tbuckley/cabot-search huggingface dataset:
Clinical consequences of profound anemia
Authors: M. Devagiri, P. Ford
Journal: Journal of Clinical Oncology (2009)

e20666 Background: Although there is an emerging trend to reduce blood transfusions, there is still very little randomized data outside of the critical care setting that identifies the risks and benefits of transfusion support. Many clinicians base the decision to transfuse primarily on the hemoglobin (Hb) level independent of symptoms. Little is known about the clinical consequences of profound anemia although there is concern that withholding transfusion will result in adverse outcomes in those with advanced age or underlying cardiovascular conditions. Methods: A retrospective chart review of 32 patients declining blood transfusions from January 2004 to June 2008 was performed to evaluate the clinical consequences of anemia. This population included a broad range of medical, surgical and obstetrical cases and their ages ranged from 84 to 28yrs (mean 53.03). The initial Hb ranged from 3.2 to 6.8 (mean 5.04).12 patients had Hb levels less than 4.9 and 3 patients had levels less than 4. Our non blood approach included simultaneous interventions to stimulate erythropoiesis, control bleeding, enhance hemostasis, minimize blood loss and maintain hemodynamic stability. Results: 6/32 patients (18.75%) had cardiac complications related to anemia like congestive heart failure, myocardial ischemia, and cardiac arrest. They occurred predominantly in patients with underlying cardiovascular disease (4/7) with increased tendency in patients with structural heart disease like Hypertrophic Obstructive Cardiomyopathy (HOCM) and critical Aortic stenosis (3/3) at Hb levels of 4.8 and 5.6. Patients without any pre-existing cardiovascular illness tolerated very low levels of Hb of 2.5 and 4 before they had cardiac arrest from anemia. 2 patients above the age of 70 tolerated the Hb levels of 2.7 and 3.3 without complications. 2 of 3 patients with Hb less than 3 had no complications.4 deaths are noted. Conclusions: This study illustrates that patients without cardiovascular co-morbidity tolerate levels of Hb as low as 3.3 without significant events. However patients with structural heart disease like Aortic stenosis and HOCM have shown the signs of decompensation at a lower degree of anemia which suggests that they need transfusion at lower degree of anemia. No significant financial relationships to disclose.
Abstract 4859: Tumor and normal classification of formalin-fixed, paraffin-embedded (FFPE) specimens by transcriptome RNA-seq
Authors: Kunbin Qu, John Morlan, Francois Collin, Carl Millward, James Stephans, Mei-Lan Liu, Jennie Jeong, Joffre Baker, Dominick Sinicropi
Journal: Cancer Research (2011)

Abstract We have used RNA-seq to profile and compare normal and cancerous human breast tissue. FFPE breast specimens from a total of 24 patients, 12 normal (N) and 12 tumor (T) specimens from surgical resections, were analyzed on an Illumina's GA IIx sequencer. Whole transcriptome RNA-Seq libraries were prepared after depletion of ribosomal RNA by a protocol developed at Genomic Health Inc. (GHI). The analysis was multiplexed across two flow cells using barcoding, with two specimens per sequencing lane (1 T and 1 closely age-matched N library from a different patient). FFPE tissue archive times ranged from 10 to 13 years and they were also closely matched within each lane. To evaluate reproducibility, triplicate libraries were created from 4 of the specimens and analyzed within and across flow cells. Libraries yielded, on average, 19 million 51 bp sequences. R2 values obtained from replicate libraries prepared from the same patient RNA were &amp;gt; 0.9 within and between flow cells. More than 80% of known genes in the human genome were detected in all patients. Several thousand intergenic transcripts were identified by an algorithm developed at GHI. A negative binomial model with tag-wise estimates of dispersion was applied to the known genes and intergenic regions. Inter-patient count variance is generally higher in the set of intergenic sequences than in the set of gene (RefSeq) sequences. Thousands of gene (RefSeq) and intergenic sequences were found to be differentially expressed between T and N tissues. We sought to build classifiers based on flow cell #1 data that could stratify T and N tissues when applied to flow cell #2 data. Sets of genes and intergenic regions were selected for analysis based on high inter-patient count variance. Support vector machine classifiers were trained and then applied to the data from flow cell #2, and also to another GHI tumor/normal RNA-Seq study. Either a set of 100 genes (RefSeq), or a set of 70 intergenic sequences accurately distinguished tumor and normal tissues. Our results offer further evidence of the potential of RNA-Seq for discovery of biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4859. doi:10.1158/1538-7445.AM2011-4859
Safety of autologous bone marrow cell injection in humans with severe ischemic heart failure
Authors: Hans F. Dohmann, Emerson C. Perin, Andre Luiz S. Sousa, Radovan Borojevic, Antonio C. Carvalho, Isabel Rossi, Suzana A. Silva, Roberto Esporcatte, Guilherme V. Silva, Hans J. Dohmann, Fernando Rangel, James T. Willerson
Journal: Journal of the American College of Cardiology (2003)
Abstract 317: p38γ MAPK regulates topoisomerase IIα activity by phosphorylation
Authors: Xiaomei Qi, Songwang Hou, Zhenkun Lou, Guan Chen
Journal: Cancer Research (2010)

Abstract DNA topoisomerase IIα (Topo IIα) is a critical target for cancer therapy and its protein expression, however, is frequently depleted by its inhibitors and strategies to maintain Topo IIα expression and thereby to sustain the Topo II drug sensitivity are still lacking. Here we show that p38γ MAPK is specifically activated by Topo II inhibitors and activated p38γ in turn phosphorylates Topo IIα, leading to increased Topo IIα protein expression through attenuating its proteasome-dependent degradation. The sensitivity of a panel of human breast cancer cell lines to Topo II inhibitors was found not to correlate with the intrinsic but with inducible Topo IIα protein expression and with endogenous protein expression of p38γ MAPK that is specifically phosphorylated in response to Topo II toxins. p38γ activation and inhibition alone were shown to increase and decrease Topo IIα expression and Topo drug toxicities. Mechanistically, p38γ MAPK phosphorylates Topo IIα at Ser 1524, leading to a decreased proteasome-dependent Topo IIα degradation. These results reveal a novel mechanism by which p38γ MAPK specifically confers Topo II drug toxicity in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 317.
TREATMENT AND STROKE RISK IN LOW RISK CHA2DS2VASC ATRIAL FIBRILLATION PATIENTS: FINDINGS FROM THE ORBIT-AF REGISTRY
Authors: Larry R. Jackson, Sunghee Kim, Jack Ansell, Gregg Fonarow, James Freeman, Bernard Gersh, Alan Go, Elaine Hylek, Peter Kowey, Kenneth Mahaffey, Daniel Singer, Laine Thomas, Eric Peterson, Jonathan Piccini
Journal: Journal of the American College of Cardiology (2016)
AB1160 Golimumab in 25 young adults affected by juvenile idiopathic arthritis (JIA) non responders to other biological agents: Preliminary data
Authors: I. Pontikaki, M. Gattinara, C. Donati, P.L. Meroni, V. Gerloni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biological agents licensed in JIA have demonstrated a favourable benefit-to-risk profile. Nevertheless, intolerance, loss and lack of efficacy or adverse events have led to try other therapeutic options. <h3>Objectives</h3> To evaluate efficacy and safety of Golimumab in young adults affected by JIA with active polyarthritis (with or without uveitis), non responders to MTX, antiCD20 and anti-IL-1 and intolerant to the first generation of antiTNF (Infliximab, Etanercept and Adalimumab). <h3>Methods</h3> In our Centre, since november '99 to dicembre 2011, 288 patients affected by refractory JIA were treated with TNF inhibitors and since May 2011, 25 patients (16 F, 9 M) affected by refractory JIA, non responders to other biologic agents, were enrolled in Golimumab (Simponi). Patients had failed MTX as monotherapy, previous TNF inhibitors, Rituximab and anti-IL1 therapy. Two patients had been treated with 8 different biologic agents, 1 patient with 7, 2 patients with 6, 5 patients with 5, 3 with 3, 7 with 2 and 3 patients with just one previous biologic agent. Two patients had a Systemic onset of JIA, 4 polyarthritis RF negative, 3 enthesitis related arthritis, 1 psoriatic arthritis, 6 oligoarthritis persistent and 9 oligoarthritis extended. Median age was of 28.7 years, median onset age 7.3 years, median disease duration 19.8 years. All patients had active disease, 8 patients had a previous history of chronic Iridocyclitis. Patients received Golimumab at the dose of 50 mg subcutaneously every month, as in RA. Fifteen patients receive Golimumab in association with MTX. <h3>Results</h3> All patients were evaluated according to EULAR criteria (DAS 28). Seventeen patients (68%) were responders, 5 patients were not evaluable because of follow-up and 3 patients were non responders (1 of these 3 pts droped-out). No adverse events were observed. No adverse events were occured. <h3>Conclusions</h3> Golimumab seems to be efficacious and well tolerated and it could be a good treatment of long lasting refractory JIA in young adults who failed other biologics. These data seem to be one of the first experiences in the use of Golimumab in young adults affected by JIA. <h3>Disclosure of Interest</h3> None Declared
DIFFERENTIATION OF TUMOR VERSUS SARCOIDOSIS USING T1-201 IN PATIENTS WITH HILAR AND MEDIASTINAL ADENOPATHY.
Authors: Alan D. Waxman, Mark S. Goldsmith, Paul M. Greif, Lalitha Ramanna, Michael B. Brachman, Doina E. Tanasescu, Daniel S. Berman, Peter Julien, John D. Friedman
Journal: Clinical Nuclear Medicine (1986)

Waxman, Alan D.; Goldsmith, Mark S.; Greif, Paul M.; Ramanna, Lalitha; Brachman, Michael B.; Tanasescu, Doina E.; Berman, Daniel S.; Julien, Peter; Friedman, John D. Author Information
18F-FDG PET/CT in Tumefactive Multiple Sclerosis
Authors: Anna Margherita Maffione, Lucia Rampin, Gaia Grassetto, Roberto L’Erario, Patrick M Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2014)

A 35-year-old man underwent contrast-enhanced MRI and 18F-FDG PET/CT for acute peripheral paresthesia, vision loss, muscle weakness, and difficulty walking. T2-weighted MRI demonstrated multiple bright periventricular supratentorial and infratentorial white matter lesions, including 2 with nodularity. Both nodular lesions showed moderate focal FDG uptake (SUVmax, 6.9 in both cases). Cerebrospinal fluid analysis showed increased levels of immunocytes and oligoclonal antibody bands. A diagnosis of acute onset tumefactive multiple sclerosis was made.
ELECTIVE ALCOHOL SEPTAL ABLATION PRE TRANSCATHETER AORTIC VALVE REPLACEMENT TO OPTIMIZE OUTCOMES IN PATIENTS WITH ASYMMETRIC SEPTAL HYPERTROPHY
Authors: Asaad A. Khan, Partho Sengupta, Jason Kovacic, Umesh Gidwani, Melissa Mattimore, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2016)
PARASYMPATHETIC REINNERVATION PROGRESSES TOGETHER WITH IMPROVED POST-EXERCISE HEART RATE RECOVERY AND QUALITY OF LIFE IN HEART TRANSPLANT RECIPIENTS
Authors: Teruhiko Imamura, Koichiro Kinugawa, Toshiro Inaba, Hisataka Maki, Masaru Hatano, Osamu Kinoshita, Kan Nawata, Minoru Ono
Journal: Journal of the American College of Cardiology (2015)
THU0067 Use of cardiovascular drugs in patients with RA, overall and in patients with a history of acute ischemic cardiac events
Authors: M. Holmqvist, J. Eriksson, J. Askling
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Data on increased cardiovascular disease (CV) risks in RA are abundant. Less is known about the use of therapeutic or prophylactic CV management in RA. Some studies report a lower use of secondary prevention drugs following acute ischemic events in RA. <h3>Objectives</h3> To compare the use of selected classes of CV drugs distributions in RA and in the general population, overall and in subjects with a history of ischemic cardiac events. <h3>Methods</h3> From the Outpatient register, we identified a population-based prevalent RA-cohort consisting of all individuals with two or more visits listing RA in non-primary outpatient care 2005-2008, with at least one visit in 2009 (n=34,133). For each subject, five general population comparators were sampled (n=170,665). From the Prescribed Drug Register, all filled prescriptions of low-dose acetylsalicylic acid (ASA), statins, beta-blockers, ACE- and AII-inhibitors, diuretics, and calcium channel blockers (antihypertensives) during 2009 were retrieved. Information on hospitalizations for myocardial infarction or unstable angina within the last five years (2005-2009) was retrieved from the Hospital Discharge Register. <h3>Results</h3> Overall, the proportion of RA-patients and comparators treated with low-dose ASA (16%vs15%) and statins (19%vs20%) were similar but the proportion of patients treated with antihypertensives was higher (50%vs42%), similarly so across sex and age-groups (Table). 1,423 (4.2%) RA-patients and 4,063 (2.4%) comparators had a history of an acute ischemic cardiac event. Among these, the use of low-dose ASA (74%vs74%), at least one antihypertensive drug (96%vs96%) was similar, but use of statins was slightly less common in RA (75%vs80%). Among subjects without an acute ischemic cardiac event within 5 years, use of low-dose ASA (8%vs9%) and statins (11vs13% were largely similar but the proportion of RA treated with antihypertensives (42%vs35%) was higher. <h3>Conclusions</h3> This preliminary analysis does not suggest any major difference in the use of secondary prophylaxis in RA with a history of ischemic cardiac events, but a slightly higher use of anti-hypertensive CV drugs in patients without a history of ischemic cardiac events. More detailed analyses will reveal whether this increased use reflects a met or unmet therapeutic need. <h3>Disclosure of Interest</h3> None Declared
FRI0369 Uc-Mscs Inhibit the Differentiation and Proliferation of T Follicular Helper Cell in Rheumatoid Arthritis
Authors: R. Liu, M. Zhou, Y. Sun, X. Li, X. Feng, L. Sun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of our study was to elucidate whether umbilical cord derived mesenchymal stem cell (UC-MSCs) had immunomodulatory effect on T follicular helper (Tfh) cell under rheumatoid arthritis (RA) background. <h3>Methods</h3> PBMCs that isolated from RA patients and healthy contorl (HC) were cocultured with UC-MSCs at a ratio of 100:1, 10:1 and 1:1 respectively through cell-to-cell contact or in a transwell system at a ratio of 1:10. After 3 days9 coculture, PBMCs were collected and the frequency of CD4+CXCR5+PD-1+T cell was examined by flow cytometry. Purified naïve T cells isolated from PBMC of RA patients were cocultured with human UC-MSCs for 4 days at a ratio of 1:10 under Tfh cell-polarizing condition. To detect the effect of MSC on Tfh proliferation, CFSE-labeled purified CD4<sup>+</sup> T cells isolated from PBMC of RA patients or HC were stimulated with anti-CD3/CD28 and cocultured with UC-MSCs for 5 days. The frequency of CD4+CXCR5+PD-1+T or CD4+CXCR5+PD-1+AnnexinV+T was examined by flow cytometry and the level of IL-21 in the cultured supernatant was measured by ELISA. The mRNA levels of indoleamine 2,3-dioxygenase (IDO), IL-10, PGE2, HGF, TGF-β and HLA-G in UC-MSCs were tested by RT-PCR. IDO activity of was measured by high-performance liquid chromatography (HPLC), and P-STAT-1/3/5 and p-Akt in UC-MSCs were tested by Western blot. IDO inhibitor 1-MT or anti-IL-10 antibody was added into UC-MSCs and Tfh cell differentiation coculture system for 5 days and then the frequency of CD4+CXCR5+PD-1+T was examined by flow cytometry. <h3>Results</h3> UC-MSCs were able to suppress the generation of Tfh cell both in RA patients and in HC in vitro, which was dose-dependent and not relied on cell-to cell contact. UC-MSCs suppressed the differentiation and proliferation of Tfh cell that was more prominent in samples from RA patients, but had no effect on Tfh cell apoptosis. The level of IL-21 in UC-MSCs and Tfh cell differentiation coculture system was significantly decreased. Dramatic increases of both IDO mRNA expression and IDO enzymatic activity were detected in UC-MSCs after coculturing with naïve T cells under Tfh cell-polarizing condition. Meanwhile, pSTAT-1/3/5 and pAkt in these UC-MSCs were increased. The addition of the IDO inhibitor 1-MT, but not anti-IL-10 antibody, could reverse the suppressive effect of UC-MSCs on the differentiation of Tfh cell. <h3>Conclusions</h3> UC-MSCs suppress Tfh cell differentiation and proliferation in RA patients, which is partially mediated by the secretion of IDO. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2202
Abstract 1023: Cytoplasmic domain of interferon-gamma receptor beta chain (IFNγR2) has an antiapoptotic activity as a Bax inhibitor
Authors: Jose Gomez, Weiyong Sun, Vivian Gama, Dagmar Hajkova, Tomoyuki Yoshida, Zhengrong Wu, John Pink, Mark Jackson, Masaru Miyagi, Shigemi Matsuyama
Journal: Cancer Research (2010)

Abstract Bax is a pro-apoptotic protein mediating intrinsic cell death signal. New Bax inhibitor was searched by using yeast-based functional screening, and Interferon Gamma Receptor Beta chain (IFNγR2) was cloned as a Bax suppressor. IFNγR2 is a receptor protein, which is a part of the IFNγ receptor complex with IFNγR1, involved in the Jak/STAT signaling pathway. Upon IFNγ binding a conformational change in the receptor complex occurs, followed by activation of Jak kinases, and STAT1. We found that the C-terminus region of IFNγR2 amino acids 296-337 (IFNγR2296-337) contains the novel Bax inhibiting domain. This portion does not contain the Jak2 binding domain, therefore IFNγR2 anti-apoptotic function is independent of the well characterized JAK/STAT signaling. IFNγR2296-337 rescued human cells from apoptosis induced by overexpression of Bax, but not Bak. Overexpression of IFNγR2 (wild type and IFNγR2296-337) rescued cells from apoptosis induced by Etoposide and Staurosporine that are known to activate Bax-mediated cell death. Interestingly, IFNγR2 inhibited apoptosis induced by the BH3 only protein Bim-EL, suggesting that IFNγR2 inhibits Bax activation by BH3 protein. The binding of Bax and the C-terminus of IFNγR2 was confirmed by co-immunoprecipitation using cell lysate and binding experiments using purified recombinant proteins. Interestingly, recombinant Bcl-2 protein competed with IFNγR2 to bind Bax in cell lysates, suggesting that IFNγR2 and Bcl-2 share a similar mechanism to bind Bax. We found that the C-terminal fragment (cytoplasmic domain) of IFNγR2 is expressed in the cytosol of transformed, and in some human prostate cancer cell lines (PC3, and DAMI cells). Our preliminary study suggests that the cytoplasmic IFNγR2 C-terminal fragment is produced by proteolytic cleavage of IFNγR2 at the plasma membrane. The cytoplasmic IFNγR2 fragment may have a certain role to confer cancer cells resistant to apoptotic stress. The discovery of anti-Bax activity of the cytoplasmic domain of INFγR2 may shed new light on the mechanism of how cell survival is controlled by IFNγ and Bax. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1023.
A Familial Syndrome of Hypocalcemia with Hypercalciuria Due to Mutations in the Calcium-Sensing Receptor
Authors: Simon H.S. Pearce, Catherine Williamson, Olga Kifor, Mei Bai, Malcolm G. Coulthard, Michael Davies, Nicholas Lewis-Barned, David McCredie, Harley Powell, Pat Kendall-Taylor, Edward M. Brown, Rajesh V. Thakker
Journal: New England Journal of Medicine (1996)

The calcium-sensing receptor regulates the secretion of parathyroid hormone in response to changes in extracellular calcium concentrations, and mutations that result in a loss of function of the receptor are associated with familial hypocalciuric hypercalcemia. Mutations involving a gain of function have been associated with hypocalcemia in two kindreds. We examined the possibility that the latter type of mutation may result in a phenotype of familial hypocalcemia with hypercalciuria.
Case 31-2015
Authors: Panos M. Fidias, Aidan A. Long, Florian J. Fintelmann, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2015)

A 29-year-old man presented with diarrhea of 1 month's duration. He had received a diagnosis of thymoma 5 years earlier; diarrhea developed during treatment with an investigational drug and worsened despite discontinuation of the drug. Diagnostic procedures were performed.
THU0375 Amyloidosis: Something to Keep in Mind When Dealing with Patients on Biologic Treatment and Persistent Inflamations
Authors: F.C. Ileana, D. Patricia, A. Melania, S. Bogdan, G. Carmen, R. Simona
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis (RA). The persistence of inflammatory syndrome in patients with RA treated with anti-TNFα agents could be caused by many factors; amyloidosis may be one of them. <h3>Objectives</h3> We evaluated the frequency of secondary amyloidosis in patients with RA treated with anti-TNFα agents. <h3>Methods</h3> This single-center longitudinal study included 144 RA patients with anti-TNFα treatment. The study was conducted between June 2011 and October 2013. All patients were clinically and biologically evaluated. In some patients with ESR&gt;20mm/h we performed biopsy of abdominal fat to appreciate the existence of amyloidosis using special stain. Infections, malignancies and other sign of active disease were excluded in the study group. <h3>Results</h3> The fat biopsy was performed at 34 of RA patients. AA amyloidosis was identified at 11 patients (32.3%). Proteinuria was found in 4/11 (36.36%), none of them had renal insufficiency. The mean age in RA patients with AA amyloidosis was 58.8 years and disease duration was 14.06 years. Most of the patients (63.63%) with AA + were treated with infliximab. All of the patients were treated with DMARDs, methotrexat alone or in combination was used in 86% of patients AA+. In the group with AA+, colchicine was included in the therapy. We found statistically significant differences between the 2 groups (with or without amyloidosis) and they were recorded as CRP value (p&lt;0.02), VASpatient (p&lt;0.02) and ESR value (p&lt;0.04). <h3>Conclusions</h3> Secondary amyloidosis could be considered as factor responsible for the persistent inflammatory syndrome in patients with RA treated with anti-TNFα agents. Administration of colchicine in the group of patients with amyloidosis has improved their clinical status. Proteinuria was found in a small number of patients. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5918