tbuckley/cabot-search huggingface dataset:
Deletion of p53 as Detected by Fluorescence In Situ Hybridization Is Associated with Significant Shorter Event-Free Survival in Patients with Multiple Myeloma Who Are Receiving Allogeneic Blood Stem Cell Transplantation.
Authors: Georgia Schilling, Timon Hansen, Jose Antonio Perez-Simon, Rainer Schwerdtfeger, Martin Bornhaeuser, Svenja Otterstetter, Doris Seeger, Judith Dierlamm, Francis Ayuk, Hossfeld Dieter Kurt, Bokemeyer Carsten, Zander R. Axel, Kroeger Nicolaus
Journal: Blood (2005)
Mitotic rate correlates with sentinel lymph node status and outcome in cutaneous melanoma greater than 1 millimeter in thickness: A multi-institutional study of 1524 cases
Authors: Mario Mandalà, Francesca Galli, Laura Cattaneo, Barbara Merelli, Eliana Rulli, Simone Ribero, Pietro Quaglino, Vincenzo De Giorgi, Jacopo Pigozzo, Vanna Chiarion Sileni, Alessandra Chirco, Pier Francesco Ferrucci, Marcella Occelli, Gianlorenzo Imberti, Dario Piazzalunga, Daniela Massi, Carlo Tondini, Paola Queirolo
Journal: Journal of the American Academy of Dermatology (2016)
Reduced-Intensity Conditioning (RIC) Followed by Allogeneic Stem Cell Transplantation (SCT) for Relapsed Lymphomas: Impact of Pre-Transplantation Factors on Long-Term Outcome.
Authors: Paolo Corradini, Anna Dodero, Marco Bregni, Fabio Ciceri, Attilio Olivieri, Lucia Farina, Pinuccia Valagussa, Rosanna Scime’, Anna Locasciulli, Francesca Patriarca, Alessandro Massimo Gianni, Corrado Tarella
Journal: Blood (2005)
OC-078 How Good are We at Looking for Osteoporosis In Chronic Pancreatitis?
Authors: TM El Menabawey, S Phillpotts, R Preedy, K Besherdas
Journal: Gut (2016)

<h3>Introduction</h3> Chronic pancreatitis is a common condition managed in the outpatient setting. One of the common complications is osteoporosis and patients have double the risk of fragility fractures compared with the general population. The National Institute of Clinical Excellence (NICE) guidance recognises chronic pancreatitis as a significant risk factor and recommends that all patients aged 50 or over should be considered for DEXA scanning if they are deemed at risk.<sup>1</sup> The purpose of this study was to assess whether patients under review for chronic pancreatitis were being referred for DEXA scanning and to pick up the rate of fragility fractures. <h3>Methods</h3> A Single Centre, retrospective analysis of all patients identified coded as having “chronic pancreatitis” under ongoing outpatient review in a large NHS Hospital Trust in North London. We reviewed their records and imaging to assess if they had ever been referred for a DEXA scan and whether they had radiological evidence of a fragility fracture whilst under review for pancreatitis. <h3>Results</h3> Of 106 patients identified, only 1 (0.94%) was referred for DEXA scanning, which did confirm osteoporosis. This patient had been referred incidentally by a GP for another reason not pertaining to their chronic pancreatitis. 14 patients (13.21%) had sustained low impact fractures (5 hip, 3 vertebral, 3 wrist, 2 distal fibula, 1 elbow). Of these fractures 6 (42.9%) had been on no bone protection at all, 6 (42.9%) had been on calcium and vitamin D supplementation, and 2 (14.3%) had been on a bisphosphonate. <h3>Conclusion</h3> Despite chronic pancreatitis being a well-recognised risk factor for osteoporosis, the investigation and active mitigation of its risk by clinicians in the outpatient setting was poor. This may have resulted in potentially avoidable osteoporotic fractures and future studies should look at whether this is a wider phenomena nationally. We would recommend that risk assessment for osteoporosis should form a part of a routine clinical review in patients under follow up for chronic pancreatitis. <h3>Reference</h3> 1 NICE. Osteroporosis: assessing the risk of fragility fracture. NICE guidelines CG146. August 2012. <h3>Disclosure of Interest</h3> None Declared
FRI0253 A 18 Month Observation in Patients with Progressive Systemic Sclerosis Treated with An Intensified B-Lymphocyte Depletion -Clinical and Immunological Response
Authors: D. Rossi, M. Saracco, S. Sciascia, R. Pellerito, V. Modena, D. Roccatello
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> B cells (BC) play a critical role in progressive systemic sclerosis (SS). BC depletion therapy is an attractive option. <h3>Objectives</h3> to evaluate the efficacy of an intensified B cell depletion therapy in patients with progressive SS <h3>Methods</h3> Eighteen patients with SS [2 males, mean age 58.33 yrs (46–82)] with severe multiorgan involvement including skin [16], lung, with pulmonary fibrosis (17 patients) and pulmonary hypertension (5), esophagous [9], with polyarthralgias [2] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (4 cases) or as a front line treatment in 14 patients with unsatisfactory therapeutic compliance. IBCDT included: Rituximab (RTX) 375mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given. <h3>Results</h3> Patients had been followed-up for a mean of 21,67 ± ds 11,05 (06–43) months. Significant decreases (p&lt;0.05) were found in Rodnan skin score (baseline: 12.28; end of follow-up: 11.67), visual activity score (baseline mean value: 6.8 mm; end of follow-up: 4.2. A significant increase (p&lt;0.05) FVC (baseline: 92.35; end of follow-up: 95.44), FEV (baseline: 86.5; end of follow-up: 90.43), DLCO (baseline: 57.15; end of follow-up: 66.75), and NTpro BNP (baseline: 345.19; end of follow-up: 62.29). PAP values did not change during the observation (baseline: 29.77mmHg; end of follow-up: 26.57). During the follow-up, pulmonary fibrosis, as established on a radiological level, was found to be ameliorated in 2 out of the 14 evaluable patients, worsened in 3, and unchanged in 9. <h3>Conclusions</h3> A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding prolonged immunosuppressive therapy particularly appealing. Our data confirm the opportunity to consider the regimens of BL depletion in the treatment of the most severe or refractory forms of SS. <h3>Disclosure of Interest</h3> None declared
Matched Unrelated Donor Stem Cell Transplantation for Relapsed or Refractory Mantle Cell Lymphoma. A Retrospective Analysis from the EBMT Lymphoma Working Party.
Authors: Irit Avivi, Carme Canals, Goli Taghipour, Jurgen Finke, Liisa Volin, Yves Beguin, Marc Boogaerts, Charles Crawley, Michael Rieger, Norbert Schmitz, Guido Kobbe, Donald Milligan, Dietger W. Niederwieser, Nigel H. Russell, Rainer Schwerdtfeger, Anna Sureda
Journal: Blood (2006)
Infusions of T Cells Armed with Anti-CD3 x Anti-Her2/neu Bispecific Antibody Modulate In Vivo Patient Immune Responses in Phase I Clinical Trials for Breast and Hormone Refractory Prostate Cancers.
Authors: Pamela A. Davol, Jonathan M. Gall, Ryan C. Grabert, Wendy B. Young, Francis J. Cummings, Ritesh Rathore, Gerald A. Colvin, Gerald J. Elfenbein, Lawrence G. Lum
Journal: Blood (2004)
The NEDD8 Activating Enzyme Inhibitor Pevonedistat Induces ER Stress/UPR-Mediated Cell Death and Rebalances Homeostasis of Pro- and Anti-Apoptotic Proteins in Favor of Cell Death in Acute Lymphoblastic Leukemia Cells
Authors: Gilles M. Leclerc, Shuhua Zheng, Guy J. Leclerc, Joanna DeSalvo, Ronan T. Swords, Julio C. Barredo
Journal: Blood (2015)
Influence Of Organ Scores On Mortality In Chronic GVHD: Results From The Chronic GVHD Consortium
Authors: Yoshihiro Inamoto, Barry E. Storer, Daniel J. Weisdorf, Georgia B. Vogelsang, Joseph Pidala, Xiaoyu Chai, Mary E. D. Flowers, Mukta Arora, Sally Arai, Jeanne Palmer, Corey S. Cutler, Madan Jagasia, Steven Z. Pavletic, Stephanie J. Lee, Paul J. Martin
Journal: Blood (2013)
SAT0356 Experience in The Use of 18F-FDG PET/CT in Patients with Polymyalgia Rheumatica in HUP la Fe
Authors: K. Arévalo Ruales, R. Negueroles Albuixech, J.L. Loaiza Gόngora, P. Sopena Novales, E. Grau Garcia, I. Martínez Cordellat, J. Valero Sanz, J. Ivorra Cortés, L. González Puig, I. Chalmeta Verdejo, C. Feced Olmos, E. Labrador Sánchez, F.M. Ortiz Sanjuan, J. Fragio Gil, C. Alcañiz Escandell, G. Poveda Marín, C. Nájera Herranz, V. Fornes Ferrer, J. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is an inflammatory disease characterized by pain and stiffness that usually affects the upper body and the pelvis. PMR is related frequently to another inflammatory disorder called giant cell arteritis (GCA), where about 50% of patients present polymyalgia. PET/CT offers functional and molecular information about inflammatory diseases that leads to the vasculitis diagnosis in an early stage, so PET/CT is a useful diagnosis tool to identify CGA associated with PMR <h3>Objectives</h3> To evaluate the incidence of GCA in patients diagnosed of PMR. <h3>Methods</h3> Prospective study from January 2011 until December 2015 including patients with PMR from the Rheumatology Department of HUP La Fe. In all cases to confirm the diagnosis of vasculitides an 18-FDG PET/CT was made. Also blood analysis that includes CRP and ERS, US and biopsy and treatment with esteroids or another DMARD was done. Statistical analysis was performed using R software 3.2.3. <h3>Results</h3> 23 patients with PMR diagnosis according to established Bird/Wood criteria were included, with a mean age at the time of PET/CT of 69.3 years (38–85). 18 were treated with steroids before PET/CT and 11 had another DMAR during follow up. In 47.8% of patients vasculitis was detected using PET/CT. Most frequent injury locations were aorta, iliac artery, and femoral artery. In these patients there is an increase in the CRP value (P=0.03) comparing to those without vasculitides. There were no significant differences in the ESR value or in the DMAR administration. <h3>Conclusions</h3> PET/CT is a useful diagnostic tool for the early diagnosis of vasculitides associated with PMR. This allows an early and adequate treatment in order to avoid structural damages within the blood vessel (aneurysms, stenosis, oclussions), reducing morbi-mortality and fatal outcomes. <h3>Disclosure of Interest</h3> None declared
Activating <i>NOTCH1</i> Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors
Authors: Renata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N. William, Bonnie S. Glisson, Michael J. Wick, Ann M. Kapoun, Amita Patnaik, Gail Eckhardt, Pamela Munster, Leonardo Faoro, Jakob Dupont, J. Jack Lee, Andrew Futreal, Adel K. El-Naggar, John V. Heymach
Journal: Journal of Clinical Oncology (2017)

Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro. The Notch1 inhibitor brontictuzumab was tested in patient-derived xenografts from patients with ACC and in a patient with ACC who was enrolled in a phase I study. Results NOTCH1 mutations occurred predominantly (14 of 15 patients) in the negative regulatory region and Pro-Glu-Ser-Thr–rich domains, the same two hotspots seen in T-cell acute lymphoblastic leukemias, and led to pathway activation in vitro. NOTCH1-mutant tumors demonstrated significantly higher levels of Notch1 pathway activation than wild-type tumors on the basis of Notch1 intracellular domain staining ( P = .004). NOTCH1 mutations define a distinct aggressive ACC subgroup with a significantly higher likelihood of solid subtype ( P &lt; .001), advanced-stage disease at diagnosis ( P = .02), higher rate of liver and bone metastasis ( P ≤ .02), shorter relapse-free survival (median, 13 v 34 months; P = .01), and shorter overall survival (median 30 v 122 months; P = .001) when compared with NOTCH1 wild-type tumors. Significant tumor growth inhibition with brontictuzumab was observed exclusively in the ACC patient-derived xenograft model that harbored a NOTCH1 activating mutation. Furthermore, an index patient with NOTCH1-mutant ACC had a partial response to brontictuzumab. Conclusion NOTCH1 mutations define a distinct disease phenotype characterized by solid histology, liver and bone metastasis, poor prognosis, and potential responsiveness to Notch1 inhibitors. Clinical studies targeting Notch1 in a genotype-defined ACC subgroup are warranted.
Widespread Usutu virus outbreak in birds in the Netherlands, 2016
Authors: JM Rijks, ML Kik, R Slaterus, RPB Foppen, A Stroo, J IJzer, J Stahl, A Gröne, MGP Koopmans, HP van der Jeugd, CBEM Reusken
Journal: Eurosurveillance (2016)

We report a widespread Usutu virus outbreak in birds in the Netherlands. Viral presence had been detected through targeted surveillance as early as April 2016 and increased mortality in common blackbirds and captive great grey owls was noticed from August 2016 onwards. Usutu virus infection was confirmed by post-mortem examination and RT-PCR. Extensive Usutu virus activity in the Netherlands in 2016 underlines the need to monitor mosquito activity and mosquito-borne infections in 2017 and beyond.
BAFF-R Aptamer/STAT3 siRNA Construct Selectively Downregulates STAT3 mRNA in BAFF-R Expressing Lymphomas in Vitro and in Vivo
Authors: Robert W. Chen, Pritsana Chomchan, Deepti Chadalavada, Jessica Alluin, jie-Hua Zhou, Stephen J. Forman, John Rossi
Journal: Blood (2012)
The Revised International Prognostic Scoring System "Molecular" (IPSS-Rm), a Validated and Dynamic Model in Treated Patients with Myelodysplastic Syndromes (MDS)
Authors: Aziz Nazha, Mayur Subhash Narkhede, Tomas Radivoyevitch, Matt Kalaycio, Bhumika J. Patel, Aaron T. Gerds, Sudipto Mukherjee, Michael Clemente, Cassandra M Hirsch, Anjali S. Advani, Bartlomiej Przychodzen, Hetty E. Carraway, Jaroslaw P. Maciejewski, Mikkael A. Sekeres
Journal: Blood (2015)
A Phase II Trial of Peri-Transplant Palifermin with Busulfan, Melphalan and Fludarabine Followed by T-Cell Depleted Hematopoietic Stem Cell Transplants in Patients with Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Evolved From MDS
Authors: Roni Tamari, Sheetal Ramnat Sheetal, Deborah Kuk, Esperanza B. Papadopoulos, Ann A. Jakubowski, Farid Boulad, Trudy N. Small, Nancy A. Kernan, Miguel A Perales, Guenther Koehne, Doris M Ponce, Sean Devlin, Jenna D Goldberg, James W. Young, Sergio A Giralt, Richard J. O'Reilly, Hugo R Castro-Malaspina
Journal: Blood (2012)
Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
Authors: Sandra P. D’Angelo, James Larkin, Jeffrey A. Sosman, Celeste Lebbé, Benjamin Brady, Bart Neyns, Henrik Schmidt, Jessica C. Hassel, F. Stephen Hodi, Paul Lorigan, Kerry J. Savage, Wilson H. Miller, Peter Mohr, Ivan Marquez-Rodas, Julie Charles, Martin Kaatz, Mario Sznol, Jeffrey S. Weber, Alexander N. Shoushtari, Mary Ruisi, Joel Jiang, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2017)

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.
StarPEG‐Heparin Hydrogels to Protect and Sustainably Deliver IL‐4
Authors: Lucas Schirmer, Passant Atallah, Carsten Werner, Uwe Freudenberg
Journal: Advanced Healthcare Materials (2016)

A major limitation for the therapeutic applications of cytokines is their short half‐life time. Glycosaminoglycans (GAGs), known to complex and stabilize cytokines in vivo, are therefore used to form 3D‐biohybrid polymer networks capable of aiding the effective administration of Interleukin‐4, a key regulator of the inflammatory response. Mimicking the in vivo situation of a protease‐rich inflammatory milieu, star‐shaped poly(ethylene glycol) (starPEG)‐heparin hydrogels and starPEG reference hydrogels without heparin are loaded with Interleukin‐4 and subsequently exposed to trypsin as a model protease. Heparin‐containing hydrogels retain significantly higher amounts of the Interleukin‐4 protein thus exhibiting a significantly higher specific activity than the heparin‐free controls. StarPEG‐heparin hydrogels are furthermore shown to enable a sustained delivery of the cytokine for time periods of more than two weeks. Primary murine macrophages adopt a wound healing supporting (M2) phenotype when conditioned with Interleukin‐4 releasing starPEG‐heparin hydrogels. The reported results suggest that GAG‐based hydrogels offer valuable options for the effective administration of cytokines in protease‐rich proinflammatory milieus such as chronic wounds of diabetic patients.
FRI0092 Influence of Temperature and Humidity on Disease Activity in Rheumatoid Arthritis
Authors: P. Mandl, F. Alasti, R. Kaltenberger, T. Krennert, G. Supp, U. Landesmann, J.S. Smolen, D. Aletaha
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To evaluate whether meteorological parameters influence disease activity in patients with rheumatoid arthritis (RA). <h3>Methods</h3> We assessed correlations between individual meteorological variables and clinical measures of disease activity: clinical disease activity index (CDAI), self-reported pain (by visual analogue scale), tender- and swollen 28 joint counts (TJC and SJC). Assessments documented in our RA database as well as the average temperature and relative humidity, obtained from the Central Institute for Meteorology and Geodynamics, were matched on a daily basis for a period of 10 years between 2005 and 2015, and analyzed using generalized estimating equations (longitudinal data analysis). <h3>Results</h3> A total of 1437 patients with RA (average disease duration at first visit: 4.88±8.63 years; 77% female, mean CDAI 17.8±11.7, mean time in study: 75 month, mean number of visits during study period: 19) were analyzed. Higher temperature and lower humidity were significantly associated with lower CDAI (p=0.0002, and p=0.0332, respectively). Regarding pain, the effects of temperature showed an interaction with humidity: while lower temperatures were associated with higher pain levels at the low and middle tertile of relative humidity, they corresponded to a lower pain level at the high tertile of relative humidity. Temperature showed a significantly negative correlation with TJC (p&lt;0.0001), while relative humidity showed a significantly positive correlation with SJC (p=0.0321). Similar to pain, there was again an interaction of temperature and humidity in the SJC analysis. <h3>Conclusions</h3> In this largest association study of meteorological parameters with RA specific outcomes both temperature and relative humidity were shown to have significant effects on disease activity. Individual measures of disease activity and pain correlated either with temperature or humidity, while the composite CDAI measure correlated with both meteorological variables. These aspects may have to be taken into account in longitudinal analyses of disease activity of RA. <h3>Disclosure of Interest</h3> None declared