tbuckley/cabot-search huggingface dataset:
Association of Mutations in <i>TBK1</i> With Sporadic and Familial Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Authors: Axel Freischmidt, Kathrin Müller, Albert C. Ludolph, Jochen H. Weishaupt, Peter M. Andersen
Journal: JAMA Neurology (2016)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative syndromes that occur sporadically or have been associated with mostly dominant inheritance of mutations in more than 30 genes. A critical issue is whether all reported mutations are disease causing or are coincidental findings. In this review we analyze the pathogenicity of nonsynonymous variants in the newly discovered gene encoding TANK-binding kinase 1 (TBK1). The available data suggest that mutations in TBK1 that cause a 50% reduction of TBK1 protein levels are pathogenic. In most cases, the almost complete loss of expression of the mutated TBK1 allele is due to loss-of-function mutations creating a premature termination codon and the degradation of the mutated messenger RNA by nonsense-mediated messenger RNA decay. In addition, TBK1 protein levels reduced by 50% have been proven for specific in-frame deletions of 1 or several amino acids, probably due to increased degradation of the mutated protein. Evaluation of many of the TBK1 missense mutations found in patients with ALS or FTD is prevented by missing data demonstrating cosegregation of the variants and incomplete knowledge about the TBK1 functions relevant for neurodegeneration. These findings suggest that haploinsufficiency of TBK1 is causative for ALS and FTD regardless of the type of mutation. Evaluation of TBK1 variants that do not cause haploinsufficiency is not possible without data demonstrating cosegregation.
PWE-144 Predicting Treatment Failure in C.Difficile Infection: A Prospective Observational Cohort Study
Authors: NM Joshi, J Goodhand, W Alazawi, S Das, M Wilks, D Rampton
Journal: Gut (2016)

<h3>Introduction</h3> C.difficile-induced diarrhoea is often refractory to treatment and can be life-threatening. As yet, there is no prospectively derived tool with which to predict treatment failure (TF) in C.difficile infection (CDI). We performed a fully powered, pragmatic, prospective observational study to create such a tool. <h3>Methods</h3> Patients with confirmed CDI were consented to enter the study within 24 hours of testing positive. Demographic data (including age, antibiotic and PPI use, smoking, ward type), clinical variables (pulse, PB, temperature) and blood test results (FBC, urea, creatinine, CRP, albumin) and faecal calprotectin on the day of diagnosis were collected. TF was defined as occurrence of any of: death while admitted, colectomy, ongoing diarrhoea at day 7, recurrent diarrhoea at &lt;30 days after initial CDI diagnosis. Case level re-structuring was used to account for missing data and forward stepwise binary regression to derive a predictive model. The model was internally validated by bootstrapping and assessed by Receiver Operated Characteristic (ROC) analysis. <h3>Results</h3> 122 patients were recruited and primarily treated by their routine clinical team with metronidazole (n = 89) or vancomycin (n = 29). 63 patients (52%) failed treatment: 28 died during their admission, 43 had continuing diarrhoea at day 7, 16 had recurrent diarrhoea within 30 days and 1 had a colectomy (some patients had TF on &gt;1 criteria). TF rate was the same whether metronidazole or vancomycin was primary therapy. Of the variables measured, only age and serum albumin predicted TF (age, p = 0.029; albumin, p = 0.0001). An equation with which to predict individual patients’ risk of TF was then derived: for ease of clinical application, a simple read off table was derived allowing prediction of outcome using the patient’s age and serum albumin. The model correctly predicted TF in 79% of cases. By ROC analysis, the model initially had an Area Under the Curve (AUC) of 0.76; in the internal validation assessment the AUC was 0.75. <h3>Conclusion</h3> A prospectively and internally validated tool with which to predict treatment failure in CDI has been derived. The tool consists of 2 variables (age and serum albumin) on the day of diagnosis of CDI. The predictive tool could be used to highlight those who might benefit from more intensive treatment, for example using fidaxomicin or faecal microbial transplant as primary CDI therapy. <h3>Disclosure of Interest</h3> None Declared
Favorable Outcomes in Patients with High Donor-Derived T Cell Count Following In Vivo T Cell Depleted Reduced Intensity Allogeneic Stem Cell Transplantation
Authors: Amir A Toor, Roy T Sabo, Harold M Chung, Catherine H Roberts, Rose H Manjili, Shiyu Song, David C. Williams, William Clark, Masoud H Manjili, John M McCarty
Journal: Blood (2011)
The JAK Inhibitor, INCB018424, Demonstrates Durable and Marked Clinical Responses in Primary Myelofibrosis (PMF) and Post-Polycythemia/Essential Thrombocythemia Myelofibrosis (Post PV/ETMF).
Authors: Srdan Verstovsek, Hagop M. Kantarjian, Animesh D. Pardanani, Deborah Thomas, Jorge Cortes, Ruben A. Mesa, William J. Hogan, John R. Redman, Sue Erickson-Viitanen, Richard Levy, Kris Vaddi, Edward Bradley, Jordan Fridman, Ayalew Tefferi
Journal: Blood (2008)
Towards Effective Immunotherapy of Multiple Myeloma: Enhanced Elimination of Myeloma Cells by Combination of Lenalidomide with the Human CD38 Monoclonal Antibody Daratumumab
Authors: Michael S. van der Veer, Michel de Weers, Berris van Kessel, Shulamiet Wittebol, Joost M Bakker, Paul W.H.I. Parren, Henk M Lokhorst, Tuna Mutis
Journal: Blood (2010)
THU0517 Women with Gout Show A Poorer Cardiovascular Profile after Structured Assessment
Authors: J.A. Bernal, M. Andrés, F. Sivera, L. Carmona, P. Vela, E. Pascual
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cardiovascular (CV) disease affects gout patients. This is thought to result from a combination of an increase in CV risk factors and crystal-led inflammation. Despite being more prevalent in men, gout also has an impact on the CV risk of women (1). To date, few studies have focused on gender differences on gout, especially in terms of CV assessment. <h3>Methods</h3> Observational, cross-sectional study. Consecutive newly-diagnosed crystal-proven gout patients seen in a tertiary hospital underwent a structured CV assessment which included risk prediction tools, carotid ultrasound and CV risk stratification according to current European guidelines. Gout features were also registered. A gender comparison in the different variables was performed, employing chi-2 tests for binary variables, and Student9s t or Mann-Whitney9s tests for quantitative variables. <h3>Results</h3> A total of 199 patients - 28 (14.1%) women and 171 (85.9%) men - were analyzed. Women were significantly older than men (72.7± 11.1 years in women vs 62± 13.0 in men, p&lt;0.001). In terms of CV risk factors, women had more commonly high blood pressure (89.3% vs 64.9%, p=0.01), diabetes (53.6% vs 18.7%, p&lt;0.001), diuretic use (78.6% vs 38.2%, p&lt;0.001), and chronic kidney disease (71.4% vs 21.3%, p&lt;0.001). Smoking background was more frequent in men (20% vs 66%, p&lt;0.001), and dyslipidemia rates were similar. Uric acid levels at diagnosis were higher (8.97 vs 7.82 mg/dL, p=0.001) in women. Regarding gout features, men showed longer disease duration (median (p25–75) 1 year (0–3.0) in women and 5 years (2.0–15.0) in men, p=0.005) and reported more gout attacks (2 attacks (1.0–3.5) in women and 5 (3.0–20.0) in men, p=0.001), with no differences between genders in the proportion of patients with tophi. No significant differences in carotid plaques were noted (50% in women and 33.6% in men, p=0.32), but ultrasound was often deemed unnecessary in women because they already presented a very high CV risk at assessment (64.3% of women and 33.7% of men, p=0.002). At final CV risk stratification, women tended to show higher CV risk than men (Figure 1). <h3>Conclusions</h3> The CV profile of women with gout seems worse than male patients in this series. Differences in gout pathogenesis between genders likely explain these results. This finding highlights the need for an optimal CV management when dealing with female gout patients. <h3>References</h3> De Vera MA. Ann Rheum Dis 2010;69:1162 <h3>Disclosure of Interest</h3> None declared
Cardioprotective role of S-nitrosylated hemoglobin from rbc
Authors: Claude A. Piantadosi
Journal: Journal of Clinical Investigation (2016)

Nitric oxide (NO) is a potent mediator of blood vessel dilation and is released by several cell sources. Red blood cells (rbc) release NO when hemoglobin that has been S-nitrosylated at Cys93 of the β-chain (βCys93) transitions from the oxygenated form to the deoxygenated form. This transition occurs in response to reduced tissue oxygenation and is an important physiologic regulator of hypoxic vasodilation. In this issue of the JCI, Zhang and colleagues demonstrate that S-nitrosylation of hemoglobin at βCys93 is important for tissue oxygenation after cardiac injury. Mice harboring mutations that prevent S-nitrosylation of βCys93 had higher rates of morbidity and mortality following cardiac injury compared with WT; however, adaptive cardiac vascularization was increased in some mutant mice and reduced cardiac injury in these animals. The results of this study reveal a previously unexplored role of S-nitrosylated hemoglobin in cardioprotection.
Improved Mobilization of CD34+ Peripheral Blood Stem Cells (PBSC) and Dendritic Cells (DCs) by AMD-3100 (AMD) in Hard to Mobilize Non-Hodgkin’s Lymphoma (NHL) Patients (pts) Mobilized with Standard Dose of G-CSF.
Authors: Yair Gazitt, Cesar O Freytes, Cagla Akay, William Bensinger, Karin Badel, Gary Calandra
Journal: Blood (2004)
MYB Overexpression Is Directly Involved in Acute Myeloid Leukemia Pathogenesis and Could Constitute a New Therapeutic Target for Patients with Aberrant Expression of This Gene.
Authors: Carmen Vicente, Ana Conchillo, Daphnie Pauwels, Iria Vazquez, Laura Garcia-Orti, Maria J. Calasanz, Idoya Lahortiga, Jan Cools, Maria D. Odero
Journal: Blood (2009)
Iron Containing Nucleosides as New Cytostatic Substances for Cancer and Leukemia Therapy, Especially for Therapy of Relapsed ALL in Childhoodtransfusion of Red Blood Cells under Shock Conditions in the Rat Microvasculature.
Authors: Aram Prokop, Thomas Wieder, Daniel Schlawe, Holger Lode, Guenter Henze, Peter T. Daniel, Hans G. Schmalz
Journal: Blood (2004)
Upregulation of Krüppel-Like Factor 4 (KLF-4) Expression as a Potential Tumor Progression Gene Product in Non-Hodgkin's Lymphoma.
Authors: Mario I. Vega, Juan vazquez-Islas, Melisa Martinez-Paniagua, Miriam Hernandez-Atenogenes, Bernardo martinez-Miguel, Altagracia Maldonado-Valenzuela, Cesar Gonzalez-Bonilla, Sara Huerta-Yepez, Otoniel Martinez-Maza, Benjamin Bonavida
Journal: Blood (2009)
Shaken baby expert witness wins High Court appeal
Authors: Clare Dyer
Journal: BMJ (2016)

Waney Squier, the paediatric neuropathologist ordered to be struck off the UK medical register for misleading courts in “shaken baby” cases,1 2 3 4 5 6 will stay on the register after winning her appeal to the High Court.

A panel of the Medical Practitioners Tribunal Service decided last March to strike her off for dishonesty, cherrypicking evidence, misleading the courts, and acting outside her area of expertise.

But the High Court judge Mr Justice Mitting acquitted her of dishonesty, finding the tribunal's determinations “in many significant respects flawed.”7

Squier, who worked at the John Radcliffe Hospital in …
Sequential Therapy with Cytarabine and Bismuth-213 (213Bi)-Labeled-HuM195 (Anti-CD33) for Acute Myeloid Leukemia (AML).
Authors: Deborah A. Mulford, Neeta Pandit-Taskar, Michael R. McDevitt, Ronald D. Finn, Mark A. Weiss, Christos Apostolidis, Alfred Morgenstern, Chaitanya R. Divgi, Steven M. Larson, David A. Scheinberg, Joseph G. Jurcic
Journal: Blood (2004)
Haploidentical Stem Cell Transplantation After Negative Depletion Of T Cells Expressing The αβ Chain Of The T-Cell Receptor (TCR) For Adults With Hematological Malignancies
Authors: Lucia Prezioso, Sabrina Bonomini, Chiara Lambertini, Chiara Schifano, Elena Rossetti, Alessandro Monti, Giannalisa Todaro, Gabriella Sammarelli, Maria Sassi, Luisa Craviotto, Elena Masselli, Cecilia Caramatti, Franco Aversa
Journal: Blood (2013)
Non-Hodgkin Lymphoma in Adolescents: Experiences in 378 Adolescent NHL Patients Treated According to Pediatric NHL-BFM Protocols.
Authors: Birgit Burkhardt, Ilske Oschlies, Wolfram Klapper, Martin Zimmermann, Andrea Meinhardt, Eva Landmann, Wilhelm Woessmann, Georg Mann, Felix Niggli, Martin Schrappe, Alfred Reiter
Journal: Blood (2009)
Reachthem: Baseline Characteristics of a 3 Year Prospective Registry of Children with Hemoglobinopathies Receiving Oral Iron Chelators in the Treatment of Transfusional Iron Overload
Authors: Bülent Antmen, Zeynep Karakas, Gonul Oktay, Mehmet Akin, Gonul Aydogan, Zafer Salcioglu, Canan Vergin, Selma Unal, Kerem Organ, Aycin Canatar, Ertan Koseoglu, Mehmet Akif Yesilipek
Journal: Blood (2012)
Histone Deacetylase Inhibitors LBH589 and LAQ824 Deplete Ezh2 and Associated Polycomb Repressive Complex 2/3 Proteins Resulting in Downregulation of HOXA9 and MEIS1 Expression in Human Acute Leukemia Cells.
Authors: Warren Fiskus, Michael Pranpat, Purva Bali, Sandhya Kumaraswamy, Sandhya Boyapalle, Kathy Rocha, Maria Balasis, Peter Atadja, Kapil Bhalla
Journal: Blood (2005)
Experimental Double Cord Blood Transplantation (DCBT) of An Expanded Unit Together with a Non-Manipulated Unit in NOD/SCID Mice.
Authors: Tony Peled, Hadas Shoham, Oshrat Golan, Dorit Ashengrau, Dima Yaacobov, Gabi Frei, Arnon Nagler, Eitan Fibach, Amnon Peled
Journal: Blood (2008)
Ki-67 Is a Strong Predictor for Central Nervous System Relapse in Patients with Mantle Cell Lymphoma (MCL)
Authors: Dai Chihara, Naoko Asano, Ohmachi Ken, Momoko Nishikori, Masataka Okamoto, Masashi Sawa, Rika Sakai, Yasushi Okoshi, Norifumi Tsukamoto, Yoshihiro Yakushijin, Shigeo Nakamura, Tomohiro Kinoshita, Michinori Ogura, Ritsuro Suzuki
Journal: Blood (2014)
Flavopiridol, Fludarabine and Rituximab Is a Highly Active Regimen in Indolent B-Cell Lymphoproliferative Disorders Including Mantle Cell Lymphoma.
Authors: Thomas S. Lin, Beth Fischer, Mollie E. Moran, Maureen M. Buckner, Roshini Shank, Eric H. Kraut, Pierluigi Porcu, Sherif S. Farag, Charles F. Eisenbeis, Dimitrios Colevas, Michael R. Grever, John C. Byrd
Journal: Blood (2005)
Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone
Authors: F. Sahr, R. Ansumana, T.A. Massaquoi, B.R. Idriss, F.R. Sesay, J.M. Lamin, S. Baker, S. Nicol, B. Conton, W. Johnson, O.T. Abiri, O. Kargbo, P. Kamara, A. Goba, J.B.W. Russell, S.M. Gevao
Journal: Journal of Infection (2016)

Convalescent blood therapy has been a promising form of treatment for Ebola Virus Disease (EVD), but less attention has been focused on it for treatment.We assessed the effectiveness of convalescent whole blood (CWB) in the treatment of consented EVD patients. We recruited 69 subjects in December 2014 up to April 2015, at the 34 Military Hospital in Wilberforce and the PTS 1 Ebola Treatment Unit in Hastings, Freetown. Forty-four were given CWB, and 25 who consented but preferred to be exempted from the CWB treatment were used to compare clinical outcomes. All were given routine treatment used at the Ebola Treatment Unit.One of 44 subjects treated with CWB dropped out of the study and 31 recovered while 12 succumbed to the disease with a case fatality rate of 27.9%. For the group that was given routine treatment without CWB, 11 died with a case fatality rate of 44%. There was a significant difference between admission viral load and viral load after the first 24 h of treatment with convalescent whole blood (P < 0.01). The odds ratio for survival with CWB was 2.3 (95% CI, 0.8-6.5).CWB is promising for treating EVD in resource-poor settings, especially in the early phases of outbreaks when resource-mobilization is done. Even though our sample size was small and the evaluation was not randomised, our results contribute to existing evidence that convalescent whole blood could be considered as a useful candidate for treating EVD. Further studies that are randomised will be required to further assess the efficacy of CWB as treatment option during any EVD outbreak.
Clinical Impact of Additional Cytogenetic Aberrations and Treatment in Pediatric t(8;21)-Positive AML: Results from an International Retrospective I-BFM-SG Study
Authors: Ardine Reedijk, Gertjan Kaspers, Marta Fiocco, Andrea Pession, Dirk Reinhardt, Martin Zimmermann, Michael Dworzak, Todd A. Alonzo, Donna Johnston, Michal Zapotocky, Barbara De Moerloose, Fynn Finita, Vincent Lee, Takashi Taga, Akio Tawa, Anne Auvrignon, Bernward Zeller, Carmen Salgado, Walentyna Balwierz, Alexander Popa, Jeffrey Rubnitz, H.B. Berna Beverloo, Christine J Harrison, Brenda Gibson
Journal: Blood (2012)
SAT0138 Left Ventricular Function at 2-Year Follow-Up in Treatment-Naive Rheumatoid Arthritis Patients Is Associated with Anti-Ccp Status: A Cohort Study
Authors: B.B. Løgstrup, D. Masic, T.B. Laurbjerg, J. Blegvad, M. Herly, L.D. Kristensen, G. Urbonaviciene, A. Hedemann-Nielsen, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In patients with rheumatoid arthritis (RA) the role of autoimmunity and especially auto antibody status and the time-course of left ventricular (LV) function is unknown. <h3>Objectives</h3> To assess LV function as well as the amount of coronary calcium by coronary computer tomography (CCT) in relation to anti-cyclic citrullinated peptide antibody (anti-CCP) status in a cohort of treatment-naive RA patients. Furthermore to assess changes in these parameters during a 2-year follow-up period. <h3>Methods</h3> Sixty-six steroid- and DMARD-naive RA patients (42 women) were included and treated with methotrexate according to the national guidelines. We assessed both the LV function by conventional echocardiography and speckle-tracking echocardiography. Furthermore, we performed CCT to estimate the amount and progression of coronary calcium. Patients were examined at he time of diagnosis and after 2-years of efficient anti-inflammatory treatment. <h3>Results</h3> All patients fulfilled the international criteria for RA. We found no clinical significant differences in LV function parameters during the 2-year follow-up period in the total population. However, we found that patients with a persistently elevated anti-CCP both had a significantly lack of improvement in S9(1±1.4 cm/s versus 0.2±0.9 cm/s; p=0.04) and had a worsening in global longitudinal systolic strain (GLS) (0.6±1.8% versus -1±2.8%; p=0.04) compared to patients with non-persistently elevated anti-CCP over a 2-year time period. Furthermore, we observed a significant correlation between ΔGLS over 2 years and anti-CCP at 2-year follow-up (r=0.36;p=0.006). It remained significantly correlated (p=0.008) after correction for relevant cofounders (age, gender, blood pressure, heart rate, and baseline GLS). The circumferential strain improved in the group with non-persistently elevated anti-CCP compared to the group with persistently elevated anti-CCP (-4.2±3.8% versus 0.3±1.9%; p=0.009). We observed a mean progression of calcium score during the 2-year follow-up period of 22.4±68.9. We observed no differences in progression in calcium score in patients with persistently elevated anti-CCP (n=12) versus not persistently elevated (n=32) (23.8±40.3 versus 22.6±68.9; p=0.96). <h3>Conclusions</h3> LV function and deformation is reduced in treatment-naive RA patients with persistently elevated anti-CCP. Deformation abnormalities is associated with the degree of anti-CCP positivity in a 2-year follow-up period. No differences in the amount of coronary calcium was observed according to inflammatory burden. <h3>Disclosure of Interest</h3> None declared
Development of the Anemia Impact Measure (AIM): A Disease-Specific Patient Reported Outcome (PRO) Instrument to Measure Anemia Symptoms and Their Impact on Functioning in Cancer Patients Receiving Chemotherapy
Authors: Leah Kleinman, Katy Benjamin, Hema Viswanathan, Maria Stoeckl Mattera, Linda D. Bosserman, Douglas W. Blayney, Dennis Revicki
Journal: Blood (2008)
Eltrombopag for Post-Transplant Thrombocytopenia: Results of Phase II Randomized Double Blind Placebo Controlled Trial
Authors: Uday R. Popat, Genevieve Ray, Roland L Bassett, Man-Yin C Poon, Benigno C. Valdez, Sergej Konoplev, Sairah Ahmed, Amin M. Alousi, Borje Andersson, Qaiser Bashir, Stefan O. Ciurea, Chitra M. Hosing, Roy Jones, Partow Kebriaei, Issa F. Khouri, Stella Kim, Yago Nieto, Amanda L. Olson, Betul Oran, Simrit Parmar, Muzaffar H. Qazilbash, Katy Rezvani, Nina Shah, Elizabeth J. Shpall, Richard E. Champlin
Journal: Blood (2015)
Phase 2 Trial of G-CSF Priming, Clofarabine, and High Dose Cytarabine (GCLAC) for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) or Advanced Myelodysplastic Syndrome or Advanced Myeloproliferative Neoplasm,
Authors: Pamela S Becker, Bruno C. Medeiros, Frederick R. Appelbaum, Bart Lee Scott, Paul C. Hendrie, Barry Storer, Sherry Pierce, Stephen H. Petersdorf, Elihu H. Estey
Journal: Blood (2011)
Effects of Anti-Glycoprotein Antibodies on Response of Immune Thrombocytopenia Patients to Thrombopoietin Receptor Agonists and on Megakaryocytes Viability
Authors: Marina Izak Karaev, Alexandra Kruse, Margaret Morrisey, Heyu Ni, Zhu Guangheng, Petra Pham, W. Beau Mitchell, James B Bussel
Journal: Blood (2015)
Do Changes in Transplant Practice Influence Risk of Therapy-Related Myelodysplasia/ Acute Myeloid Leukemia after Autologous Hematopoietic Cell Transplantation (aHCT) for Non-Hodgkin Lymphoma (NHL)?
Authors: Can-Lan Sun, Jennifer Berano-Teh, Patrick Halliday, Lindsey Hageman, Maya Ramamurthy, Saro Armenian, Alicia Gonzales, Liezl Atencio, Liton Francisco, F. Lennie Wong, Auayporn Nademanee, Robert W Chen, Margaret O'Donnell, Joseph Rosenthal, Leslie L. Popplewell, Shirong Wang, Stephen J. Forman, Ravi Bhatia, Smita Bhatia
Journal: Blood (2014)
Bendamustine-Rituximab (BR) Replaces R-CHOP As “Standard of Care” in the Treatment of Indolent Non-Hodgkin Lymphoma in German Hematology Outpatient Centres
Authors: Wolfgang Ulrich Knauf, Wolfgang Abenhardt, Arnd Nusch, Renate Grugel, Norbert Marschner
Journal: Blood (2012)
Second-line chemotherapy (CT2) in advanced biliary tract cancer (aBTC) patients (pts) progressed to first-line chemotherapy (CT1) with gemcitabine plus platinum: where are we now?
Authors: L. Fornaro, S. Cereda, F. Leone, G. Aprile, S. Lonardi, N. Silvestris, D. Santini, M. Milella, A. Palloni, A. Barbera, L. Ferrari, R. Filippi, F. Bergamo, C. Vivaldi, C. Caparello, G. Musettini, G. Pasquini, A. Falcone, M. Reni, G. Brandi, E. Vasile
Journal: Annals of Oncology (2015)