tbuckley/cabot-search huggingface dataset:
PTH-130 Facilitation of Blood Donation amongst Haemochromatosis Patients: a UK Pilot
Authors: B Marrow, J Clarkson, C Chapman, S Masson
Journal: Gut (2013)

<h3>Introduction</h3> The standard medical therapy for haemochromatosis is removal of iron by regular phlebotomy<sup>1</sup>. Current EASL guidelines recommend that blood taken from uncomplicated haemochromatosis patients should be made available through national blood transfusion services<sup>1</sup>. However, this practise varies widely across Europe and is often hindered by administrative difficulties. Here, we aim to describe a pilot facilitating the process of blood donation amongst haemochromatosis patients in the UK. <h3>Methods</h3> A dedicated haemochromatosis clinic was established. At this clinic, patients with uncomplicated haemochromatosis interested in becoming blood donors were offered a simple information leaflet. One page provided information about eligibility; the second formed a self-referral application to be countersigned by the responsible physician. Upon receipt of referral, patients were contacted by members of the local Blood Service. Data on clinical characteristics including genotype, alcohol consumption, BMI, co-morbidities and previous blood donation was collected. <h3>Results</h3> Patients attending (n = 101) since the introduction of this service (Aug 2011) are included. The median age was 57 (22–82) and the majority 70 (69%) were male. Most (89%) were C282Y homozygotes; the remainder were H63D/C282Y compound heterozygotes. The majority (91%) had uncomplicated haemochromatosis; however many were ineligible for blood donation by virtue of age (20%), co-morbidity (17%), or induction therapy (15%). Prior to the introduction of this service, there were 3 regular blood donors. Since the introduction of this service, of those potentially eligible (n = 40) 23 (58%) showed interest in blood donation, 20 (50%) applied, 17 (43%) are eligible and have registered. In total, there are now 13 regular blood donors, including 10 new who have donated 27 pints of blood (median 2[1–6]). <h3>Conclusion</h3> There is an interest and willingness to donate blood through NHS Blood and Transplant amongst uncomplicated haemochromatosis patients undergoing therapeutic phlebotomy. Since the introduction of this facilitation process, we have significantly increased the number of regular blood donors amongst this cohort. If this process was undertaken nationally or more widely across Europe, this could have a significant impact on the availability of this precious resource. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> European Association for the Study of the Liver. EASL Clinical Practice Guidelines for HFE Hemochromatosis. J Hepatol (2010) 53:3–22
COST COMPARISON ACROSS HEART FAILURE PATIENTS WITH REDUCED AND PRESERVED EJECTION FRACTIONS: ANALYSES OF INPATIENT DECOMPENSATED HEART FAILURE ADMISSIONS
Authors: Natalia Olchanski, Amanda Vest, Pallavi Rane, Joshua Cohen, Peter Neumann, Adrian Kielhorn, Harshali Patel, Juan Maya, David DeNofrio
Journal: Journal of the American College of Cardiology (2016)
SP0204 Barriers and Opportunities for Patient Organisations in Economically Disadvantaged European Countries
Authors: A. Koutsogianni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Southern European countries have been seriously attacked the last years by an economic crisis which has affected the life of their citizens in many ways. Among others financial crisis has seriously affected many aspects of life including the Health sector and has led to the severe degradation of health care system in these countries. Therefore issues like access to care, early diagnosis, appropriate rehabilitation and social support for people with rheumatic diseases are not considered as granted anymore and the access to these services is an issue for Southern European countries. <h3>Methods</h3> Validated surveys measure the effects and implications of crisis on the quality of life of people with RMSDs. <h3>Conclusions</h3> The current crisis despite the gloomy prospects maybe a starting point for reviewing practices of the past in health care system and a more equitable distribution of costs to the benefit of citizens. Equal attention should also be paid to the cooperation of all stakeholders inviting people with RMSDs to be involved in the decision making process related to health care services and in the design of a fair and more inclusive health care system. <h3>Disclosure of Interest</h3> None Declared
Oral chlorhexidine and microbial contamination during gastroscopy. Implications for transgastric surgery. A randomised trial.
Authors: A Meller Donatsky, BJ Holzknecht, M Arpi, P Vilmann, S Meisner, L Nannestad Jørgensen, J Rosenberg
Journal: Endoscopy (2012)

Background: A concern associated with transgastric natural orifice transluminal endoscopic surgery (TG-NOTES) is the risk of contamination and intraabdominal infection with microbes introduced from the access route. An effective decontamination regimen is needed before the technique can be implemented in routine clinical practice. The aim of this study was to evaluate the effect of oral decontamination with chlorhexidine on? microbial contamination of the endoscope during a gastroscopy.
P4-14-04: Tolerance of Docetaxel: Is Obesity a Risk Factor for Toxicity? A Pilot Study.
Authors: D Parent, A Rallet, N Jovenin, G Yazbek, H Cure, J-B Rey
Journal: Cancer Research (2011)

Abstract Background Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation of docetaxel and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI). Methods A retrospective study was carried out. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome, mucositis, and neuropathy were assessed in both groups. Patients receiving concomitant therapies leading to similar adverse events were excluded (e.g. cyclophosphamide, 5-FU, …). The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test. Results Among the 49 patients, 18 (37%) presented with a BMI &amp;gt; 30 kg/m2. The median age was 53 years-old in the group BMI &amp;gt; 30 and 55 years-old in the group BMI &amp;lt; 30 (p = 0.9383). The median dose intensity delivered was 91% (74-100%) in the group BMI&amp;gt; 30 and 97.7% (75-100%) in the group BMI &amp;lt; 30 (p = 0.06). The median value for albumin was 75 g/L (59-86 g/L) in the BMI &amp;gt; 30 and 71 g/L (56-79 g/L) in the BMI &amp;lt; 30 (p = 0.122). Toxicity in both groups was as follows: No neuropathy was observed in both groups. Conclusions Obese patients (BMI &amp;gt; 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study as patients had normal albumin levels. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI &amp;lt; 30 seems to demonstrate greater susceptibility to the molecule for these patients. Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-04.
Magnetically steerable gastric capsule endoscopy is equivalent to flexible endoscopy in the detection of markers in an excised porcine stomach model: results of a randomized trial
Authors: Melissa Hale, Imdadur Rahman, Kaye Drew, Reena Sidhu, Stuart Riley, Praful Patel, Mark McAlindon
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Capsule endoscopy is well tolerated but control of its movement is needed in order to visualize the whole gastric surface. Technological developments have produced an external magnet to allow manipulation of the capsule within the gastric cavity. The aim of this study was to compare magnetically steerable gastric capsule endoscopy (MSGCE) with flexible endoscopy for the detection of beads in a porcine stomach. <b>Materials and methods:</b> Beads were sewn onto the mucosal surface of 12 ex vivo porcine stomachs. Each model was examined by flexible endoscopy and MSGCE by two blinded investigators. MSGCE was performed according to a protocol using positional changes and magnetic steering. Outcome measures were number and location of beads identified, and duration of procedure. <b>Results:</b> Flexible endoscopy identified 79 /90 beads (88 %), and MSGCE identified 80 /90 (89 %). The difference in sensitivities was 1.11 (95 % confidence interval 0.06 – 28.26). Thus, MSGCE was noninferior to flexible endoscopy. Mean examination times for flexible endoscopy and MSGCE were 3.34 minutes and 9.90 minutes, respectively. <b>Conclusion:</b> MSGCE was equivalent to conventional flexible endoscopy in the detection of beads in a porcine stomach model.
AB0752 Mediastinal fibrosis combined with behÇet’s disease: Five case reports
Authors: I. Gharsallah, S. Boussaid, L. Metoui, F. Ajili, N. Ben Abdelhafidh, B. Louzir, L. Bassem, S. Othmeni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Intrathoracic manifestations other then vascular aneurysm and thrombosis are rare in the course of Behçet's disease. Mediastinal fibrosis is also unusual. <h3>Methods</h3> Three cases of Behçet's disease with initial mediastinal fibrosis are reported. Diagnosis means, pathogenic mechanisms and therapeutic modalities are also more precisely defined. <h3>Results</h3> Three male patients (21, 25 and 27 years of age, respectively) were hospitalized for progressive vena cava superior syndrome accompanied by mediastinal fibrosis demonstrated by MRI and/or CT scan which both showed infiltration of the mediastinal fat. Multiple calcifications were also present in one patient. Histology was performed in one case. Thrombosis of the vena cava superior and innominata veins was associated with fibrosis in all three cases. Thrombosis of venae subclavia and left jugularis was also present in one case. Other manifestations leading to the diagnosis of Behçet's disease were demonstrated by the patient's history and, in one case, occurred on the fourth day of hospitalization. After initiation of a treatment including corticoids, anticoagulants and colchicine, the outcome was favorable in two cases. The third patient died. <h3>Conclusions</h3> Mediastinal fibrosis combined with Behçet's disease has rarely been described. However, it should be included in manifestations of the disease. The causative process which might be vasculitis has to be demonstrated. <h3>Disclosure of Interest</h3> None Declared
Abstract 2082: The microRNA-101 regulates the expression of EP4 receptor in colon cancers
Authors: Anupama Chandramouli, Lenka Stankova, Jennifer M. Davenport, Renee Shanas, Jenae M. Owens, Bonnie J. LaFleur, Achyut K. Bhattacharyya, Mark A. Nelson
Journal: Cancer Research (2010)

Abstract Colorectal cancer (CRC) is one of the most devastating cancers in the United States and is characterized by the accumulation of prostaglandin PGE2. PGE2 exerts its biological function via four transmembrane G protein coupled receptors (EP1-4), among which the prostanoid EP4 receptor is the most relevant. However, its expression in human CRC specimens has not been fully understood. Therefore, we wanted to clarify the expression of EP4 receptor in human tissue specimens. We collected a total of 40 CRC tissue specimens representing different stages of disease and performed immunohistochemistry (IHC) analysis. The specimens were graded for intensity and extent of staining of the EP4 receptor. Here we show that cancer tissues (n = 15) expressed significantly higher EP4 receptor staining as compared to normal colonic (n = 16) and adenoma (n = 9) tissues. We also performed western blot analysis on paired cancer and normal tissue specimens from this cohort and confirmed that the EP4 protein levels were elevated in cancer as compared to normal tissues whereas there was no difference in the expression of EP2 receptor. By contrast, the mRNA expression of the EP4 receptor gene (PTGER4) was down-regulated in these tumors as compared to paired normal tissue. We postulated that the increased EP4 receptor protein levels observed in tumors occurs by post transcriptional mechanisms. Therefore, to address this issue, we performed in silico analysis of the 3′UTR of PTGER4 gene for microRNA binding sites. We identified a consensus microRNA-101 (miR-101) seed sequence within the 3′UTR, proximal to the coding region, of the PTGER4 gene. Interestingly we observed a correlation between loss of miR-101 levels and increase in EP4 receptor protein levels in human CRC tissue specimens as compared to paired normal colonic tissue, by RT-PCR analysis. In order to directly assess this correlation, we ectopically expressed mir-101 plasmid in colon cancer cells and demonstrated that it could suppress endogenous levels of EP4 receptor protein. Together, these findings show that EP4 receptor is significantly elevated in human CRC and suggest, for the first time, that miR-101 may negatively regulate the expression of EP4 receptor by post-transcriptional mechanisms. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2082.
SP0183 Multifactorial Pathogenesis of Osteoporosis in Sle
Authors: I.E. Bultink
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune disease that usually affects women during the childbearing ages. Because survival of SLE patients has improved dramatically over the last decades, attention is now more focused on complications of the disease and/or its treatment, that contribute to increased morbidity and mortality. Osteoporosis and fractures are important disease complications in patients with SLE. In recent studies, a high frequency of low bone mineral density and both peripheral and vertebral fractures has been demonstrated in SLE patients. The incidence of symptomatic fractures is increased 1.2 to 4.7-fold in patients with SLE [1]. In addition, prevalent vertebral fractures are present in 20-26% of these relatively young patients [2]. The etiology of bone loss in SLE is supposed to be multifactorial, involving traditional osteoporosis risk factors, inflammation, metabolic factors, serological factors, hormonal factors, and medication-induced adverse effects [2]. A recent 6-year follow-up study in Dutch SLE patients revealed, that low 25-hydroxyvitamin D serum levels at baseline, low body mass index and baseline use of antimalarial drugs were associated with bone loss [3]. In addition, a dose-dependent relationship between glucocorticoid use and spine bone loss was demonstrated. The results of this study have implications for daily clinical practice, because low 25-hydroxyvitamin D levels are highly frequent in SLE patients, antimalarials are “anchor drugs” for the treatment of SLE, and the majority of SLE patients is on chronic glucocorticoid treatment. Importantly, several risk factors associated with osteoporosis in SLE are modifiable by lifestyle measures or medication. <h3>References</h3> Bultink IEM et al. Osteoporos Int 2013 Dec 3 [Epub ahead of print] Bultink IE. Arthritis Care Res (Hoboken) 2012;64:2-8 Jacobs J et al. Osteoporos Int 2013;24:1827-33 <h3>Disclosure of Interest</h3> I. Bultink Consultant for: Servier Laboratories; Merck &amp; Co <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6115
IS RIVAROXABAN ASSOCIATED WITH SHORTER INPATIENT STAYS AND LOWER HOSPITAL COSTS VERSUS HEPARIN/WARFARIN IN LOW-RISK PULMONARY EMBOLISM PATIENTS?
Authors: Craig I. Coleman, Erin Weeda, W. Frank Peacock, Gregory Fermann, Concetta Crivera, Jeff Schein, Christine Kohn
Journal: Journal of the American College of Cardiology (2016)
Abstract SY29-03: Regulation and function of the Hippo-YAP pathway in organ size, tumorigenesis, and metastasis
Authors: Kun-Liang Liang Guan
Journal: Cancer Research (2012)

Abstract Regulation and function of the Hippo-YAP pathway in organ size, tumorigenesis and metastasis Kun-Liang Guan, Department of Pharmacology and Moores Cancer Center, University of California at San Diego, USA The Yes-associated protein (YAP) is a transcription co-activator that plays a critical role in organ size control by promoting cell proliferation and inhibiting apoptosis. YAP is a human oncogene amplified or overexpressed in some human cancers. YAP represents the major downstream of the Hippo tumor suppressor pathway. The Lats tumor suppressor kinase in the Hippo pathway phosphorylates and inactivates YAP. Recent studies have demonstrated regulation of the Hippo pathway by cell-cell contact, cell adhesion, and mechanical stress. Cell attachment to extracellular matrix (ECM) is crucial to cell physiology such as cell polarity, cell motility, and cell proliferation. In normal cells, loss of attachment to ECM induces a specific type of apoptosis, termed anoikis. In metastatic cancer cells, resistance to anoikis allows their survival in circulation and dispersion to distant anatomic sites leading to tumor metastasis. We have observed that cell detachment activates the Hippo pathway kinases Lats1/2 and leads to YAP phosphorylation and inhibition. The detachment-induced YAP inactivation is required for anoikis. Furthermore, actin and microtubule organization mediates Lats1/2 activation in response to cell detachment. Moreover, Lats2 downregulation is tightly associated with metastatic prostate cancer, indicating a role of the Hippo pathway in tumor metastasis. Our findings provide an important connection from cell attachment and cytoskeleton organization to cell proliferation, anoikis, and cancer metastasis through the Hippo pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY29-03. doi:1538-7445.AM2012-SY29-03
Complete pathological response according to hormonal status, c-erbB2 and P53 in two neoadjuvant treatments in locally advanced breast cancers.
Authors: S Giacchetti, J Lehmann-Che, A De Roquancourt, C Cuvier, E Turpin, M Marty, P Bertheau, H de Thé, M Espie
Journal: Cancer Research (2009)

Abstract Abstract #5107 Background: We previously showed that the p53 mutation is the major factor for response to dose-dense epirubicin-cyclophosphamide regimen (PLoS Med. 2007; Lancet 2002). Some years ago Taxanes became a standart treatment in neoadjuvant setting. We study two regimens of neoadjuvant anthracycline-based chemotherapy combined with high dose cyclophosphamide (C), or with Taxotere in locally advanced breast cancers (LABC) with respect to pathologic complete response (pCR).&amp;#x2028; Materials and methods: Between 1990 and 2003, 219 patients (pts) with LABC and/or inflammatory breast cancers (IBC) from one institution received 6 cycles (c) of dose dense C (1.2g/m2 d1)-epirubicin (E) (75mg/m2d1) q2w (SIM regimen). From 2003 to 2008, 132 pts with LABC and/or IBC from the same institution received 4 c of E (75mg/m2 d1) C(750mg/m2 d1) q3w followed by 4c of docetaxel 100mg/m2 d1q3w (ECT regimen). Surgery was done after chemotherapy and pCR was defined as no residual invasive tumour in breast and lymph nodes.&amp;#x2028; Results: 139/219 SIM pts (63.4 %) and 96/132 ECT (72.7 %) pts had frozen biopsies, surgery after chemotherapy, ER, c-erbB2 determination (IHC and /or RT-PCR) and p53 done by yeast functional complementation assay (FASAY) and were thus included in our study.&amp;#x2028; &amp;#x2028; &amp;#x2028; &amp;#x2028; Conclusion:The high performance of the FASAY assay allows the demonstration of p53 role in the prediction of histological response in the ECT, as previously for the SIM regimen. In p53 mutant tumors, especially in ER- and ER- c-erbB2 negative tumors, high dose cyclophosphamide combined with E seems significantly better than Taxane regimen and needs to be studied prospectively. Future trials should determine the best regimen for p53 WT tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5107.
Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD
Authors: Ian H. de Boer, Leila Zelnick, Maryam Afkarian, Ernest Ayers, Laura Curtin, Jonathan Himmelfarb, T. Alp Ikizler, Steven E. Kahn, Bryan Kestenbaum, Kristina Utzschneider
Journal: Journal of the American Society of Nephrology (2016)

Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m 2 ) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P &lt;0.01). Insulin clearance correlated with insulin sensitivity ( r =0.72; P &lt;0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P &lt;0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, −0.7; 95% confidence interval, −1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, −85; 95% confidence interval, −160 to −10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.