tbuckley/cabot-search huggingface dataset:
AB0105 Inhibition of A Streptococcal Cell Wall Model of Arthritis Flare by Repository Corticotropin Injection
Authors: P. Higgins, D. Decker, P. Becker
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Repository corticotropin injection (RCI), a melanocortin peptide preparation, is FDA approved as adjunctive therapy for short term administration to tide patients over acute episodes or exacerbations of rheumatoid arthritis (RA), but has not been studied in an animal model of arthritis flare. <h3>Objectives</h3> To test the efficacy of RCI in a <i>Streptococcal</i> cell wall-induced model of arthritis flare in rats [1]. <h3>Methods</h3> Dark Agouti rats were primed on day 0 by an intra-articular injection of a proteoglycan/polysaccharide (PGPS) preparation from <i>Streptococcal</i> cell wall into the right ankle and vehicle (phosphate buffered saline) into the left. On days 14 and 28, transient arthritic flares were induced in the ankle by intravenous injection of PGPS. Caliper measurements of the right and left paw diameters were made daily beginning on the day of induction of the first flare. RCI was administered subcutaneously at doses of 40, 160, and 400 U/kg beginning day 1 after induction of the first flare and dosed every other day until animals were sacrificed on day 35, after recovery from the second flare. Arthritis was assessed by measuring the diameter difference between the right (PGPS injected) and left ankles. Histologic analysis was performed on the paws obtained at sacrifice (day 35). <h3>Results</h3> RCI dose-dependently inhibited paw swelling in rats after induction of both the first and second arthritic flares. Doses of 160 U/kg and 400 U/kg inhibited physical signs of the first flare by 69% (p&lt;0.01) and 86% (p&lt;0.001) and inhibited the second flare by 87% (p&lt;0.0001) and 90% (p&lt;0.0001), respectively. Histologic analysis showed that inflammatory cell infiltration into joints was significantly decreased by 53% (p&lt;0.01) and 77% (p&lt;0.0001) at the 160 and 400 U/kg doses of RCI, respectively, and that total histopathologic damage scores, which included measures of pannus, cartilage damage, bone resorption and periosteal bone formation were significantly reduced by 78% and 91% at 160 and 400 U/kg, respectively. <h3>Conclusions</h3> These preclinical results demonstrate the efficacy of RCI in an animal model of RA flare and support the potential clinical benefit of the drug for the treatment of inflammatory arthritis exacerbations. <h3>References</h3> Schopf L, Anderson K, Jaffee B. Rat models of arthritis: Similarities, differences, advantages, and disadvantages in the identification of novel therapeutics. In: C Stevenson, L Marshall, D Morgan (eds): In Vivo Models of Inflammation. 2006 Birkhauser Verlag, Basel. 1–34. <h3>Disclosure of Interest</h3> P. Higgins Employee of: Mallinckrodt, D. Decker Employee of: Mallinckrodt, P. Becker Employee of: Mallinckrodt
A Phase II Trial of Panobinostat, an Orally Available Deacetylase Inhibitor (DACi), in Patients with Primary Myelofibrosis (PMF), Post Essential Thrombocythemia (ET), and Post Polycythemia Vera (PV) Myelofibrosis
Authors: Daniel J DeAngelo, Ayalew Tefferi, Warren Fiskus, Ruben A. Mesa, Carole S. Paley, Martha Wadleigh, David S. Snyder, Kebede Begna, Michael S. Ondovik, Jessica Rine, Kapil N. Bhalla
Journal: Blood (2010)
THU0087 Subclinical Carotid Atherosclerosis in Rheumatoid Arthritis: Role of Serum Cathepsin S and Cystatin C
Authors: B. Tejera Segura, A. De Vera González, M. González-Gay, I. Ferraz-Amaro
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Although Cystatin C relation with atherosclerosis has been studied before in RA patients, cathepsin S association with subclinical atherosclerosis has not been previously considered in RA patients. This could help to better stratify or predict the development of cardiovascular diseases in RA. <h3>Objectives</h3> To assess if serum cathepsin S and cystatin C, two novel markers of cardiovascular disease risk (CVDR), are associated with subclinical carotid atherosclerosis in RA patients. <h3>Methods</h3> Serum cystatin C and cathepsin S levels, carotid intima-media thickness (cIMT) and carotid plaques were assessed in a cross-sectional study involving 178 RA patients. All of them were 18 years or older and fulfilled the 2010 ACR/EULAR classification criteria. <h3>Results</h3> Patients with a mean ± SD age of 55 ± 11 years were included. Regarding cardiovascular risk factors, 35% of the patients had hypertension, 32% dyslipidemia and 15% diabetes. Disease duration was 7 (IQR 4–15) years. Patients had moderate-active disease as shown by DAS28 (3.74 ± 1.91). One third (35%) of them were taking prednisone, 86% were under disease-modifying antirheumatic drugs and 22% were taking anti-TNF-alpha or other biologic therapies. The mean cIMT was 0.670 ± 0.143 mm, and 66 patients (37%) had carotid plaques in the carotid ultrasound assessment. Both cystatin C and cathepsin S were significantly associated with hypertension, diabetes and dyslipidemia. However, neither positive rheumatoid factor nor prednisone use were associated with cystatin C or cathepsin S. A trend for lower levels of cystatin C was observed in patients undergoing anti-TNF-alpha therapy (<i>log</i> beta coef. -0.20 (-0.44–0.04), p=0.09). An association between disease activity scores with higher levels of cystatin C but not with cathepsin S was found. Cystatin C levels were also associated with cIMT in the subgroup of patients included in the higher quartile of cIMT (OR 1.31, 95%CI [1.00–1.72], p=0.04) after adjusting for traditional cardiovascular risk factors, age and sex. An association between serum cystatin C levels and carotid plaques was also found in the univariate analysis (OR 1.37, 95%CI [1.06–1.76], p=0.02). However, this significant association was lost after adjusting for traditional cardiovascular risk factors and age. Cathepsin S was not associated with cIMT or carotid plaques. <h3>Conclusions</h3> High cystatin C serum levels identify a subgroup of RA patients with high risk of subclinical atherosclerotic disease. <h3>Disclosure of Interest</h3> None declared
Coagulation complications following trauma
Authors: Wenjun Z. Martini
Journal: Military Medical Research (2016)

Traumatic injury is one of the leading causes of death, with uncontrolled hemorrhage from coagulation dysfunction as one of the main potentially preventable causes of the mortality. Hypothermia, acidosis, and resuscitative hemodilution have been considered as the significant contributors to coagulation manifestations following trauma, known as the lethal triad. Over the past decade, clinical observations showed that coagulopathy may be present as early as hospital admission in some severely injured trauma patients. The hemostatic dysfunction is associated with higher blood transfusion requirements, longer hospital stay, and higher mortality. The recognition of this early coagulopathy has initiated tremendous interest and effort in the trauma community to expand our understanding of the underlying pathophysiology and improve clinical treatments. This review discusses the current knowledge of coagulation complications following trauma.
PWE-063 Annual Review of Patients with Coeliac Disease in The Community? – A Patient Survey
Authors: E Copeland, J Smith, K Eaton, S Gupta
Journal: Gut (2016)

<h3>Introduction</h3> Patients with stable coeliac disease in Croydon are discharged back to their General Practitioners with a yearly follow-up protocol. We conducted a patient survey to evaluate its uptake and to ascertain the views of patients about their follow-up. <h3>Methods</h3> An online survey was designed and sent to all patients registered with Croydon group of Coeliac UK and had an e-mail address in February 2015. A reminder was sent to all members after 6 weeks. The responses were computed in May 2015, presented to Croydon Coeliac UK members and sent to the CCG. Paper copies were also given out at a group meeting. <h3>Results</h3> Of the 233 registered members, the survey questionnaire was sent electronically to about 200 patients at 9 post codes in Croydon. There were 101 responses of which 82 were complete. 94% responders were over 18 years of age. 60% patients never received an appointment from their GP for an annual follow-up (n = 84). Only 50% patients had a follow-up in the previous year. Most recent review was conducted by GP in 37% cases, GP practice nurse in 8%, Deititian in 20%, local gastroenterologist 32% (n = 76). Overall 80% patients had seen a dietitian (n = 85). 70% (n = 87) had been offered DEXA scan for bone mineral density. About 65% had a blood test in the last year (n = 87). Calcium, haematinics, vitamin D, coeliac antibodies were checked in about 40–50% patients (n = 34) with 66% receiving feedback on the results (n = 47). Apart from enquiry about gluten free diet in 78% cases, all other questions relating to coeliac disease were discussed in less than 40% cases (n = 60). Vaccinations were discussed in only 8% cases and membership of Coeliac UK in 18%. Only 43% of patients were offered a yearly follow-up while 7% were referred to the hospital gastroenterologist (n = 57). When asked about the expectations of patients, 90% wanted an annual follow-up (n = 78) with 37% preferring to see their GP, 9% GP practice nurse, 21% dietitians, 27% gastroenterologist (n = 75). Of the 77 respondents, 46% said they would be happy to attend dietitian led group sessions, 38% preferred not to while 17% had no opinion. <h3>Conclusion</h3> The annual follow-up of patients with coeliac disease in the community is patchy. The quality of this appointment is also inadequate. If these results can be replicated more widely, there may be a place for specialist community clinics with links between GP, dietitians and local gastroenterologists. <h3>Disclosure of Interest</h3> None Declared
General practices must appoint whistleblowing guardian
Authors: Jacqui Wise
Journal: BMJ (2016)

All GP clinics must appoint a “freedom to speak up” guardian to make it easier for staff to raise concerns, under new whistleblowing guidance drawn up by NHS England.1

The guidance comes after Robert Francis QC recommended that the principles outlined in his Freedom to Speak Up report be adapted for primary care.2 A national whistleblowing policy is already in place for secondary care.3

NHS England said that all NHS staff working in primary care should be encouraged to raise …
Jak2 V617F Induced TNF Resistance as a Mechanism of Clonal Expansion In Myeloproliferative Neoplasm
Authors: Angela G. Fleischman, Karl J. Aichberger, Curtis L Petersen, Shirin Doratotaj, Thomas G Bumm, Heike L. Pahl, Brian J Druker, Michael W Deininger
Journal: Blood (2010)
NIMG-30AN MRS AND PET GUIDED BIOPSY TOOL FOR ULTRASOUND-BASED INTRA-OPERATIVE NEURO-NAVIGATIONAL SYSTEMS
Authors: Matthew Grech-Sollars, Babar Vaqas, Gerard Thompson, Lesley Honeyfield, Kevin O'Neil, Adam D Waldman
Journal: Neuro-Oncology (2015)

BACKGROUND: Heterogeneity in glioma limits tumour characterisation using stereotactic biopsy; it is frequently not possible to target the most aggressive tumour components reliably from conventional structural imaging. In vivo MR spectroscopy (MRS) and PET allow cellular metabolism relevant to proliferation to be imaged non-invasively. Intra-operative PET and MRI is however costly, cumbersome and not widely available. Intra-operative ultrasound provides near real-time structural imaging for surgical guidance. Here we combine PET and MRS with ultrasound neuro-navigation to guide surgical biopsy from brain gliomas. METHODS: An intra-operative neuronavigation tool was developed as part of a study to sample high choline tumour components identified by MRS and 18F-methylcholine PET. Spatially co-registered PET and MRS data were integrated into structural datasets and loaded into a commercial SonoWand intra-operative image guidance system. High and low choline uptake/metabolite regions were represented as colour coded hollow spheres for targeted biopsy. To date two patients have had surgery using this method. RESULTS: The operating surgeons found the 3D spherical targets readily identifiable on the interactive navigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated MRS choline ratios in an otherwise low-grade tumour. The other showed low choline markers, and was histologically low grade throughout. CONCLUSIONS: Functional and physiological PET and MRI data can be combined and usefully represented to the surgeon in ultrasound-based neuronavigation for optimised tumour sampling; which will inform treatment decisions, and allow better validation of imaging biomarkers against tissue features. This approach can also be applied to other imaging methods such as perfusion and fMRI to improve stratification and minimise morbidity in maximal surgical resection.
Addressing Spiritual Distress
Authors: Danish Zaidi
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Matched Unrelated Donor Allogeneic Stem Cell Transplantation in High Risk Acute Lymphoblastic Leukemia (ALL) After a Preparative Regimen of Hyperfractionated Total Body Irradiation and High-Dose Etoposide – A Feasibility Study within the German Multicenter Study Group for Adult ALL.
Authors: Dietrich W. Beelen, Renate Arnold, Theis Terwey, Nina K. Steckel, Nicola Goekbuget, Hoelzer Dieter
Journal: Blood (2009)
Selective Inhibition of HDAC6 Decreases Viability of Cutaneous T-Cell Lymphoma and Improves Immune Recognition
Authors: Tessa Knox, Maritza Lienlaf, Patricio Perez-Villarroel, Calvin Lee, Eva Sahakian, John J. Powers, Fengdong Cheng, Jorge Canales, Danay Marante, Ed Seto, Eduardo M. Sotomayor, Alejandro Villagra, Pedro Horna
Journal: Blood (2014)
Motivation for Psychological Treatment Predicts Favorable Outcomes in Multimodal Interdisciplinary Treatment for Chronic Somatoform Pain
Authors: Julian A. Stewart, Niklaus Egloff, Roland von Känel, Johannes Grolimund, Martina Studer, Martin grosse Holtforth
Journal: Psychotherapy and Psychosomatics (2016)

Chronic somatoform pain is a frequently occurring disorder that can induce 37 impairment, and disability [1].Multimodal interdisciplinary represents the treatment of 38 choice [2]; it typically combines psychotherapy, physical therapy and medical interventions [3].39 In other words, psychotherapy is a central component within a multimodal interdisciplinary 40 treatment setting [3] and it is also considered to be effective for the treatment of chronic pain [4].41 Motivation for psychotherapy has been defined as a construct encompassing components of 42 negative illness consequences, psychosocial lay etiology, positive psychotherapeutic treatment 43 expectations and a general openness to psychotherapy [5].According to the IMMPACT 44 recommendations, core effectiveness outcomes of chronic pain treatment include pain intensity, 45 global rating of improvement, physical functioning and emotional functioning [6].Means to 46 fulfill some of these requirements are numerical rating scales (NRS) to measure pain intensity 47 and depressive symptom scales to assess emotional functioning [7].Whereas the importance of 48 psychotherapy motivation for treatment outcomes has been shown for domains such as 49 somatization syndrome [8], to our knowledge, as yet, no studies have tested prognostic effects of 50 psychotherapy motivation on outcomes of multimodal interdisciplinary treatment for chronic 51 somatoform pain.52
Pipkiia and Beta-Globin: Transcripts Differentially Expressed in Reticulocytes and Associated with High Levels of Hb H in Two Siblings with Hb H Disease.
Authors: Maria F. Sonati, Marcia R. Wenning, Maricilda P. Mello, Tiago G. Andrade, Carolina Lanaro, Dulcineia M. Albuquerque, Sara Saad Titular, Fernando F. Costa Titular
Journal: Blood (2007)
A phase I/II clinical trial of sorafenib in combination with cisplatin and docetaxel in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).
Authors: Panayiotis Savvides, Pawan Kumar, Maura L. Gillison, Ted Teknos
Journal: Journal of Clinical Oncology (2014)

TPS6103 Background: There is rapid accumulation of data pointing to a potential role of sorafenib in the setting of recurrent/metastatic SCCHN. The combination of sorafenib to a cisplatin-docetaxel doublet backbone was chosen for further development for many reasons, including that cisplatin-containing combination regimens have been associated with higher response rates when compared with carboplatin ones and cisplatin containing regimens remain the first choice for firstline treatment and taxane-cisplatin combination regimens appear to be preferable to 5FU-cisplatin combination regimens given equal efficacy and better toxicity profile. In addition, we have generated preclinical data suggesting that sorafenib enhances the antitumor effect of chemotherapy and radiation by downregulating ERCC-1 and XRCC-1 DNA repair proteins. If validated in the clinical setting, ERCC-1 downregulation by sorafenib has the potential to improve cisplatin efficacy not only in patients with SCCHN, but across multiple tumor types, as high ERCC1 expression has been associated with shortened survival outcomes in numerous primary tumors. Methods: A short Phase I followed by a phase II single arm clinical trial as first line in patients with recurrent/metastatic SCCHN. A total of 3-18 and 29 patients might be needed for the phase I and II portions of the trial, respectively. Correlative studies: A total of three biopsies (blood and tumor samples) will be obtained. 1) Pre-treatment biopsy; 2) Research biopsy obtained at the end of a two week period of sorafenib monotherapy; 3) Research biopsy obtained at the end of two chemotherapy cycles. Proposed correlative studies include: a) Sorafenib target proteins analysis by Immunohistochemistry (IHC) for: 1) pERK1/2 (activated form of ERK1/2); 2) ERCC-1 (DNA repair protein); 3) pVEGFR2 (activated form of VEGFR2); 4) CD31 staining (tumor angiogenesis); 5) Activated caspase-3 staining for apoptotic cells; b) ERCC-1 gene expression analysis by RT-PCR; c) VEGF and IL-6 analysis by ELISA. Clinical trial information: NCT02035527.Phase I dose levels. Cisplatin (mg/m2/21 days)* Docetaxel (mg/m2/21 days)* Sorafenib (mg /bid)** DL-2 75 50 200 DL-1 75 50 400 DL 1 75 75 400
Population Pharmacokinetics of Busulfan in Patients with Beta Thalassaemia Major Undergoing HSCT Reveals Body Weight, GSTA1 and CYP3A4 Promoter Polymorphisms as Main Covariates Explaining the Inter-Individual Variation.
Authors: Poonkuzhali Balasubramanian, John Carl Panetta, Salamun Desire, Shaji R Velayudhan, Vikram Mathews, Biju George, Auro Viswabandya, Mammen Chandy, Alok Srivastava
Journal: Blood (2009)
The Addition of Plerixafor Allows Adequate PBSC Collection in Multiple Myeloma and Lymphoma Patients Poor –mobilizers After Chemotherapy and G-CSF.
Authors: Alessandra D'Addio, Antonio Curti, Valeria Giudice, Maria Rosa Motta, Simona Rizzi, Elisa Dan, Simona Taioli, Michele Baccarani, Roberto M Lemoli
Journal: Blood (2009)
Preclinical Development and In Vivo Evaluation Of Next-Generation Compstatin Analogs With Improved Systemic Profiles: A Novel Option For The Treatment Of Paroxysmal Nocturnal Hemoglobinuria
Authors: Daniel Ricklin, Antonio M. Risitano, Edimara S. Reis, Patrizia Ricci, Yijun Huang, Zhuoer Lin, Hui Chen, Caterina Pascariello, Maddalena Raia, Luigi Del Vecchio, Fabrizio Pane, Ranillo R. G. Resuello, Robert A. DeAngelis, John D. Lambris
Journal: Blood (2013)
STAT1 regulates marginal zone B cell differentiation in response to inflammation and infection with blood-borne bacteria
Authors: Ting-Ting Chen, Ming-Hsun Tsai, John T. Kung, Kuo-I Lin, Thomas Decker, Chien-Kuo Lee
Journal: The Journal of Experimental Medicine (2016)

Marginal zone B (MZ B) cells can rapidly produce antibody in response to infection with blood-borne encapsulated pathogens. Although TLR-mediated activation of MZ B is known to trigger humoral immune response, the signal cascade directing this response remains undefined. Here, we demonstrate that STAT1 plays an essential role in TLR-mediated antibody response of MZ B cells. Further, the TLR-induced IgM response is impaired in a type I and type II IFN-independent manner. Although activation, proliferation, and apoptosis are not affected, both differentiation into plasma cells and IgM production are impaired in Stat1−/− MZ B cells. Interestingly, STAT1 directly regulates the expression of Prdm1 (encodes BLIMP-1) by binding to its promoter, and Prdm1 expression is reduced in Stat1−/− MZ B cells. Restoration of BLIMP-1 to cells rescues TLR-induced IgM response. Moreover, Stat1−/− mice are more susceptible to S. pneumoniae infection, which can be rescued by the serum of bacteria-primed WT mice. The increased susceptibility to S. pneumoniae infection in Stat1−/− mice is also intrinsic to STAT1 requirement in MZ B cells. Collectively, these results define a differential regulation of TLR-mediated activation and differentiation of MZ B cells by STAT1 and reveal a STAT1-dependent, but IFN-independent, antibody response during infection and inflammation.
Addition of Rituximab Improves Progression-Free and Overall Survival in Patients with B-Cell Lymphoma Receiving Doxorubicin-Containing Chemotherapy
Authors: Tatsunori Sakai, Hirokazu Nagai, Tomoyuki Watanabe, Naokuni Uike, Seiichi Okamura, Takahiro Yano, Fumio Kawano, Shuichi Hanada, Kazutaka Sunami, Hirokazu Ikeda, Morio Sawamura, Tetsuo Nishiura, Tomomitsu Hotta, Keizo Horibe
Journal: Blood (2007)
Spontaneous Apoptosis and Proliferation Predict Disease Progression within ZAP-70 Negative B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: Giovanni Del Poeta, Maria Ilaria Del Principe, Pasquale Niscola, Luca Maurillo, Adriano Venditti, Francesco Buccisano, Maria Irno Consalvo, Carla Mazzone, Paola Panetta, Massimo Degan, Irene Pasqua, Antonio Bruno, Valter Gattei, Francesco Lo Coco, Sergio Amadori
Journal: Blood (2005)
Efficacy and Safety of a First-Line Combined Therapeutic Approach for Young CLL Patients Stratified According to the Biological Prognostic Features: First Analysis of the GIMEMA Multicenter LLC0405 Study
Authors: Francesca Romana Mauro, Agostino Cortelezzi, Stefano Molica, Luca Laurenti, Vincenzo Liso, Rita Rizzi, Angelo Michele Carella, Francesco Di Raimondo, Roberto Marasca, Giuseppe Fioritoni, Maura Brugiatelli, Caterina Musolino, Francesco Lauria, Francesco Buccisano, Francesco Zaja, Vincenzo Callea, Fortunato Morabito, Massimo Massaia, Giuseppe Gentile, Ilaria Del Giudice, Maria Stefania De Propris, Irene Della Starza, Marilisa Marinelli, Simona Santangelo, Mauro Nanni, Marco Vignetti, Antonietta Graziosi, Giorgina Specchia, Antonio Cuneo, Anna Guarini, Robert Foà
Journal: Blood (2008)