tbuckley/cabot-search huggingface dataset:
AB0482 A Prospective Study in Premenopausal Women with Systemic Lupus Erythematosus Supplemented with Two Different Regimens of Vitamin D: Efficacy and Safety at Twelve Months of Follow Up
Authors: F. Dall'ara, L. Andreoli, S. Piantoni, N. Piva, A. Tincani
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) patients (pts) are at risk for low vitamin D (VitD) levels because of lack of sun exposure. The current strategies of VitD supplementation do not seem to be sufficient not only for the prophylaxis of osteoporosis, but perhaps also to bring out the immunomodulatory effects of VitD that were highlighted by some <i>in vitro</i> studies. Few prospective studies are available on the effects of VitD supplementation SLE pts. <h3>Objectives</h3> To evaluate at 12 months of follow-up (T12) the efficacy, safety and the effects on SLE disease activity of an oral Cholecalcipherol supplementation given with 2 different regimens in a cohort of SLE pts. <h3>Methods</h3> 34 premenopausal SLE women were enrolled. A group of 18 pts (group S) were given “standard” regimen of supplementation (Cholecalcipherol 25.000UI once/month).The other 16 pts (group I) were given an “intensive” regimen (Cholecalcipherol 300.000UI bolus, then 50.000UI once/month). The circulating levels of 25-OH VitD were dosed every 3 months with a chemiluminescence assay kindly performed by the manufacturer (DiaSorin S.p.A.,Italy). <h3>Results</h3> At baseline (T0) there was no significant difference in VitD levels in the 2 groups. After 3, 6, 9 and 12 months “group I” showed significantly higher VitD levels (median at T12: 32.0vs24.8 p=0,04). There were no significant differences upon season of enrollment. At T0 there was no difference in the proportion of sufficient pts (&gt;30 ng/ml) between groups (S:50%, I:56%), while at T12 sufficient pts were 28% in S and 75% in I (p=0.02). No significant variations in the levels of calcium, phosphorus and PTH were observed. No cases of PTH suppression. There were 3 cases of transitory mild hypercalciuria (2 in I, 1 in S). The pts had clinically quiescent disease (median SLEDAI 2 in S, 4 in I), but serologically active disease (positive anti-DNA and/or complement consumption in nearly 50% of the pts). No statistically significant variation in the titers of anti ds-DNA and in the levels of C3, C4, CH50 was observed at T12 in both groups. <h3>Conclusions</h3> Intensive supplementation with VitD has a safe profile as the standard regimen but it is able to induce sufficient levels in a larger number of pts. No particular effects on serological SLE parameters was noted, probably due to the stable remission state of the pts. More data will come from the second year of the study in which patients will switch to the other group of supplementation. <h3>References</h3> Cutolo M. et al.Vitamin D endocrine system and the immune response in rheumatic diseases. Vitam Horm.2011;86:327-51 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1825
Abstract 4861: Triple-negative breast cancers establish a systemic environment that drives malignant progression of otherwise indolent disseminated tumors via EGF and IGF
Authors: Zafira Castano, Timothy Marsh, Ramya Tadipatri, Hanna Kuznetsov, Fatima Al-Sahour, Mahnaz Paktinaz, Sandra S. McAllister
Journal: Cancer Research (2012)

Abstract Breast cancer recurrence rates are variable, suggesting that tumor cells disseminate from primary sites at an early stage but remain indolent for extended periods of time before progressing to symptomatic disease. Little is known about mechanisms that cause otherwise dormant tumors to become overt cancers, making it difficult to predict which breast cancer patients are likely to relapse and therefore likely to benefit from preemptive therapy. To address these challenges, we use a human breast tumor xenograft model in which aggressively growing breast cancers (“instigators”) promote the growth of otherwise indolent breast cancers (“responders”) that have disseminated to distant sites. These pro-tumorigenic systemic effects are established by instigating tumors, in large part, through their mobilization of bone marrow cells (BMCs) that are subsequently recruited to the responding breast tumors, where they create a tumor-supportive microenvironment. We report here that the mechanisms of establishing tumor-supportive systemic environments depend upon the molecular-histopathological subtype of the instigating breast cancer. Instigating cell lines and primary tumor surgical specimens, derived from patients with either triple-negative breast cancer (TNBC) or luminal breast cancer (LBC), established different subtype-specific systemic environments that impinged in different ways upon the malignant features of responding tumor cells and their microenvironment. In particular, the TNBC-induced responding tumor microenvironment was characterized by elevated levels of epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF1). EGF and IGF acted on responding tumor cells in a paracrine manner to induce expression of factors that play a role in tumor-initiation, embryonic stem cell maintenance, and epithelial-mesenchymal transition. Pharmacological administration of EGFR and IGF1R inhibitors prevented responding tumors from acquiring the TNBC-induced malignant features, thus maintaining them in an indolent state. Our results demonstrate that microenvironmental composition, as well as tumor cell phenotypic plasticity and molecular properties, are strongly influenced by the host systemic macroenvironment. Our work suggests that the crosstalk between disseminated tumor cells and their microenvironment can be exploited therapeutically to improve outcomes for patients with TNBC. 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 4861. doi:1538-7445.AM2012-4861
Some Emotional Aspects of the Treatment of Diabetes Mellitus and the Role of the Physician
Authors: Samuel Stearns
Journal: New England Journal of Medicine (1953)

DURING the past decade it has become increasingly evident that although the over-all incidence of degenerative vascular disease increases with the duration of diabetes, patients under good control show significantly fewer complications than those who have been poorly controlled.1 2 3 4 Fully 70 per cent of the members of the American Diabetes Association subscribe to the concept of normoglycemia as a major objective of treatment, and another 23 per cent to the goal of aglycosuria.5 These objectives are not achieved in the majority of patients. Although statistics are difficult to obtain, reports from two large clinics indicate that only 13.5 per cent . . .
A7.9 Repeat renal biopsies help to tailor immunosuppression in lupus nephritis
Authors: A Pakozdi, R Rajakariar, M Sheaff, D Pyne
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Lupus nephritis (LN) is the major cause of morbidity and mortality in patients with systemic lupus erythematosus. The role of repeat kidney biopsies (RB) to guide treatment or to predict outcome and prognosis has been controversial. In this retrospective study we focused on histological characteristics of RBs and aimed to identify any clinical variables useful to predict histological changes. <h3>Methods</h3> In a large single-centre cohort of 257 patients from 1988–2014 with biopsy proven LN, 58 (23%) had two or more biopsies (a total of 68 RBs). LN classes based on glomerular pathology were defined according to the ISN/RPS classification. Clinical and laboratory data were obtained from electronic records of patients. <h3>Results</h3> The median time between initial and RB was 33 months [IQR, 15–84]. Caucasians (n = 7) had a lower RB rate of 14% compared to blacks (n = 36, 32%; p = 0.010). Indication for RB was worsening proteinuria (n = 38, 71%; of which 23 had associated rising creatinine, 61%), rise in serum creatinine alone (n = 6, 11%) and lack of treatment response (n = 9, 17%) defined as &lt;50% reduction in proteinuria. At time of RB, 25 (78%) had raised dsDNA, 33 (73%) had low complements. LN class transition occurred in 33 (49%), most commonly from class II or V to III or IV (n = 11, 36%). Swith from a proliferative to a pure non-proliferative class was rare (n = 3, 4.4%). 5 RB (7%) showed inactive lesions either due to FSGS or advanced sclerosing LN. 42 (65%) had a change in their treatment regime. Immunosuppression was more likely to be escalated in case of a class switch (93%, p = 0.000). The histological transition could not be predicted by any serological or biochemical variables. <h3>Conclusion</h3> Over a 1/3 of our LN patients showed histological transition to a more aggressive class, based on which the majority (93%) had treatment escalation. Histological transition could not be predicted by clinical values. Hence, we conclude that RB remains an important tool to guide management of selected patients with LN, in particular those with initial class II or V who flare.
EFFICACY AND SAFETY OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITORS TREATMENT IN FAMILIAL HYPERCHOLESTEROLEMIA: A COMPREHENSIVE META-ANALYSIS OF ALL RANDOMIZED CLINICAL TRIALS
Authors: Armaghan Y. Soomro, Mark Ediger, Bhavi Pandya, Muhammad Rehan Raza, Zaka Khan, Mustafain Meghani, Thomas Vazzana, James Lafferty
Journal: Journal of the American College of Cardiology (2016)
Abstract 1258: The frequency of CD11c+ cells within the gastric cancer tissue is associated with favorable prognosis.
Authors: Jingting Jiang, Changping Wu, Binfeng Lu
Journal: Cancer Research (2013)

Abstract Aim: CD11c is a marker for dendritic cells which help initiating adaptive antitumor immunity. The study was designed to investigate correlation between the frequency of CD11c+ cells in the gastric cancer tissue and the clinical and pathological parameters of gastric cancer patients. Methods: CD11c expression in gastric cancer tissues was examined by immunohistochemistry. Surface CD11c expression on the leukocytes within cancer tissues was examined by flow cytometry. Results: The number of CD11c+ cells was higher in gastric cancer tissues than that in gastritis or gastric polyps tissues. The number of CD11c+ cells in tumor specimens from the early-stage gastric cancer was significantly higher than that in specimens from the late-stage gastric cancer (t=2.77,P=0.0064). Flow cytometry found that CD11c surface expression was stronger in specimens from the early stages than those from the late stages of gastric cancer. The Univariate analysis revealed that the frequency of intratumoral CD11c+ cells showed association with gender and tumor location, and was reversely correlated with tumor size, depth of infiltration, nodal metastasis, tumor histological grade and cancer stages. The median survival time (MST) for the subgroups of patients with stronger and weaker CD11c expression were 67.0 months (95%CI, 39.0-112.0 months) and 29.0 months (95%CI, 21.0-39.0 months), respectively. And MSTs were significantly different between the CD11c higher and lower subgroups (χ2=11.6425,P=0.0006). Among patients who suffered from late-stage diseases, those with higher numbers of intratumoral CD11c cells had a significantly lower risk of death than those with lower numbers of CD11c cells (χ2=8.549,P=0.0035), and the lowered risk of death was statistically significant after adjusting gender, age, tumor size and infiltrating depth (RR=0.52,95%CI=0.29-0.94). Conclusions: The number of CD11c+ cells within gastric cancer tissue is a favorable prognostic marker for gastric cancer. Our study suggests gradual elimination of dendritic cells is characteristic of gastric cancer progression. Citation Format: Jingting Jiang, Changping Wu, Binfeng Lu. The frequency of CD11c+ cells within the gastric cancer tissue is associated with favorable prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1258. doi:10.1158/1538-7445.AM2013-1258 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4709: EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells <i>in vitro</i>.
Authors: Takumi Kumai, Yasuaki Harabuchi, Hiroya Kobayashi
Journal: Cancer Research (2013)

Abstract Despite immunotherapy is a promising approach for cancer treatment, there are many obstacles remain to be overcome. The characteristics of tumor evasion of immune surveillance are produced by decreased expression of immune molecules and secretion of immunoregulatory cytokines. To break these tumor microenvironment which act as suppressor of antitumor immunology, we evaluated the value of EGFR inhibitors as immune-modulators. Following two days EGFR tyrosine kinase inhibitor treatment, expression of HLA-DR molecule of head and neck squamous cancer (HNSCC) cell lines were increased, meanwhile EGFR blocking antibody treatment augmented HLA-DR expression. Furthermore, EGFR inhibitors decreased spontaneous secretion of IL-8 and TGF-β from HNSCC cell lines. To confirm the immune supporting activity of EGFR inhibitors, tumor antigen specific CD4 helper T lymphocyte (HTL) responses to EGFR-expressing tumor were investigated. We identified novel EGFR HTL epitope using MHC class II binding algorithms. The candidate EGFR peptide elicited HTL responses against EGFR-expressing HNSCC in vitro. The EGFR peptide shares high homology to HER2, HER-3 and c-Met, so that these were able to stimulate EGFR peptide reactive HTLs responses in a HLA-DR restricted manner indicating that the EGFR peptide serves a universal tumor-associated peptide in HER family and c-Met. Finally, we evaluated EGFR reactive HTL responses against HNSCC cell lines treated with EGFR inhibitors. As a result, EGFR inhibitors drastically increased HTL IFN-γ production and cytotoxic response. Since HER family and c-MET have been considered as targets of alternative pathway of EGFR inhibition, therapeutic strategy combining EGFR inhibitors with novel HTL epitope identified in this study might be attractive option for antitumor immunotherapy. Citation Format: Takumi Kumai, Yasuaki Harabuchi, Hiroya Kobayashi. EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4709. doi:10.1158/1538-7445.AM2013-4709
Additional Analysis of WJTOG0105 Comparing Second and Third-Generation Regimens with TRT in Unresectable Stage III NSCLC
Authors: H. Kaneda, M. Satouchi, Y. Chiba, N. Yamamoto, Y. Nishimura, Y. Fujisaka, S. Kudoh, T. Hida, S. Atagi, K. Nakagawa
Journal: Annals of Oncology (2013)
ESTUDIO RETROSPECTIVO Y COMPARATIVO DE LA LIGADURA ENDOSCÓPICA VS APC EN EL TRATAMIENTO DE LAS ECTASIAS VASCULARES ANTRALES. EXPERIENCIA EN UN HOSPITAL DE TERCER NIVEL
Authors: A Rincon, JM Alcivar, R Leon, S Sobrino, J Caballero, T Lopez, JM Bozada
Journal: Endoscopy (2014)

Introducción: Las ectasias vasculares antrales (GAVE) son un causa infrecuente de sangrado gastrointestinal. El tratamiento endoscópico habitual consiste en coagulación con argón plasma (APC). Recientemente se han publicado trabajos sobre la ligadura endoscópica con bandas (LEB) como alternativa al tratamiento convencional.
FRI0430 Validation of Preliminary Algorithm for Differential Diagnosis of Thrombocytopenia in Patients with Systemic Lupus Erythematosus
Authors: M. Kuwana, Y. Okazaki, H. Hanaoka, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Prehospital airway management for adult trauma patients remains controversial. We sought to review the frequency that paramedic non-drug assisted intubation or attempted intubation is performed for trauma patients in Ontario, Canada, and determine its association with mortality. <h3>Methods</h3> We conducted a retrospective cohort study using the Ontario Trauma Registry9s Comprehensive Data Set for 2002–2009. Eligible patients were greater than 16 years of age, had an initial Glasgow Coma Score of less than 9 and were cared for by ground-based non-critical care paramedics. The primary outcome was mortality. Outcomes were compared between patients undergoing prehospital intubation versus basic airway management. Logistic regression analyses were used to quantify the association between prehospital intubation and mortality. <h3>Results</h3> Of the 2229 patients included in the analysis, 671 (30.1%) underwent prehospital intubation. Annual rates of prehospital intubation declined from 33.7% to 14.0% (p<sub>trend</sub>&lt;0.0001) over the study period. Unadjusted death rates were 66.0% versus 34.8% in the intubation and basic airway groups, respectively (p&lt;0.0001). Intubation in the prehospital setting was associated with a heightened risk of mortality (adjusted OR 2.8, 95% CI 1.1 to 7.6). <h3>Conclusions</h3> Prehospital non-drug assisted intubation for trauma is being performed less frequently in Ontario, Canada. Within our study population, paramedic non-drug assisted intubation or attempted intubation was associated with a heightened risk of mortality.
Abstract 266: The interaction between MUC1 and erbB3 promotes erbB3 signaling and cell survival
Authors: Hsin-Yuan Su, Joyce A. Schroeder
Journal: Cancer Research (2010)

Abstract MUC1 is an oncogenic glycoprotein overexpressed in more than 90% of metastatic breast cancers. The expression of MUC1 has been linked to promote cell transformation by interacting with a number of known oncogenes, including the erbB receptors. When coexpressed, MUC1 strongly promotes erbB1-dependent breast cancer in the WAP-TGFalpha transgenic mouse model and inhibits ligand-mediated ubiquitination and degradation of erbB1. ErbB1 belongs to a receptor tyrosine kinase superfamily, including erbB1/EGFR, erbB2/neu, erbB3 and erbB4, all of which have been implicated in cancer progression. ErbB3 is one of the dimerization partners for erbB1 implicated in invasive breast cancer and may be responsible for the resistance to erbB1-directed therapy. In the present study, we set out to understand the effect of interaction between MUC1 and erbB3 on erbB3 stability and signaling. We show that the expression of MUC1 inhibits the degradation of neuregulin1beta (NRG1beta)-stimulated erbB3 and prolongs NRG1beta-dependent dpERK and pAKT activation in BT20 breast cancer cell line. By cell proliferation assay, we demonstrate that MUC1 promotes NRG1beta-dependent survival signals in BT20 cells. ErbB1 is found to complex with erbB3 only in the presence of MUC1 and NRG1beta stimulation. In addition, MUC1 forms a complex with erbB1 and erbB3 only in the presence of NRG1beta stimulation. In summary, the interaction between MUC1 and erbB3 results in inhibition of ligand-induced degradation of erbB3 receptor and prolongation of erbB3 downstream signaling, especially ERK and AKT activation, which leads to cell survival. The possible mechanism is through the formation of functional erbB1/erbB3 heterodimers facilitated by MUC1 expression. 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 266.
PTU-094 Immunisation of IBD patients on biologic therapy: an English district hospital experience: Abstract PTU-094 Table 1
Authors: J Kayani, A Piotrowicz
Journal: Gut (2012)

<h3>Introduction</h3> Patients with IBD remain at risk of preventable infections due to immunomodulatory drugs. The European Crohns and Colitis Organisation (ECCO) Consensus document<sup>1</sup> recommends immunising all such patients to Human Papilloma Virus (HPV-in females under 18 years), Influenza, Pneumococcus and Hepatitis B (in seronegative patients). We investigated our practice over the last 5 years. <h3>Methods</h3> All 29 patients contactable on our Biologics9 Register agreed to take part. Twenty-six remained on maintainance biologics. All had received at least one immunomodulatory drug prior to their commencement. Patients were asked if they had been immunised or offered it prior to or during their biologic therapy. <h3>Results</h3> Responses in Abstract PTU-094 table 1. While 83% were offered influenza immunisation—28% declined all invitations and a similar number declined yearly offers of the immunisation. This was despite a number of pandemic flu scares. All patients reported that influenza and pneumococcal vaccination occurred at the instigation of Primary Carers. All those who received Hepatitis B immunisation did so as a result of Occupational or Travel requirement and those who were offered HPV did so as part of other national recommendations. <h3>Conclusion</h3> A recent survey of Australian Gastroenterologists found 30%–55% had never recommended such immunisations.<sup>2</sup> Others have found that most Gastroenterologists feel that Primary carers are responsible.<sup>3</sup> Primary carers however use National guidelines<sup>4</sup> that have no specific recommendations for Hepatitis B and HPV in patients on immunosurpressants. Gastroenterologists therefore need to promote awareness of ECCO guidelines to ensure best coverage for patients as well as advocating standardisation in National and Professional guidelines. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Rahier JF</b>, <i>et al.</i> European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. <i>Journal of Crohn9s and Colitis</i> 2009;<b>3</b>:47–91. 2. <b>Gupta A</b>, Macrae FA, Gibson PR. Vaccination and screening for infections with inflammatory bowel disease: a survey of Australian gastroenterologists. <i>Internal Medicine Journal</i> 2011;<b>41</b>:462–7. 3. <b>Wasan SK</b>, Skolnik PR, Farraye FA. A 24 Year Old patient with Crohn9s disease starting immunosurpressive therapy: vaccination issues to consider. <i>Clin Gastroenterol Hepatol</i> 2010;<b>8</b>:1013–16. 4. <i>Chapter 7 in Immunisations against infectious disease (the Green Book)-UK Dept of Health Online Guidelines</i>. 2006 (Nov 2011 update).