tbuckley/cabot-search huggingface dataset:
Abstract 4959: Multispectral imaging of chromogenic multiplex IHC assays as an alternative to fluorescent methods
Authors: Christopher A. Kerfoot, Sherif Girees, Lisa M. Dauffenbach
Journal: Cancer Research (2010)

Abstract Detection and analysis of two or more co-localized antigens by light microscopy has been hindered by the difficulty in discerning and quantifying overlaying chromogens. Performing multi-analyte immunohistochemistry has many potential benefits and applications in the field of drug target evaluation and patient screening, including: 1) determination and quantification of immunoreactivity co-localization; 2) evaluation of spatial relationships between immunoreactive cell types; 3) signal transduction pathway activation studies; 4) reduction in tissue depletion; and 5) decreased reagent utilization. Multiplex immunofluorescence is not widely used as an analytical technique for clinical samples due to its lower sensitivity than chromogenic methods and concerns about autofluorescence in formalin-fixed tissue. Through the use of multispectral imaging, the absorption pattern of overlapping chromogens can be spectrally unmixed into quantitative individual dye components. This process works accurately when chromogens are developed to a lower intensity than typical for most standard pathology laboratories. The chromogens must be developed to a point where they do not scatter light or block subsequent chromogenic development. The current study was performed to define the accuracy of spectral unmixing of chromogens and evaluate whether interference existed between chromogens. Stained samples were imaged using multispectral imaging, and quantitative grayscale images for each analyte were created by spectral unmixing. The grayscale images were analyzed using image analysis software to determine the overall expression levels of each analyte. Development with Vulcan Red followed by DAB produced little interference, while high density development with DAB decreased the subsequent Vulcan Red staining intensity. Vulcan Red, DAB and hematoxylin unmixed properly and quantitatively. In summary, when multiplexed chromogenic IHC assays were developed using methods optimized for multispectral imaging, the technique demonstrated excellence performance characteristics without suffering from drawbacks commonly associated with fluorescence-based techniques. 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 4959.
Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice
Authors: Jochen Reinöhl, Klaus Kaier, Holger Reinecke, Claudia Schmoor, Lutz Frankenstein, Werner Vach, Alain Cribier, Friedhelm Beyersdorf, Christoph Bode, Manfred Zehender
Journal: New England Journal of Medicine (2015)

Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards.We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013.In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined.The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).
A rare case of acute pancreatitis induced by a gastrointestinal stromal tumor arising from the gastric fundus
Authors: J. Sun, X. Shen, Z. Li, J. Zhu
Journal: Endoscopy (2012)

An 82-year-old woman presented as an emergency with a 20-hour history of abdominal distension and acute epigastric pain radiating to her back. The pain was associated with nausea, vomiting, anorexia, and weight loss. Physical examination revealed midepigastric tenderness with a palpable mass. Pertinent laboratory values included a high white blood cell count of 21.5 × 109/L, a C-reactive protein (CRP) level of 17.8 mg/L, a serum amylase of 1200 units/L, and urinary amylase of 2000 units/L. An abdominal computed tomography (CT) scan showed a 4.0 × 4.0 × 8.0-cm duodenal mass, but no regional lymph node or distant metastases ([Fig. 1]). The diagnosis of pancreatitis was proposed.
THU0024 High Mortality in North American Indigenous People with Systemic Lupus Erythematosus (SLE):
Authors: R. Puar, C. Hitchon, C. Peschken
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Lupus outcomes including mortality have been found to be worse in most ethnic minorities, including African Americans, Asians, and Hispanics, but little is known about North American Indigenous people (NAI). <h3>Objectives</h3> To compare mortality in NAI SLE patients to Caucasian SLE patients followed at a single centre. <h3>Methods</h3> Patients from a single academic center were followed from 1990-2013 using a custom database. Variables included date of birth, diagnosis, year of disease onset, ethnicity, clinic visits dates, and vital status if known. Records of all patients with a diagnosis of SLE (≥4 American College of Rheumatology criteria) were abstracted. For patients who had not been seen in the last 2 years, updated vital status was obtained from the hospital medical records department. Ethnicity was by self-report, and categorized into NAI, Caucasian and other. The age at diagnosis, disease duration and age at last follow up or age at death was calculated and compared between ethnic groups. Survival time was compared between NAI and Caucasians using Kaplan Meier and Cox proportional hazard models. <h3>Results</h3> A total of 807 patients with SLE were identified: 201 (25%) patients were NAI, 501 (62%) were Caucasian, and the remaining 105 (13%) were of other ethnic backgrounds and were excluded from subsequent analyses. NAI patients were younger at diagnosis (NAI =32±15 years vs. Caucasian =37±15 years; p=0.001) and had a shorter disease duration at last follow up compared to Caucasians: (NAI =11±9 years vs. Caucasian =15±11 years; p=0.001.) More NAI had died by the end of the follow-up period (NAN =25% vs. Caucasian =18% p&lt;0.001) and mean age at death was much younger in NAI (NAI =50±16 years vs. Caucasian =63±16 yrs p=0.001). Survival rates were significantly worse in NAI compared to Caucasians: 5 year survival was 92% vs. 97%; 10 year survival 85% vs. 92%; 15year survival 78% vs. 88% respectively (p&lt;0.001). In a cox proportional hazards model, the risk of death overall was higher for the NAI (hazard ratio 3.3; 95%CI: 2.3-4.8) than for Caucasians, as was the risk of death following diagnosis (hazard ratio 2.1; 95%CI: 1.4-3.1). <h3>Conclusions</h3> While mortality in our Caucasian lupus patients was comparable to recent reports in other regions, mortality was high in NAI patients, beginning within five years of diagnosis and continuing to increase over time, even though NAI patients were younger at diagnosis. While further research to identify the determinants of this excess mortality is ongoing, this study demonstrates the urgent need for improved care delivery for NAI with SLE to decrease the significant morbidity and mortality burden from this disease. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2408
Myxovirus as a Possible Etiologic Agent in Subacute Inclusion-Body Encephalitis
Authors: Cheng-Mei Shaw, G. Colin Buchan, Coldevin B. Carlson
Journal: New England Journal of Medicine (1967)

SUBACUTE inclusion-body encephalitis (Dawson) and subacute sclerosing leukoencephalitis (Van Bogaert) are now generally considered to be the same entity1 characterized by inflammatory changes in the cerebra1 gray matter, with intranuclear inclusions in neurons and glia and with variably severe demyelination and gliosis of the white matter.The etiology of this form of encephalitis has remained undefined, although the intranuclear inclusions and recent transmissions to animals by inoculation of brain or cerebrospinal fluid from patients2 3 4 have given strong presumptive evidence that the disease is caused by one or more viral agents. The nature of the virus and the possibility that multiple . . .
Recruiting New Physicians, Part III
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2013)

The final phase of the recruitment effort is to make sure that the candidate fulfills the needs of the group and to try to make as sure as possible that the candidate would be happy in the new position. This means there must be a very candid exchange of information regarding the goals and expectations of the group and the individual, and how the group’s expectations will be measured. It also means making sure that there is a good fit between the culture of the group and the desires of the candidate. Furthermore, a substantial effort should be made to make sure the candidate (and his family) will be happy in the practice location.
Epigenetic Control of Estrogen Synthesis in Human Preadipocytes and Breast Cancer Cells.
Authors: K. Knower, S. To, S. To, E. Simpson, E. Simpson, C. Clyne, C. Clyne
Journal: Cancer Research (2009)

Abstract Estrogen plays a significant role in the development and progression of breast cancer (BC). Cytochrome aromatase p450, encoded by the gene CYP19, is the key enzyme catalyzing the synthesis of estrogens from androgens. In post-menopausal women, adipose tissue becomes the major site for estrogen production and an increase in CYP19 expression in mammary adipose is strongly linked to the hormone-dependent progression of BC. Therefore, understanding CYP19 regulation in BC is critical for the development of therapeutic measures. Previous studies of CYP19 regulation in BC have mainly focussed on hormone-induced regulation of transcription via upstream tissue- and promoter-specific regulatory regions. While this is clearly important, it is increasingly evident that epigenetic regulation of expression, such as DNA methylation, is also a common factor in the progression of cancers. The aim of this study was to investigate whether CYP19 expression is under epigenetic regulation and to determine if such mechanisms contribute to the tissue- and promoter-specific expression of CYP19 observed in BC.CYP19 transcripts in cancer-free primary human breast adipose fibroblasts (BAFs) stimulated with cytokines and glucocorticoids (e.g. TNFα and dexamethasone) are derived from the distal promoter 1.4, whereas breast tumour-derived factors (e.g. prostaglandin E2) induce a regulatory switch to proximal promoters 1.3 and II. DNA from BAFs maintained under these two conditions was treated with sodium bisulfite allowing for methylation analysis of CpG dinucleotides. Methylation mapping revealed a stochastic heterogeneous level of methylation among 9 CpG sites (promoter 1.4) and 11 CpG sites (promoters 1.3 and II) in untreated BAFs.No correlation was observed between promoter methylation and promoter activation after response to stimuli. However, treatment of BAFs with 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, increased total CYP19 mRNA expression up to 40-fold, primarily via promoter 1.4 thorugh up-regulation of trans-acting factors, suggesting CYP19 is under tonic inhibition by methylation in BAFs. Similar results were also obtained in four BC cell lines. Ongoing work has elucidated trans-acting factors of CYP19 epigenetically silenced in BAFs. These studies uncover a new layer of complexity in the regulation of aromatase expression in BC and may identify new targets for epigenetic therapy, including DNA methylation inhibitors. These findings will translate to BC by determining the methylation state of CYP19 in clinical BC specimens, and by correlation with clinicopathological parameters such as steroid receptor status, grade and stage. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1147.
LONG-TERM PROGNOSIS IN MENTAL ILLNESS
Authors: WILLIAM L. HOLT, WINIFRED M. HOLT
Journal: American Journal of Psychiatry (1952)

All of the 141 patients admitted in 1921 to Westborough State Hospital soon after study at the Boston Psychopathic Hospital were investigated 30 years later. Only 7% of the group could not be traced. The study included age, diagnoses, time spent in hospital, condition on discharge, community adjustment, age at death, and cause of death. In this cross-section sample, 26% of all admissions traced were recovered before death or when seen after 30 years. It was noteworthy that the dementia præcox patients, constituting 42% of the group, accounted for 39% of the surviving patients in the community and 35% of all recovered patients. Where no significant diagnostic disagreement occurred throughout successive hospitalizations, only 13% of dementia præcox patients were recovered. Where the last hospital diagnosis was accepted as valid, 23% of dementia præcox patients were recovered at death or when seen after 30 years and an additional 6% were much improved.
Case 29-2008
Authors: Mark A. Goldstein, David B. Herzog, Madhusmita Misra, Pallavi Sagar
Journal: New England Journal of Medicine (2008)

A 19-year-old man was admitted to this hospital because of acute abdominal pain, which had begun the previous day. Imaging studies disclosed dilatation of the colon and small bowel, with no obstruction or free air. Administration of fluids and laxatives resulted in resolution of the pain. The patient had had anorexia nervosa since the age of 14 years and had recently lost several kilograms of weight. He was admitted to the psychiatric inpatient unit, and a treatment plan was established.
Effect of carfilzomib, lenalidomide, and dexamethasone (KRd) vs lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma (RMM) by line of therapy: Secondary analysis from an interim analysis of the phase III study ASPIRE (NCT01080391).
Authors: Meletios A. Dimopoulos, A. Keith Stewart, S. Vincent Rajkumar, Tamás Masszi, Albert Oriol, Roman Hajek, Laura Rosinol, David Samuel DiCapua Siegel, Georgi Mihaylov, Vesselina Goranova-Marinova, Peter Rajnics, Aleksandr Suvorov, Ruben Niesvizky, Andrzej J. Jakubowiak, Jesus F. San Miguel, Heinz Ludwig, Naseem J. Zojwalla, Philippe Moreau, Antonio Palumbo
Journal: Journal of Clinical Oncology (2015)

8525 Background: Previously reported results from ASPIRE (N = 792 patients) showed that KRd significantly improved progression-free survival (PFS) vs Rd in RMM with a favorable benefit-risk profile (Stewart et al. N Engl J Med2015;372:142–52). A secondary analysis of efficacy and safety results from patients treated with KRd or Rd after first relapse (1 prior line of therapy) vs ≥ 2 prior lines of therapy are presented. Methods: Adults with RMM who received 1–3 prior lines were eligible. Patients were randomized (1:1) to KRd or Rd. All patients received lenalidomide (25 mg) on days 1–21 and dexamethasone (40 mg) on days 1, 8, 15, and 22 of a 28-day cycle. Patients in the KRd arm received carfilzomib as a 10-min infusion on days 1, 2, 8, 9, 15, and 16 during cycles 1–12 (20 mg/m2 [days 1 and 2 of cycle 1]; 27 mg/m2thereafter). Carfilzomib was omitted on days 8 and 9 during cycles 13–18 and was not administered beyond 18 cycles. Results: Median PFS for patients receiving 1 prior line (n = 341) was 29.6 months (95% confidence interval [CI]: 23.2–33.5) for KRd vs 17.6 months (95% CI: 15.0–22.2) for Rd (hazard ratio [HR]: 0.694; P= .0083). Median PFS for patients receiving ≥ 2 prior lines (n = 451) was 25.8 months (95% CI: 22.2–31.0) for KRd vs 16.7 months (95% CI: 13.9–22.0) for Rd (HR: 0.688; P= .0017). No grade ≥ 3 adverse events (AEs) occurred ≥ 5.0% more frequently with KRd vs Rd in patients who received 1 prior line of therapy; hypokalemia was the only grade ≥ 3 AE that occurred ≥ 5.0% more frequently with KRd (11.0%) vs Rd (3.4%) in patients who received ≥ 2 prior lines. For patients on KRd, neutropenia was the only grade ≥ 3 AE that occurred ≥ 5.0% more frequently after ≥ 2 prior lines (32.4%) vs 1 prior line of therapy (26.4%). Conclusions: The use ofKRd after first relapse led to a 1-year improvement in median PFS vs Rd compared with a 9-month improvement in median PFS vs Rd in pts with ≥ 2 prior lines of therapy, with similar HRs. KRd had a favorable benefit–risk profile after 1 and ≥ 2 prior lines of therapy in patients with RMM. Clinical trial information: NCT01080391.
AB0535 Effects of disease activity and physical functions on sexual life in patients with ankylosing spondylitis
Authors: E. Ozcan, S. Esmaeilzadeh, E. I. Sen, A. Rezvani, T. Baysak, A. Karan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study is to evaluate the sexual functions in patients with Ankylosing Spondylitis (AS) and to determine the relationships between sexual problems and disease activity as well as physical function. <h3>Methods</h3> Atotal of 64 consecutive and unselected patients with AS who were referred to the Rheumatologic Rehabilitation Unit were included in this study. Patients completed a self-administered questionnaire on sexual activity. Disease activity and physical function were assessed with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI), respectively. The BASDAI/BASFI scores in patients with and without sexual problems were compared with Mann-WhitneyU test. <h3>Results</h3> Themean age of the patients was 37.5±8.4 (20-55) years, 85.9% (n=55) of the patients were male. 26.6% of patients mentioned that AS affected adverselytheir sexual life; and 34.4% of patients had physically limitations on sexual intercourse due to the AS. 42.2% of patients specified that during the exacerbation of AS, their sexual relationship was affected adversely. There was a decrease in sexual problems during the remission phase in 28.1% of the patients. Among the patients whose sexual life affected due to the AS, either the BASDAI (p=0.040) and the BASFI (p=0.016) scores were significantly high compared to those who did not affect. Furthermore, the patients who had physical problems during sexual intercourse, the BASDAI (p=0.004) and the BASFI (p=0.011) scores were significantly highcompared to those who did not have the physical problem. <h3>Conclusions</h3> Thesefindings suggest that both disease activity and limitations in physical functioning are associated with sexual activity in patients with AS. Finally, in conjunction with treatment protocols, emphasis on the impact of AS on sexual functions, also any attempts to improve the physical functions and control the disease activity will increase the efficacy of medical care and rehabilitation programs in patients with AS. <h3>Disclosure of Interest</h3> None Declared
SAT0398 Diagnostic value of anti mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: A multicentric study by firma group
Authors: E. Bartoloni, A. Alunno, O. Bistoni, N. Bizzaro, G. Morozzi, A. Doria, A. Mathieu, M. Lotzniker, F. Allegri, V. Riccieri, C. Alpini, A. Gabrielli, M. Tampoia, R. Gerli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In recent years the diagnostic approach to rheumatoid arthritis (RA) significantly changed. Among new serological assays, an ELISA test detecting antibodies directed against recombinant mutated citrullinated vimentin (anti-MCV), a protein widely expressed in the synovium, has been introduced to improve diagnosis. Anti-MCV appear slightly more or as sensitive as anti-cyclic citrullinated protein antibodies (anti-CCP), but less specific. However, its additional diagnostic value with respect to anti-CCP both in early and established RA is controversial. <h3>Objectives</h3> Evaluate the diagnostic performance of anti-MCV assay in RA and to compare it to a standard anti-CCP test and the recently developed assay targeting viral citrullinated peptide 2 (VCP2) (1,2) in a large cohort of RA patients and healthy and disease controls. <h3>Methods</h3> Sera (n=512) from long-standing RA patients (n=285) and healthy and disease controls (n=227) were randomly collected. Anti-CCP were measured by the routine method used in each Center. As 4 different assays were used, anti-CCP values were normalized and expressed as a ratio. Anti-VCP IgG were detected by the 2nd generation method (Astra Diagnostici, Milan, Italy) and anti-MCV by the available ELISA kit (Orgentec Diagnostika GmbH, Mainz, Germany). The receiver-operating characteristic (ROC) curve was calculated to determine the optimal cutoff values for each antibody assay. <h3>Results</h3> At the calculated cutoff value of 55 U/mL, anti-MCV resulted to have a sensitivity of 59% and a specificity of 92%. In comparison, anti-CCP (calculated cutoff of 5 U/mL) and anti-VCP2 (calculated cutoff of 21 AU) displayed a sensitivity of 77% and 61% and a specificity of 96% and 95%, respectively. Of interest, a high percentage of healthy subjects as well as Epstain Barr and hepatitis C virus-infected patients resulted anti-MCV positive at the manufacturer recommended cutoff value of 20 U/mL. <h3>Conclusions</h3> In our large cohort of RA patients, at the calculated cutoff of 55 U/mL, anti-MCV demonstrated lower sensitivity than anti-CCP and VCP2 test, thus not allowing to confirm previously published data. Moreover, the high rate of detection in infectious diseases limits its diagnostic value in undifferentiated arthritis. On the basis of our results, an international validated anti-MCV cutoff value to standardize the results is surely needed. <h3>References</h3> Bizzaro N et al., J Clin Pathol 2011;64:1139 Pratesi F et al., Clin Exp Immunol 2011;164:337 <h3>Disclosure of Interest</h3> None Declared