tbuckley/cabot-search huggingface dataset:
Abstract P3-06-26: Serum anti-p53 antibody titers predict pathological response to preoperative chemotherapy in women with HER2 positive or triple negative breast cancer.
Authors: T Yoshiyama, Y Nakamura, A Igawa, A Saruwatari, T Shigechi, N Ueda, S Kuba, M Ishida, S Nishimura, K Nishiyama, S Ohno
Journal: Cancer Research (2012)

Abstract Background: In SABCS 2009, we reported that the high level of serum anti-p53 antibody titers was associated with response to preoperative chemotherapy in cases with primary breast cancer (SABCS 2009). Prognostic meaning of pathological complete response (pCR) after preoperative chemotherapy differs among various subtype, and there is a close relationship between pCR and prognosis in cases with HER2 positive or triple negative disease. The aim of this study is to evaluate the association between the high level of serum anti-p53 antibody titers and pCR in patients with HER2-positive or triple negative breast cancer. Patients and Methods: In this study, we analyzed 196 women with operable early stage breast cancer (T1-T3, N0-1) treated with preoperative chemotherapy and definitive curative surgery since 2002 to 2011. All of the patients received four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 q3w) followed by four cycles of docetaxel (75 mg/m2 q3w). The serum anti-p53 antibody titers were assessed by ELISA with the anti-p53 EIA Kit II (MESACUP anti-53 Test: MBL) in the pre-treatment serum samples. The test's cut-off value was determined to be 1.3 IU/ml based on reference distribution in healthy control individuals. The association between serum anti-p53 antibody titers and pCR was analyzed. Results: The subtype of tumors of 196 patients were classified to 86 of ER+/HER2−, 24 of ER+/HER2+, 29 of ER−/HER2+ and 57 of ER−/HER2−. The pCR was achieved 49 of 196 patients (25%). The pCR rate were 7%(6/86), 33%(8/24), 48%(14/29) and 37%(21/57) in the subtype of ER+/HER2−, ER+/HER2+, ER−/HER2+ and ER−/HER2− respectively. The range of serum anti-p53 antibody titers in the serum samples of 196 patients was between 0.40 and 5610 (the median was 0.40 and the average was 85.2). Excluding 86 cases with ER+/HER2−, relationship between serum anti-p53 antibody titers and pCR was evaluated. According to serum anti-p53 antibody titers with the patients of pCR, cut-off value of serum anti-p53 antibody titers was set to be 6 IU/ml. The pCR was observed in nine of 12 cases (75%) with high serum anti-p53 antibody titers, which was significantly higher than those with low titers (35%: 34/98; p = 0.01). Multivariate analysis showed that the only high anti-p53 antibody titer was an independent predictive factor for pCR due to preoperative chemotherapy (p = 0.01). Conclusion: p53 mutation analysis using serum anti-p53 antibody titers might be a useful predictive test for response to preoperative chemotherapy in patients especially with HER2 positive or triple negative breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-26.
FRI0421 Longitudinal variations in reporting doctor-diagnosed arthritis reflect contemporaneous severity of symptoms and disability
Authors: G. Peeters, L. Parkinson, E. Badley, W.J. Brown, A. Dobson, G. Mishra
Journal: Annals of the Rheumatic Diseases (2013)

Background There is an ongoing discussion in the literature regarding the assessment of osteoarthritis in research.1 Self-report is often regarded as inferior as it corresponds poorly with clinical diagnosis.2 Moreover, half the participants who report having the condition, report not having it at a later interview.3 Objectives To examine whether longitudinal variations in reporting doctor-diagnosed arthritis reflect concurrent fluctuations in anti-inflammatory drug use, joint pain/stiffness and physical functioning. Methods Data were from 8,153 participants in the Australian Longitudinal Study on Women's Health. Based on self-report of doctor-diagnosed arthritis on surveys in 2001, 2004, 2007 and 2010, the participants were classified according to pattern of arthritis reporting (eg. 0-0-0-0 = "no" on all surveys, 0-1-0-1 = "no-yes-no-yes"). Anti-inflammatory drug use was derived from self-reported medication data. Frequency of joint pain/stiffness was assessed as never/rarely/sometimes versus often. Physical functioning was assessed with the SF-36. Results In this sample, 42.9% reported having arthritis on at least one survey, with half of these cases reporting not having arthritis at a later survey. Proportions of participants using anti-inflammatory drugs and reporting joint pain/stiffness were higher and mean physical functioning was lower when participants reported having arthritis. Conclusions Variation in self-reported arthritis coincided with fluctuations in disease severity on the symptom and functional level. Variations in reporting of arthritis should not be ignored in longitudinal studies. 1. Nelson AE, Jordan JM. Defining osteoarthritis: a moving target. Osteoarthritis Cartilage 2011. 2. Kriegsman DM, et al. Self-reports and general practitioner information on the presence of chronic diseases in community dwelling elderly. A study on the accuracy of patients' self-reports and on determinants of inaccuracy. J Clin Epidemiol 1996;49(12):1407-17. 3. Beckett M, et al. Do health interview surveys yield reliable data on chronic illness among older respondents? Am J Epidemiol 2000;151(3):315-23. Disclosure of Interest None Declared
FRI0306 Costs and working capacity among patients with systemic lupus erythematosus (SLE) in working-age (18-64 years)
Authors: C. Bexelius, K. Wachtmeister, P. Skare, L. Jönsson, R. F. van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The objective of this study is to describe work capacity and costs related to this among Swedish patients with systemic lupus erythematosus (SLE) of working age (18-64 years) <h3>Methods</h3> A questionnaire was sent to members of the Swedish Rheumatology Association with a self-reported diagnosis of SLE, requesting information on demographics and disease characteristics, resource utilization, informal care and loss of productivity fatigue and HRQoL in relation to SLE during the last 12 months. Only patients in working age (18-64 years) were included in this analysis. Mean annual SLE-related costs per patient were estimated from a societal perspective. All costs were translated from SEK to Euro (€) according to 2013 currency (SEK/€=8.87) <h3>Results</h3> Out of the 339 patients that answered the questionnaire, 234 were of working age and included in the analysis. Mean age was 48 (SD 11.6), 96% were female, 65% were employed and 21% were early retired. Total mean annual costs for all patients in working age were €29,323 out of which €20,327 were indirect costs. Those who were employed reported working 30 hours a week on average and 53% stated having reduced their number of working hours due to SLE. Among those employed, 33% reported having changed working duties due to their SLE and 57% reported being less effective while at work (on average 39% reduced effectiveness). Thirty percent of all employed patients reported that they had been on either long or short term sick leave (mean 48 (SD 81) days) and 15% reported being on long term sick leave from their employment. Of the patients who reported being retired, 86% stated being retired due to their SLE. <h3>Conclusions</h3> This study demonstrates that annual costs among Swedish patients with SLE of working age are high (€29,323), and that more than two thirds of total costs are indirect costs. The high indirect costs are a reflection of high absenteeism, decreased productivity while at work and a high proportion of early retirement among this patient group. <b>Disclosure of Interest</b>: C. Bexelius Grant/research support from: GSK, Employee of: Christin Bexelius were at the time of conduction employed by OptumInsight, a consultacy agency within Health Economy and Outcome Research., K. Wachtmeister Employee of: GlaxoSmithKline, Sweden, P. Skare Employee of: GlaxoSmithKline, Sweden, L. Jönsson Grant/research support from: GSK, Merck, Pfizer, Amgen and UCB., Consultant for: GSK, Merck, Pfizer, Amgen and UCB., Employee of: OptumInsight, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB
Amiodarone-Induced Vortex Keratopathy
Authors: Tommy C Y Chan, Vishal Jhanji
Journal: New England Journal of Medicine (2015)

A 50-year-old woman was reported seeing halos around lights through both eyes for a few weeks. Slit-lamp examination showed a whorl-like pattern of corneal epithelial deposits bilaterally, characterizing amiodarone-induced vortex keratopathy.
Abstract 3454: Bcl-xL anti-apoptotic network is dispensable for emergence and maintenance of CML but required for disease progression, and represents an alternative target for halting survival of blast crisis CML progenitors.
Authors: Jason Harb, Paolo Neviani, Justin E. Ellis, Gregory J. Ferenchak, Brenda I. Chyla, Peter Hokland, Denis Claude Roy, Michael A. Caligiuri, Guido Marcucci, Claudia S. Huettner, Danilo Perrotti
Journal: Cancer Research (2013)

Abstract The dismal outcome of blast crisis chronic myelogenous leukemia (CML-BC) patients underscores the need for a better understanding of the mechanisms responsible for the development of drug-resistance and disease progression. We generated an inducible mouse model in which simultaneous expression of p210 BCR-ABL1 and deletion of bcl-x occurs within hematopoietic stem and progenitor cells. Absence of Bcl-xL did not affect the development of the chronic phase-like myeloproliferative disease; however, none of the deficient mice progressed to an advanced phenotype, suggesting the importance of the anti-apoptotic Bcl-xL signaling network for the progressing early progenitor cell survival. Indeed, pharmacologic inhibition of Bcl-xL with the Bcl-xL/Bcl-2 antagonist ABT-263, combined with activation of the Bcl-xL-regulator BAD, through the PP242-mediated inhibition of mTORC1/2, markedly augmented apoptosis of BCR-ABL1+ cell lines and primary CD34+ progenitors from CML-BC but not from healthy donors, regardless of the drug-resistance effect induced by bone marrow stromal cell-generated signals. Accordingly, shRNA-mediated downregulation of BAD and the BCR-ABL1-target hnRNP A1, which promotes translation of Bcl-xL but not Bcl-2, impaired the ability of PP242 to potentiate the effect of ABT-263, and mimicked the anti-leukemic activity of ABT-263, respectively, in primary leukemic CD34+ progenitors and/or CML-BC cell lines. Thus, suppression of the antiapoptotic potential of Bcl-xL together with activation of Bad represents a novel potential pharmacologic approach for treatment of those patients undergoing blastic transformation. Citation Format: Jason Harb, Paolo Neviani, Justin E. Ellis, Gregory J. Ferenchak, Brenda I. Chyla, Peter Hokland, Denis Claude Roy, Michael A. Caligiuri, Guido Marcucci, Claudia S. Huettner, Danilo Perrotti. Bcl-xL anti-apoptotic network is dispensable for emergence and maintenance of CML but required for disease progression, and represents an alternative target for halting survival of blast crisis CML progenitors. [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 3454. doi:10.1158/1538-7445.AM2013-3454
P6 Managing acute pulmonary embolism in the outpatient setting: initial experiences and outcomes in a UK district general hospital
Authors: J. P. Corcoran, J. E. S. Park, C. Goode, C. W. H. Davies
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Outpatient (OP) management of low risk cases of pulmonary embolism (PE) can be as effective as inpatient (IP) management and reduce length of stay (LOS) (1). Concerns exist regarding the safety of this strategy, with a wide range of adverse outcomes reported (2). In our hospital a treatment pathway was implemented to identify low risk individuals diagnosed with PE suitable for OP management, based on the European Society of Cardiology PE Guidelines (2008) (Abstract P6 figure 1). The aim of this study was to retrospectively review all cases of acute PE in a 6-month period, to determine appropriateness of management as OP and assess LOS, venous thromboembolism (VTE) recurrence and anticoagulation related adverse events. <h3>Methods</h3> Episodes of PE occurring between January and June 2010 were identified through clinical coding (ICD-10: I26). Clinical notes were reviewed and data collected for LOS, time to diagnostic investigation, risk stratification (troponin, echocardiography and adverse clinical features), IP/OP management, recurrence of VTE, bleeding events, respiratory clinic follow-up and mortality. <h3>Results</h3> 102 cases were identified of which 90 had acute PE. 81 sets of clinical notes were available. 24 (29.6%) patients were managed as OP. This group was younger than those treated as IP (59.30±3.84 vs 64±2.12, p&lt;0.05). The LOS was significantly shorter for OP: (1.87±0.27 vs 8.79±0.77 days; p&lt;0.0001). There were no episodes of recurrent VTE or bleeding events at 90 days in either group, and only one readmission for anticoagulation related events (high INR; IP group). Three patients (3.7%) died within 90 days (1 from sepsis, 1 from metastatic carcinoma and 1 from congestive cardiac failure). We identified a number of patients with low risk who were not treated as OP for a various reasons. All patients with OP management were subsequently followed by Respiratory team. <h3>Conclusions</h3> Out patient management of diagnosed PE in a carefully selected group is practical, safe and decreases LOS using existing OP DVT services. The use of risk stratification assists identification of safe OP management.
Abstract 839: A novel Gemini vitamin D analog represses a stem cell marker CD44 and its variant CD44v6 and inhibits CD44-Met signaling in breast cancer
Authors: Jae Young So, Amanda K. Smolarek, Hubert Maehr, Millan Uskokovic, Li Cai, Fang Liu, Nanjoo Suh
Journal: Cancer Research (2011)

Abstract CD44, a transmembrane glycoprotein that is involved in cell-cell interaction and cell adhesion, has been recognized as a key cell-surface marker for breast cancer stem cells. The CD44 positive breast cancer cells are enriched in residual breast tumors after conventional therapies, suggesting CD44 as an important therapeutic target to block the recurrence of breast cancer. To investigate CD44 expression during tumor progression, we used the CD44 overexpressing MCF10DCIS.com cell line as a model for breast cancer progression. We injected MCF10DCIS.com cells into immunodeficient mice and analyzed the resulting tumors after 1, 2, 3, 4 and 5 weeks from cell injection. MCF10DCIS.com cells formed ductal carcinoma in situ like lesion by week 2 and invasive tumor lesions by week 3. CD44 proteins were highly expressed in the membrane of epithelial cells in mammary tumors, suggesting that human MCF10DCIS.com cell line might be a useful model for studying therapeutic agents targeting CD44 positive breast cancer cells. We previously reported that a Gemini vitamin D analog, BXL0124, significantly down-regulated the expression level of CD44 in MCF10DCIS.com cells in vitro and in DCIS xenograft tumors. In the present study, we demonstrated that BXL0124 strongly repressed the protein expression level of two alternative splicing variants of CD44, CD44v3 and CD44v6, in MCF10DCIS.com xenografted tumors. Because these CD44 variants are closely associated with breast cancer growth and invasion, the repression of CD44 variants by BXL0124 in MCF10DCIS.com xenograft tumors may contribute to the inhibitory effect of BXL0124 on tumor growth and invasion. We further investigated the effect of BXL0124 on the Met receptor, which is known to interact with CD44v6 for its downstream signaling transduction to control cancer invasion and metastasis. The treatment with BXL0124 decreased the protein expression level of CD44v6 and inhibited hepatocyte growth factor (HGF)-induced Met signaling in cultured MCF10DCIS.com cells. In the CD44 promoter assay, mutation of p53 binding site in the CD44 promoter abolished the repression of CD44 transactivation by BXL0124, indicating that p53 is necessary for the repression of CD44 by BXL0124. In conclusion, BXL0124 repressed CD44 expression in a p53-dependent manner and inhibited CD44-Met signaling in MCF10DCIS.com cells. Our study suggests the Gemini vitamin D analog, BXL0124, is a potentially useful agent in inhibiting breast cancer by targeting CD44 expressing cancer stem cells. 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 839. doi:10.1158/1538-7445.AM2011-839
The<i>Journal</i>from 1812 to 1989 at NEJM.org
Authors: Edward W. Campion, Pamela W. Miller, Jean Costello, Ellen Duff, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2010)

If information is not in digital form, it may as well not exist for today's researchers.That is what we have heard from those who oversee medical and scientific libraries.For several centuries, doing serious research meant spending hours in a major library, usually deep in the solitude of the stacks, exploring through heavy, bound volumes of the print literature.There was no alternative.And until this summer, for readers of the Journal there was no alternative for all that was published before 1993, since that is where the full-text online archive began.That has now changed.At NEJM.org, every issue of the Journal is available in electronic form all the way back to the first article, "Remarks on Angina Pectoris" by John Warren,
Functional Assessment of the Right Ventricle with Gated Myocardial Perfusion SPECT
Authors: Surjit Singh Wadhwa, Martin Caralon, Donna Abbati
Journal: Clinical Nuclear Medicine (2002)

Background The evaluation of right ventricular function can provide valuable information in a variety of cardiac and noncardiac conditions. Functional assessment of the right ventricle is difficult because of its anatomy and geometry. The authors describe a method for assessing right ventricular function using gated myocardial perfusion SPECT. Methods In 20 patients, right and left ventricular ejection fractions (RVEF, LVEF) were determined using gated blood-pool scintigraphy (GBPS) and gated myocardial perfusion SPECT (GSPECT). To avoid contamination with right atrial activity, the two-frame method was adopted for gated blood-pool data when RVEF was measured. In nine patients with normal right ventricles, an index of wall thickening for the right ventricle was derived from the peak systolic and diastolic counts in the free wall. Results Linear correlation between the two methods adopted for calculation of LVEF and RVEF was good. Bland-Altman analysis revealed good agreement between the two methods with no specific bias. The mean LVEF was 47.9 ± 12% (GBPS) and 47.3 ± 12.4 (GSPECT). The mean RVEF was 43.2 ± 9.6% (GBPS) and 44.2 ± 8.5% (GSPECT). In both cases, the values were not significantly different. The mean wall motion index was 35%. There was no correlation between the wall thickness index and ejection fraction, but the index was greater in patients with a normal right ventricle compared with those with reduced RVEF. Conclusions Gated SPECT offers an alternative to GBPS for the functional assessment of the right ventricle. Using GSPECT will allow the simultaneous assessment of both the right and left ventricles.
Apolipoprotein A-I Gene Polymorphism Associated with Premature Coronary Artery Disease and Familial Hypoalphalipoproteinemia
Authors: Jose M. Ordovas, Ernst J. Schaefer, Deeb Salem, Ryk H. Ward, Charles J. Glueck, Carlo Vergani, Peter W.F. Wilson, Sotirios K. Karathanasis
Journal: New England Journal of Medicine (1986)

Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.
Clinical course and proposed treatment strategy for ERCP-related duodenal perforation: a multicenter analysis
Authors: Young-Joo Jin, Seok Jeong, Jin Kim, Jae Hwang, Byung Yoo, Jong Moon, Sang Park, Ho Kim, Dong Lee, Yong Jeon, Don Lee
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Endoscopic retrograde cholangiopancreatography (ERCP)-related duodenal perforation is rare but can cause high mortality. Our aim was to assess the clinical outcomes of these events. <b>Method: </b>A total of 59 patients who were diagnosed as having ERCP-related duodenal perforation at six institutions between 2000 and 2007 were enrolled in this multicenter retrospective study. We evaluated complications and mortality associated with ERCP-related duodenal perforation according to injury detection time (IDT), peritoneal irritation signs (PIS), systemic inflammation signs (SIS), and treatment modality in these patients. <b>Results:</b> Of the 59 patients, 41 (69.5 %) and 18 (30.5 %) underwent medical and surgical treatment, respectively. Duodenal perforation-related death was observed in five patients, who had received medical therapy (n = 2) and surgical therapy (n = 3). Among medically treated patients, seven patients (17.1 %) underwent endoscopic clipping immediately after the injury; surgery was not required as a salvage therapy and there were no complications or deaths among these patients. The remaining 34 patients received antibiotics combined with therapeutic fasting and intravenous hydration. Duodenal perforation-related complications depended significantly on IDT (<i>P</i> = 0.0001), treatment modality (<i>P</i> = 0.008), PIS (<i>P</i> = 0.003), and SIS (<i>P</i> = 0.010). The duodenal perforation-related mortality was significantly related to IDT (<i>P</i> = 0.008) and PIS (<i>P</i> = 0.001). <b>Conclusions:</b> IDT, PIS, and SIS appear to be important prognostic factors following ERCP-related duodenal perforation. Medical therapy can be suggested as an initial treatment strategy for ERCP-related duodenal perforation, and if possible, endoscopic clipping is strongly recommended. However, surgical treatment should be considered if the perforation is not expected to seal spontaneously, or if the continuing leakage causes PIS or SIS.