HR 2.91, P = 0.043) in patients with GAD+, but no differences were detected in the hazards of severe hypoglycemia, CVD, and mortality. Among new insulin users (n = 304), patients with GAD+ had larger reductions in HbA1c than patients with GAD−after 12 months of insulin use (−2.30 ± 3.80% [25 ± 42 mmol/mol] vs −0.72 ± 1.86% [8 ± 20 mmol/mol], P = 0.05). CONCLUSIONS Anti-GAD positivity identifies a group of patients with a different prognosis compared with patients without antibodies and those with type 1 diabetes. Patients with GAD+ responded differently to insulin compared with patients with GAD−.
SAT-425-Serum metabolites as diagnostic biomarkers for cholangiocarcinoma, hepatocellular carcinoma and primary sclerosing cholangitis
Authors: Jesús María Banales, Mercedes Iñarrairaegui, Ander Arbelaiz, Piotr Milkiewicz, Jordi Muntané, Luis Muñoz-Bellvis, Adelaida La Casta, Luis M. Gonzalez, Enara Arretxe, Cristina Alonso, Ibon Martínez-Arranz, Ainhoa Lapitz, Alvaro Santos-Laso, Matías A Avila, María Luz Martínez-Chantar, Luis Bujanda, Jose Marin, Bruno Sangro, Rocio IR Macias
Journal: Journal of Hepatology (2019)
SAT-205-Associated risk factors for hepatitis E seroprevalence among liver transplant recipients
Authors: Petra Dinjar Kujundžić, Oktavija Rode Ðaković, Adriana Vince, Jelena Prpić, Lorena Jemeršić, Branko Kolarić, Ana Ostojić, Anna Mrzljak
Journal: Journal of Hepatology (2019)
SAT-245-Prospective evaluation of the impact of hepatitis C cure on sexual dysfunction
Authors: Zoe Mariño, Sergio Rodriguez-Tajes, Sabela Lens, Concepció Bartres, Loreto Nacar, Anna Pla, Anna Miralpeix, Mónica Gonzalez, Joaquim Sarquella, Lydia Sastre, Ricard Navinés, Rocío Martin-Santos, Xavier Forns
Journal: Journal of Hepatology (2019)
Extended-spectrum β-lactamase–producing Enterobacteriaceae among geckos (Hemidactylus brookii) in a Ghanaian hospital
Authors: D. Eibach, M. Nagel, S. Lorenzen, B. Hogan, C. Belmar Campos, M. Aepfelbacher, N. Sarpong, J. May
Journal: Clinical Microbiology and Infection (2019)
Association of hemophagocytic lymphohistiocytosis (HLH) with poor outcomes in adults with NK- and T-cell lymphoma (NKTCL).
Authors: Mithun Vinod Shah, Thomas E. Witzig, Megan O'Byrne, Prashant Kapoor, Alexandra P. Wolanskyj, Andew L. Feldman, Brian K. Link, James Robert Cerhan, Matthew John Maurer, Sameer Ashok Parikh
Journal: Journal of Clinical Oncology (2015)

8561 Background: HLH is a rare life threatening disorder characterized by extreme activation of immune system. In adults, HLH may be secondary to malignancies, including NKTCL. There is limited knowledge about the differences in presenting features and outcomes of patients with NKTCL when associated with HLH and in those without HLH. Methods: All adult patients diagnosed with HLH per HLH-04 criteria seen at Mayo Clinic, Rochester were identified. Cases of NKTCL-associated HLH comprised of those with biopsy-proven NKTCL and a diagnosis of HLH within 1 month of each other. The comparison cohort comprised of adult patients with newly diagnosed NKTCL without HLH enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE prospective study. The study was approved by Mayo Clinic IRB. Results: We identified 20 patients with NKTCL-associated HLH; median age at diagnosis was 61 years, and 80% were male. At diagnosis, median serum ferritin was 4392 mcg/L (range, 1409-107100). In contrast to 147 NKTCL patients without HLH identified from the SPORE study, patients with NKTCL-associated HLH were more likely to be males, and have low serum albumin, high LDH, elevated creatinine, and ECOG performance status ≥ 2 at presentation. Of the 20 patients with NKTCL-associated HLH, 7 received CHOP, 4 received etoposide in addition to CHOP, and 5 received other intensive chemotherapy. Two patients received therapy according to the HLH-04 protocol, and 2 did not receive any NKTCL- or HLH-specific treatment. The median OS for NKTCL-associated HLH was 2.3 months vs. 45.1 months for NKTCL without HLH (p< 0.0001). After a median follow-up of 1.4 months, 14 (70%) patients with NKTCL-associated HLH had died. Death was secondary to progressive lymphoma in 12 (86%) patients. After adjusting for International Prognostic Index (IPI), the diagnosis of HLH in patients with NKTCL was independently associated with significantly shorter survival (HR = 8.5, p< 0.0001). Conclusions: Adult patients with NKTCL-associated HLH have an extremely poor outcome, even after adjusting for the IPI score. Standard therapy for NKTCL-associated HLH is ineffective and novel approaches are needed.
THU-087-A 3-dimensional dynamic model to explore the immunomodulatory properties of the extracellular matrix and their implications in liver fibrosis
Authors: Claire McQuitty, Dipa Natarajan, Wing Tung Ma, Lisa Sassi, Riccardo Rayan Siena, Omolola Ajayi, Alessandro Pellegata, Antonio Riva, Paolo De Coppi, shilpa Chokshi, Luca Urbani
Journal: Journal of Hepatology (2019)
TCTAP A-079 True Effect of Catheter-based Renal Denervation Across a Broad Spectrum of Patients: A Systematic Review and Meta-analysis
Authors: Lawrence Yu-min Liu, Po-Lin Lin, Feng-Ching Liao, Wei-Ru Chiou, Shu-I. Lin, Ying-Hsiang Lee
Journal: Journal of the American College of Cardiology (2019)
Scam Awareness Related to Incident Alzheimer Dementia and Mild Cognitive Impairment
Authors: Patricia A. Boyle, Lei Yu, Julie A. Schneider, Robert S. Wilson, David A. Bennett
Journal: Annals of Internal Medicine (2019)

Background: Decreased scam awareness may be an early indicator of impending Alzheimer dementia and its precursor, mild cognitive impairment, but prior studies have not systematically examined the associations between scam awareness and adverse cognitive outcomes. Objective: To test the hypothesis that low scam awareness is associated with increased risk for incident Alzheimer dementia, mild cognitive impairment, and Alzheimer disease pathology in the brain. Design: Prospective cohort study of aging. Setting: Community-based study in the greater Chicago metropolitan area. Participants: 935 older persons initially free of dementia. Measurements: Scam awareness was measured via questionnaire, incident Alzheimer dementia and mild cognitive impairment were documented in detailed annual cognitive and clinical evaluations, and Alzheimer disease neuropathology was quantified after death among a subset of persons who died (n = 264). Proportional hazards models examined associations between scam awareness and incident Alzheimer dementia and mild cognitive impairment. Regression models examined associations between scam awareness and Alzheimer disease pathology, particularly β-amyloid burden and tau tangle density. Results: During a mean of about 6 years (SD, 2.4) of observation, 151 persons (16.1%) developed Alzheimer dementia. Low scam awareness was associated with increased risk for Alzheimer dementia (hazard ratio [HR], 1.56 [95% CI, 1.21 to 2.01]; P < 0.001), such that each 1-unit increase in scam score (indicating lower awareness) was associated with about a 60% increase in dementia risk. Low scam awareness was also associated with increased risk for mild cognitive impairment (HR, 1.47 [CI, 1.20 to 1.81]; P < 0.001). These associations persisted even after adjustment for global cognitive function. Finally, low scam awareness was associated with a higher burden of Alzheimer pathology in the brain, particularly β-amyloid (estimated increase [±SE] in β-amyloid per 1-unit increase in scam score, 0.22 ± 0.10 unit; P = 0.029). Limitation: The measure of scam awareness used here is too weak for prediction at the individual level. Conclusion: Low scam awareness among older persons is a harbinger of adverse cognitive outcomes and is associated with Alzheimer disease pathology in the brain. Primary Funding Source: National Institute on Aging.
Gastrointestinal diagnosis using non-white light imaging capsule endoscopy
Authors: Gerard Cummins, Benjamin F. Cox, Gastone Ciuti, Thineskrishna Anbarasan, Marc P. Y. Desmulliez, Sandy Cochran, Robert Steele, John N. Plevris, Anastasios Koulaouzidis
Journal: Nature Reviews Gastroenterology & Hepatology (2019)
External validation of a survival score for limited stage small cell lung cancer treated with chemoradiotherapy
Authors: L. Käsmann, R. Abdo, J. Taugner, C. Eze, M. Dantes, O. Roengvoraphoj, C. Belka, F. Manapov
Journal: Annals of Oncology (2019)

Background: In 2016, a survival score for limited stage small cell lung cancer (LS-SCLC) patients was developed to characterize prognostic sub-groups who underwent multimodal treatment. Herein, we validate the score in an independent external patient cohort. Methods: We reviewed the medical charts of 78 LS-SCLC patients treated with CRT at our institution. The survival score was calculated by independent prognostic factors: gender, Karnofsky performance status (50-70% vs. 80-100%), Tumor sub-stage (very limited vs. limited disease) and hemoglobin level before the start of radiation (<12 g/dl vs. ≥12 g/dl). Scoring points were derived from 2-year survival rates divided by 10 and the individual values for each prognostic factor were tallied. Three risk subgroups were defined (high, intermediate vs. low-risk: 9-13, 14-18 vs.19-26 points). Results: Median overall survival in the validation cohort was 17 months (range: 1-123months). The 2-year survival rates were 0% in the high, 35% in the intermediate and 43% in the low-risk subgroup, respectively (p = 0.018). The difference in 2-year survival between the high and intermediate risk subgroups was significant (p = 0.007), whereas the 2yr-OS between the intermediate and low risk was not (p = 0.602). After stratification for the concurrent treatment mode, 2-year survival rates were 0% in the high, 60% in the intermediate and 58% in the low-risk subgroups, respectively (p = 0.004). Conclusions: The survival score was reproducible to estimate 2-year survival rates of patients with LS-SCLC, especially in the high and intermediate-risk subgroups. In order to better characterize the prognostic difference between intermediate and low-risk patients, the scoring system needs further optimization. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Umbilical cord blood versus unrelated donor transplantation in adults with primary refractory or relapsed acute myeloid leukemia: a report from Eurocord, the Acute Leukemia Working Party and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the EBMT
Authors: Frédéric Baron, Myriam Labopin, Annalisa Ruggeri, Gerhard Ehninger, Fransesca Bonifazi, Matthias Stelljes, Jaime Sanz, Gernot Stuhler, Alberto Bosi, Nicolaus Kröger, Maria Teresa Van Lint, Arnold Ganser, Edouard Forcade, Mohamad Mohty, Eliane Gluckman, Arnon Nagler
Journal: Blood Cancer Journal (2019)

Abstract The role of umbilical cord blood transplantation (CBT) in acute myeloid leukemia (AML) patients with active disease at allogeneic hematopoietic cell transplantation (allo-HCT) remains poorly investigated. In this study, we compared transplantation outcomes of 2963 patients with primary refractory or relapsed AML given CBT, 10/10 HLA-matched UD, or 9/10 HLA-matched UD allo-HCT from 2004 to 2015 at EBMT-affiliated centers. Neutrophil engraftment and complete remission rates in CBT, UD 10/10, and UD 9/10 recipients were 75 and 48%, 93 and 69%, and 93 and 70%, respectively. In multivariate Cox analyses, in comparison with CBT ( n = 285), UD 10/10 recipients ( n = 2001) had a lower incidence of relapse (HR = 0.7, P = 0.001), a lower incidence of non relapse mortality (HR = 0.6, P &lt; 0.001), better GVHD-free and leukemia-free survival (GRFS, HR = 0.8, P &lt; 0.001) and better survival (HR = 0.6, P &lt; 0.001). Further, in comparison with CBT, 9/10 UD recipients ( n = 677) also had a lower incidence of relapse (HR = 0.8, P = 0.02), a lower incidence of nonrelapse mortality (HR = 0.7, P = 0.008), better GRFS (HR = 0.8, P = 0.01) and better survival (HR = 0.7, P &lt; 0.001). In summary, these data suggest that in AML patients with active disease at transplantation, allo-HCT with UD results in better transplantation outcomes than CBT.
Naegeli–Franceschetti–Jadassohn syndrome and dermatopathia pigmentosa reticularis: intrafamilial overlap of phenotypes in patients with the same <i> <scp>KRT</scp> 14 </i> frameshift variant
Authors: B. Burger, I. Spoerri, E. Imahorn, H. Wariwoda, T. Leeb, P. H. Itin
Journal: British Journal of Dermatology (2019)
The Limitations of “Boilerplate” Language in Informed Consent: Single IRB Review of Multisite Genetic Research in Military Personnel
Authors: Benjamin S. Wilfond, Jennifer Zabrowski, Liza M. Johnson
Journal: The American Journal of Bioethics (2019)

"The Limitations of “Boilerplate” Language in Informed Consent: Single IRB Review of Multisite Genetic Research in Military Personnel." The American Journal of Bioethics, 19(4), pp. 81–82
Abstract 17975: Anemia in Heart Failure With Preserved Ejection Fraction: Insights From the TOPCAT trial
Authors: Eileen O'Meara, Christopher T Kenwood, Inder S Anand, Akshay S Desai, Simon De Denus, Nancy K Sweitzer, Jerome L Fleg, Thao Huynh, Sonja M McKinlay, Bertram Pitt, Marc A Pfeffer, Jean L Rouleau
Journal: Circulation (2015)

Introduction: Anemia predicts higher rates of mortality and HF hospitalizations in patients with heart failure (HF). We sought to determine the factors associated with anemia in TOPCAT, a large randomized trial that tested the effects of spironolactone in patients with HF and preserved EF (HFpEF). Methods: Amongst the 3445 patients enrolled in TOPCAT, 3422 had available baseline hemoblobin. All significant factors assessed in baseline characteristic comparisons were put in a saturated multivariable logistic regression model along with randomized treatment assignment. The stepwise elimination method was used to obtain a parsimonious model identifying factors associated with anemia. Results: The overall prevalence of anemia (hemoglobin, Hgb &lt; 12g/dL in women and &lt; 13g/dL in men) was 28.5% (974 patients), with higher prevalence in patients enrolled in the Americas (41%) than in Russia/Georgia (15.4%). Previous hospitalization for HF, randomization in the Americas, older age, insulin-treated diabetes, orthopnea, peripheral edema, lower eGFR, lower diastolic BP, lower HR, and longer QRS duration were independent correlates of anemia; whereas female gender, white race, higher BMI, known dyslipidemia, left ventricular hypertrophy, and eating meals at home were independently associated with the absence of anemia (Table). Conclusions: Anemia in HFpEF is associated with multiple markers of increased cardiovascular risk, and of more advanced HF. We identified new factors associated with the absence of anemia, such as eating most meals at home. Complex interactions may underlie the observed relationships, including medications, and causality cannot be inferred from our observations.
SAT-300-Prospective liver biopsy-based prevalence of non-alcoholic fatty liver disease and steatohepatitis among a large middle-aged population utilizing FibroScan, LiverMultiscan and magnetic resonance elastography to guide liver biopsy
Authors: Stephen Harrison, Katharine Roberts, Christopher Lisanti, Ryan Schwope, Katherine Cebe, Valérie Paradis, Pierre Bedossa, James Aden, Jennifer Whitehead, Angelo Paredes
Journal: Journal of Hepatology (2019)
LBP-10-A structurally engineered fatty acid, icosabutate, rapidly normalises elevated plasma ALTand gamma-glutamyl transferase (GGT) concentrations in a study population at high risk of NAFLD/NASH
Authors: David A. Fraser, Xiao-Yu Wang, Marta Iruarrizaga-Lejarreta, Ditte Denker Thorbek, Tore Skjaeret, Michael Feigh, Cristina Alonso, John Kastelein, Detlef Schuppan
Journal: Journal of Hepatology (2019)
SAT-117-Enhanced liver fibrosis score is an accurate non-invasive predictor of clinically significant and high-risk portal hypertension
Authors: Benedikt Simbrunner, Rodrig Marculescu, Philipp Schwabl, Bernhard Scheiner, Theresa Bucsics, Matthias Pinter, Alek Stadlmann, David JM Bauer, Mattias Mandorfer, Michael Trauner, Thomas Reiberger
Journal: Journal of Hepatology (2019)
Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1
Authors: Ewelina Mamcarz, Sheng Zhou, Timothy Lockey, Hossam Abdelsamed, Shane J. Cross, Guolian Kang, Zhijun Ma, Jose Condori, Jola Dowdy, Brandon Triplett, Chen Li, Gabriela Maron, Juan C. Aldave Becerra, Joseph A. Church, Elif Dokmeci, James T. Love, Ana C. da Matta Ain, Hedi van der Watt, Xing Tang, William Janssen, Byoung Y. Ryu, Suk See De Ravin, Mitchell J. Weiss, Benjamin Youngblood, Janel R. Long-Boyle, Stephen Gottschalk, Michael M. Meagher, Harry L. Malech, Jennifer M. Puck, Morton J. Cowan, Brian P. Sorrentino
Journal: New England Journal of Medicine (2019)

Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia.We performed a dual-center, phase 1-2 safety and efficacy study of a lentiviral vector to transfer IL2RG complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1.Eight infants with SCID-X1 were followed for a median of 16.4 months. Bone marrow harvest, busulfan conditioning, and cell infusion had no unexpected side effects. In seven infants, the numbers of CD3+, CD4+, and naive CD4+ T cells and NK cells normalized by 3 to 4 months after infusion and were accompanied by vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. The eighth infant had an insufficient T-cell count initially, but T cells developed in this infant after a boost of gene-corrected cells without busulfan conditioning. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four infants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven.Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic effects and resulted in multilineage engraftment of transduced cells, reconstitution of functional T cells and B cells, and normalization of NK-cell counts during a median follow-up of 16 months. (Funded by the American Lebanese Syrian Associated Charities and others; LVXSCID-ND ClinicalTrials.gov number, NCT01512888.).