tbuckley/cabot-search huggingface dataset:
S135 Long-term outcomes in patients referred to a specialised weaning centre; The impact of referral source, non-invasive ventilation and diagnosis
Authors: MG Davies, D Horton, R Chadwick, NS Oscroft, TG Quinnell, JM Shneerson, IE Smith
Journal: Thorax (2013)

<h3>Introduction </h3> The expansion of specialised weaning centres serving networks of external ICUs has been recommended by the NHS commissioning board. However, data are limited for this proposed model of care. Papworth Hospital provides a multi-disciplinary weaning service in-line with these recommendations. <h3>Methods </h3> We analysed the records of patients transferred to our service for weaning from invasive ventilation (IMV) between 1992–2011 inclusive. Patients were categorised according to diagnosis (neuromuscular, COPD, post-surgical, non-COPD respiratory, chest-wall disorders and others). <h3>Results </h3> 458 patients receiving IMV (92% via tracheostomy) were transferred (mean age 61 years, 259 (57%) male, 421 (92%) from external ICUs with a median ICU stay of 33 days. On arrival, 422 (92%) were ventilator-dependent and 37 (8%) required nocturnal IMV. The median PaCO<sub>2</sub> was 10 kPa. Neuromuscular problems included Motor Neurone Disease (21%), Tetraplegia (12%), Muscular Dystrophies (11%), and Myotonic Dystrophy (9%). 417 (91%) patients survived to hospital discharge, with 330 (72%) weaned from IMV (median stay 24 days if decannulated, 37 days if IMV continued). Non-invasive ventilation (NIV) facilitated weaning in 79%. From the date of ICU admission, 63% of the whole cohort were alive at 1 year, 43% at 3 years, and 33% at 5 years. When adjusted for case-mix, survival was similar for external and in-house referrals. At least 343 (82%) survivors were discharged home. Further outcome data are summarised in Table 1. COPD patients had the lowest rate of death and/or failed decannulation (13%); further, long-term NIV was associated with a significant increase in survival (p = 0.01), despite normocapnia (5.9kPa) if completely weaned. 33% neuromuscular patients required long-term IMV, typically due to bulbar problems, although 65% were discharged home. Continued IMV in other groups conferred a very poor prognosis. <h3>Conclusions </h3> These data confirm high levels of survival and discharge home in patients referred to a specialised weaning service. Repatriation to the referring ICU was rarely necessary. NIV was important in the graded withdrawal of IMV and the provision of domiciliary care. In COPD, NIV use on discharge was associated with improved survival. Overall outcomes were favourable when compared to international data and are supportive of current national service plans.
EARLY DETECTION AND TREATMENT OF SUPRAVENTRICULAR ARRHYTHMIA WITH REMOTE MONITORING CAN PREVENT ITS PROGRESSION IN PACEMAKER PATIENTS: THE RANDOMIZED, MULTICENTER SETAM TRIAL
Authors: Mohamed El Oualid Amara, Christian Montagnier, Saïda Cheggour, Michel Boursier, Claude Gully, Claude Barnay, Frédéric Georger, Antoine Deplagne, Stéphane Fromentin, Marcin Mlotek, Jérôme Taïeb
Journal: Journal of the American College of Cardiology (2015)
A1.31 Monoclonal antibodies from CD19<sup>+</sup>synovial B cells of RA patients with tertiary lymphoid structures display a strong immunoreactivity towards citrullinated histones from neutrophils NETs
Authors: Elisa Corsiero, Emanuela Carlotti, Hedda Wardemann, William Robinson, Paola Migliorini, Federico Pratesi, Costantino Pitzalis, Michele Bombardieri
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated proteins. Moreover, RA patients are characterised by increased neutrophils in their synovial fluid, in particular at early stage of the disease. Recent evidence suggests a critical role of neutrophils in sustaining the inflammatory response in the RA joint. Around 40% of patients display synovial tertiary lymphoid structures (TLS) with functional B cell follicles supporting a germinal-centre response and local autoantibody production. However, the nature of the main (auto)antigenic reactivity of synovial B cells is unknown. Here we characterised the autoreactive B cell response of lesional B cells isolated from TLS + RA synovium. <h3>Materials and Methods</h3> Single CD19<sup>+</sup> B cells were FACS sorted from synovial cell suspension of 4 TLS + RA patients. RNA was used to amplify Ig VH and VL genes and PCR products were cloned and expressed as recombinant monoclonal antibodies displaying identical specificity of the original B cells. Recombinant antibodies were then tested 1) to determine the frequency of polyreactive clones and 2) to define their immunoreactivity towards native and citrullinated antigens using a synovial antigen microarray platform. <h3>Results</h3> We obtained 139 individual VH sequences of which 33% were IgM, 40% IgG, 27% IgA and 175 VL sequences and we generated a total of 66 complete (H + L chains) recombinant monoclonal antibodies. Analysis of the VH gene somatic mutation rate showed evidence of antigen selection and intra-synovial clonal diversification. No skewed distribution of the VH and VL gene usage was observed. Around 30% of synovial monoclonal antibodies were reactive towards citrullinated histones in the antigen microarray, in particular citH2A and citH2B. This reactivity was confirmed by citH2A and citH2B ELISA. Moreover, when the synovial monoclonal antibodies were tested on neutrophil extracellular traps (NETs), which contained citrullinated histones, reactivity towards NETs proteins but not neutrophil nuclear antigens was observed. <h3>Conclusions</h3> Here we provided novel evidence that highly mutated, locally differentiated B cells within RA synovial germinal centre-like structures display a strong immunoreactive bias towards citrullinated histones which likely derived from neutrophil NETs that continuously form in the RA synovial fluid. This suggests that citrullinated histones are the main antigens driving in situ B cell activation and differentiation sustaining the humoral autoimmune response within the RA joints.
Abstract 4431: NFATc1 silencing increases sensitivity of pancreatic cancer cells to phosphosulindac
Authors: Onika T. Murray, Kvetoslava Vrankova, Francis Johnson, Basil Rigas
Journal: Cancer Research (2012)

Abstract Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. Current chemotherapeutic agents have limited efficacy and play a minor role in its treatment. We previously determined that the novel agent phosphosulindac (P-S) significantly prevents colon cancer and have now extended our studies into pancreatic cancer. Microarray data demonstrated a 5-fold increase in the gene expression of Nuclear Factor of Activated T-cells (NFAT) in MIA PaCa-2 cells after 2 h of treatment with P-S. NFATc1 and NFATc2 isoforms have been shown to be up-regulated in pancreatic cancer. To determine the role NFATc1 played in response to treatment with our compound, we developed a NFATc1 shRNA model in BxPC-3 and GFP positive MIA PaCa-2 cells, and a NFATc1 overexpression model in GFP labeled MIA PaCa-2 cells. Knockdown of NFATc1 expression by shRNA was confirmed by western blot and qRT-PCR. A 2-fold decrease in IC50 of P-S was observed in NFATc1 shRNA cells. In contrast, overexpression of NFATc1 increased the IC50 of P-S by 1.2-fold. The ability of our compound to reduce cell viability more potently in NFATc1 shRNA cells prompted us to assess the effect of the protein on tumor growth in a MIA PaCa-2 xenograft. 5-6 week old female BALB/c nude mice were subcutaneously injected with NFATc1 wt, knock-down, and overexpression GFP labeled MIA PaCa-2 cells. Animals were treated for 5 weeks, euthanized and tumor volume assessed. We observed a 50% reduction in tumor volume in NFATc1 wt, 63% reduction in NFATC1 knock-down, and a 26% reduction in NFATc1 overexpression xenograft. NFATc1 localization is indicative of its activity, with nuclear localization being the active form. We assessed OCT-embedded sections of our xenograft tissue to determine the localization of NFATc1 in GFP labeled tumor cells. Confocal microscopy data showed that in comparison to control, P-S treated tissue demonstrated decreased nuclear localization of the protein, indicating that P-S may suppress the activation of NFATc1. We observed a similar trend in NFATc1 knock-down and overexpression tissue, though our compound demonstrated a greater effect on tumor reduction in NFATc1 knock-down mice. We conclude that P-S is a potentially important agent for the treatment of pancreatic cancer and that our compound may play a role in NFATc1 localization and activation. 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 4431. doi:1538-7445.AM2012-4431
Cerebellar atrophy in schizophrenia and affective disorder
Authors: W R Yates, C G Jacoby, N C Andreasen
Journal: American Journal of Psychiatry (1987)

The authors evaluated 108 patients with schizophrenia, 50 patients with affective disorder, and 74 age- and sex-matched control subjects by CAT scan for evidence of global cerebellar atrophy. No difference was found between control subjects and schizophrenic patients or between control subjects and patients with affective disorder. This study does not confirm previous reports linking cerebellar atrophy to schizophrenia.
Emergency Department Visits for Adverse Events Related to Dietary Supplements
Authors: Andrew I. Geller, Nadine Shehab, Nina J. Weidle, Maribeth C. Lovegrove, Beverly J. Wolpert, Babgaleh B. Timbo, Robert P. Mozersky, Daniel S. Budnitz
Journal: New England Journal of Medicine (2015)

Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited.
Abstract 276: Docosahexaenoic acid alters the spatio-temporal segregation and activation of EGF receptor
Authors: Harmony F. Turk, Joanne R. Lupton, Robert S. Chapkin
Journal: Cancer Research (2010)

Abstract We have previously demonstrated that dietary docosahexaenoic acid (DHA, 22:6n-3), a component of fish oil, profoundly alters the biochemical make up of colonocyte lipid rafts/caveolae microdomains. Since epidermal growth factor receptor (EGFR, ErbB1) is considered a major target for treatment of colorectal cancer and its activation can be regulated by manipulating the lipid composition of the membrane, we further elucidated the effects of DHA with respect to the EGFR signaling axis. Immortalized mouse colonocytes (YAMC cells) were treated with fatty acids (50 μM) for 72 h and stimulated in the presence or absence of EGF (0-50 ng/mL) for 0-10 min and receptor stimulation was assessed by determining levels of phosphotyrosine-EGFR. Downstream signaling was evaluated by measuring Akt, ERK 1/2, and Stat3 phosphorylation. EGFR phosphorylation was increased &amp;gt;2-fold (p&amp;lt;0.05) in DHA treated cells compared to control. Erk 1/2 activation was significantly increased &amp;gt;4-fold, while Stat 3 activation was decreased by 2-fold (p&amp;lt;0.05). No change in activation of Akt was observed. In addition, chronically inflamed (DSS treated) and carcinogen (AOM) injected C57BL/6 mice were maintained on diets ± DHA (fish oil) for 18 wks. Protein from scraped colonic mucosa was analyzed for EGFR phosphorylation and downstream signaling. DHA-fed animals displayed &amp;gt;2-fold (p&amp;lt;0.05) increase in EGFR phosphorylation compared to corn oil fed animals. Total Erk 1/2 and activated Erk 1/2 were significantly increased in DHA-fed animals. Stat3 phosphorylation was decreased by ∼3-fold (p&amp;lt;0.05). Akt activation showed no change. These data indicate that although DHA treatment results in an unexpected increase in EGFR phosphorylation, aspects of downstream signaling are suppressed. This could, in part, explain why fish oil feeding promotes colonocyte apoptosis and inhibits tumor growth. This work was supported in part by NIH grants CA59034, P30ES09106. 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 276.
OUTCOMES WITH PREDILATATION VERSUS NO PREDILATATION IN ROUTINE CLINICAL PRACTICE WITH THE LOTUS VALVE: RESULTS FROM THE FIRST 500 PATIENTS ENROLLED IN THE RESPOND STUDY
Authors: Nicolas M. Van Mieghem, David Hildick-Smith, Sabine Bleiziffer, Jochen Woehrle, Daniel Blackman, Mohamed Abdel-Wahab, Ulrich Gerckens, Axel Linke, Peter Wenaweser, Oyvind Bleie, Karl E. Hauptmann, Dimitar Divchev, Dominic Allocco, Keith D. Dawkins, Volkmar Falk
Journal: Journal of the American College of Cardiology (2016)
Clinical Epidemiology of Toxic-Oil Syndrome
Authors: Edwin M. Kilbourne, Josf, G. Rigau-Perez, Clark W. Heath, Matthew M. Zack, Henry Falk, Manuel Martin-Marcos, Ana de Carlos
Journal: New England Journal of Medicine (1983)

An epidemic of a new illness involving multiple organ systems began in Spain in May 1981, with 19,828 cases and 315 deaths reported by June 1, 1982. An epidemiologic investigation has linked the occurrence of illness with ingestion of an unlabeled, illegally marketed cooking oil. To elucidate the natural history of this illness, we reviewed the medical records of 121 patients in one severely affected town 100 km northwest of Madrid. The findings during the first week after onset were those of a febrile, pneumonia-like illness. Gastrointestinal findings and striking eosinophilia became prominent later in the first month. Although the disease followed a self-limited course in many patients, severe neuromuscular manifestations (myalgia severe enough to restrict movement, motor deficits, atrophy of major muscle groups, and contractures of the jaw and extremities) occurred late in the course of the illness (an average of 96 days after onset) in 23 per cent of the patients. The onset of disease early in the epidemic and particularly severe initial systemic findings were associated with progression to neuromuscular illness.
OP0131 Incidence of rheumatoid arthritis in the UK using the 2010 ACR/EULAR classification criteria for RA; and comparison with estimates using the 1987 ACR criteria:
Authors: J. Humphreys, S. Verstappen, M. Lunt, K. Hyrich, T. Marshall, D. Symmons
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The development of new classification criteria for rheumatoid arthritis (RA) calls for a re-estimation of RA incidence rates. The new criteria purport to have increased sensitivity to identify RA in patients with early inflammatory arthritis (EIA). <h3>Objectives</h3> To estimate the age and sex-specific incidence of RA in Norfolk, England using the new criteria <h3>Methods</h3> This study included all patients aged ≥16 notified to the Norfolk Arthritis Register (NOAR), a primary-care based inception cohort of patients with EIA, from 1990-5 with symptom onset in 1990. The Norwich Health Authority population based on the 1991 census was the denominator. Age and sex specific incidence rates using both 1987 and 2010 classification criteria were calculated at baseline visit, annually for the first 3 years and at 5 years. At each follow up both criteria sets were applied cross-sectionally and cumulatively, i.e. once a patient had satisfied a particular criterion that result was carried forward to future assessments. <h3>Results</h3> 283 patients were notified to NOAR with symptom onset in 1990. 23 were excluded as an alternative diagnosis was made by their rheumatologist. The overall incidence rate (IR) when applying the 2010 criteria at baseline was 54/100 000 for women and 25/100 000 for men, compared to 44/100 000 for women and 19/100 000 for men using 1987 criteria at baseline. Age and sex-specific IRs using the 2010 classification criteria at baseline were similar to cumulative IRs applying the 1987 criteria up to 5 years. IRs using both criteria sets converged when applied cumulatively. However, 10 patients (4%) satisfied the 1987 criteria cumulatively after 5 years but never satisfied the new criteria, and 37 (14%) satisfied the new criteria but never satisfied the 1987 criteria. <h3>Conclusions</h3> The 2010 classification criteria aim to identify early, those patients with EIA who, in the absence of appropriate treatment, would go on to develop persistent, erosive and disabling RA. This study shows that the new criteria classify at baseline similar numbers of patients as having RA, as the previous criteria would have taken up to 5 years to identify. A small proportion of patients (18%) satisfied only one set of classification criteria over 5 years. Those patients who satisfied the 1987 criteria but not the 2010 had more hand joint involvement, symmetrical arthritis and morning stiffness. These results provide important information for health economics evaluation and healthcare planning. <h3>Disclosure of Interest</h3> None Declared
Abstract 4748: Identification of HLA-A*0201 and A*2402-restricted epitope peptides derived from mucin 5AC (MUC5AC) gene expressed in human pancreatic cancer as a potential target for immunotherapy
Authors: Sadaaki Yamazoe, Hiroaki Tanaka, Takehiko Iwauchi, Eiji Noda, Ryosuke Amano, Naoshi Kubo, Kazuya Muguruma, Toru Inoue, Tsutomu Takashima, Nobuya Yamada, Masakazu Yashiro, Kiyoshi Maeda, Naoyoshi Onoda, Tetsuji Sawada, Bunzo Nakata, Masaichi Ohira, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2010)

Abstract MUC5AC was previously identified to be de novo expressed in the majority of pancreatic ductal adenocarcinoma. For the development of pancreatic cancer immunotherapy, we studied the significance of MUC5AC expressed in pancreatic ductal adenocarcinoma and the capability of MUC5AC as a target for immunotherapy of pancreatic cancer. By immunohistochemical analysis of 102 specimens, MUC5AC is absent from all cell types of the normal pancreas, but arise de novo in 85% of invasive ductal adenocarcinoma. Clinicopathlogically, tumors with lymph node metastasis had significantly higher expression of MUC5AC than those without node metastasis. To validate the potentiality of cancer vaccine, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to MUC5AC. We screened 20 candidate peptides derived from MUC5AC gene sequence for each of human leukocyte antigen (HLA) - A*0201 and A*2402. As a result, we successfully established CTL clones stimulated by MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) peptide that have specific cytotoxic activities against each of the HLA-A*0201 and A*2402-positive target cells pulsed with the candidate peptide. Subsequent analysis of each CTL clones also revealed their cytotoxic activities against pancreatic cancer cells expressing MUC5AC. A cold target inhibition assay further confirmed that each CTL clones specifically recognized the major histocompatibility complex (MHC) class I-peptide complex. Our results suggested that MUC5AC is a novel tumor-associated antigen recognized by CTL, and MUC5AC-A02-1398 (FLNDAGACV) and MUC5AC-A24-716 (TCQPTCRSL) are HLA-A*0201 and A*2402-restricted epitope peptides that can induce potent and specific immune responses against pancreatic cancer cells expressing MUC5AC. 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 4748.
SAT0217 High Resolution Computed Tomography as A Diagnostic Determinant of Fibrotic Lung Changes in Connective Tissue Diseases
Authors: S.M. Rashad, K.M. Darwish, W.A. Hassan, S.A. Saad
Journal: Annals of the Rheumatic Diseases (2014)

Robotic navigational bronchoscopy (RNB) allows for high navigational success but diagnostic yield remains moderate due to near-miss of the target lesion. Needle based confocal laser endomicroscopy (nCLE) allows real-time lung cancer detection at the needle tip. We aim to assess feasibility, safety and needle repositioning based on nCLE-guidance during robotic bronchoscopy to reduce the current near-miss rate. Patients with suspected peripheral lung cancer based on (PET-)CT-scan underwent fluoroscopy and radial EBUS guided RNB. After lesion detection, an 18G needle containing the CLE probe, imaged the target area followed by TBNA and biopsies. In case of non-lesional CLE-imaging, readjustment of the robotic bronchoscope was performed. 17 patients were included (final diagnosis n=15 cancer, n=1 epithelioid granuloma, n =1 non-diagnostic) with a mean lesion size of 15 mm (range 8-30 mm). No complications occurred. In 14/15 (93%) of patients with cancer, nCLE-imaging detected a malignant pattern. In one patient alveolar parenchyma/ airway wall was visualized. One patient with a malignant nCLE pattern but negative robotic bronchoscopic lesion sampling was diagnosed with malignancy after surgery. In 6 patients (35%), nCLE guidance resulted in readjustment of the robotic bronchoscope with optimization of the sampling location, resulting in a diagnostic yield of 82%, (14/17, 13 patients with malignancy and 1 patient with epithelioid granuloma). In conclusion, robotic navigational bronchoscopy combined with nCLE-imaging is feasible, safe and can serve as a real-time guidance tool to fine-tune the sampling location to improve the diagnosis of peripheral lung cancer.
Abstract SY19-01: Chemical genetic investigations of protein and lipid kinase signaling.
Authors: Kevan M. Shokat
Journal: Cancer Research (2013)

Abstract Kinases are highly regulated enzymes with diverse mechanisms controlling their catalytic output. Inhibitor discovery efforts for kinases have produced ATP-competitive compounds, allosteric regulators, irreversible binders, and highly specific inhibitors. These distinct classes of small molecules have revealed many novel aspects about kinase-mediated signaling and some have progressed from simple tool compounds into clinically validated therapeutics. My presentation will explore several small-molecule inhibitors for kinases highlighting elaborate mechanisms by which kinase function is modulated. A complete surprise of targeted kinase drug discovery has been discovery of ATP-competitive inhibitors that behave as agonists, rather than antagonists, of their direct kinase target. These studies hint at a connection between ATP binding site occupancy and networks of communication that are independent of kinase catalysis. Indeed, kinase inhibitors have been found that induce changes in protein localization, protein-protein interactions, and even enhancement of catalytic activity of the target kinase. The relevance of these findings to the therapeutic efficacy of kinase inhibitors and to the future identification of new classes of drug targets will be discussed. Citation Format: Kevan M. Shokat. Chemical genetic investigations of protein and lipid kinase signaling. [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 SY19-01. doi:10.1158/1538-7445.AM2013-SY19-01