tbuckley/cabot-search huggingface dataset:
Abstract 2551: Correlation Between the Number of Lipid Core Containing Plaques Identified by a Near Infrared Spectroscopy System and Histologic Findings
Authors: Zhihua He, Craig M Gardner, Sean P Madden, Edward L Hull, Jennifer B Lisauskas, Stephen T Sum, Cory M Doucet, Thomas M Meese, Nisse V Clark, Tianchen Shi, James E Muller
Journal: Circulation (2008)

A catheter-based near infrared spectroscopy (NIRS) system has recently been cleared by the FDA for detection of lipid core containing plaques of interest (LCP) and lipid core burden index (LCBI) in patients undergoing coronary arteriography. NIRS data are plotted as a map (chemogram) of pullback distance versus rotation, with yellow indicating lipid (see below). Analyses for LCP were based on a 2mm block chemogram and LCBI. An algorithm has been developed to perform automated enhancement of the chemogram and facilitate calculation of the number of LCPs (nLCP) in a segment of artery. The goal is to determine if the enhanced algorithm performs as well as the previously validated LCP and LCBI measures, as determined by histology in human coronary autopsy specimens. NIRS data were obtained from 181 segments from 78 hearts and compared with histology at 2 mm intervals. The image analysis was applied to the chemogram and the nLCP calculated. The ROC analysis of the nLCP versus presence of fibroatheroma in each segment yielded an AUC of 0.84 (95% CI 0.77– 0.89). When one or more LCP was detected, 87% sensitivity and 70% specificity were observed for detection of fibroatheroma. The Spearman correlation between nLCP and LCBI was 0.83 (p-value ≤0.0001). The correlation coefficient of nLCP between repeat pullbacks was 0.83 (p-value ≤0.0001). The number of NIRS-detected LCP in chemograms identified with image enhancement correlates well with previously validated measures and the presence of fibroatheroma by histology. This method has the potential to enhance the clinical utility of the chemogram.
Abstract 272: Hyperhomocysteinemia Potentiated the Impairment of Hydrogen Sulfide-induced Endothelium-derived Hyperpolarization-mediated Vascular Relaxation in Diabetic Db/db Mice
Authors: Zhongjian Cheng, Xiaohua Jiang, Xinggui Shen, Pu Fang, Raj Kishore, Chris Kevil
Journal: Circulation Research (2015)

Background: Cumulative evidence indicates that plasma homocysteine (Hcy) level is positively correlated with cardiovascular mortality in Type 2 diabetic patients. Aims: To explore the effects and mechanisms of elevated plasma Hcy level[[Unable to Display Character: &amp;#8213;]] hyperhomocysteinemia (HHcy) on endothelial function in db/db mice. Methods and Results: HHcy was induced in diabetic db/db and non-diabetic db/+ mice fed with a high methionine diet (HM, 2% methionine) for 8 weeks (plasma tHcy=54.31±5.4 and 34.21±4.15 μM). Endothelial function was examined in small mesenteric arteries (SMA) using myographs. In non-diabetic mice, HHcy did not change vascular relaxation to acetylcholine (Ach); whereas, nitric oxide (NO)- and prostacyclin (PGI2)-mediated relaxation to Ach were impaired. Interestingly, endothelium-derived hyperpolarization factor (EDHF)-mediated relaxation to Ach was improved. In diabetic mice, HHcy potentiated the impairment of NO-, PGI2- and EDHF-mediated relaxation to Ach. Moreover, sodium hydrogen sulfide (NaHS), a donor of hydrogen sulfide (H2S), induced EDHF-mediated relaxation which was impaired in diabetic mice and potentiated by HHcy. NS309, a non-specific calcium-activated potassium channel (Kca) activator, significantly improved H2S- and Ach-induced EDHF-mediated relaxation in diabetic mice with HHcy. Tram-34, an intermediate conductance Kca (IK) blocker, but not small conductance Kca blocker apamin, diminished HHcy-induced impairment of EDHF-mediated relaxation in diabetic mice, suggesting that IK inactivation plays a major role. Free sulfide was decreased in plasma and SMA of diabetic mice which was potentiated with HHcy. Superoxide generation was increased and potentiated by HHcy in lung ECs from diabetic mice. Moreover, PEG-SOD improved vascular relaxation in diabetic mice with HHcy. Finally, tyrosine nitration of IK was increased in human cardiac microvascular endothelial cells (ECs) treated with either D-glucose (25 mM) or DL-Hcy (500 μM) for 48h, which was potentiated by a combination of D-glucose and DL-Hcy. Conclusions: H2S is a major EDHF in resistant arteries in mouse. H2S-contributed EDHF-mediated vascular relaxation was impaired in diabetes and was potentiated by HHcy via oxidative stress and IK inactivation.
Phase I trial of dimethyl fumarate, temozolomide, and radiation therapy in glioblastoma multiforme.
Authors: Danielle A. Shafer, Zhi-jian Chen, Timothy Harris, Mary Beth Tombes, Ellen Shrader, Kathryn Strickler, Alison A. Ryan, Paul Dent, Mark Gordon Malkin
Journal: Journal of Clinical Oncology (2017)

2060 Background: Evidence is increasing for altered immune responses in malignant gliomas. Tumor-associated microglia/macrophages infiltrate human glioma tissue and produce cytokines that promote glioma growth, invasion and angiogenesis. Dimethyl fumarate (DMF), approved for relapsing-remitting multiple sclerosis, is toxic to in vitro activated microglial cells. Based on pre-clinical data demonstrating synergism with radiation (RT) and temozolomide (TMZ), we conducted a phase I study of DMF in patients with newly-diagnosed glioblastoma (GBM) in combination with RT and TMZ. Methods: Using a standard 3+3 dose escalation design (3 dose levels: 120 mg bid, 240 mg bid and 240 mg tid), newly-diagnosed GBM patients received daily DMF with RT (60 Gy) and concurrent TMZ 75 mg/m2 daily, followed by adjuvant DMF (continuously) and TMZ for up 6 maintenance cycles (150-200 mg/m2 on days 1-5 of each 28 day cycle). The maximum tolerated dose (MTD) was defined as the dose with ≤ 1/6 dose-limiting toxicities (DLT). The MTD was determined by evaluation of DLTs during the first 6 weeks of therapy. Results: Twelve patients were treated at the three dose levels, and no DLT was identified. There were no unexpected toxicities. The most common toxicities were lymphopenia (11 grade 3/4 events) and thrombocytopenia (2 grade 3/4 events). The only grade 3/4 non-heme toxicity was a grade 3 hemorrhoid event. Of the 12 evaluable patients, one remains on active treatment in maintenance phase. Three patients completed all treatment (concurrent and maintenance) with stable disease. Two patients had a partial response (RANO criteria) but then experienced disease progression during maintenance. Five patients had disease progression during study treatment and one patient chose to withdraw from the study during maintenance. Conclusions: These data suggest that DMF may be safely combined with RT and TMZ in GBM patients. A phase II study is under consideration. Clinical trial information: NCT02337426.
Genetic susceptibility to COPD (multiple letters)
Authors: C. Ruse, S. G. Parker, P. Burton, A. Wardlaw, J. J. Yim, G. Y. Park, C. T. Lee, Y. W. Kim, Sungkoo Han, Y. S. Shim, Chul Gyu Yoo, M. Yoshikawa, K. Hiyama, S. Ishioka, H. Maeda, A. Maeda, A. Budhi, M. Yamakido
Journal: Thorax (2000)
Prospective randomized biomarker study of metformin and lifestyle intervention for prevention in obese postmenopausal women at increased risk for endometrial cancer.
Authors: Melinda S. Yates, Karen Basen-Engquist, Qian Zhang, Rosemarie Schmandt, Meena Medepalli, Denise R Nebgen, Beth Soletsky, Erma J Levy, Bryan M. Fellman, Diana L Urbauer, Karen H. Lu
Journal: Journal of Clinical Oncology (2017)

1551 Background: Obesity significantly increases risk of endometrial cancer (EC) through systemic metabolic effects and local tissue action, driven by estrogen and dysregulated insulin signaling. EC is most commonly diagnosed in postmenopausal women. Metformin, an antidiabetes drug, and lifestyle intervention were evaluated for effects on endometrial proliferation and serum biomarkers, in parallel with weight loss. Methods: Obese postmenopausal women were randomized into 4 groups for a 16 week intervention using a 2 (metformin 1700 mg/day vs placebo) x 2 (lifestyle intervention vs no lifestyle intervention) factorial design based on the Diabetes Prevention Program. Pre- and post-intervention endometrial biopsies were assessed for proliferation (% Ki67+). Body weight and serum markers were measured pre- and post-intervention (estrone, FSH, DHEA-S, SHBG, IGF-1, adiponectin, omentin, insulin, glucose, A1C, ALT, triglycerides, and others). Results: Of 576 women approached for the study, 29 women were randomized and 26 completed the study. Similar adherence was seen for placebo and metformin, with 88% and 94% of doses taken, respectively. Adverse events were grade 1 or 2, most commonly flatulence, headache, and diarrhea. Metformin+lifestyle group lost the most weight (-7.4%), followed by lifestyle (-5.2%), metformin only (-3.1%), and placebo (+0.1%). Endometrial proliferation was not changed. Overall proliferation was low (7.1% at baseline) with substantial variability even in this postmenopausal cohort. Biopsies produced limited endometrium, precluding evaluation of other tissue markers. Metformin significantly increased serum DHEA (p = 0.002). SHBG increased (p = 0.031) and insulin decreased with lifestyle intervention (p = 0.035) but were not statistically significant after multiple comparisons correction. Conclusions: Metformin and lifestyle intervention produced positive changes in serum markers and weight loss. While it is known that obese postmenopausal women are at increased risk for EC, improved biomarkers are needed to stratify risk and test prevention strategies, particularly at the endometrial tissue level. Clinical trial information: NCT01697566.
Preoperative neutrophil lymphocyte ratio as a predictor of outcomes in patients with early stage non-small cell lung cancer.
Authors: Pradnya Dinkar Patil, Sagar Rakshit, Arnab Basu, Nathan A. Pennell, James Stevenson, Usman Ahmad, Paul Elson, Sudish C. Murthy, Vamsidhar Velcheti
Journal: Journal of Clinical Oncology (2016)

e23069 Background: The neutrophil lymphocyte ratio (NLR), a surrogate marker for systemic inflammation, has been shown to have prognostic value in predicting outcomes in various cancers. We analyzed a cohort of patients with early stage NSCLC with the hypothesis that an elevated pre-operative NLR predicts worse OS and RFS. Methods: Patients with NSCLC treated at Cleveland Clinic from 2006 to 2014 with early stage resectable lung cancer were included. NLR was categorized into three categories < 2.5, 2.5-7.5, ≥ 7.5 based on a recursive portioning algorithm. Univariable analysis was performed to identify the factors that influenced OS and RFS. For categorical variables, Wilcoxon rank sum test was used for factors with two categories, Kruskal-Wallis test for > 2 unordered categories, Jonckheere-Terpstra test for > 2 ordered categories. t-test was used for correlations. A multivariable proportional hazards model was then used to assess the impact of NLR on OS and RFS after adjusting for age, gender, tumor size, pathological stage and histology. Results: 781 patients were included in the study. Baseline demographics, pathological stage and their correlation with NLR are described in the table. The 5-year OS was 73 ± 2% (NLR < 2.5), 60 ± 3% (NLR 2.5-7.5) and 38 ± 8% (NLR ≥ 7.5); RFS at 5 years was 59 ± 4% (NLR < 2.5), 49 ± 3% (NLR 2.5-7.5) and 27 ± 7% (NLR ≥ 7.5). In a multivariable analysis, preoperative NLR was associated with poorer OS with a HR of 1.31 (1.03-1.67) p = 0.03 and RFS with a HR 1.32 (1.07-1.64), p = 0.009. Conclusions: High preoperative NLR predicts worse outcome in patients with early stage NSCLC. Understanding the tumor immune contexture and biologic mechanisms in these patients may inform future clinical trial designs using immunotherapy in this population. Variable N (%) or median (range) NLR median (range) P value Male 420 (54%) 2.96 (0.05-41.23) < 0.0001 Female 361 (46%) 2.47 (0.54-30.36) Age < 70 476 (61%) 2.64 (0.53-41.23) .001 Age ≥ 70 305 (39%) 2.97 (0.05-31.67) ANC (K/πL) 4.8 (1.0-23.5) ALC (K/πL) 1.7 (0.2-119.8) Stage 1A 278 (37%) 2.53 (0.63-22.50) < .0001 1B 160 (21%) 2.60 (0.54-31.67) 2A 126 (17%) 2.94 (0.53-41.23) 2B 77 (10%) 3.13 (0.85-22.90) 3 101 (13%) 3.00 (0.53-12.19) 4 11 (1%) 3.58 (0.77-7.57)
Comparative Anticoagulant Effects of Recombinant Thrombomodulin, Antithrombin, and Unfractionated Heparin, Hematological Implications
Authors: Zafar Siddiqui, Parul Aggarwal, Omer Iqbal, Debra Hoppensteadt, Mary Lewis, Schuharazad Abro, Kazuhisa Tsuruta, Jawed Fareed
Journal: Blood (2016)
Moral Dilemma in the ER
Authors: Mustafa Al-Shamsi
Journal: Annals of Internal Medicine (2017)

On Being a Doctor20 June 2017Moral Dilemma in the ERMustafa Al-Shamsi, MDMustafa Al-Shamsi, MDFrom Ministry of Health, Basra, Iraq.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2206 Audio Reading - “Moral Dilemma in the ER” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Moral Dilemma in the ER," by M. Al-Shamsi. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail On a cold, rainy evening last January, I arrived in my ER for a night shift. The place was already crowded; I could catch the ever-present scent of death; and I imagined, that evening as always, the presence of the souls of the deceased. Sign-out was perfunctory—fortunately, none of the patients was critical.I had a headache and was tired. I had been on the wards since morning and had not slept well for 2 days. I waited for a placid sunset that might spell a slow evening. On a similar night, I might see 7 to 10 patients. I ... Author, Article, and Disclosure InformationAffiliations: From Ministry of Health, Basra, Iraq.Corresponding Author: Mustafa Al-Shamsi, MD, Ashar Main Street, Ashar Central Mail, Box 113, Basra, Iraq 42001; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Moral Dilemma in the ER” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Moral Dilemma in the ER," by M. Al-Shamsi. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 June 2017Volume 166, Issue 12Page: 909-910KeywordsCardiopulmonary resuscitationFearHeadachesHeart rateLungsNursesOxygenSafetyThoraxVital signs ePublished: 20 June 2017 Issue Published: 20 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
不同文化传统的国家中饮酒模式与缺血性心脏病的关系：心肌梗死前瞻性流行病学研究（PRIME研究）
Authors: Jean-Bernard, Ruidavets, Pierre, Ducimetiere, Alun, Evans, Michele, Montaye, Bernadette, Haas, Annie, Bingham, John, Yamell, Philippe, Amouyel, Dominique, Arveiler, Frank, Kee
Journal: BMJ (2011)
Case 19-2017 — A 53-Year-Old Woman with Leg Numbness and Weakness
Authors: William S. David, Michael P. Bowley, William A. Mehan, John H. Shin, Elizabeth R. Gerstner, John C. DeWitt
Journal: New England Journal of Medicine (2017)

A 53-year-old woman was admitted to the hospital because of progressive asymmetric hypoesthesia and weakness in the legs. Urinary retention, absence of rectal tone, and saddle anesthesia developed. A diagnostic test was performed.
Procedural Experience for Transcatheter Aortic Valve Replacement and Relation to Outcomes
Authors: John D. Carroll, Sreekanth Vemulapalli, Dadi Dai, Roland Matsouaka, Eugene Blackstone, Fred Edwards, Frederick A. Masoudi, Michael Mack, Eric D. Peterson, David Holmes, John S. Rumsfeld, E. Murat Tuzcu, Frederick Grover
Journal: Journal of the American College of Cardiology (2017)
Efficacy of Adoptive Immunotherapy By Donor Lymphocyte Infusions after Allogeneic Stem Cell Transplantation from Related an Unrelated Donors: A Single Center Retrospective Analysis
Authors: Philipp Hemmati, Christin Vogelsänger, Theis Terwey, Christian Jehn, Lam G. Vuong, Igor Wolfgang Blau, Olaf Penack, Bernd Dörken, Renate Arnold
Journal: Blood (2016)
Antitumor activity and safety of FPA144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody, in patients with FGFR2b+ gastric cancer and advanced solid tumors.
Authors: Jeeyun Lee, Johanna C. Bendell, Sun Young Rha, Yung-Jue Bang, Lee Clark, Hong Xiang, Kristen L. Pierce, Kartik Krishnan, Robert S. Sikorski, Drew W. Rasco
Journal: Journal of Clinical Oncology (2016)

2502 Background: FGFR2b-overexpressing gastric cancer is a distinct setting with poor prognosis. FPA144, a humanized monoclonal IgG1 antibody directed against FGFR2b, has been engineered for enhanced ADCC and specific FGFR2 signaling blockade. FPA144-001 is a two-part first-in-human Phase 1 study of FPA144 monotherapy: Part 1 dose escalation in patients with advanced solid tumors (Part 1A) and advanced gastric cancer (Part 1B); and Part 2 expansion to evaluate the safety, PK and early efficacy in selected gastric cancer patients treated at the recommended dose (RD). Methods: Part 1A was a 3+3 design to assess safety and PK of FPA144 and to establish a RD. Patients with gastric cancer were enrolled in parallel Part 1B cohorts to provide gastric cancer PK. Part 2 eligibility requires a diagnosis of gastric cancer and tissue for FGFR2b expression analysis. Tumor testing is done centrally using a proprietary FGFR2b-selective IHC assay. Results: Part 1 of the study enrolled 27 patients – 19 in Part 1A and 8 in Part 1B, including 6 patients with FGFR2b-overexpressing gastric cancer tumors in Part 1B. No DLTs, treatment-related SAEs or treatment delays were observed during dose escalation; 15mg/kg q2w is the dose being explored in Part 2. Fatigue and decreased appetite were the most common treatment-related AEs. In Part 1A, a patient with recurrent bladder cancer treated at 3mg/kg had radiographic and metabolic disappearance of lesions by day 50. Of 6 FGFR2b-overexpressing gastric cancer patients in Part 1B, 2 achieved PRs (1 confirmed, 1 unconfirmed at time of analysis) and 3 demonstrated SD as best response (2 confirmed, 1 unconfirmed). Initial PK analysis demonstrates that FPA144 exposure in subjects with gastric cancer is similar to that in other solid malignancies. Updated safety, PK, and efficacy data will be presented. Conclusions: FPA144, an afucosylated monoclonal antibody directed against FGFR2b, has a well-tolerated safety profile: no DLTs in dose escalation and no treatment-related SAEs to date. Early evidence of single-agent anti-tumor effect in patients with FGFR2b-overexpressing gastric cancer and bladder cancer has been observed. Clinical trial information: NCT02318329.
Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies
Authors: Xavier Ayrignac, Gaël Nicolas, Clarisse Carra-Dallière, Didier Hannequin, Pierre Labauge
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Adult-onset genetic leukoencephalopathies and leukodystrophies are increasingly recognized as a heterogeneous group of disorders with new diagnostic approaches and potential treatments. In the new era of genomics, the challenging interpretation of individual genetic variations requires an accurate phenotypic description and classification. Clinical and magnetic resonance imaging (MRI)–based approaches have been proposed to improve the diagnostic process of adult-onset leukoencephalopathies. Cerebral calcifications, when associated with white matter hyperintensities, are of major importance in the decision-making process to focus the diagnosis among the diversity of rare causes. <h3>Observations</h3> This literature review demonstrated that the morphologic features and topography of the calcifications observed in a careful combined analysis of computed tomographic and MRI scans may help indicate the diagnosis of adult-onset genetic leukoencephalopathies. Vascular genetic leukoencephalopathies are an important cause of leukoencephalopathy with calcifications. Among them,<i>COL4A1</i>-related disorders are frequently associated with spotlike calcifications in the basal ganglia. Adult-onset leukoencephalopathy with axonal spheroids, a probably underestimated disorder, is associated with a specific pattern of calcifications: small, symmetric, sparing the basal ganglia, and a stepping stone appearance in the frontal pericallosal region. Moreover, disorders primarily associated with basal ganglia calcifications, such as primary familial brain calcifications, can be associated with marked leukoencephalopathy. <h3>Conclusions and Relevance</h3> The number of identified causes of adult-onset genetic leukoencephalopathies has recently increased. A diagnostic algorithm should take into account the pattern of calcifications to better target the genetic analyses.
Expression of androgen receptor and epidermal growth factor receptor in invasive breast cancer: A retrospective study of 1,438 patients from China.
Authors: Junqing Chen, Zhanhong Chen, Xiaojia Wang
Journal: Journal of Clinical Oncology (2017)

e12587 Background: Triple-negative breast cancer (TNBC) is lack of clinically efficient targeted therapies and usually more aggressive with higher rate of distant metastasis and poor overall survival as compared with other breast cancer subtypes. Recent evidence demonstrates that androgen receptor (AR) and epidermal growth factor receptor (EGFR) are involved in the pathogenesis of TNBC. The aim of this study was to explore the expression of AR and EGFR in invasive breast cancer and evaluate the potential of AR and EGFR as biomarkers in TNBC. Methods: In this retrospective study, we analyzed 1438 patients with invasive breast cancer in our hospital from 2015 to 2016. Estrogen receptor (ER) expression, progesterone receptor (PR) expression, Ki-67 index, AR and EGFR expression were detected by immunohistochemical assay. HER2 state was determined by immunohistochemical and FISH assay. χ2 test was used for the analysis. Results: Among 1438 breast cancer patients, 272 (18.9%) cases were TNBC and 1165 (81.0%) cases were non-TNBC. TNBC patients had a low AR expression as compared with non-TNBC patients (29.8% vs 90.2%). There was a significant difference in AR expression in TNBC compared in non-TNBC ( P= 0.000). In contrast, TNBC patients had a high EGFR expression as compared with non-TNBC patients (90.9% vs 21.1%) ( P= 0.000). There was also a significant difference in Ki-67 index in TNBC compared in non-TNBC (89.9% vs 70.1%) ( P= 0.000). AR-positive TNBC patients had a low Ki-67 index expression as compared to AR-negative TNBC (82.7% vs 93.6%). No significant difference of EGFR expression was found between AR-positive TNBC and AR-negative TNBC. Conclusions: AR expression is associated with Ki-67 index and may be as a potential biomarker for targeted therapy in AR-positive TNBC patients.