tbuckley/cabot-search huggingface dataset:
PTU-128 A Web-based Survey To Investigate Physicians’ And Intensivists’ Attitudes To Critical Care Admission For Cirrhosis And Multiple Organ Dysfunction
Authors: P Berry, SJ Thomson, M Peck, T Standley
Journal: Gut (2014)

<h3>Introduction</h3> Hospital admissions for cirrhosis and related complications are rising and patients are getting younger. Hence, physicians are increasingly faced with making difficult referrals to intensive care for patients with multiple organ dysfunction. We examined the attitudes of a mixed cohort of physicians and intensivists, including trainees, to compare critical care admission decisions for a range of medical diagnoses including cirrhosis. <h3>Methods</h3> A web survey containing eight clinical scenarios, including one describing a 45 year old man with severely decompensated ALD (bilirubin 410 umol/L), sepsis and renal failure (prior to resuscitation) was advertised via email to trusts in the south of England. Respondents were asked to rate the degree with which they would advocate for ICU admission on a scale on 1–10 (1 = would not consider ICU, 10 = insist on ICU). All cases had similar SOFA scores (10–11). Other cases included pneumonia, chronic airways disease, GI bleeding with loss of output, relapsed myeloma, post operative aspiration, ruptured AAA, and CKD requiring renal replacement. Opinions on the level of organ support to be offered, or alternatively the ceilings of de-escalated care were further explored. <h3>Results</h3> Of 144 respondents, 23% were consultant physicians, 22% consultant anaesthetists and 22% specialist trainees. Mean advocacy score for ALD was 7.2, which ranked 4 out of 8 scenarios. COPD scored lowest, with a mean score of 4.9, acute on chronic kidney disease highest with 8.5. 55% would strongly advocate for escalation (score 8, 9 or 10). Of the 21 who did not favour escalation to ICU (score 1–5), “unlikely to survive ICU admission” (80%) and “end stage organ disease” (85%) were the most frequently cited reasons, and 6 cited “lifestyle decision”. 9 recommended making the patient DNACPR and 3 would institute palliative care measures. Of the majority who would consider escalation, 69% recommended “No limits on care – full escalation”. In a separate question 34% of all respondents said they “frequently” (12%) or “sometimes” (21%) considered resource utilisation or cost when making individual clinical decisions on escalation of care. <h3>Conclusion</h3> Most respondents favoured escalation of care to some degree, however a significant minority interpreted the same clinical information with a degree of prognostic pessimism. Continued education regarding early opportunities to improve prognosis in decompensated liver disease is required. <h3>Disclosure of Interest</h3> None Declared.
Abstract 4037: Higher Expressions of miR-21, miR-106a, miR-181b, and miR-203 are Associated with Poor Prognosis in Colorectal Cancer Patients
Authors: Liselle Bovell, Venkat R. Katkoori, Chandrakumar Shanmugam, Choo H. Lee, Sreelatha Meleth, Harvey L. Bumpers, William E. Grizzle, Upender Manne
Journal: Cancer Research (2010)

Abstract Background: MicroRNAs (miRNAs) are a family of small (20- to 24-nucleotide) non-coding RNAs that regulate gene expression at the post-transcriptional level. Although miRNAs are potential prognostic biomarkers in colorectal cancers (CRCs), their value based on the patient race/ethnicity has not been examined. Thus, this study evaluated the prognostic value of miRNAs for CRCs in African-Americans (Blacks) and non-Hispanic Caucasians (Whites). Methods: TaqMan® microRNA assays and qRT-PCR were used to quantify the expression profiles of a panel of miRNAs (miR-20a, miR-21, miR-106a, miR-181b, and miR-203) in CRCs and corresponding benign tissues collected from 104 Blacks and 114 Whites. The expression profiles were correlated with patient overall survival, and p values were calculated by the log-rank test. Results: For both racial groups, all five miRNAs had higher expression in CRCs (&amp;gt;1.0 fold; range, 1.23 to 7.52) compared to their corresponding controls. Univariate Kaplan-Meier analyses demonstrated that increased expression of miR-106a was associated with decreased overall survival of both Blacks and Whites (p=0.040 and p=0.049, respectively). Increased expressions of miR-181b and miR-203 were each significantly associated with short patient survival of Blacks (p=0.009 and 0.003, respectively), but not Whites (p=0.117 and p=0.071, respectively). When Blacks and Whites were combined, over-expression of miR-21 was associated with poor patient survival (p=0.049), but statistical significance was not reached when the values were analyzed based on race. In contrast, increased expression of miR-20a was not associated with survival of either Blacks (p=0.193), Whites (p=0.242), or the combined patient population (p=0.072). Conclusions: These findings suggest that, for all CRC patients, over-expression of miR-21 and miR-106a are associated with poor prognosis, whereas over-expression of miR-181b and miR-203 are associated with poor outcomes for Blacks. These findings suggest that, in prognostic assessment of miRNAs in CRC, patient race/ethnicity should be considered. These studies were supported by NCI/NIH grants, U54-CA118948 and R01-CA098932-01. 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 4037.
Abstract 454: Targeting macrophages in a preclinical model of malignant mesothelioma
Authors: Collin M. Blakely, Nikita Kolhatkar, Magnus Johansson, Adam Beltran, Dario Barbone, Raphael Bueno, David Sugarbaker, Thierry Jahan, David Jablons, V. Courtney Broaddus, Lisa M. Coussens
Journal: Cancer Research (2011)

Abstract Malignant pleural mesothelioma (MPM) is a debilitating, incurable cancer that exhibits a high degree of resistance to standard chemotherapy; thus, we sought to identify novel therapeutic targets for treatment. In the vast majority of cases, MPM is associated with exposure to asbestos fibers, which result in a chronic pro-inflammatory state. As such, we hypothesized that MPMs were infiltrated by leukocytes possessing tumor-potentiating activities. To address this, we evaluated MPMs, resected from 26 patients, by flow cytometry and found that tumors were highly infiltrated with macrophages (31 ± 4.6% of total CD45+), a percentage that is significantly higher that that observed in other thoracic malignancies (NSCLC cancer, 9%; esophageal, 4%). Since recent experimental data has revealed that tumor-associated macrophages (TAMs) secrete proangiogenic, prosurvival, and proinvasive factors that foster tumor progression, we evaluated macrophage-depletion in MPM as a novel therapeutic strategy. Using a syngeneic murine transplantation model and liposomal-encapsulated clodronate that efficiently deplete phagocytic macrophages, as monotherapy, and in combination with chemotherapy, we revealed a significant decrease in tumor growth and a decrease in tumor-burden in tumor-bearing mice depleted of macrophages. Furthermore, when macrophage-depletion was combined with the cytotoxic agents gemcitabine and TRAIL, an even greater reduction in tumor burden was observed as compared to mice treated with either agent alone. These studies indicate that: 1) mesothelioma-associated macrophages provide a protumor function, and 2) depletion of mesothelioma-associated macrophages may improve efficacy of cytotoxic chemotherapy. Ongoing studies to reveal the effect of macrophage-depletion plus chemotherapy in limiting MPM development in NF2ko/+ mice exposed to asbestos are underway. This work was supported by an NIH T32 training grant to Dr. Blakely, and by a DoD Mesothelioma Program grant (PR080717) to Drs. Broaddus and Coussens. 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 454. doi:10.1158/1538-7445.AM2011-454
549 INHIBITION OF p53 MITIGATES ETHANOL-INDUCED TIGAR UPREGULATION, REDUCTIVE STRESS AND SUBSEQUENTLY IMPROVES HEPATIC INSULIN SIGNALING IN THE LIVERS OF ETHANOL-FED LONG–EVANS RATS
Authors: Z. Derdak, A. Sousa, A. Wu, J. Wands
Journal: Journal of Hepatology (2013)
Aperistalsis of the Esophagus in Patients with Connective-Tissue Disorders and Raynaud's Phenomenon
Authors: Mary Betty Stevens, Perry Hookman, Charles I. Siegel, John R. Esterly, Lawrence E. Shulman, Thomas R. Hendrix
Journal: New England Journal of Medicine (1964)

EXTENSIVE clinical data have been accumulated during recent years that support the view that scleroderma is a systemic disease. In addition to cutaneous involvement, which remains the cardinal diagnostic feature, widespread visceral lesions are found in the majority of patients with this disorder.Involvement of the gastrointestinal tract is especially common. Since Ehrmann's1 initial observation of dysphagia in a patient with scleroderma, much attention has been directed toward defining the character of the esophageal lesion. Radiographic studies2 , 3 and measurements of intraluminal pressures4 5 6 have shown the primary defect of the So-Called "sclerodermatous" esophagus to be the loss of peristalsis. Despite the . . .
Accumulation of Tc-99m HMDP in Ovarian Serous Papillary Adenocarcinoma Reflecting Ongoing Calcification
Authors: T Kikuchi, Y Sugawara, M Kajihara, S Nakata, T Mochizuki, J Ikezoe, T Katayama
Journal: Clinical Nuclear Medicine (2001)

KIKUCHI, TAKANORI M.D.*; SUGAWARA, YOSHIFUMI M.D.*; KAJIHARA, MAKOTO M.D.*; NAKATA, SHIGERU C.N.M.T.*; MOCHIZUKI, TERUHITO M.D.*; IKEZOE, JUNPEI M.D.*; KATAYAMA, TOMIHIRO M.D.† Author Information
Abstract 3184: Diagnostic value of Annexin A1 as a marker for myoepithelial cells in normal breast glands but is lost in malignant breast glands
Authors: Yahya I. Elshimali, Yanyuan Wu, Daniel Chen, Jaydutt V. Vadgama
Journal: Cancer Research (2011)

Abstract Introduction: Annexin AI belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins. Annexin I has been of interest for use as a potential target for anticancer drugs. Upon induction by modified NSAIDS and other potent anti-inflammatory drugs, annexin I inhibits the NF-κB signal transduction pathway, which is exploited by cancerous cells to proliferate and avoid apoptosis. ANXA1 inhibits the activation of NF-κB by binding to the p65 subunit. Methods: We used immunohistochemistry stain of Annexin A1 monoclonal antibody to study its expression in 100 cases of breast tissue, 50 cases of normal tissue vs. 50 cases of malignant tissue, using tissue micro array (TMA). Results: Our analysis show a decreased expression of Annexin A1 in malignant tissues compared to non-malignant tissues. Annexin A1 stains myoepithelial cells in 95 % of normal glands, but it is absent in 90 % of the periphery malignant glands. This is most likely due to the absence of the myoepithelial cells. Conclusion: We conclude that Annexin A1 has diagnostic value in breast pathology by staining myoepithelial cells of normal gland in addition to its characteristic in staining of normal ductal cells at different intensity. Annexin A1 could be used as a biomarker for myoepithelial cells in surgical pathology practice. 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 3184. doi:10.1158/1538-7445.AM2011-3184
Incidence of venous thromboembolism in COPD: linking inflammation and thrombosis?
Authors: Mareike Lankeit, Matthias Held
Journal: European Respiratory Journal (2016)

Chronic obstructive pulmonary disease (COPD) is a major health burden and expected to become the third leading cause of death by 2030 \[1, 2]. Acute exacerbations with aggravation of respiratory symptoms are associated with an acceleration of progressive lung function decline and significant worsening of prognosis (in-hospital mortality rate, 10%; 3-year mortality rate, 49%) [2]. Management of patients with COPD presenting with worsening dyspnoea remains challenging and, in approximately one-third of cases, the underlying cause cannot be identified [2]. Importantly, evidence is accumulating that, in a relevant proportion of patients presenting with symptoms of an exacerbation of COPD, the underlying condition is an acute episode of pulmonary embolism. Of all the studies published over the past 10 years, which investigated the prevalence of pulmonary embolism in patients hospitalised for exacerbation of COPD [3–12\] (table 1), those with a prospective study design including a standardised protocol for pulmonary embolism examination (highlighted in bold in table 1 [3, 5–7, 9–11] reported a high prevalence of pulmonary embolism (14.4% (203 of 1406 patients); range 3.3–29.1%). On the other hand, retrospective population data from 58 392 000 patients hospitalised with COPD from 1979 to 2003 registered in the United States National Hospital Discharge Survey suggest that, in patients with COPD, both deep vein thrombosis (632 000 patients (1.08%)) and pulmonary embolism (381 000 patients (0.65%)) are generally underdiagnosed in clinical practice [13]. Furthermore, in a retrospective observational study including 436 consecutive patients with acute pulmonary embolism, COPD was identified as an independent predictor of a delayed diagnosis [14]. Given the therapeutic and prognostic implications of a (missed) diagnosis of acute pulmonary embolism, it appears crucial to increase awareness of this clinical condition [15], identify predictors of pulmonary embolism in patients with COPD exacerbation [11] and incorporate pulmonary embolism into the differential diagnosis work-up of COPD patients presenting with worsening dyspnoea. Impact of systemic inflammation to an increased prevalence and incidence of VTE in COPD patients <http://ow.ly/UgU1a>
Irradiation of the Nasopharynx in Children with Infectious Asthma
Authors: Harry L. Mueller, Carlyle G. Flake
Journal: New England Journal of Medicine (1952)

THE therapeutic effect of irradiation in allergic diseases, principally asthma, has been the subject of investigation and discussion since 1906, when Schilling, as reported by MacInnis,1 observed that asthmatic patients were frequently relieved after fluoroscopy. Other reports appeared from time to time, but Maytum2 studied it thoroughly in 1939, reporting some 215 cases treated by irradiation over the mediastinum in whom the effect was found to be only temporary in any case and, in 47 per cent of those observed, a complete failure. In 1945, a study made by Army Air Force Surgeons3 of several thousand children and adults with . . .
Abstract 4435: Overexpression of Rhotekin confers gastric cancer cells resistance to interferon-α-mediated growth inhibition
Authors: Tsun-Ying Yin, Ya-Wen Hsiao, Wen-Hsin Peng, Mei-June Wang, Jeou-Yuan Chen
Journal: Cancer Research (2012)

Abstract Tumor infiltrating lymphocytes (TILs) are frequently detected in a variety of malignancies, including gastric cancer (GC). TILs are known to produce high level of interferon-gamma (IFN-γ) in GC, but fail to suppress tumor growth. We have previously shown that Rhotekin (RTKN), the gene encoding the Rho effector RTKN, is overexpressed in human GC, and its expression is correlated with disease progression. In this study, we show that RTKN expression efficiently blocks IFN-γ-mediated anti-growth and immunologic responses, suggesting a role of RTKN in attenuating tumor immunosurveillance during GC pathogenesis. We show that RTKN attenuates STAT1 phosphorylation in response to IFN-γ, and confers increased resistance to IFN-γ-mediated growth suppression in GC cells through inhibiting the expression of STAT1-dependent downstream target genes, including cyclin-dependent kinase inhibitor p21 and antiapoptotic genes BCL-2 and BCL-xL. Conversely, elimination of RTKN expression by knockdown approach facilitates IFN-γ-mediated STAT1 phosphorylation and promotes IFN-γ-mediated growth arrest and apoptosis. We further show that RTKN-mediated inhibition of STAT1 phosphorylation can be reversed by the treatment of sodium orthovanadate, a tyrosine phosphatase inhibitor, suggesting the involvement of tyrosine phosphatases in RTKN-mediated process. In support, our data show that RTKN suppresses IFN-γ-mediated STAT1 phosphorylation partly through facilitating the interactions of SHP2 and STAT1. In summary, our data suggest that RTKN overexpression confers growth advantages to GC by evading immunosurveillance through suppression of IFN-γ-mediated anti-tumor activity. 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 4435. doi:1538-7445.AM2012-4435
Mebrofenin Clearance Rate for Liver Function Testing
Authors: Mark Tulchinsky, Kyaw N. Tun
Journal: Clinical Nuclear Medicine (2012)

This study aimed to assess which region of interest results in the best intraobserver reproducibility of mebrofenin clearance rate (MCR) processing.Mebrofenin clearance rate was calculated according to Ekman's formalism. Processing methods included smaller left ventricular (LV) versus larger regions, nearly the whole heart (WH), which were applied to either anterior (ANT) or geometric mean (GEO) data. Each variation was processed twice by an expert operator, and Pearson linear correlation (r) was used to test for reproducibility.Studies from 50 patients (16 women) were available for processing. Mean (SD) for age, model for end-stage liver disease, and Child scores were 54 (10) years (range, 23-70 y), 13.1 (4.9) (range, 6-30), and 7.8 (2.1) (range, 5-14), respectively. The linear correlation equations (r, significance) between the 2 processing takes were y=0.34x+4.3 (r=0.5442, P<0.0001) for MCR-LV-ANT, y=0.94x+0.33 (r=0.9464, P<0.0001) for MCR-LV-GEO, y=0.87x+0.50 (r=0.9760, P<0.0001) for MCR-WH-ANT, and y=0.92x+0.24 (r=0.9898, P<0.0001) for MCR-WH-GEO. The MCR-WH-GEO method had statistically better reproducibility when compared with the other methods.The highest reproducibility was found with the technique that used geometric mean data and the larger blood pool region of interest. Further work should address training approaches that foster optimal interoperator reproducibility, which could allow for wider implementation of this liver function parameter.
Abstract 2626: Apoptosis-related single nucleotide polymorphisms and the risk of non-small cell lung cancer in a case-control study of women
Authors: Anand Pathak, Angela S. Wenzlaff, Michele L. Cote, Greg R. Keele, Susan Land, Ann G. Schwartz
Journal: Cancer Research (2012)

Abstract Background: Often, lung cancer is diagnosed at later stages, resulting in a 15% 5-year survival rate. Improved survival is seen for those with early stage disease, thus it is crucial to identify genetic markers that can identify those at the highest risk for early disease. In this study, we focused on understanding the risk of developing non-small cell lung cancer (NSCLC) associated with germline single nucleotide polymorphisms (SNPs) in apoptosis related genes among women in the Detroit metropolitan area. Methods: 453 cases of NSCLC and 478 control subjects were examined in a population based case-control study. Since the allele frequency differed significantly in over 74% of the SNPs between whites and African Americans, analysis was stratified by race. Eight SNPs found not to be in HWE were excluded from the study, leaving 97 SNPs in 32 apoptosis related genes examined for association with risk of lung cancer. Odds ratios and 95% confidence intervals were estimated from unconditional logistic regression models using a dominant model, stratified by race, and adjusted for age, pack years smoked, ever/never smoking status, family history of lung cancer, history of COPD, BMI and education. Results: Among whites, a polymorphism in APAF-1 (rs1007573) was associated with a 2.86 fold increase in risk of lung cancer among smokers (95% CI: 1.58-5.16). SNPS in CD40 rs3765459 and rs1535045 were associated with a reduced risk of lung cancer among white smokers. After carrying out a backwards elimination procedure, only APAF-1 rs1007573 and CD40 rs1535045 remained as significant predictors of risk. Both of these SNPs were found to be noteworthy, as per the False Discovery Reporting Percentage (FDRP) method. In African Americans, 7 SNPs were found to be significantly associated with NSCLC. After the backwards elimination procedure, only SNPs in ATM rs1801516 (OR=24.15, 95% CI: 3.50-166.55), TNF rs1800629 (OR= 0.42, 95% CI: 0.18-0.99) and p63 rs6790167 (OR: 2.85, 95% CI:1.33-6.09) were found to be significant. Testing these SNPs using the FDRP method revealed that only p63 (rs6790167) was noteworthy. Indeed, this locus may represent an important target in NSCLC, as previous SNPs in p63 have been reported to increase the risk of lung cancer in larger GWAS studies. Conclusions: We report two significant SNPs associated with NSCLC risk in whites (APAF-1 rs1007573 and CD40 rs1535045) and one significant SNP in African Americans (p63 rs6790167) as potentially important contributors to NSCLC. 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 2626. doi:1538-7445.AM2012-2626
Abstract 4039: Loss of imprinting in PEG3, MEST and ARHI/DIRAS3 in invasive breast cancer
Authors: Timothy M. Barrow, Rachel E. Ellsworth, Holly R. Harris, Ludovic Barault, Allyson Valente, Craig D. Shriver, Karin B. Michels
Journal: Cancer Research (2012)

Abstract Genomic imprinting is the epigenetic regulation of genes to enable monoallelic expression according to parental origin. Imprinting is established in the germline and is particularly important in the regulation of fetal development; loss of imprinting (LOI) has been implicated in the development of a variety of childhood disorders and several cancer types. We investigated loss of imprinting in PEG3, MEST and ARHI/DIRAS3 in breast cancer. Blood and tissue samples from women with benign breast disease or no abnormalities (n = 52) and patients with invasive breast cancer (n = 37) were provided by the Clinical Breast Care Project at the Walter Reed Army Medical Center (Washington, USA). DNA extracted from the samples was bisulfite converted and the methylation status of the three genes determined by pyrosequencing. Loss of PEG3 imprinting was observed in 2% of benign tissues and 34% of invasive cancers. LOI in MEST was similarly observed in 4% of benign tissues and 39% of invasive cancers, while in ARHI/DIRAS3 it was observed in 11% of benign samples and 54% of invasive ones. LOI was not observed in blood samples for any of the three genes, suggesting that these epigenetic alterations are highly tissue-specific. There was no correlation between the methylation profiles of the three genes (Spearman's rank correlation coefficient; p = &amp;gt;0.25). Loss of imprinting in PEG3, MEST and ARHI/DIRAS3 appears to be a frequent event in breast cancer, and it is more common in invasive forms than benign proliferative breast disease. The impact of the observed methylation changes upon allele-specific expression is currently investigated. 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 4039. doi:1538-7445.AM2012-4039