tbuckley/cabot-search huggingface dataset:
P118 Post discharge pulmonary rehabilitation for acute exacerbation COPD does not always reduce re-admission rates
Authors: SE Roberts, N Kodumooru, S Purcell, A Williamson, H Broomfield, LJ Restrick, M Stern
Journal: Thorax (2013)

<h3>Introduction</h3> Post-discharge pulmonary rehabilitation (PR) within 7–10 days after discharge from hospital admission for acute exacerbation of COPD (AECOPD) has been shown not only to result in the well-described benefits of PR (reduced breathlessness, improved exercise performance and health-related quality of life), but also to reduce emergency department attendances over a 3 month period. We report the outcomes of a locally-provided post-exacerbation PR (PEPR) pilot study for patients admitted to hospital with AECOPD, and compares outcomes and subsequent 90-day re-admission rates with published RCT data showing re-admission reduction from 33 to 7%<sup>1</sup>. <h3>Methods</h3> Patients were recruited during AECOPD admission to start PR within 10 days of discharge from hospital. Taxi transport was offered to all patients.Outcome measures chosen were change in: 6-Minute Walking Test (6MWT), Hospital Anxiety and Depression Score (HADS), Chronic Respiratory Disease Questionnaire (CRDQ), and 90-day re-admission rates. <h3>Results</h3> 43 patients were offered PEPR, 32 started and 21/32 (66% of starters, 49% of all referrals) completed the course (&gt;11/16 sessions). Mean (range) age was 67(40–86) years and mean (SD) %predicted FEV<sub>1</sub> 32(15)%. Median time (range) between discharge from hospital and starting PEPR was 8(0–17) days. There were clinically significant improvements in 6MWT median (range) 27%(-40- + 233) and CRDQ dyspnoea domain 0.79(-0.60– + 3.00). There was no clear effect on 90-day re-admission rate: 45% patients who started PEPR were re-admitted v 58% who were offered but declined PEPR. Local 90-day re-admission rate for all 2012 AECOPD admissions was 39%. <h3>Conclusion</h3> This study failedto replicate published reductions in re-admission rates in a patient population that was more severe than the comparison study, mean%predicted FEV<sub>1 </sub>32% v 52%<sup>1</sup>. Value of PEPR programmes in reducing AECOPD re-admission rates needs further investigation across disease severity spectrum. An additional area that would benefit from further investigation is completion rate for PEPR<sup>2</sup>; completion rate from referral for PEPR at 49% compares to 43% for our standard PR programme. <h3>References</h3> Seymour <i><i>et al</i></i>. Outpatient pulmonary rehabilitation following acute exacerbations of COPD. <i>Thorax</i> 2010;65:423–428 National Institute of Health Research, HTA no 13/24 ‘does starting PR early following AECOPD improve adherence and outcomes compared to starting rehabilitation later?’
DIAGNOSTIC COMPARISON OF CARDIAC MAGNETIC RESONANCE WITH ENDO MYOCARDIAL BIOPSY IN SUBJECTS WITH DILATED CARDIOMYOPATHY: A SEGMENT-BY-SEGMENT ANALYSIS
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Koya Ozawa, Takashi Nakayama, Marehiko Ueda, Yoshihide Fujimoto, Takashi Kishimoto, Satoshi Ota, Yukio Nakatani, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2016)
PTU-114 Hepatology Specialist Nurse Led External Jugular Venepuncture; Is It Safe And Effective?
Authors: LD Morris, S Frayne, J Wadsworth, M Mansoor, Y Reddy
Journal: Gut (2014)

<h3>Introduction</h3> Difficult venous access is a significant problem for a proportion of patients with chronic hepatitis C and a history of intravenous drug use. It can impede access to treatment and cause distress for the patient. Sampling blood through external jugular venepuncture (EJV) is highly successful. This enables more patients to be assessed and treated with antiviral therapy whilst participating in clinical trials. Our aim was to assess the efficacy of an EJV service in a large district general hospital, led by a Hepatology Specialist Nurse. <h3>Methods</h3> Data was collected prospectively, recording the number of attempts needed to successfully complete EJV. All procedures were performed by an experienced hepatology nurse. Patients who underwent EJV were invited to provide feedback on overall satisfaction. <h3>Results</h3> Between February 2012 and October 2013, external jugular venepuncture was attempted on 130 occasions in 57 chronic hepatitis C patients. The mean age of the patients was 39 (range 30–61) and there were 46 males and 11 females. Genotype distribution was mostly 3a (46%) and 1a (33%). 80% of EJV procedures (n = 103) were performed successfully on the first attempt, rising to 92% on the second attempt. In five patients (8%), EJV failed due to: previous neck surgery (1), vein thrombosis (3) and patient anxiety (1). No procedural complications were reported. Patient experience was 100% positive. <h3>Conclusion</h3> External jugular venepuncture is a useful method of blood sampling from patients with chronic hepatitis C and difficult venous access, allowing for monitoring of their therapy. A Specialist Nurse Led EJV service is safe, effective and is well received by patients. Due to this success, a number of our patients have been enrolled in clinical trials. <h3>Disclosure of Interest</h3> None Declared.
Abstract 912: The tumor promoting activity of the prostaglandin E2 EP4 receptor in mouse skin
Authors: Melissa S. Simper, Rebecca A. Bowen, Inok Surh, Susan M. Fischer
Journal: Cancer Research (2011)

Abstract Chronic inflammation has recently been suggested to be involved in cancer development, and cyclooxygenase-2 (COX-2), a key mediator of the inflammatory response, is known to be upregulated in several cancers. COX-2 is responsible for the production of prostaglandins, and prostaglandin E2 (PGE2) is the major prostaglandin involved in inflammation. PGE2 binds to four receptors (EP1-EP4), and the EP4 receptor has recently been shown to be important in carcinogenesis, depending on the tissue in which it is expressed. To determine the role of EP4 in skin carcinogenesis, transgenic mice were generated that overexpress EP4 in the basal layer of the epidermis under the control of the bovine keratin 5 promoter (BK5.EP4 Tg). Using a two-stage chemical carcinogenesis protocol, the BK5.EP4 Tg mice were shown to develop both papillomas and squamous cell carcinomas earlier than wild type (WT) mice. However, a tumor observed before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment on one BK5.EP4 Tg mouse suggested that TPA was not necessary for the promotion of the tumors. Therefore a 7,12-dimethylbenz[a]anthracene (DMBA)-only carcinogenesis protocol was performed, and by 30 weeks, the BK5.EP4 Tg mice developed more carcinomas compared to none on the WT mice. Immunohistochemistry performed on DMBA-treated mice demonstrated that the BK5.EP4 Tg epidermis began to detach 48 hours after treatment with total detachment occurring 5 days after treatment, while WT mice had only increased epidermal thickening. Caspase-3, MMP-9, and MMP-7 expression also were upregulated in the BK5.EP4 Tg mice at the same time detachment of the epidermis was occurring. Ki67 analysis showed an initial increase in proliferation in WT mice that slowly declined back to normal levels, while the BK5.EP4 Tg mice instead had a sustained increase in proliferation, which occurred during reepithelialization of the epidermis. These data suggest that overexpression of EP4 in the mouse skin can increase tumorigenesis, possibly through the wounding of the skin and the subsequent epidermal regeneration acting as a tumor promoter. Supported by CA100140. 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 912. doi:10.1158/1538-7445.AM2011-912
P260 Managing the indeterminate CT pulmonary angiogram: do we get it right?
Authors: E. L. O'Dowd, J. D. Birchall, R. J. Berg
Journal: Thorax (2010)

<h3>Introduction</h3> Around 5% of CT pulmonary angiograms (CTPA) are indeterminate, usually due to incomplete contrast enhancement of pulmonary arteries, motion artefact or difficulty interpreting small peripheral filling defects. While BTS guidelines propose good quality negative CTPA as sufficient grounds to not treat for pulmonary embolism (PE), response to indeterminate CTPA is not addressed. No previous study has investigated variation in radiologists′ reporting and clinicians′ response to indeterminate CTPA′s. <h3>Methods</h3> Records of 51 patients with indeterminate CTPA were retrospectively reviewed for radiologist′s reporting, clinicians′ documentation of such, and clinical outcomes. <h3>Results</h3> Reports included “no large central PE” (n=25), “no obvious PE within the limitations of the study” (n=14), “unable to exclude segmental/subsegmental PE” (n=5), and “equivocal filling defects of uncertain significance” (n=4). 17/51 (33%) stated: “PE cannot be excluded.” Further imaging was suggested in only 2 cases. Clinicians documented recognition of technical shortcomings, reported by radiologists, in only 16/51 cases (31%), and recorded “no PE” in 29/51 (57%). Clinicians assessed pre-test probability in 8/51 (8%). 36 patients had the diagnosis of PE dismissed without further tests, of whom 26 were treated for other acute cardio-respiratory conditions revealed on CTPA. 0 had one or more additional tests (repeat CTPA, V/Q scan or Doppler u/s), confirming thrombo-embolic disease in 2. Further investigation was significantly more likely following scans stating “PE cannot be excluded” than all other reports; both overall (47% vs 6%, p&lt;0.001), and excluding patients with alternative acute cardio-respiratory diagnoses (66% vs 15%, p&lt;0.005). 3 patients with indeterminate filling defects were anti-coagulated for PE. Of 2 patients with no filling defects reported, but anti-coagulated on grounds of clinical suspicion and indeterminate scan, 1 presented 2 weeks later with bleeding complications. Anticoagulation was discontinued when review and further investigation suggested PE was, in retrospect, unlikely. One untreated patient re-presented after 2 weeks with non-fatal PE. <h3>Conclusion</h3> There is a lack of clear guidance, and considerable variation in radiological reporting of, and clinicians′ response to indeterminate CTPA. Un-ambiguous reporting, repeat clinical assessment, appropriate consideration of alternative diagnoses, and further investigation where appropriate may reduce the risks of missed diagnosis or unwarranted anti-coagulation.
Biomarkers associated with pathologic complete response to neoadjuvant chemotherapy in women with locally advanced breast cancer: results from the I-SPY TRIAL (CALGB 150007/150012 &amp; ACRIN 6657).
Authors: C Livasy, L Carey, A DiMichelle, D Cowan, D Little, J Markey, D Moore, I-SPY Clinical Investigators, L Dressler
Journal: Cancer Research (2009)

Abstract Abstract #5102 Background: The I-SPY trial is a multi-institutional study of locally advanced breast cancers in which serial biopsies of breast tumors are performed at multiple timepoints, allowing comparison of tumor biomarker status pretreatment, during treatment, and after treatment. The primary objective is to identify markers of response to neoadjuvant chemotherapy. The aim of this study was to identify immunohistochemical biomarkers associated with pathologic complete response (pCR).&amp;#x2028; Methods: Eligible patients had biopsy-confirmed primary breast cancer measuring at least 3 cm. Required initial treatment was an anthracycline based neoadjuvant chemotherapy regimen: AC followed by T (91%), AC without T (6%), and chemotherapy beyond AC +/- T 2%. Immunohistochemistry (IHC) for HER2, EGFR, p53, Bcl2 and Ki-67 was performed centrally on core samples at baseline. Estrogen receptor and progesterone receptor results were obtained from each institution. Proxy IHC tumor subtypes were defined as follows: luminal A (ER or PR+/HER2-), luminal B (ER or PR+/HER2+), basal-like (ER-/PR-/HER2-), and HER2 (ER-/PR-/HER2+). Following completion of chemotherapy, post-surgical excision/mastectomy cases were reviewed centrally to determine residual cancer burden including pCR rate.&amp;#x2028; Results: 221 patients were enrolled and completed therapy. The median age was 49 years, with a range of 27-69. Median tumor size was 6 cm; 58% had clinically positive nodes. The positive rate for each biomarker was as follows: ER+ (57%), PR+ (47%), HER2+ (23%), EGFR+ (14%), p53+ (44%), Bcl2+ (49%), Ki-67 index ≥25% (38%), Ki-67 index ≥10% but &amp;lt;25% (34%), and Ki-67 index &amp;lt;10% (27%). The pCR rates based on biomarkers results are shown in the table below.&amp;#x2028; &amp;#x2028; Conclusion:&amp;#x2028; For patients with locally advanced breast cancer, pCR to neoadjuvant chemotherapy was associated with tumor HER2 overexpression, hormone receptor-negative status, high Ki-67 index, EGFR expression, and absence of Bcl2 expression. Luminal A tumors, defined by IHC proxy, showed a very low pCR rate following neoadjuvant chemotherapy.&amp;#x2028; Support: CALGB CA31964 and CA33601, ACRIN U01 CA079778 and CA080098, NCI SPORE CA58207. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5102.
138 CROSSTALK BETWEEN c-myc OVEREXPRESSING HEPATOCYTES AND HEPATIC STELLATE CELLS FACILITATES THE ONSET OF LIVER FIBROSIS
Authors: Y.A. Nevzorova, W. Hu, U. Haas, J. Freimuth, F. Tacke, C. Trautwein, C. Liedtke
Journal: Journal of Hepatology (2013)
Abstract 838: A metabolomic analysis revealed the involvement of deoxycytidine kinase and CTP synthase in the sensitivity of human pancreatic cancer cells to gemcitabine
Authors: Koji Nishi, Yurika Fujimura, Akito Nishimuta, Masahiro Sugimoto, Tomoyoshi Soga, Yusuke Tanigawara
Journal: Cancer Research (2012)

Abstract Gemcitabine (GEM), a pyrimidine nucleoside analogue, is used in patients with pancreatic cancer as the standard chemotherapeutic agent. However, pancreatic cancer cells often show resistance to GEM in vivo and vitro. In this study, we explored the factors involved in the sensitivity of GEM in human pancreatic cancer cells, Miapaca-2 and AsPC-1, by a metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The sensitivity of Miapaca-2 (IC50: 66 nM) to GEM was higher than that of AxPC-1 (IC50: 16 nM), whereas there were little differences in the growth rates of these cells. This result indicates that the difference in the sensitivities between Miapaca-2 and AsPC-1 is not dependent on their growth rates. At 12 hr after adding GEM, intracellular level of GEM in Miapaca-2 was higher than that in AsPC-1, whereas levels of GEM monophosphate, diphosphate and triphosphate in Miapaca-2 were lower than that in AsPC-1. In addition, expression level of deoxycytidine kinase (dCK), which catalyzes the reaction from GEM to GEM monophosphate, in Miapaca-2 was lower than that in AsPC-1. Expression levels of human equilibrium transporter (hENT1), which is known to major transporter of GEM, were similar in both cells. These results suggest that dCK is rate-limiting enzyme in GEM phosphorylation and one of the factors involved in the sensitivity. In pyrimidine metabolism, GEM was observed to inhibit CTP synthase, which converts UTP to CTP, resulting increase in UTP level, decrease in CTP level and depletion of dCTP in both cells at 12 hr after adding GEM. The degree of increase in UTP and decrease in CTP was lower in Miapaca-2 than that of AsPC-1. Indeed, the ratio of UTP to CTP in Miapaca-2 was about 2.5, whereas that of AsPC-1 was about 11. In addition, the expression level of CTP synthase in Miapaca-2 was higher than that in AsPC-1. Ribonucleotide reductase, which catalyzes the conversion of CDP to dCDP, is known to be inhibited by GEM diphosphate and be involved in the sensitivity of pancreatic cancer cells to GEM. GEM decreased CDP in AsPC-1. This may be caused by inhibiting CTP synthase. Expression level of ribonucleotide reductase in Miapaca-2 was higher than that in AxPC-1. Therefore, ribonucleotide reductase also may be involved in the sensitivity to GEM. Furthermore, we previously found that GEM mainly inhibited CTP synthase in pyrimidine metabolism, resulting in depletion of dCTP. Our current study suggests that dCK, CTP synthase and ribonucleotide reductase are involved in the sensitivity of pancreatic cancer cells to GEM. 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 838. doi:1538-7445.AM2012-838
SAT0539 The Risk of Future Attacks in Patients with Incident Gout: a Population-Based
Authors: T. Bongartz, N. Zleik, M. Clement, H. Khun, C. Crowson, E. Matteson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> While there appears to be consensus that non-pharmacological uric acid lowering therapies (diet and lifestyle modifications) should be initiated in every patient presenting with gout, there is much less agreement as to when urate lowering drugs should be considered. Expert opinion ranges from starting uric acid lowering therapy after the first attack of gouty arthritis through a more cautious approach where therapy is only started in patients with more than 3 attacks per year. We aimed to assemble a population based cohort of patients with newly diagnosed gout to determine the risk of additional flares after an initial gout attack and explore the role of various demographic, clinical and laboratory predictors that may aid the clinician in quantifying this risk. <h3>Methods</h3> We examined a population-based incidence cohort of patients with gout, diagnosed according to the New York, Rome or ACR preliminary criteria. All subjects were followed longitudinally through their complete community medical records, until death, migration or July 1<sup>st</sup> 2012. We used a conditional frailty model (accounting for multiple flares per subject) to explore risk factors of subsequent flares. <h3>Results</h3> 46 patients with incident gout were followed for a mean (SD) of 12.9 (8.6) years. The majority of patients were male (70%) and the mean age (SD) at gout onset was 66.0 (14.8) years. Isolated podagra was the most common form of joint involvement at disease onset (72%). The mean (SD) serum uric acid level was 8.1 (2.2) mg/dl. 28 patients (61%) developed at least 1 subsequent flare, with a total of 101 subsequent flares during the entire follow-up period. Patients with the highest risk of subsequent flares had an initial joint involvement other than first MTP joint (odds ratio 3.9, 95% CI 1.03, 14.77) and a high serum uric acid level at baseline (OR 1.69, 95% CI 1.26, 2.27), Age and sex were not significant predictors of subsequent flare risk. <h3>Conclusions</h3> The majority of patients in our population-based cohort did develop at least one subsequent flare after an initial diagnosis of gout. Joint involvement other than the first MTP joint and serum uric acid level were significant predictors of subsequent flares and should be taken into account when deciding on the timing of uric acid lowering therapy. <h3>Disclosure of Interest</h3> None Declared
AB1037 Bone mineral density reference database in algerian male population: Study in douera city
Authors: N. Hammoumraoui, M. El Rakaawi, C. Haouichat, D. Hanoune, S. Abrouk, F. Sadouki, R. Allat, H. Djoudi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The diagnosis of osteoporosis is based on patients bone mineral density (BMD) values that are compared to reference values. Clinical studies that have compared BMD between populations showed that according to the reference curve used, the number of osteoporotic patients may vary and lead to an unnecessary treatment or inversely. It seemed us more appropriate to determine these values in a sample of an Algerian population. Few data are available about bone mineral density in normal men. <h3>Objectives</h3> to Determine the values of bone mineral density in healthy young men (aged from 21 to 39 years for the T-score), and to determine values of bone mineral density in healthy men (aged from 40 to 74years old for the Z-score). <h3>Methods</h3> It is a descriptive cross-sectional uni-centric study carried out in a randomly sampled population throughout 52 districts. A minimum of 30 subjects were included in each 5-years age group ranging from 20 to 74 years. Non-inclusion criteria: any situation suggesting the presence of osteoporosis, which can interfere with bone metabolism or with BMD measureament. Psychiatric illness and alcoholism. BMD was measured at the hip and spine using a Hologic Discovery 2000 densitometer (Hologic Inc., Waltham, MA). Statistical analysis was performed using SPSS version 8.0. <h3>Results</h3> three hundred and thirty one men (331) were included. Eleven (11) groups were obtained (5-Years age groups) and mean BMD values were calculated for each one. The BMD values at the total hip and total spine (sites most used in practice) are respectively (mean ± SD) 1.023±0.119 g/cm<sup>2</sup> and 1.038±0.125 g/cm<sup>2</sup>. The average bone density at various sites of the hip and spine are maximum before age 40. Analysis of T-score at the hip and spine, shows that the incidence of osteoporosis was overestimated by 9.4% comparatively when using NHANES reference. The bone mineral loss is very low over the years and is not significant. <h3>Conclusions</h3> This study showed that BMD of our population is different from a normal range and this could lead to misclassify significant percentage of subjects and overestimate the prevalence of osteoporosis. This difference has already been proven in several populations. Experts strongly recommend the use of local references. <h3>Disclosure of Interest</h3> None Declared
OUTCOMES OF DOSE ESCALATION WITH ADALIMUMAB (ADA) IN INFLAMMATORY BOWEL DISEASE
Authors: A Dillon, C Rowan, D Gibson, D Keegan, K Byrne, H Mulcahy, G Cullen, G Doherty
Journal: Gut (2013)

<h3>Introduction</h3> Anti-TNF therapy is highly effective for induction and maintenance of remission in IBD. Subcutaneous agents such as adalimumab are licensed with a fixed dosing schedule irrespective of body weight. <h3>Aims/Background</h3> We aimed to study the frequency and outcomes of dose escalation with adalimumab and evaluate any relationship to patient body weight. <h3>Method</h3> A retrospective study of patients who commenced ADA therapy identified from a prospectively maintain database of &gt;3.000 patients with IBD attending a single centre. <h3>Results</h3> n=143 patients were identified who received adalimumab (ADA) for treatment of inflammatory bowel disease. 25 patients were excluded from the final analysis due to insufficient data. Data on n=118 patients were analysed (99 patients with Crohn9s Disease, 18 patients with UC, one patient with IBD-U). 62/118 (53%) were male. 43/118 (36%) required dose escalation of ADA from every other week to weekly therapy. The median interval from initiation to dose escalation was 366 days (IQR 153 to 731). The mean body weight at initiation of therapy was similar between both groups (69.5 versus 69.9 kgs, p=ns). The time to dose escalation was not significantly associated with the use of concomitant immunomodulator therapy or with smoking history (current versus ex/never). 28/43 (65%) of patients who received dose escalation responded and 90% remain well on therapy with a median follow up of 1430 days (3.9 years). 15/43 (35%) failed to respond to dose escalation of whom 9 patients underwent surgery and 3 switched to another anti-TNF agent. The mean CRP at dose escalation was higher in the non-responders to to dose escalation than in the responder group (mean CRP 25.2 versus 9.1 mg/dL, p=0.05). <h3>Conclusion</h3> Dose escalation with ADA is required in over a third of IBD patients but results in a sustained clinical response in the majority of cases. The study results suggests that an ADA dosing strategy based on measurement of ADA levels or inflammatory biomarkers rather than a weight based dosing strategy might help optimise results of therapy.